Knowledge Base | What's New | Contact Us |

Available 2D QSAR/Fingerprint Models (kca)


Models that are provided free of charge with ICM-VLS are shaded green.

modelnamenof_ligandq2tagTissueADRcategoryDiseaseFunctionDrug_Mechanism
kca5HT1A5-hydroxytryptamine receptor 1A69880.6225Nature11159Detected in lymph nodes, thymus and spleen. Detected in activated T cells, but not in resting T cells. <a class="attribution" href="P08908#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P08908#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>Asthenia
Cardiac failure congestive
Dry eye
Dry mouth
Insomnia
Orthostatic hypotension
Peripheral coldness
Priapism
Psychotic disorder
Raynaud's phenomenon
G-protein coupled receptor 1Anxiety disorder, unspecified
Brain ischemia
Cocaine dependence
Depression
Detrusor hyperreflexia
Mood [affective] disorders
Skeletal muscle associated spasticity
Urinary incontinence
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase. Serotonin 1a (5-HT1a) receptor agonist: Ergoloid
Serotonin 1a (5-HT1a) receptor partial agonist: Aripiprazole, Buspirone, Methysergide, Vilazodone
kca5HT1B5-hydroxytryptamine receptor 1B17480.7157Detected in cerebral artery smooth muscle cells (at protein level). Detected in brain cortex, striatum, amygdala, medulla, hippocampus, caudate nucleus and putamen. <a class="attribution" href="P28222#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="P28222#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a> <a class="attribution" href="P28222#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a>Gestational hypertension
Orthostatic hypotension
Psychotic disorder
G-protein coupled receptor 1Anxiety disorder, unspecified
Migraine
Obsessive-compulsive disorder
Pulmonary hypertension
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase. Serotonin 1b (5-HT1b) receptor agonist: Almotriptan, Eletriptan, Ergoloid, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan
kca5HT1D5-hydroxytryptamine receptor 1D16700.8155Detected in brain neocortex and caudate nucleus (at protein level). <a class="attribution" href="P28221#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Dyskinesia
Gestational hypertension
Orthostatic hypotension
Somnolence
Tachycardia
G-protein coupled receptor 1Migraine
Obsessive-compulsive disorder
Vascular headache
Vomiting
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase. Serotonin 1d (5-HT1d) receptor agonist: Almotriptan, Dihydroergotamine, Eletriptan, Ergotamine, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan
kca5HT1F5-hydroxytryptamine receptor 1F5030.7445G-protein coupled receptor 1Migraine This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase. Serotonin 1f (5-HT1f) receptor agonist: Almotriptan, Eletriptan
kca5HT2A5-hydroxytryptamine receptor 2A56740.6546Nature11159Detected in brain cortex (at protein level). Detected in blood platelets. <a class="attribution" href="P28223#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Akathisia
Anticholinergic syndrome
Corneal pigmentation
Dermatitis allergic
Dry mouth
Dystonia
Ejaculation disorder
Electrocardiogram change
Erectile dysfunction
Extrapyramidal disorder
Fibrocystic breast disease
Galactorrhoea
Gynaecomastia
Hypercholesterolaemia
Hyperprolactinaemia
Hyperthermia
Insomnia
Lenticular opacities
Lipid metabolism disorder
Mania
Miosis
Mydriasis
Nasal congestion
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Tachycardia
Tardive dyskinesia
Weight increased
G-protein coupled receptor 1Acute ureteric colic
Anxiety disorder, unspecified
Arterial embolism and thrombosis
Cocaine dependence
Depression
Diabetic nephropathy
Diabetic neuropathy
Essential (primary) hypertension
Migraine
Schizophrenia
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins. Serotonin 2a (5-HT2a) receptor antagonist: Aripiprazole, Asenapine, Carphenazine, Chlorpromazine, Chlorprothixene, Clozapine, Cyclobenzaprine, Droperidol, Haloperidol, Haloperidol Decanoate, Iloperidone, Loxapine, Lurasidone, Mesoridazine, Mirtazapine, Molindone, Nefazodone, Olanzapine, Paliperidone, Pimozide, Promazine, Quetiapine, Risperidone, Thioridazine, Thiothixene, Trazodone, Trifluoperazine, Trimipramine, Ziprasidone
kca5HT2B5-hydroxytryptamine receptor 2B27190.5664Nature11159Ubiquitous. Detected in liver, kidney, heart, pulmonary artery, and intestine. Detected at lower levels in blood, placenta and brain, especially in cerebellum, occipital cortex and frontal cortex. <a class="attribution" href="P41595#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P41595#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P41595#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="P41595#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a> <a class="attribution" href="P41595#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Dry mouth
Dyskinesia
Extrapyramidal disorder
Insomnia
Nasal congestion
Orthostatic hypotension
G-protein coupled receptor 1Anxiety disorder, unspecified
Migraine
P-chloroamphetamine-induced hyperglycemia
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins. Serotonin 2b (5-HT2b) receptor antagonist: Methysergide
Serotonin 2b (5-HT2b) receptor partial agonist: Methylergonovine
kca5HT2C5-hydroxytryptamine receptor 2C44290.6349Nature11159Detected in brain. <a class="attribution" href="P28335#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>Akathisia
Dermatitis allergic
Dry mouth
Dystonia
Ejaculation disorder
Extrapyramidal disorder
Galactorrhoea
Hypercholesterolaemia
Hyperthermia
Insomnia
Lipid metabolism disorder
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Psychotic disorder
Tachycardia
Tardive dyskinesia
G-protein coupled receptor 1Acute ureteric colic
Cocaine dependence
Motor disorder
Schizophrenia
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins. Serotonin 2c (5-HT2c) receptor agonist: Lorcaserin
Serotonin 2c (5-HT2c) receptor antagonist: Carphenazine, Chlorprothixene, Cyclobenzaprine, Loxapine, Methixene, Methysergide, Mirtazapine, Nefazodone, Olanzapine, Quetiapine, Risperidone, Thioridazine, Trazodone, Trifluoperazine, Trimipramine, Ziprasidone
kca5HT3A5-hydroxytryptamine receptor 3A16680.6877Nature11159Expressed in cerebral cortex, amygdala, hippocampus, and testis. Detected in monocytes of the spleen and tonsil, in small and large intestine, uterus, prostate, ovary and placenta. <a class="attribution" href="P46098#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a>ligand-gated ion channelAlcohol dependence
Alcoholism
Irritable bowel syndrome
Nausea and vomiting
Pruritus
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel. Serotonin 3a (5-HT3a) receptor antagonist: Alosetron, Dolasetron, Granisetron, Metoclopramide, Ondansetron, Palonosetron
kca5HT3B5-hydroxytryptamine receptor 3B10450.6419Expressed in the brain cortex, in the caudate nucleus, the hyppocampus, the thalamus and the amygdala. Detected in the kidney and testis as well as in monocytes of the spleen, small and large intestine, uterus, prostate, ovary and placenta. <a class="attribution" href="O95264#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="O95264#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>Euphoric moodligand-gated ion channelDiarrhea
Irritable Bowel Syndrome (IBS)
kca5HT4R5-hydroxytryptamine receptor 48440.6991Isoform 5-HT4(A) is expressed in ileum, brain, and atrium, but not in the ventricle. <a class="attribution" href="Q13639#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>G-protein coupled receptor 1Alzheimer's disease
Cardiac arrhythmias
Dementia
Diarrhoea-predominant irritable bowel syndrome
Drug dependence
Irritable bowel syndrome
Psychiatric illness
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulates adenylate cyclase. Serotonin 4 (5-HT4) receptor agonist: Cisapride, Metoclopramide
Serotonin 4 (5-HT4) receptor partial agonist: Tegaserod
kca5HT5A5-hydroxytryptamine receptor 5A5930.7954G-protein coupled receptor 1Bipolar affective disorder
Depression
Schizophrenia
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.
kca5HT5B5-hydroxytryptamine receptor 5B860.5778Expressed predominantly in the central nervous system; in the hippocampus, habenula, and the doral raphe.G-protein coupled receptor 1This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins. Probably involved in anxiety and depression.
kca5HT6R5-hydroxytryptamine receptor 622920.6988Expressed in several human brain regions, most prominently in the caudate nucleus.Akathisia
Dry mouth
Dystonia
Extrapyramidal disorder
Galactorrhoea
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Tardive dyskinesia
G-protein coupled receptor 1Irritable bowel syndrome
Nausea and vomiting
Pruritus in chronic liver disease
Schizophrenia
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulates adenylate cyclation.
kca5HT7R5-hydroxytryptamine receptor 714610.6044Isoform <a href="#P34969-2" onclick="ensureIsoformSequenceVisible('P34969-2'); return true;">A</a> is the predominant isoform in spleen, caudate and hippocampus. Isoform <a href="#P34969-3" onclick="ensureIsoformSequenceVisible('P34969-3'); return true;">B</a> is expressed at lower levels. Isoform <a href="#P34969" onclick="ensureIsoformSequenceVisible('P34969'); return true;">D</a> is a minor isoform in term of expression. <a class="attribution" href="P34969#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>Akathisia
Dystonia
Ejaculation disorder
Hyperthermia
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Tardive dyskinesia
G-protein coupled receptor 1Migraine
Neuropsychiatric disorders
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulates adenylate cyclation.
kcaA4Amyloid beta A4 protein2580.5755Expressed in all fetal tissues examined with highest levels in brain, kidney, heart and spleen. Weak expression in liver. In adult brain, highest expression found in the frontal lobe of the cortex and in the anterior perisylvian cortex-opercular gyri. Moderate expression in the cerebellar cortex, the posterior perisylvian cortex-opercular gyri and the temporal associated cortex. Weak expression found in the striate, extra-striate and motor cortices. Expressed in cerebrospinal fluid, and plasma. Isoform <a href="#P05067-4" onclick="ensureIsoformSequenceVisible('P05067-4'); return true;">APP695</a> is the predominant form in neuronal tissue, isoform <a href="#P05067-8" onclick="ensureIsoformSequenceVisible('P05067-8'); return true;">APP751</a> and isoform <a href="#P05067" onclick="ensureIsoformSequenceVisible('P05067'); return true;">APP770</a> are widely expressed in non-neuronal cells. Isoform <a href="#P05067-8" onclick="ensureIsoformSequenceVisible('P05067-8'); return true;">APP751</a> is the most abundant form in T-lymphocytes. Appican is expressed in astrocytes. <a class="attribution" href="P05067#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="P05067#ref27" onclick="ensureReferenceVisible('ref27')">Ref.27</a>APPAlzheimer's disease
Dementia
Pancreatic cancer
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions.
kcaAA1RAdenosine receptor A163880.6098Nature11159G-protein coupled receptor 1Analgesics
Asthma
Cardiac arrhythmias
Chronic ileitis
Inflammation
Inflammatory bowel disease
Insulin resistance (obesity-related)
Noninsulin-dependent diabetes mellitus
Pain
Renal failure
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Adenosine A1 receptor antagonist: Theophylline
kcaAA2ARAdenosine receptor A2a65940.682Nature11159Angina pectoris
Flushing
Palpitations
G-protein coupled receptor 1Analgesics
Brain injury
Depression
Dyskinesia
Inflammation
Ischemia reperfusion injuries
Neurodegenerative diseases
Neuropsychiatric disorders
Oxygen-induced retinopathy
Pain
Parkinson's disease
Renal diseases
Receptor for adenosine, and the activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Adenosine A2 receptor antagonist: Pentoxifylline
Adenosine A2a receptor agonist: Regadenoson
kcaAA2BRAdenosine receptor A2b34020.674PalpitationsG-protein coupled receptor 1Asthma Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Adenosine A2b receptor antagonist: Theophylline
Adenosine receptor agonist: Adenosine
Adenosine receptor antagonist: Caffeine, Theophylline, Theophylline Glycinate
kcaAA3RAdenosine receptor A337310.6903Nature11159G-protein coupled receptor 1Cancer, unspecific
Chronic ileitis
Depression
Inflammatory bowel disease
Myocardial ischemia and reperfusion injury
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. possible role in reproduction.
kcaAAKB15'-AMP-activated protein kinase subunit beta-1980.51335'-AMP-activated protein kinase beta subunitNon-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
kcaAAKB25'-AMP-activated protein kinase subunit beta-2630.70775'-AMP-activated protein kinase beta subunitNon-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
kcaAAKG15'-AMP-activated protein kinase subunit gamma-1860.50265'-AMP-activated protein kinase gamma subunitAMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
kcaAAKG25'-AMP-activated protein kinase subunit gamma-2630.7077Isoform B is ubiquitously expressed except in liver and thymus. The highest level is detected in heart with abundant expression in placenta and testis.5'-AMP-activated protein kinase gamma subunitWolff-Parkinson-White syndrome (WPWS) [MIM:194200]: A supernormal conduction disorder characterized by the presence of one or several accessory atrioventricular connections, which can lead to episodes of sporadic tachycardia. Note=The disease is caused by mutations affecting the gene represented in this entry. Cardiomyopathy, familial hypertrophic 6 (CMH6) [MIM:600858]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. CMH6 patients present Wolff-Parkinson-White ventricular preexcitation, enlarged myocytes without myofiber disarray, and glycogen- containing cytosolic vacuoles within cardiomyocytes. Note=The disease is caused by mutations affecting the gene represented in this entry. Glycogen storage disease of heart lethal congenital (GSDH) [MIM:261740]: Rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise. Note=The disease is caused by mutations affecting the gene represented in this entry.AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
kcaAAKG35'-AMP-activated protein kinase subunit gamma-3630.7077Skeletal muscle, with weak expression in heart and pancreas.5'-AMP-activated protein kinase gamma subunitAMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
kcaABC3ADNA dC->dU-editing enzyme APOBEC-3A8250.6769Expressed in peripheral leukocytes with higher expression in CD14-positive phagocytic cells. Highly expressed in keratinocytes and in periphery blood monocytes. Also detected in non-lymphoid tissues including lung and adipose tissues. Found at high levels in colorectal adenocarcinoma, Burkitt's lymphoma and chronic myelogenous leukemia.cytidine and deoxycytidylate deaminaseDNA deaminase (cytidine deaminase) with restriction activity against viruses, foreign DNA and mobility of retrotransposons. Exhibits antiviral activity against adeno- associated virus (AAV) and human T-cell leukemia virus type 1 (HTLV-1) and may inhibit the mobility of LTR and non-LTR retrotransposons. Selectively targets single-stranded DNA and can deaminate both methylcytosine and cytosine in foreign DNA. Can induce somatic hypermutation in the nuclear and mitochondrial DNA. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.
kcaABC3GDNA dC->dU-editing enzyme APOBEC-3G10000.5248Expressed in spleen, testes, ovary and peripheral blood leukocytes and CD4+ lymphocytes. Also expressed in non-permissive peripheral blood mononuclear cells, and several tumor cell lines; no expression detected in permissive lymphoid and non-lymphoid cell lines. Exists only in the LMM form in peripheral blood-derived resting CD4 T-cells and monocytes, both of which are refractory to HIV-1 infection. LMM is converted to a HMM complex when resting CD4 T-cells are activated or when monocytes are induced to differentiate into macrophages. This change correlates with increased susceptibility of these cells to HIV-1 infection.cytidine and deoxycytidylate deaminaseDNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. Exhibits potent antiviral activity against vif-deficient HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination- independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single-or double- stranded RNA. Exhibits antiviral activity also against simian immunodeficiency viruses (SIVs), hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV). May inhibit the mobility of LTR and non-LTR retrotransposons.
kcaABCA1ATP-binding cassette sub-family A member 1560.7731Widely expressed, but most abundant in macrophages.ABC transporterAtherosclerotic cardiovascular disease
Cardiovascular disease, unspecified
Hypercholesterolemia
Low high density lipoprotein syndromes
Camp-dependent and sulfonylurea-sensitive anion transporter. Key gatekeeper influencing intracellular cholesterol transport.
kcaABCG2ATP-binding cassette sub-family G member 23290.6919Anaemia
Thrombocytopenia
ABC transporter
kcaABL1Tyrosine-protein kinase ABL121580.6348protein kinaseMyeloma disease
kcaABL2Abelson tyrosine-protein kinase 22310.6301protein kinaseMyeloma disease
kcaACACAAcetyl-CoA carboxylase 13740.6358Expressed in brain, placental, skeletal muscle, renal, pancreatic and adipose tissues; expressed at low level in pulmonary tissue; not detected in the liver.Acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:613933]: An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth. Note=The disease is caused by mutations affecting the gene represented in this entry.Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
kcaACESAcetylcholinesterase35390.7768Isoform <a href="#P22303-2" onclick="ensureIsoformSequenceVisible('P22303-2'); return true;">H</a> is highly expressed in erythrocytes. <a class="attribution" href="P22303#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>Diarrhoea
Nausea
Salivary hypersecretion
type-B carboxylesterase/lipaseAlzheimer's disease
Cognitive deficits
Hypoxic-ischemic encephalopathy
Motor neurone disease
Parkinson's disease
Rapidly hydrolyzes choline released into the synapse. Acetylcholinesterase activator: Pralidoxime
Acetylcholinesterase inhibitor: Ambenonium, Demecarium, Donepezil, Echothiophate, Edrophonium, Galantamine, Hexafluorenium, Isoflurophate, Neostigmine, Pyridostigmine
kcaACH10Neuronal acetylcholine receptor subunit alpha-103830.4898Nature11159Expressed in inner-ear tissue, tonsil, immortalized B-cells, cultured T-cells and peripheral blood lymphocytes. <a class="attribution" href="Q9GZZ6#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q9GZZ6#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Death
Hypotension
Lung disorder
Muscle twitching
Respiratory disorder
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelAnalgesics
Neuropathic pain
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma.
kcaACHAAcetylcholine receptor subunit alpha4780.6128Isoform 1 is only expressed in skeletal muscle. Isoform 2 is constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus.ligand-gated ion channelMultiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. Note=The disease is caused by mutations affecting the gene represented in this entry. Note=The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs. Myasthenic syndrome, congenital, slow-channel (SCCMS) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early- onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. Congenital myasthenic syndrome slow-channel type is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes. Note=The disease is caused by mutations affecting the gene represented in this entry. Myasthenic syndrome, congenital, fast-channel (FCCMS) [MIM:608930]: A congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. Due in most cases to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential. Note=The disease is caused by mutations affecting the gene represented in this entry.After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHA2Neuronal acetylcholine receptor subunit alpha-24690.5979Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Hypotension
Lung disorder
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelAnesthesia
Postoperative residual curarisation
kcaACHA3Neuronal acetylcholine receptor subunit alpha-312340.6535ligand-gated ion channelAfter binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHA4Neuronal acetylcholine receptor subunit alpha-425500.7115Agitation
Apnoea
Bradycardia
Bronchospasm
Death
Hypotension
Irritability
Laryngospasm
Lung disorder
Nystagmus
Respiratory depression
Respiratory disorder
Respiratory failure
Salivary hypersecretion
Shock
ligand-gated ion channelAlzheimer's disease
Analgesics
Drug dependence
Frontal lobe epilepsy
Neurodegenerative diseases
Pain
After binding acetylcholine, the achr responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Neuronal acetylcholine receptor; alpha4/beta2 agonist: Nicotine, Nicotine Polacrilex, Varenicline
kcaACHA5Neuronal acetylcholine receptor subunit alpha-53320.5372Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Hypotension
Lung disorder
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelAnalgesics
Pain, unspecific
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHA6Neuronal acetylcholine receptor subunit alpha-63580.5422ligand-gated ion channelAfter binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHA7Neuronal acetylcholine receptor subunit alpha-718550.6188Agitation
Apnoea
Bradycardia
Bronchospasm
Irritability
Laryngospasm
Nystagmus
Respiratory depression
Respiratory disorder
Salivary hypersecretion
Shock
ligand-gated ion channelAlzheimer's disease
Analgesics
Drug dependence
Neuropsychiatric disorders
Pain
Schizophrenia
After binding acetylcholine, the achr responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHA9Neuronal acetylcholine receptor subunit alpha-93430.5525Expressed in cochlea, keratinocytes, pituitary gland, B-cells and T-cells. <a class="attribution" href="Q9UGM1#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q9UGM1#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="Q9UGM1#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Hypotension
Lung disorder
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelAnalgesics
Neuropathic pain
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma. May also regulate keratinocyte adhesion.
kcaACHBAcetylcholine receptor subunit beta4890.6167ligand-gated ion channelMyasthenic syndrome, congenital, slow-channel (SCCMS) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early- onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. Congenital myasthenic syndrome slow-channel type is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes. Note=The disease is caused by mutations affecting the gene represented in this entry. Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (CMS-ACHRD) [MIM:608931]: A post-synaptic congenital myasthenic syndrome. Congenital myasthenic syndromes (CMS) are inherited disorders of neuromuscular transmission that stem from mutations in presynaptic, synaptic, or postsynaptic proteins. Note=The disease is caused by mutations affecting the gene represented in this entry.After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHB2Neuronal acetylcholine receptor subunit beta-223670.7167Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Hypotension
Laryngospasm
Lung disorder
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelAlzheimer's disease
Analgesics
Drug dependence
Frontal lobe epilepsy
Neurodegenerative diseases
Pain, unspecified
Parkinson's disease
After binding acetylcholine, the achr responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHB3Neuronal acetylcholine receptor subunit beta-33700.5274ligand-gated ion channelAfter binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHB4Neuronal acetylcholine receptor subunit beta-411180.6631Apnoea
Bradycardia
Bronchospasm
Cardiac arrest
Respiratory failure
Salivary hypersecretion
ligand-gated ion channelSpecific cognitive deficits associated with aging and neurological diseases After binding acetylcholine, the achr responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHDAcetylcholine receptor subunit delta1410.6744ligand-gated ion channelMultiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. Note=The disease is caused by mutations affecting the gene represented in this entry. Myasthenic syndrome, congenital, slow-channel (SCCMS) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early- onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. Congenital myasthenic syndrome slow-channel type is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes. Note=The disease is caused by mutations affecting the gene represented in this entry. Myasthenic syndrome, congenital, fast-channel (FCCMS) [MIM:608930]: A congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. Due in most cases to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential. Note=The disease is caused by mutations affecting the gene represented in this entry.After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACHGAcetylcholine receptor subunit gamma1360.6822ligand-gated ion channelMultiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. Note=The disease is caused by mutations affecting the gene represented in this entry. Multiple pterygium syndrome, Escobar variant (EVMPS) [MIM:265000]: Non-lethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis. Note=The disease is caused by mutations affecting the gene represented in this entry.After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
kcaACK1Activated CDC42 kinase 15280.7018The Tyr-284 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. It also shows a significant increase in expression in prostate cancers during the progressive stages.protein kinaseNon-receptor tyrosine-protein and serine/threonine- protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr- 287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR.
kcaACM1Muscarinic acetylcholine receptor M135740.6946Nature11159Anticholinergic syndrome
Constipation
Cycloplegia
Diabetic eye disease
Dry mouth
Dry skin
Dysphagia
Dysuria
Extrapyramidal disorder
Hyperpyrexia
Hyperthermia
Hyperventilation
Hypohidrosis
Intraocular pressure increased
Mydriasis
Neuroleptic malignant syndrome
Photophobia
Suppressed lactation
Tachycardia
Urinary retention
Vision blurred
G-protein coupled receptor 1Alzheimer's disease
Bronchospasm (histamine induced)
Cognitive deficits
Schizophrenia
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Muscarinic acetylcholine receptor M1 agonist: Cevimeline
Muscarinic acetylcholine receptor M1 antagonist: Anisotropine, Atropine, Benztropine, Biperiden, Clidinium, Cycrimine, Dicyclomine, Diphemanil, Diphenidol, Ethopropazine, Glycopyrrolate, Hexocyclium, Isopropamide, Mepenzolate, Methixene, Methscopolamine, Oxyphencyclimine, Oxyphenonium, Procyclidine, Propantheline, Scopolamine, Tridihexethyl, Trihexyphenidyl
kcaACM2Muscarinic acetylcholine receptor M230710.6528Nature11159Anticholinergic syndrome
Constipation
Cycloplegia
Diabetic eye disease
Dry mouth
Dry skin
Extrapyramidal disorder
Gastric hypomotility
Hyperpyrexia
Intraocular pressure increased
Mydriasis
Salivary hypersecretion
Tachycardia
Urinary incontinence
Urinary retention
Vision blurred
G-protein coupled receptor 1Alzheimer's disease
Analgesics
Autoimmune cardiomyopathy
Bronchoconstriction (cold air-induced)
Chronic obstructive pulmonary disease, unspecified
Hypothermia
Neurogenic bladder
Pain, unspecified
Tremor, unspecified
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Muscarinic acetylcholine receptor M2 agonist: Bethanechol
Muscarinic acetylcholine receptor M2 antagonist: Atropine, Darifenacin, Fesoterodine, Oxybutynin, Propantheline, Solifenacin, Tolterodine, Trospium
kcaACM3Muscarinic acetylcholine receptor M327840.7141Nature11159Anticholinergic syndrome
Constipation
Cycloplegia
Diabetic eye disease
Dry mouth
Dry skin
Dysphagia
Extrapyramidal disorder
Hyperpyrexia
Intraocular pressure increased
Mydriasis
Salivary hypersecretion
Tachycardia
Urinary retention
Vision blurred
G-protein coupled receptor 1Airway hyperreactivity
Urge incontinence
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Muscarinic acetylcholine receptor M3 agonist: Acetylcholine, Bethanechol, Carbachol, Cevimeline, Methacholine, Pilocarpine
Muscarinic acetylcholine receptor M3 antagonist: Aclidinium, Anisotropine, Atropine, Clidinium, Cyclopentolate, Darifenacin, Dicyclomine, Diphemanil, Fesoterodine, Glycopyrrolate, Hexocyclium, Ipratropium, Isopropamide, Mepenzolate, Methscopolamine, Oxybutynin, Oxyphencyclimine, Oxyphenonium, Propantheline, Solifenacin, Tiotropium, Tolterodine, Tridihexethyl, Tropicamide, Trospium
kcaACM4Muscarinic acetylcholine receptor M419200.7243Anticholinergic syndrome
Constipation
Cycloplegia
Dry mouth
Dysphagia
Extrapyramidal disorder
Mydriasis
Salivary hypersecretion
Tachycardia
Throat irritation
Urinary incontinence
Urinary retention
Vision blurred
G-protein coupled receptor 1Analgesics
Manic disorder
Neurologic and psychiatric diseases
Pain, unspecified
Parkinsonian symptoms
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.
kcaACM5Muscarinic acetylcholine receptor M518610.6744Anticholinergic syndrome
Constipation
Cycloplegia
Dry mouth
Dry skin
Extrapyramidal disorder
Mydriasis
Orthostatic hypotension
Tachycardia
Urinary incontinence
Urinary retention
G-protein coupled receptor 1Opioid dependence
Schizophrenia
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.
kcaACVL1Serine/threonine-protein kinase receptor R3920.6291protein kinaseAdvanced cancers, age-related macular degeneration On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for TGF-beta. May bind activin as well.
kcaADA17Disintegrin and metalloproteinase domain-containing protein 1717760.7099Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney.Inflammatory bowel disease
Inflammatory diseases
Neuroimmunological diseases
Cleaves the membrane-bound precursor of tnf-alpha to its mature soluble form. Responsible for the proteolytic release of several other cell-surface proteins, including p75 tnf-receptor, interleukin 1 receptor type II and p55 tnf-receptor.
kcaADA1AAlpha-1A adrenergic receptor47580.7316Nature11159Expressed in heart, brain, liver and prostate, but not in kidney, lung, adrenal, aorta and pituitary. Within the prostate, expressed in the apex, base, periurethral and lateral lobe. Isoform <a href="#P35348-4" onclick="ensureIsoformSequenceVisible('P35348-4'); return true;">4</a> is the most abundant isoform expressed in the prostate with high levels also detected in liver and heart. <a class="attribution" href="P35348#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="P35348#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P35348#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Anxiety
Bradycardia
Carbohydrate metabolism disorder
Cerebral haemorrhage
Dyskinesia
Dysuria
Ejaculation disorder
Fear
Gangrene
Gestational hypertension
Hyperhidrosis
Hypertension
Insomnia
Intranasal paraesthesia
Irritability
Nasal congestion
Nasal discomfort
Nasal dryness
Nervous system disorder
Orthostatic hypotension
Pallor
Palpitations
Psychotic disorder
Pulmonary oedema
Restlessness
Sleep disorder
Sneezing
Sudden death
Tachycardia
Vasoconstriction
Ventricular arrhythmia
G-protein coupled receptor 1Benign prostate hyperplasia
Hypertrophic vascular disease
This alpha-adrenergic receptor mediates its action by association with g proteins that activate a phosphatidylinositol- calcium second messenger system, and its effect is mediated by G(q) and G(11) proteins. Adrenergic receptor alpha-1 agonist: Alfuzosin, Metaraminol, Methoxamine, Midodrine, Phenylephrine
Adrenergic receptor alpha-1 antagonist: Carvedilol, Doxazosin, Prazosin, Tamsulosin, Terazosin, Trimipramine
Alpha-1a adrenergic receptor agonist: Phenylpropanolamine, Phenylpropanolamine Polistirex
Alpha-1a adrenergic receptor antagonist: Dapiprazole, Silodosin
kcaADA1BAlpha-1B adrenergic receptor43990.7387Anxiety
Bradycardia
Cerebral haemorrhage
Depressed level of consciousness
Dyskinesia
Ejaculation disorder
Fear
Gangrene
Gestational hypertension
Hyperhidrosis
Intranasal paraesthesia
Nasal congestion
Nasal discomfort
Nasal dryness
Nervous system disorder
Orthostatic hypotension
Pallor
Palpitations
Pulmonary oedema
Respiration abnormal
Sneezing
Tachycardia
Vasoconstriction
G-protein coupled receptor 1Shy-Drager syndrome This alpha-adrenergic receptor mediates its action by association with g proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaADA1DAlpha-1D adrenergic receptor45060.7484Anxiety
Bradycardia
Cerebral haemorrhage
Dyskinesia
Fear
Gestational hypertension
Hyperhidrosis
Intranasal paraesthesia
Nasal congestion
Nasal dryness
Neurosis
Orthostatic hypotension
Pallor
Palpitations
Tachycardia
Vasoconstriction
G-protein coupled receptor 1Hypertension This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
kcaADA2AAlpha-2A adrenergic receptor21580.6774Nature11159Bradycardia
Cerebral haemorrhage
Depressed level of consciousness
Dyskinesia
Ejaculation disorder
Fear
Gangrene
Gestational hypertension
Hallucination
Intranasal paraesthesia
Nasal congestion
Nasal discomfort
Nasal dryness
Nervous system disorder
Neurosis
Orthostatic hypotension
Pallor
Palpitations
Priapism
Respiration abnormal
Sneezing
Somnolence
Urinary incontinence
Vasoconstriction
G-protein coupled receptor 1Heart failure
Hypertension
Ischemic heart disease
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine. Adrenergic receptor alpha-2 agonist: Apraclonidine, Brimonidine, Clonidine, Dexmedetomidine, Guanabenz, Guanfacine, Levonordefrin, Methyldopa, Methyldopate, Tizanidine
Adrenergic receptor alpha-2 antagonist: Mirtazapine
kcaADA2BAlpha-2B adrenergic receptor18400.578Nature11159Bradycardia
Cerebral haemorrhage
Depressed level of consciousness
Dyskinesia
Fear
Gestational hypertension
Hallucination
Intranasal paraesthesia
Nasal congestion
Nasal dryness
Neurosis
Orthostatic hypotension
Pallor
Respiration abnormal
Sneezing
Urinary incontinence
Vasoconstriction
G-protein coupled receptor 1Heart failure
Hypertension
Ischemic heart disease
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline. Adrenergic receptor alpha agonist: Ergotamine, Naphazoline, Oxymetazoline, Tetrahydrozoline
Adrenergic receptor alpha antagonist: Alseroxylon, Ergoloid, Phenoxybenzamine, Phentolamine, Rauwolfia Serpentina, Tolazoline
kcaADA2CAlpha-2C adrenergic receptor19130.6631Nature11159Bradycardia
Cerebral haemorrhage
Depressed level of consciousness
Dyskinesia
Fear
Gestational hypertension
Hallucination
Intranasal paraesthesia
Nasal congestion
Nasal dryness
Neurosis
Orthostatic hypotension
Pallor
Priapism
Respiration abnormal
Sneezing
Somnolence
Urinary incontinence
Vasoconstriction
G-protein coupled receptor 1Neuropsychiatric disorders
Raynaud's syndrome
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
kcaADCY1Adenylate cyclase type 1790.8034Brain, retina and adrenal medulla.adenylyl cyclase class-4/guanylyl cyclaseDietary shortage This is a calmodulin-sensitive adenylyl cyclase. May be involved in regulatory processes in the central nervous system. It may play a role in memory acquisition and learning.
kcaADCY5Adenylate cyclase type 51290.7723adenylyl cyclase class-4/guanylyl cyclaseDyskinesia, familial, with facial myokymia (FDFM) [MIM:606703]: A disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages. Note=The disease is caused by mutations affecting the gene represented in this entry.This is a membrane-bound, calcium-inhibitable adenylyl cyclase.
kcaADKAdenosine kinase4920.5936Widely expressed. Highest level in placenta, liver, muscle and kidney.carbohydrate kinase PfkBAnalgesics
Central and peripheral nervous system diseases
Epilepsy
Inflammation
Inflammatory bowel disease
Pain, unspecified
Toxoplasmosis
Atp dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.
kcaADRB1Beta-1 adrenergic receptor18940.6416Nature11159Angina pectoris
Anxiety
Arrhythmia
Asthenia
Atrioventricular block
Bradycardia
Bronchospasm
Cardiac failure
Cardiac failure congestive
Deafness transitory
Dry eye
Fear
Hallucination
Lung disorder
Metabolic disorder
Neurotoxicity
Palpitations
Peripheral coldness
Psychotic disorder
Raynaud's phenomenon
Sleep disorder
G-protein coupled receptor 1Anxiety disorder, unspecified
Asthma
Cardiac arrhythmias
Cardiovascular disease, unspecified
Coronary heart disease
Dilated cardiomyopathy
Glaucoma
Hypertension
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximatively equal affinity. Beta-1 adrenergic receptor agonist: Dobutamine, Dopamine
Beta-1 adrenergic receptor antagonist: Acebutolol, Atenolol, Betaxolol, Bisoprolol, Esmolol, Levobetaxolol, Levobunolol, Metipranolol, Metoprolol, Nadolol, Nebivolol, Oxprenolol, Penbutolol, Propafenone, Propranolol, Sotalol, Timolol
Beta-1 adrenergic receptor partial agonist: Pindolol
kcaADRB2Beta-2 adrenergic receptor22550.7145Nature11159Angina pectoris
Anxiety
Arrhythmia
Atrioventricular block
Bradycardia
Bronchospasm
Cardiac arrest
Cardiac failure
Cardiac failure congestive
Dry eye
Fear
Myocardial infarction
Neurotoxicity
Palpitations
Peripheral coldness
Raynaud's phenomenon
Sleep disorder
Tachycardia
Tension
Tremor
Vasodilatation
Ventricular arrhythmia
G-protein coupled receptor 1Anxiety disorder, unspecified
Asthma
Cardiac arrhythmias
Chronic obstructive pulmonary disease, unspecified
Depression
Glaucoma
Hypertension
Inflammation
Multiple sclerosis
Obstructive airway disease
Respiratory distress syndrome
Skeletal muscle wasting
Skeletal muscle weakness
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine. Beta-2 adrenergic receptor agonist: Albuterol, Arformoterol, Bitolterol, Dobutamine, Formoterol, Indacaterol, Isoetharine, Levosalbutamol, Metaproterenol, Pirbuterol, Protokylol, Ritodrine, Salmeterol, Terbutaline, Vilanterol
Beta-2 adrenergic receptor antagonist: Esmolol, Levobunolol, Metipranolol, Nadolol, Nebivolol, Oxprenolol, Penbutolol, Propafenone, Propranolol, Sotalol, Timolol
Beta-2 adrenergic receptor partial agonist: Pindolol
kcaADRB3Beta-3 adrenergic receptor18120.6921Nature11159Expressed mainly in adipose tissues.Angina pectoris
Arrhythmia
Atrioventricular block
Bradycardia
Bronchospasm
Cardiac failure
Cardiac failure congestive
Dry eye
Hallucination
Palpitations
Peripheral coldness
Psychotic disorder
Raynaud's phenomenon
Sleep disorder
G-protein coupled receptor 1Cardiac arrhythmias
Erectile dysfunction
Gain weight in patients with morbid obesity
Hypertension
Hypertonicity of bladder
Noninsulin-dependent diabetes mellitus
Obesity
Overactive bladder disorder
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis. Adrenergic receptor beta agonist: Isoproterenol
Adrenergic receptor beta antagonist: Carteolol, Carvedilol, Dronedarone
Beta-3 adrenergic receptor agonist: Mirabegron
kcaAGTR1Type-1 angiotensin II receptor24330.8225Nature11159Liver, lung, adrenal and adrenocortical adenomas.DizzinessG-protein coupled receptor 1Cardiovascular disease, unspecified
Heart failure
Hypertension
Ischemic stroke
Parkinson's disease
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Type-1 angiotensin II receptor antagonist: Azilsartan Medoxomil, Candesartan Cilexetil, Eprosartan, Irbesartan, Losartan, Olmesartan Medoxomil, Saralasin, Telmisartan, Valsartan
kcaAGTR2Type-2 angiotensin II receptor18980.6118In adult, highly expressed in myometrium with lower levels in adrenal gland and fallopian tube. Expressed in the cerebellum. Very highly expressed in fetal kidney and intestine. <a class="attribution" href="P50052#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a>G-protein coupled receptor 1Hypertension Receptor for angiotensin ii. May have a role in cell morphogenesis and related events in growth and development.
kcaAGTRAType-1A angiotensin II receptor15700.7769G-protein coupled receptor 1Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system.
kcaAGTRBType-1B angiotensin II receptor18040.7112G-protein coupled receptor 1Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system.
kcaAHRAryl hydrocarbon receptor2280.5852
kcaAK1BAAldo-keto reductase family 1 member B10850.6599Found in many tissues. Highly expressed in small intestine, colon and adrenal gland.aldo/keto reductaseActs as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.
kcaAK1C1Aldo-keto reductase family 1 member C11610.8158Expressed in all tissues tested including liver, prostate, testis, adrenal gland, brain, uterus, mammary gland and keratinocytes. Highest levels found in liver, mammary gland and brain.aldo/keto reductaseConverts progesterone to its inactive form, 20-alpha- dihydroxyprogesterone (20-alpha-OHP). In the liver and intestine, may have a role in the transport of bile. May have a role in monitoring the intrahepatic bile acid concentration. Has a low bile-binding ability. May play a role in myelin formation.
kcaAK1C2Aldo-keto reductase family 1 member C23000.7439Expressed in fetal testes. Expressed in fetal and adult adrenal glands.aldo/keto reductase46,XY sex reversal 8 (SRXY8) [MIM:614279]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. Note=The disease is caused by mutations affecting the gene represented in this entry.Works in concert with the 5-alpha/5-beta-steroid reductases to convert steroid hormones into the 3-alpha/5-alpha and 3-alpha/5-beta-tetrahydrosteroids. Catalyzes the inactivation of the most potent androgen 5-alpha-dihydrotestosterone (5-alpha- DHT) to 5-alpha-androstane-3-alpha,17-beta-diol (3-alpha-diol). Has a high bile-binding ability.
kcaAKT1RAC-alpha serine/threonine-protein kinase23410.7807Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. <a class="attribution" href="P31749#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a> <a class="attribution" href="P31749#ref39" onclick="ensureReferenceVisible('ref39')">Ref.39</a> <a class="attribution" href="P31749#ref52" onclick="ensureReferenceVisible('ref52')">Ref.52</a>protein kinaseAdvanced, Relapsed/Refractory Multiple Myeloma
Brain ischemic insult
Breast cancer
Cancer, unspecific
Diabetes mellitus
Glioblastoma Multiforme (GBM)
Huntington's disease
Non-Hodgkin's Lymphoma
Non-small Cell Lung Cancer
Parkinson's disease
Recurrent Malignant Glioma
Refractory, Rare Sarcoma's
Seizure
Solid tumors
Stroke
General protein kinase capable of phosphorylating several known proteins.
kcaAKT2RAC-beta serine/threonine-protein kinase13180.8008Expressed in all cell types so far analyzed.protein kinaseNote=Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. With AKT3, plays also a pivotal role in the biology of glioblastoma. Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note=The disease is caused by mutations affecting the gene represented in this entry. Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) [MIM:240900]: A disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures. Note=The disease is caused by mutations affecting the gene represented in this entry.AKT2 is one of 3 closely related serine/threonine- protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)- response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.
kcaAKT3RAC-gamma serine/threonine-protein kinase10940.773In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.protein kinaseNot Available
kcaAL5APArachidonate 5-lipoxygenase-activating protein2940.7232MAPEGArthritis
Asthma
Cardiovascular Disorders
Coronary Artery Disease and Heart Attack
Inflammatory Disorders, Unspecified
Psoriasis
Seems to be required for the activation of 5-lo (5- lipoxygenase). Flap could play an essential role in the transfer of arachidonic acid to 5-lo. Flap binds to mk-886, a compound that blocks the biosynthesis of leukotrienes.
kcaALDRAldose reductase12660.6419Highly expressed in embryonic epithelial cells (EUE) in response to osmotic stress. <a class="attribution" href="P15121#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Gastrointestinal disorderaldo/keto reductaseAnalgesics
Diabetic complications
Diabetic neuropathy
Diabetic retinopathy
Neuropathic pain
Noninsulin-dependent diabetes mellitus
Catalyzes the nadph-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
kcaALKALK tyrosine kinase receptor13010.7278Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells.protein kinaseNote=A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas. Note=A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A. Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Note=The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth.Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.
kcaAMPNAminopeptidase N8310.7395Expressed in epithelial cells of the kidney, intestine, and respiratory tract; granulocytes, monocytes, fibroblasts, endothelial cells, cerebral pericytes at the blood-brain barrier, synaptic membranes of cells in the CNS. Also expressed in endometrial stromal cells, but not in the endometrial glandular cells. Found in the vasculature of tissues that undergo angiogenesis and in malignant gliomas and lymph node metastases from multiple tumor types but not in blood vessels of normal tissues. A soluble form has been found in plasma. It is found to be elevated in plasma and effusions of cancer patients.peptidase M1Coronaviruses infections
Severe acute respiratory syndrome
Tumors
Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May be involved in the metabolism of regulatory peptides of diverse cell types.
kcaANDRAndrogen receptor21400.6843Nature11159
VirtualToxLab
Isoform <a href="#P10275-2" onclick="ensureIsoformSequenceVisible('P10275-2'); return true;">2</a> is mainly expressed in heart and skeletal muscle. <a class="attribution" href="P10275#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Acne
Amenorrhoea
Azoospermia
Bone disorder
Breast pain
Cushingoid
Depression
Electrolyte imbalance
Endocrine disorder
Epiphyses premature fusion
Gynaecomastia
Hepatic function abnormal
Hirsutism
Hypercalcaemia
Infertility
Jaundice cholestatic
Libido decreased
Menstrual disorder
Metrorrhagia
Oedema
Osteoporosis
Priapism
Virilism
Weight increased
nuclear hormone receptorProstate cancer
Spinal and bulbar muscular atrophy
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Androgen Receptor agonist: Danazol, Dromostanolone Propionate, Ethylestrenol, Fluoxymesterone, Methyltestosterone, Nandrolone Decanoate, Nandrolone Phenpropionate, Oxandrolone, Oxymetholone, Stanozolol, Testosterone, Testosterone Cypionate, Testosterone Enanthate, Testosterone Propionate
Androgen Receptor antagonist: Bicalutamide, Enzalutamide, Flutamide, Nilutamide
kcaAOC3Membrane primary amine oxidase1760.5319Strongly expressed on the high endothelial venules of peripheral lymph nodes and on hepatic endothelia. Also highly expressed in appendix, lung and small intestine. Expressed also in adipose tissue, in bone marrow, colon, heart, kidney, ovary, pancreas, placenta, prostate, skeletal muscle, spleen and testis. <a class="attribution" href="Q16853#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q16853#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>copper/topaquinone oxidaseInflammation Cell adhesion protein that participate in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an l-selectin- independent fashion. Has a monoamine oxidase activity.
kcaAOFAAmine oxidase [flavin-containing] A18780.6141Nature11159Heart, liver, duodenum, blood vessels and kidney.Dry mouth
Hyperhidrosis
Irritability
Mania
Psychotic disorder
flavin monoamine oxidaseDepression
Mood [affective] disorders
Social phobias
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. Mao-A preferentially oxidizes biogenic amines.
kcaAPAFApoptotic protease-activating factor 16350.569Ubiquitous. Highest levels of expression in adult spleen and peripheral blood leukocytes, and in fetal brain, kidney and lung. Isoform 1 is expressed in heart, kidney and liver.Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP. Isoform 6 is less effective in inducing apoptosis.
kcaAPEX1DNA-(apurinic or apyrimidinic site) lyase2220.6218DNA repair enzymes AP/ExoAOvarian cancer
Tumors
Repairs oxidative dna damages in vitro. May have a role in protection against cell lethality and suppression of mutations. Removes the blocking groups from the 3' termini of the dna strand breaks generated by ionizing radiations and bleomycin.
kcaAPH1AGamma-secretase subunit APH-1A3020.6457Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain. Isoform 1 and isoform 2 are nearly expressed at the same level.APH-1Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex.
kcaAPH1BGamma-secretase subunit APH-1B3020.6457Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain. <a class="attribution" href="Q8WW43#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>APH-1Alzheimer's Disease
kcaATP4APotassium-transporting ATPase alpha chain 15840.5712Found in gastric mucosa.cation transport ATPaseAcid-related diseases
Gastric acid hypersecretion
Gastric ulcer
Gastroesophageal reflux disease
Catalyzes the hydrolysis of atp coupled with the exchange of h(+) and k(+) ions across the plasma membrane, and is responsible for acid production in the stomach. Potassium-transporting ATPase inhibitor: Dexlansoprazole, Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole
kcaATP4BPotassium-transporting ATPase subunit beta5530.5711XRequired for stabilization and maturation of the catalytic proton pump alpha subunit and may also involved in cell adhesion and establishing epithelial cell polarity.
kcaATRSerine/threonine-protein kinase ATR1120.6924Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.PI3/PI4-kinaseSeckel syndrome 1 (SCKL1) [MIM:210600]: A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation. Note=The disease is caused by mutations affecting the gene represented in this entry. Cutaneous telangiectasia and cancer syndrome, familial (FCTCS) [MIM:614564]: A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well. Note=The disease is caused by mutations affecting the gene represented in this entry.Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication.
kcaATS4A disintegrin and metalloproteinase with thrombospondin motifs 42450.7052Expressed in brain, lung and heart. Expressed at very low level in placenta and skeletal muscles.Osteoarthritis Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. Could also be a critical factor in the exacerbation of neurodegeneration in alzheimer's disease.
kcaATS5A disintegrin and metalloproteinase with thrombospondin motifs 54410.5627Expressed at low level in placenta primarily but also detected in heart and brain, cervix, uterus, bladder, esophagus, rib cartilage, chondroblastoma, fibrous tissue and a joint capsule from an arthritic patient.Osteoarthritis Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period.
kcaAURKAAurora kinase A27580.7107Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines.protein kinaseColorectal Cancer
Lymphoma, Unspecified
Solid tumors
kcaAURKBAurora kinase B21250.7131High level expression seen in the thymus. It is also expressed in the spleen, lung, testis, colon, placenta and fetal liver. Expressed during S and G2/M phase and expression is up-regulated in cancer cells during M phase. <a class="attribution" href="Q96GD4#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q96GD4#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>protein kinaseNot Available
kcaAURKCAurora kinase C1290.6052Isoform <a href="#Q9UQB9" onclick="ensureIsoformSequenceVisible('Q9UQB9'); return true;">1</a> and isoform <a href="#Q9UQB9-2" onclick="ensureIsoformSequenceVisible('Q9UQB9-2'); return true;">2</a> are expressed in testis. Elevated expression levels were seen only in a subset of cancer cell lines such as Hep-G2, Huh-7 and HeLa. Expression is maximum at M phase. <a class="attribution" href="Q9UQB9#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>protein kinaseLeukemia, Myeloid
Solid tumors
kcaB2CL1Bcl-2-like protein 15910.6964Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain.Bcl-2Anaplastic Large Cell Lymphomas
Colorectal cancer
Mesothelioma
Potent inhibitor of cell death. Isoform bcl-x(l) anti- apoptotic activity is inhibited by association with siva isoform 1. Inhibits activation of caspases (by similarity). Appears to regulate cell death by blocking the voltage-dependent anion channnel.
kcaB2CL2Bcl-2-like protein 2550.7701Expressed (at protein level) in a wide range of tissues with highest levels in brain, spinal cord, testis, pancreas, heart, spleen and mammary glands. Moderate levels found in thymus, ovary and small intestine. Not detected in salivary gland, muscle or liver. Also expressed in cell lines of myeloid, fibroblast and epithelial origin. Not detected in most lymphoid cell lines. <a class="attribution" href="Q92843#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>Bcl-2Chronic lymphocytic leukemia
Hematologic malignancies
Lymphoid malignancies
Small cell lung cancer
Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.
kcaBACE1Beta-secretase 131620.6683Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata. <a class="attribution" href="P56817#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a> <a class="attribution" href="P56817#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a>peptidase A1Alzheimer's disease Responsible for the proteolytic processing of the amyloid precursor protein (app). Cleaves at the amino terminus of the a-beta peptide sequence, between residues 671 and 672 of app, leads to the generation and extracellular release of beta-cleaved soluble liquid.
kcaBACE2Beta-secretase 25510.5391Brain. Present in neurons within the hippocampus, frontal cortex and temporal cortex (at protein level). Expressed at low levels in most peripheral tissues and at higher levels in colon, kidney, pancreas, placenta, prostate, stomach and trachea. Expressed at low levels in the brain. Found in spinal cord, medulla oblongata, substantia nigra and locus coruleus. Expressed in the ductal epithelium of both normal and malignant prostate.peptidase A1Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C- terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672.
kcaBADBcl2-associated agonist of cell death970.8944Expressed in a wide variety of tissues.Bcl-2Promotes cell death. Successfully competes for the binding to Bcl-X(L), Bcl-2 and Bcl-W, thereby affecting the level of heterodimerization of these proteins with BAX. Can reverse the death repressor activity of Bcl-X(L), but not that of Bcl-2 (By similarity). Appears to act as a link between growth factor receptor signaling and the apoptotic pathways.
kcaBCL2Apoptosis regulator Bcl-25210.7321Expressed in a variety of tissues.Bcl-2Chronic lymphocytic leukemia
Prostate cancer (hormone refractory)
Waldenstrom's macroglobulinemia
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. appears to function in a feedback loop system with caspases.
kcaBCRBreakpoint cluster region protein3020.7037Leukemia, chronic myeloid (CML) [MIM:608232]: A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. Note=The gene represented in this entry is involved in disease pathogenesis. Note=A chromosomal aberration involving BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.
kcaBIRC2Baculoviral IAP repeat-containing protein 21610.7059Present in many fetal and adult tissues. Mainly expressed in adult skeletal muscle, thymus, testis, ovary, and pancreas, low or absent in brain and peripheral blood leukocytes.IAPMulti-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin- protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin- protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase- dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.
kcaBKRB1B1 bradykinin receptor8230.6295Nature11159G-protein coupled receptor 1Diabetic nephropathy
Inflammatory diseases
Ischemic vascular disease
Prostate cancer
This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
kcaBKRB2B2 bradykinin receptor6790.745Nature11159Ubiquitous. Widespread in normal smooth muscle tissue and neurons. <a class="attribution" href="P30411#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a>G-protein coupled receptor 1Alzheimer's disease
Analgesics
Arthritis
Asthma
Brain Cancer
Cardiac hypertrophy
Cardiovascular disease, unspecified
Cerebral edema
Chronic rhinitis
Colitis
Diabetic disorders
Diabetic nephropathy
Hepatorenal syndrome
Hereditary Angioedema (HAE)
Hypertension
Liver Disease
Lung cancer
Myocardial infarction
Pancreatitis
Pediatric
Restenosis
Sepsis
Tissue injury
Traumatic brain injuries
Visceral pain
Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Bradykinin B2 receptor antagonist: Icatibant
kcaBMP1Bone morphogenetic protein 13950.6341Ubiquitous.peptidase M12AFibrotic disease Cleaves the c-terminal propeptides of procollagen i, ii and iii. Induces cartilage and bone formation.
kcaBMR1ABone morphogenetic protein receptor type-1A910.5942Highly expressed in skeletal muscle.protein kinaseJuvenile polyposis syndrome (JPS) [MIM:174900]: Autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers. Note=The disease is caused by mutations affecting the gene represented in this entry. Polyposis syndrome, mixed hereditary 2 (HMPS2) [MIM:610069]: A disease is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. Note=The disease is caused by mutations affecting the gene represented in this entry. Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for BMP-2 and BMP-4.
kcaBRAFSerine/threonine-protein kinase B-raf7520.7597Brain and testis.protein kinaseMalignant melanoma
Melanoma
Pancreatic cancer
Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron. Serine/threonine-protein kinase B-raf inhibitor: Dabrafenib, Regorafenib, Sorafenib, Vemurafenib
kcaBRS3Bombesin receptor subtype-32620.5938In germ cells in testis. Lung carcinoma cells.G-protein coupled receptor 1Cancer, unspecific
Obesity
Role in sperm cell division, maturation, or function. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaBTKTyrosine-protein kinase BTK8930.5141Predominantly expressed in B-lymphocytes.protein kinaseAcute lymphoblastic leukaemia
B cell immunodeficiency
Plays a crucial role in b-cell ontogeny. Transiently phosphorylates gtf2i on tyrosine residues in response to b cell receptor crosslinking.
kcaC11B1Cytochrome P450 11B1, mitochondrial5030.5657cytochrome P450Adrenocortical tumour
Cushing's syndrome
Cytochrome P450 11B1 inhibitor: Mitotane
kcaC11B2Cytochrome P450 11B2, mitochondrial5170.6577cytochrome P450Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency) [MIM:203400]: Autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal. Note=The disease is caused by mutations affecting the gene represented in this entry. Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency) [MIM:610600]: Autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18- hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum. Note=The disease is caused by mutations affecting the gene represented in this entry. Familial hyperaldosteronism 1 (FH1) [MIM:103900]: A disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol. There is significant phenotypic heterogeneity, and some individuals never develop hypertension. Note=The disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2.Preferentially catalyzes the conversion of 11- deoxycorticosterone to aldosterone via corticosterone and 18- hydroxycorticosterone.
kcaC1SComplement C1s subcomponent1220.8238peptidase S1Hereditary Angioedema
Inflammation
C1s b chain is a serine protease that combines with c1q and c1s to form c1, the first component of the classical pathway of the complement system. C1r activates c1s so that it can, in turn, activate c2 and c4.
kcaCAC1BVoltage-dependent N-type calcium channel subunit alpha-1B8180.651Nature11159Isoform Alpha-1b-1 and isoform Alpha-1b-2 are expressed in the central nervous system, but not in skeletal muscle or aorta.Flushing
Oedema peripheral
calcium channel alpha-1 subunitAnalgesics
Cardiovascular disease, unspecified
Cerebral ischemia
Malignant pain
Neuropathic pain
Voltage-sensitive calcium channels (vscc) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release and gene expression. Voltage-gated N-type calcium channel alpha-1B subunit blocker: Levetiracetam, Ziconotide, Ziconotide Acetate
kcaCAC1CVoltage-dependent L-type calcium channel subunit alpha-1C7250.6778Nature11159Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle. <a class="attribution" href="Q13936#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q13936#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="Q13936#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>Arrhythmia
Flushing
Gingival hyperplasia
Oedema peripheral
calcium channel alpha-1 subunitHeart Disease
Heart transplant
kcaCAC1DVoltage-dependent L-type calcium channel subunit alpha-1D5380.6574Expressed in pancreatic islets and in brain, where it has been seen in cerebral cortex, hippocampus, basal ganglia, habenula and thalamus. Expressed in the small cell lung carcinoma cell line SCC-9. No expression in skeletal muscle. <a class="attribution" href="Q01668#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Arrhythmia
Diplopia
Flushing
Oedema peripheral
calcium channel alpha-1 subunitHepatitis, virus not identified
Sinoatrial node dysfunction
Voltage-sensitive calcium channels (vscc) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release and gene expression.
kcaCAC1FVoltage-dependent L-type calcium channel subunit alpha-1F820.8104Expression in skeletal muscle and retina.calcium channel alpha-1 subunitNight blindness, congenital stationary, 2A (CSNB2A) [MIM:300071]: A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Note=The disease is caused by mutations affecting the gene represented in this entry. Cone-rod dystrophy, X-linked 3 (CORDX3) [MIM:300476]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa. Note=The disease is caused by mutations affecting the gene represented in this entry. Aaland island eye disease (AIED) [MIM:300600]: A retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity due to foveal hypoplasia, nystagmus, astigmatism, protan color vision defect, myopia, and defective dark adaptation. Except for progression of axial myopia, the disease can be considered to be a stationary condition. Electroretinography reveals abnormalities in both photopic and scotopic functions. Note=The disease is caused by mutations affecting the gene represented in this entry.Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA).
kcaCAC1HVoltage-dependent T-type calcium channel subunit alpha-1H8590.5106Expressed in kidney, liver, heart, brain. Isoform <a href="#O95180-2" onclick="ensureIsoformSequenceVisible('O95180-2'); return true;">2</a> seems to be testis-specific.Extrapyramidal disordercalcium channel alpha-1 subunitAnalgesics
Migraine
Occlusive peripheral vascular disease
Pain
Vertigo of central and peripheral origin
kcaCAC1SVoltage-dependent L-type calcium channel subunit alpha-1S3940.538Skeletal muscle specific.calcium channel alpha-1 subunitPeriodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. Note=The disease is caused by mutations affecting the gene represented in this entry. Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A sporadic muscular disorder characterized by episodic weakness and hypokalemia during a thyrotoxic state. It is clinically similar to hereditary hypokalemic periodic paralysis, except for the fact that hyperthyroidism is an absolute requirement for disease manifestation. The disease presents with recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest. Thyrotoxic periodic paralysis can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
kcaCAH1Carbonic anhydrase 131800.6958Aplastic anaemia
Decreased appetite
Electrolyte imbalance
Glycosuria
Gout
Haemolysis
Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Hyponatraemia
Pancreatic disorder
Pancreatitis
Purine metabolism disorder
Thrombocytopenia
Xanthopsia
alpha-carbonic anhydraseGlaucoma
Hypertension
Pancreatic cancer
Reversible hydration of carbon dioxide. Carbonic anhydrase I inhibitor: Acetazolamide, Dichlorphenamide, Methazolamide, Methocarbamol
kcaCAH12Carbonic anhydrase 1211480.7381Highly expressed in colon, kidney, prostate, intestine and activated lymphocytes. Expressed at much higher levels in the renal cell cancers than in surrounding normal kidney tissue. Moderately expressed in pancreas, ovary and testis.Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Photosensitivity reaction
Purine metabolism disorder
Thrombocytopenia
alpha-carbonic anhydraseColorectal cancer
Gastrointestinal cancers
Pancreatic cancer
Renal failure
Reversible hydration of carbon dioxide. Carbonic anhydrase XII inhibitor: Acetazolamide, Dichlorphenamide
kcaCAH13Carbonic anhydrase 133040.6688Electrolyte imbalance
Haemorrhagic diathesis
Hypokalaemia
Paraesthesia
alpha-carbonic anhydrase
kcaCAH14Carbonic anhydrase 144470.5968High expression in all parts of the central nervous system and lower expression in adult liver, heart, small intestine, colon, kidney, urinary bladder and skeletal muscle.Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Photosensitivity reaction
Purine metabolism disorder
alpha-carbonic anhydraseRenal failure Reversible hydration of carbon dioxide.
kcaCAH2Carbonic anhydrase 238060.7374Aplastic anaemia
Decreased appetite
Electrolyte imbalance
Glycosuria
Gout
Haemolysis
Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatic disorder
Pancreatitis
Photosensitivity reaction
Pulmonary oedema
Purine metabolism disorder
Purpura
Thrombocytopenia
Xanthopsia
alpha-carbonic anhydraseGlaucoma
Pancreatic cancer
Renal failure
Reversible hydration of carbon dioxide. Carbonic anhydrase II inhibitor: Acetazolamide, Brinzolamide, Dichlorphenamide, Dorzolamide, Methazolamide, Topiramate
kcaCAH3Carbonic anhydrase 31470.5709Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Paraesthesia
alpha-carbonic anhydrase
kcaCAH4Carbonic anhydrase 43650.5999Expressed in the endothelium of the choriocapillaris in eyes (at protein level). Not expressed in the retinal epithelium at detectable levels. <a class="attribution" href="P22748#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a>Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemolytic anaemia
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatic disorder
Pancreatitis
Photosensitivity reaction
Purine metabolism disorder
Thirst
Thrombocytopenia
Xanthopsia
alpha-carbonic anhydraseGlaucoma
Pancreatic cancer
Renal failure
Salivary glands cancer
Reversible hydration of carbon dioxide. Carbonic anhydrase IV inhibitor: Acetazolamide, Dichlorphenamide, Methazolamide, Topiramate
kcaCAH5ACarbonic anhydrase 5A, mitochondrial2870.5356Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Purine metabolism disorder
alpha-carbonic anhydrase
kcaCAH5BCarbonic anhydrase 5B, mitochondrial2350.6276Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Purine metabolism disorder
alpha-carbonic anhydrase
kcaCAH6Carbonic anhydrase 62700.68Major constituent of saliva.Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Purine metabolism disorder
Thrombocytopenia
alpha-carbonic anhydrasePancreatic cancer
Salivary glands cancer
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
kcaCAH7Carbonic anhydrase 74770.6182alpha-carbonic anhydraseReversible hydration of carbon dioxide.
kcaCAH9Carbonic anhydrase 916900.6485Expressed primarily in carcinoma cells lines. Expression is restricted to very few normal tissues and the most abundant expression is found in the epithelial cells of gastric mucosa.Aplastic anaemia
Electrolyte imbalance
Glycosuria
Gout
Haemorrhagic diathesis
Hyperuricaemia
Hypokalaemia
Pancreatitis
Purine metabolism disorder
Thrombocytopenia
alpha-carbonic anhydraseBladder cancer
Head and neck squamous cell carcinomas
Pancreatic cancer
Renal cell carcinoma
Reversible hydration of carbon dioxide. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
kcaCALCACalcitonin gene-related peptide 1560.7483calcitoninMigraine and Cluster Headaches
kcaCALRLCalcitonin gene-related peptide type 1 receptor6620.6161Predominantly expressed in the lung and heart.G-protein coupled receptor 2Cluster Headaches
Diabetes mellitus
Migraine
Opioid dependence
This is a receptor for calcitonin gene-related peptide type 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
kcaCAN1Calpain-1 catalytic subunit7040.5371Ubiquitous.peptidase C2Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
kcaCAN2Calpain-2 catalytic subunit13160.7407Ubiquitous.peptidase C2Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Proteolytically cleaves MYOC at 'Arg-226' (PubMed:17650508).
kcaCARM1Histone-arginine methyltransferase CARM11190.6434Overexpressed in prostate adenocarcinomas and high-grade prostatic intraepithelial neoplasia.class I-like SAM-binding methyltransferaseMethylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg- 2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA- stabilizing properties and the half-life of their target mRNAs.
kcaCASP1Caspase-17640.7661Expressed in larger amounts in spleen and lung. Detected in liver, heart, small intestine, colon, thymus, prostate, skeletal muscle, peripheral blood leukocytes, kidney and testis. No expression in the brain. <a class="attribution" href="P29466#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>peptidase C14ABrain inflammation
Cerebral ischemia
Diabetic retinopathy
Inflammation
Thiol protease that cleaves il-1 beta between an asp and an ala, releasing the mature cytokine which is involved in a variety of inflammatory processes. Specifically inhibited by the cowpox virus crma protein.
kcaCASP2Caspase-2640.6894Expressed at higher levels in the embryonic lung, liver and kidney than in the heart and brain. In adults, higher level expression is seen in the placenta, lung, kidney, and pancreas than in the heart, brain, liver and skeletal muscle.peptidase C14AInvolved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
kcaCASP3Caspase-320540.8363Highly expressed in lung, spleen, heart, liver and kidney. Moderate levels in brain and skeletal muscle, and low in testis. Also found in many cell lines, highest expression in cells of the immune system.peptidase C14AChronic experimental allergic encephalomyelitis
Dysregulation of apoptosis
Multiple sclerosis
Neurodegenerative diseases
Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(adp-ribose) polymerase (parp) at a 216-asp-|-gly-217 bond. Cleaves and activates sterol regulatory element.
kcaCASP6Caspase-61990.704peptidase C14ANot Available
kcaCASP7Caspase-74260.7976Highly expressed in lung, skeletal muscle, liver, kidney, spleen and heart, and moderately in testis. No expression in the brain.peptidase C14AInvolved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly- 217' bond. Overexpression promotes programmed cell death.
kcaCASP8Caspase-83960.7571Isoform <a href="#Q14790" onclick="ensureIsoformSequenceVisible('Q14790'); return true;">1</a>, isoform <a href="#Q14790-5" onclick="ensureIsoformSequenceVisible('Q14790-5'); return true;">5</a> and isoform <a href="#Q14790-7" onclick="ensureIsoformSequenceVisible('Q14790-7'); return true;">7</a> are expressed in a wide variety of tissues. Highest expression in peripheral blood leukocytes, spleen, thymus and liver. Barely detectable in brain, testis and skeletal muscle.peptidase C14ANot Available
kcaCASRExtracellular calcium-sensing receptor5130.5946Expressed in the temporal lobe, frontal lobe, parietal lobe, hippocampus, and cerebellum. Also found in kidney, lung, liver, heart, skeletal muscle, placenta. <a class="attribution" href="P41180#ref43" onclick="ensureReferenceVisible('ref43')">Ref.43</a>G-protein coupled receptor 3Hyperparathyroidism, unspecified Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system. Calcium sensing receptor positive allosteric modulator: Cinacalcet
kcaCATBCathepsin B14090.6549peptidase C1Acute otitis media
Arthritis
Ischemia
Tumor angiogenesis
Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
kcaCATDCathepsin D12480.6141Expressed in the aorta extrcellular space (at protein level). <a class="attribution" href="P07339#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a>peptidase A1Alzheimer's disease
Breast cancer
Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly alzheimer's disease.
kcaCATECathepsin E740.5444Expressed abundantly in the stomach, the Clara cells of the lung and activated B-lymphocytes, and at lower levels in lymph nodes, skin and spleen. Not expressed in resting B- lymphocytes.peptidase A1May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte depletion in the thymus, and in neuronal degeneration and glial cell activation in the brain.
kcaCATFCathepsin F520.5006High expression levels in heart, skeletal muscle, brain, testis and ovary; moderate levels in prostate, placenta, liver and colon; and no detectable expression in peripheral leukocytes and thymus.peptidase C1Autoimmune diseases Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
kcaCATGCathepsin G2500.6573peptidase S1Alpha 1 Antitrypsin Deficiency
Atopic Dermatitis
Chronic Obstructive Pulmonary Disease (COPD)
kcaCATKCathepsin K19290.6653Predominantly expressed in osteoclasts (bones).peptidase C1Bone Metastases
Cancer, unspecific
Osteoporosis
Postmenopausal Women with Osteoporosis
Rheumatoid arthritis
Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid ph. May play an important role in extracellular matrix degradation.
kcaCATL1Cathepsin L118540.6645peptidase C1Autoimmune diseases
Melanoma
Important for the overall degradation of proteins in lysosomes.
kcaCATSCathepsin S17330.6493peptidase C1Autoimmune diseases
Psoriasis and Psoriatic Disorders
Thiol protease. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin l and cathepsin n.
kcaCBPB1Carboxypeptidase B870.5355Pancreas.peptidase M14
kcaCCKARCholecystokinin receptor type A21520.5828Nature11159G-protein coupled receptor 1Acid-related diseases
Alcoholism
Gastroesophageal Reflux Disease (GERD)
Gastrointestinal Diseases and Disorders, miscellaneous
Gastrointestinal motility disorders
Irritable Bowel Syndrome (IBS)
Obesity
Pancreatic Cancer
Receptor for cholecystokinin. Has a 1000-fold higher affinity for cck rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G protein. Cholecystokinin A receptor agonist: Ceruletide
kcaCCNA1Cyclin-A111900.6327Very high levels in testis and very low levels in brain. Also found in myeloid leukemia cell lines.cyclinMay be involved in the control of the cell cycle at the G1/S (start) and G2/M (mitosis) transitions. May primarily function in the control of the germline meiotic cell cycle and additionally in the control of mitotic cell cycle in some somatic cells.
kcaCCNA2Cyclin-A212680.6198cyclinEssential for the control of the cell cycle at the G1/S (start) and the G2/M (mitosis) transitions.
kcaCCNB2G2/mitotic-specific cyclin-B25780.542cyclinEssential for the control of the cell cycle at the G2/M (mitosis) transition.
kcaCCNB3G2/mitotic-specific cyclin-B35780.542Testis specific. In testis, it is expressed in developing germ cells, but not in Leydig cells. Weakly or not expressed in other tissues.cyclinCyclins are positive regulatory subunits of the cyclin- dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division. Its tissue specificity suggest that it may be required during early meiotic prophase I.
kcaCCND1G1/S-specific cyclin-D19440.7461cyclinBreast cancer
Cancer, unspecific
Essential for the control of the cell cycle at the g1/s (start) transition.
kcaCCND2G1/S-specific cyclin-D21550.6007cyclinRegulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D2/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex (By similarity).
kcaCCND3G1/S-specific cyclin-D31710.5715cyclinRegulatory component of the cyclin D3-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity. Component of the ternary complex, cyclin D3/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.
kcaCCNE1G1/S-specific cyclin-E111160.6023Highly expressed in testis and placenta. Low levels in bronchial epithelial cells. <a class="attribution" href="P24864#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>cyclinHepatocellular carcinoma Essential for the control of the cell cycle at the g1/s (start) transition.
kcaCCNE2G1/S-specific cyclin-E27890.5874According to PubMed:9858585, highest levels of expression in adult testis, thymus and brain. Lower levels in placenta, spleen and colon. Consistently elevated levels in tumor- derived cells compared to non-transformed proliferating cells. According to PubMed:9840927: low levels in thymus, prostate, brain, skeletal muscle, and kidney. Elevated levels in lung. According to PubMed:9840943 highly expressed in testis, placenta, thymus and brain. In a lesser extent in small intestine and colon.cyclinEssential for the control of the cell cycle at the late G1 and early S phase.
kcaCCNT1Cyclin-T11500.5507Ubiquitously expressed.cyclinRegulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin-T1) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to productive elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II). In case of HIV or SIV infections, binds to the transactivation domain of the viral nuclear transcriptional activator, Tat, thereby increasing Tat's affinity for the transactivating response RNA element (TAR RNA). Serves as an essential cofactor for Tat, by promoting RNA Pol II activation, allowing transcription of viral genes.
kcaCCR1C-C chemokine receptor type 17020.6217Widely expressed in different hematopoietic cells.G-protein coupled receptor 1Autoimmune diseases
Chronic inflammatory diseases
Ovarian cancer
Renal fibrosis
Receptor for a c-c type chemokine. Binds to mip-1-alpha, mip-1 delta, rantes, and mcp-3 and, less efficiently, to mip-1- beta or mcp-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell.
kcaCCR2C-C chemokine receptor type 214860.5943G-protein coupled receptor 1Inflammatory demyelination
Multiple Sclerosis (MS)
Obese Insulin-resistant Subjects
Rheumatoid arthritis
Receptor for the mcp-1, mcp-3 and mcp-4 chemokines. Transduces a signal by increasing the intracellular calcium ions level. Alternative coreceptor with cd4 for hiv-1 infection.
kcaCCR3C-C chemokine receptor type 310960.777In eosinophils as well as trace amounts in neutrophils and monocytes.G-protein coupled receptor 1Allergic diseases Receptor for a c-c type chemokine. Binds to eotaxin, eotaxin-3, mcp-3, mcp-4, rantes and mip-1 delta. Subsequently transduces a signal by increasing the intracellular calcium ions level. Alternative coreceptor with cd4 for hiv-1 infection.
kcaCCR4C-C chemokine receptor type 43930.6113Predominantly expressed in the thymus, in peripheral blood leukocytes, including T-cells, mostly CD4+ cells, and basophils, and in platelets; at lower levels, in the spleen and in monocytes. Detected also in macrophages, IL-2-activated natural killer cells and skin-homing memory T-cells, mostly the ones expressing the cutaneous lymphocyte antigen (CLA). Expressed in brain microvascular and coronary artery endothelial cells. <a class="attribution" href="P51679#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>G-protein coupled receptor 1Asthma High affinity receptor for the c-c type chemokines tarc/scya17 and mdc/scya22. The activity of this receptor is mediated by g(i) proteins which activate a phosphatidylinositol- calcium second messenger system. Can function as a chemoattractant homing receptor.
kcaCCR5C-C chemokine receptor type 519940.6798Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung. <a class="attribution" href="P51681#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P51681#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>G-protein coupled receptor 1Human immunodeficiency virus [HIV] disease Receptor for a c-c type chemokine. Binds to MIP-1-alpha, MIP-1-beta and rantes and subsequently transduces a signal by increasing the intracellular calcium ions level. May play a role in the control of granulocytic lineage proliferation or differentiation. C-C chemokine receptor type 5 antagonist: Maraviroc
kcaCCR8C-C chemokine receptor type 81630.5901G-protein coupled receptor 1Allergic diseases Receptor for the chemokines scya1/i-309, scya4/mip-1- beta and scya17/tarc. May regulate monocyte chemotaxis and thymic cell line apoptosis. Alternative coreceptor with cd4 for hiv-1 infection.
kcaCD5R1Cyclin-dependent kinase 5 activator 112960.6376Brain and neuron specific.cyclin-dependent kinase 5 activatorp35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.
kcaCDC7Cell division cycle 7-related protein kinase9760.6402protein kinaseSeems to phosphorylate critical substrates that regulate the G1/S phase transition and/or DNA replication. Can phosphorylates MCM2 and MCM3.
kcaCDK1Cyclin-dependent kinase 126720.5764Isoform <a href="#P06493-2" onclick="ensureIsoformSequenceVisible('P06493-2'); return true;">2</a> is found in breast cancer tissues.protein kinaseCancer, unspecific
Malaria
Plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into s-phase and mitosis. P34 is a component of the kinase complex that phosphorylates the repetitive carboxyl-terminus of rna polymerase ii.
kcaCDK2Cyclin-dependent kinase 247750.6502protein kinaseAcute lymphoblastic leukemia (ALL)
Acute myeloid leukemia (AML)
Advanced Solid tumors
B-cell malignancies
Cancer, unspecific
Cardiovascular disease, unspecified
Chronic lymphocytic leukemia (CLL)
Hepatocellular Carcinoma (HCC)
Nasopharyngeal Cancer (NPC)
Non-Hodgkin's Lymphoma
Non-small Cell Lung Cancer
Solid tumors
Viral infection, unspecified
Probably involved in the control of the cell cycle. Interacts with cyclins a, d, or e. Activity of cdk2 is maximal during s phase and g2.
kcaCDK4Cyclin-dependent kinase 415700.6925protein kinaseCancer, unspecific
Insulin-dependent diabetes mellitus
Squamous cell carcinoma
Probably involved in the control of the cell cycle.
kcaCDK5Cyclin-dependent kinase 525820.6006Isoform <a href="#Q00535" onclick="ensureIsoformSequenceVisible('Q00535'); return true;">1</a> is ubiquitously expressed. Accumulates in cortical neurons (at protein level). Isoform <a href="#Q00535-2" onclick="ensureIsoformSequenceVisible('Q00535-2'); return true;">2</a> has only been detected in testis, skeletal muscle, colon, bone marrow and ovary. <a class="attribution" href="Q00535#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="Q00535#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a>protein kinaseAlzheimer's disease
Bladder cancer
Probably involved in the control of the cell cycle. Interacts with d1 and d3-type g1 cyclins. Can phosphorylate histone h1, tau, map2 and nf-h and nf-m. Also interacts with p35 which activates the kinase.
kcaCDK9Cyclin-dependent kinase 96470.5352Ubiquitous.protein kinaseCancer, unspecific
Heart disease, unspecified
Leukemia, Unspecified
Lymphoma, Unspecified
Multiple Myeloma
Solid tumors
Member of the cyclin-dependent kinase pair (cdk9/cyclin t) complex, also called positive transcription elongation factor b (p-tefb), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the ctd.
kcaCEGTCeramide glucosyltransferase1390.7476Found in all tissues examined. <a class="attribution" href="Q16739#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>glycosyltransferase 2Sphingolipid storage disorders May serve as a "flippase" as well as a glucosyltransferase that transfers glucose to ceramide. Ceramide glucosyltransferase inhibitor: Miglustat
kcaCEL2AChymotrypsin-like elastase family member 2A1400.6049Pancreas. Not detected in keratinocytes.peptidase S1Acts upon elastin.
kcaCETPCholesteryl ester transfer protein8120.5564Expressed by the liver and secreted in plasma.BPI/LBP/PluncAtherosclerosis
Coronary atherosclerosis
Hypercholesterolemia
Hyperlipidemia
Peripheral Vascular Disease
Involved in the transfer of insoluble cholesteryl esters in the reverse transport of cholesterol.
kcaCFTRCystic fibrosis transmembrane conductance regulator1560.8298Expressed in the respiratory airway, including bronchial epithelium, and in the female reproductive tract, including oviduct (at protein level).ABC transporterCystic fibrosis (CF) [MIM:219700]: A common generalized disorder of the exocrine glands which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes. It is the most common genetic disease in Caucasians, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry. Congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]: Important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens. Note=The disease is caused by mutations affecting the gene represented in this entry.Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
kcaCHK1Serine/threonine-protein kinase Chk128150.756Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. <a class="attribution" href="O14757#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="O14757#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>protein kinaseSolid tumors
kcaCHK2Serine/threonine-protein kinase Chk211030.64High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.protein kinaseSolid tumors
kcaCHLECholinesterase26520.8034Detected in blood plasma (at protein level). Present in most cells except erythrocytes. <a class="attribution" href="P06276#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P06276#ref21" onclick="ensureReferenceVisible('ref21')">Ref.21</a>Bradycardia
Salivary hypersecretion
type-B carboxylesterase/lipaseAlzheimer's disease
Schizophrenia
Cholinesterases; ACHE & BCHE inhibitor: Rivastigmine, Tacrine
kcaCLK4Dual specificity protein kinase CLK411940.5306Expressed in liver, kidney, heart, muscle, brain and endothelial cells.protein kinaseDual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
kcaCLTR1Cysteinyl leukotriene receptor 18170.7474Widely expressed, with highest levels in spleen and peripheral blood leukocytes. Lower expression in several tissues, such as lung (mostly in smooth muscle bundles and alveolar macrophages), placenta, small intestine, pancreas, colon and heart.G-protein coupled receptor 1Asthma Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. stimulation by ltd4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer. Cysteinyl leukotriene receptor 1 antagonist: Montelukast, Zafirlukast
kcaCLTR2Cysteinyl leukotriene receptor 24150.6942Widely expressed, with highest levels in the heart, placenta, spleen, peripheral blood leukocytes and adrenal gland. In lung, expressed in the interstitial macrophages, and slightly in smooth muscle cells.G-protein coupled receptor 1Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol- calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.
kcaCMA1Chymase4160.5133Mast cells in lung, heart, skin and placenta. Expressed in both normal skin and in urticaria pigmentosa lesions. <a class="attribution" href="P23946#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>peptidase S1Asthma
Atopic dermatitis
Cardiovascular disease, unspecified
Inflammation
Myocardial infarction
Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.
kcaCNR1Cannabinoid receptor 156890.7002Nature11159Widely expressed. <a class="attribution" href="P21554#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>G-protein coupled receptor 1Analgesics
Inflammatory bowel disease
Migraine
Pain, unspecified
Involved in cannabinoid-induced cns effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Cannabinoid CB1 receptor agonist: Dronabinol, Nabilone
kcaCNR2Cannabinoid receptor 247570.6757Preferentially expressed in cells of the immune system with higher expression in B-cells and NK cells (at protein level). Expressed in skin in suprabasal layers and hair follicles (at protein level). Highly expressed in tonsil and to a lower extent in spleen, peripheral blood mononuclear cells, and thymus. <a class="attribution" href="#ref17" onclick="ensureReferenceVisible('ref17');">Ref.17</a> could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root ganglion sensory neurons (at protein level). <a class="attribution" href="P34972#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="P34972#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P34972#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a> <a class="attribution" href="P34972#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a> <a class="attribution" href="P34972#ref18" onclick="ensureReferenceVisible('ref18')">Ref.18</a> <a class="attribution" href="P34972#ref19" onclick="ensureReferenceVisible('ref19')">Ref.19</a>G-protein coupled receptor 1Analgesics
Pain, unspecified
Involved in cannabinoid-induced cns effects through G-protein mediated inhibition of adenylate cyclase. Could be a receptor for anandamide.
kcaCOMTCatechol O-methyltransferase590.5645Brain, liver, placenta, lymphocytes and erythrocytes.class I-like SAM-binding methyltransferaseParkinson's disease Catalyzes the o-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like l-dopa, alpha-methyl dopa and isoproterenol. Catechol O-methyltransferase inhibitor: Entacapone, Tolcapone
kcaCP17ASteroid 17-alpha-hydroxylase/17,20 lyase4960.5663cytochrome P450Benign prostate hyperplasia
Prostate cancer
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (dhea) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Cytochrome P450 17A1 inhibitor: Abiraterone Acetate
kcaCP19AAromatase16710.619Brain, placenta and gonads. <a class="attribution" href="P11511#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a> <a class="attribution" href="P11511#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P11511#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a> <a class="attribution" href="P11511#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Paincytochrome P450Breast cancer
Endometriosis
Estrogen disorders
Male infertility
McCune-Albright syndrome
Neurodegenerative diseases
Peripheral precocious puberty
Catalyzes the formation of aromatic c18 estrogens from c19 androgens. Cytochrome P450 19A1 inhibitor: Aminoglutethimide, Anastrozole, Exemestane, Letrozole, Testolactone
kcaCP1A1Cytochrome P450 1A11120.6619Lung, lymphocytes and placenta.cytochrome P450Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
kcaCP1A2Cytochrome P450 1A213730.5219cytochrome P450
kcaCP2D6Cytochrome P450 2D630320.6166VirtualToxLabcytochrome P450Insomnia Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
kcaCP3A4Cytochrome P450 3A441020.6131VirtualToxLabExpressed in prostate and liver. According to some authors, it is not expressed in brain (<a class="attribution" href="#ref19" onclick="ensureReferenceVisible('ref19');">Ref.19</a>). According to others, weak levels of expression are measured in some brain locations (<a class="attribution" href="#ref22" onclick="ensureReferenceVisible('ref22');">Ref.22</a> and <a class="attribution" href="#ref20" onclick="ensureReferenceVisible('ref20');">Ref.20</a>). Also expressed in epithelium of the small intestine and large intestine, bile duct, nasal mucosa, kidney, adrenal cortex, epithelium of the gastric mucosa with intestinal metaplasia, gallbladder, intercalated ducts of the pancreas, chief cells of the parathyroid and the corpus luteum of the ovary (at protein level). <a class="attribution" href="P08684#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P08684#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a> <a class="attribution" href="P08684#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a> <a class="attribution" href="P08684#ref19" onclick="ensureReferenceVisible('ref19')">Ref.19</a> <a class="attribution" href="P08684#ref20" onclick="ensureReferenceVisible('ref20')">Ref.20</a> <a class="attribution" href="P08684#ref22" onclick="ensureReferenceVisible('ref22')">Ref.22</a>Abdominal pain upper
Diabetes mellitus
Headache
Hyperlipidaemia
Lipodystrophy acquired
Oedema peripheral
cytochrome P450Hypothalamic-pituitary ACTH function
kcaCP3A5Cytochrome P450 3A5700.5266cytochrome P450Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
kcaCRFR1Corticotropin-releasing factor receptor 123480.5667Nature11159Predominantly expressed in the cerebellum, pituitary, cerebral cortex and olfactory lobe. <a class="attribution" href="P34998#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>G-protein coupled receptor 2Anxiety Disorders
Depression
Innate anxiety
Irritable Bowel Syndrome (IBS)
Obesity
Stress-related disorders
This is a receptor for corticotropin releasing factor. Shows high-affinity crf binding. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
kcaCRFR2Corticotropin-releasing factor receptor 22250.3013Nature11159G-protein coupled receptor 2Angiogenesis
Congestive Heart Failure
Eating disorders
Obesity
Stress-related disorders
This is a receptor for corticotropin releasing factor. Shows high-affinity crf binding. Also binds to urocortin i, ii and iii. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
kcaCSF1RMacrophage colony-stimulating factor 1 receptor16060.7392protein kinaseBone marrow transplant
Febrile neutropenia
Non-myeloid cancer
kcaCSK21Casein kinase II subunit alpha11020.652protein kinaseBreast cancer
Cancer, unspecific
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha and alpha' chains contain the catalytic site. Participates in wnt signaling.
kcaCSK2BCasein kinase II subunit beta1430.6582casein kinase 2 subunit betaParticipates in Wnt signaling (By similarity). Plays a complex role in regulating the basal catalytic activity of the alpha subunit.
kcaCXCR1C-X-C chemokine receptor type 12860.6846G-protein coupled receptor 1Acute respiratory distress syndrome
Asthma
Human cytomegalovirus infections
Lung injury
Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of il-8 to the receptor causes activation of neutrophils. This response is mediated via a g-protein that activate a phosphatidylinositol-calcium second messenger system.
kcaCXCR2C-X-C chemokine receptor type 25750.6717G-protein coupled receptor 1Acute respiratory distress syndrome
Asthma
Chronic Obstructive Pulmonary Disease (COPD)
Colorectal cancer
Lung injury
Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of il-8 to the receptor causes activation of neutrophils. This response is mediated via a g-protein that activate a phosphatidylinositol-calcium second messenger system.
kcaCXCR3C-X-C chemokine receptor type 38460.63Isoform <a href="#P49682" onclick="ensureIsoformSequenceVisible('P49682'); return true;">1</a> and isoform <a href="#P49682-2" onclick="ensureIsoformSequenceVisible('P49682-2'); return true;">2</a> are mainly expressed in heart, kidney, liver and skeletal muscle. Isoform <a href="#P49682" onclick="ensureIsoformSequenceVisible('P49682'); return true;">1</a> is also expressed in placenta. Expressed in T-cells (at protein level). <a class="attribution" href="P49682#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P49682#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>G-protein coupled receptor 1Autoimmune diseases
Focal stroke
Inflammatory Disorders, Unspecified
Insulin-dependent diabetes mellitus
Multiple sclerosis
Psoriasis and Psoriatic Disorders
Receptor for scyb9/mig, scyb10/inp10 and scyb11/itac.
kcaDCKDeoxycytidine kinase1010.7937DCK/DGKRequired for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
kcaDCMCMalonyl-CoA decarboxylase, mitochondrial2620.6469Expressed in fibroblasts and hepatoblastoma cells (at protein level). Expressed strongly in heart, liver, skeletal muscle, kidney and pancreas. Expressed in myotubes. Expressed weakly in brain, placenta, spleen, thymus, testis, ovary and small intestine.Malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360]: Autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. Note=The disease is caused by mutations affecting the gene represented in this entry.Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation.
kcaDEFMPeptide deformylase, mitochondrial570.6657Ubiquitous.polypeptide deformylaseRemoves the formyl group from the N-terminal Met of newly synthesized proteins (By similarity).
kcaDGAT1Diacylglycerol O-acyltransferase 15360.5274membrane-bound acyltransferaseLowering cholesterol Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl coa as substrates.
kcaDGLASn1-specific diacylglycerol lipase alpha580.6045Highly expressed in brain and pancreas.AB hydrolaseSpinocerebellar ataxia 20 (SCA20) [MIM:608687]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA20 is an autosomal dominant, adult-onset form characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia. Note=The disease may be caused by mutations affecting the gene represented in this entry. A copy number variation consisting of a 260-kb duplication at chromosome 11q12.2-12.3 is responsible for SCA20. The critical gene within the duplicated segment may be DAGLA.Catalyzes the hydrolysis of diacylglycerol (DAG) to 2- arachidonoyl-glycerol (2-AG), the most abundant endocannabinoid in tissues. Required for axonal growth during development and for retrograde synaptic signaling at mature synapses.
kcaDHB1Estradiol 17-beta-dehydrogenase 13410.5844short-chain dehydrogenases/reductasesBreast cancer (hormone-sensitive) Favors the reduction of estrogens and androgens. Also has 20-alpha-hsd activity. Uses preferentially NADH.
kcaDHB2Estradiol 17-beta-dehydrogenase 23210.513short-chain dehydrogenases/reductasesCapable of catalyzing the interconversion of testosterone and androstenedione, as well as estradiol and estrone. Also has 20-alpha-HSD activity. Uses NADH while EDH17B3 uses NADPH.
kcaDHI1Corticosteroid 11-beta-dehydrogenase isozyme 120010.668Widely expressed. Highest expression in liver.short-chain dehydrogenases/reductasesCognitive deficits (age- and dementia-associated)
Diabetes Mellitus Type 2
Metabolic disorder, unspecified
Neurodegenerative diseases
Noninsulin-dependent diabetes mellitus
Obesity
Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone.
kcaDHI2Corticosteroid 11-beta-dehydrogenase isozyme 24320.5541Found in placenta, kidney, pancreas, prostate, ovary, small intestine and colon.short-chain dehydrogenases/reductasesTumors Catalyzes the conversion of cortisol to the inactive metabolite cortisone. modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.
kcaDHSOSorbitol dehydrogenase800.6821Expressed in kidney and epithelial cells of both benign and malignant prostate tissue. Expressed in epididymis (at protein level). <a class="attribution" href="Q00796#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a> <a class="attribution" href="Q00796#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a> <a class="attribution" href="Q00796#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a>zinc-containing alcohol dehydrogenaseDiabetic complications
Myocardial ischemia
kcaDLG4Disks large homolog 4550.6598Brain.MAGUKAnalgesics
Chronic neuropathic pain
Opioid dependence
Interacts with the cytoplasmic tail of nmda receptor subunits. May be involved in synaptogenesis.
kcaDOT1LHistone-lysine N-methyltransferase, H3 lysine-79 specific640.7847class I-like SAM-binding methyltransferaseHistone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.
kcaDPEP1Dipeptidase 11670.777peptidase M19Bacterial infections Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. converts leukotriene D4 to leukotriene E4; it may play an important role in the regulation of leukotriene activity. Renal dipeptidase inhibitor: Cilastatin
kcaDPOLBDNA polymerase beta1900.5114DNA polymerase type-XRepair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.
kcaDPP2Dipeptidyl peptidase 214260.7478Detected in seminal plasma (at protein level).peptidase S28Plays an important role in the degradation of some oligopeptides.
kcaDPP4Dipeptidyl peptidase 436280.655Expressed specifically in lymphatic vessels but not in blood vessels in the skin, small intestine, esophagus, ovary, breast and prostate glands. Not detected in lymphatic vessels in the lung, kidney, uterus, liver and stomach (at protein level). Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon. <a class="attribution" href="P27487#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P27487#ref32" onclick="ensureReferenceVisible('ref32')">Ref.32</a>peptidase S9BAutoimmune diseases
Diabetes mellitus
Malignancies
Noninsulin-dependent diabetes mellitus
Obesity
Removes n-terminal dipeptides sequentially from polypeptides having unsubstituted n-termini provided that the penultimate residue is proline. It plays a role in t cell activation. Dipeptidyl peptidase IV inhibitor: Alogliptin, Linagliptin, Saxagliptin, Sitagliptin
kcaDPP8Dipeptidyl peptidase 814900.7468Ubiquitously expressed, with highest levels in testis, placenta, prostate, muscle and brain.peptidase S9BDipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2. May play a role in T-cell activation and immune function.
kcaDPP9Dipeptidyl peptidase 910720.7832Ubiquitously expressed, with highest levels in liver, heart and muscle, and lowest levels in brain.peptidase S9BDipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.
kcaDRD1D(1A) dopamine receptor24470.6178Nature11159Detected in caudate, nucleus accumbens and in the olfactory tubercle. <a class="attribution" href="P21728#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>Agranulocytosis
Akathisia
Amenorrhoea
Cataract
Cholestasis
Corneal opacity
Corneal pigmentation
Dermatitis allergic
Dermatitis exfoliative
Dry mouth
Dyskinesia
Dystonia
Ejaculation disorder
Electrocardiogram change
Endocrine disorder
Extrapyramidal disorder
Eyelash discolouration
Fibrocystic breast disease
Galactorrhoea
Gynaecomastia
Hypercholesterolaemia
Hyperprolactinaemia
Hyperthermia
Hypothermia
Insomnia
Lenticular opacities
Lipid metabolism disorder
Menstrual disorder
Miosis
Mydriasis
Nasal congestion
Neuroleptic malignant syndrome
Neutropenia
Orthostatic hypotension
Parkinsonism
Photosensitivity reaction
Tachycardia
Tardive dyskinesia
Weight increased
G-protein coupled receptor 1Parkinson's disease This is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase. Dopamine D1 receptor agonist: Fenoldopam
Dopamine D1 receptor antagonist: Methylergonovine
kcaDRD2D(2) dopamine receptor93720.6186Nature11159Akathisia
Amenorrhoea
Cataract
Cholestasis
Constipation
Convulsion
Corneal opacity
Corneal pigmentation
Dermatitis allergic
Dermatitis exfoliative
Dry mouth
Dyskinesia
Dystonia
Ejaculation disorder
Electrocardiogram change
Endocrine disorder
Erectile dysfunction
Extrapyramidal disorder
Eyelash discolouration
Fibrocystic breast disease
Galactorrhoea
Gynaecomastia
Hypercholesterolaemia
Hyperprolactinaemia
Hyperthermia
Hypothermia
Insomnia
Lenticular opacities
Lipid metabolism disorder
Menstrual disorder
Miosis
Mydriasis
Nasal congestion
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Sexual dysfunction
Tachycardia
Tardive dyskinesia
Urinary retention
Vision blurred
Weight increased
G-protein coupled receptor 1Anxiety disorder, unspecified
Attention deficit hyperactivity disorder
Cocaine dependence
Cognitive deficits
Delusional disorder
Depression
Disabling peak-dose dyskinesias
Erectile dysfunction
Gastric emptying disorders
Gilles de la Tourette's disorder
Nausea and vomiting
Neuroleptic malignant syndrome
Neurological diseases
Parkinson's disease
Psychiatric illness
Respiratory diseases
Schizophrenia
Vomiting
This is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase. Dopamine D2 receptor agonist: Cabergoline
Dopamine D2 receptor antagonist: Acetophenazine, Asenapine, Chlorprothixene, Fluphenazine, Fluphenazine Decanoate, Fluphenazine Enanthate, Iloperidone, Mesoridazine, Metoclopramide, Molindone, Paliperidone, Perphenazine, Prochlorperazine, Thiethylperazine, Thiothixene, Triflupromazine, Trimipramine
Dopamine D2 receptor modulator: Benzquinamide
Dopamine D2 receptor partial agonist: Aripiprazole
kcaDRD3D(3) dopamine receptor38080.6503Nature11159Brain.Akathisia
Amenorrhoea
Dyskinesia
Dystonia
Ejaculation disorder
Electrocardiogram change
Extrapyramidal disorder
Galactorrhoea
Gynaecomastia
Hyperprolactinaemia
Hyperthermia
Hypothermia
Menstrual disorder
Nasal congestion
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Tardive dyskinesia
Weight increased
G-protein coupled receptor 1Drug dependence
Neurological diseases
Psychiatric illness
Respiratory diseases
Schizophrenia
This is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase. Dopamine D3 receptor agonist: Levodopa
Dopamine D3 receptor antagonist: Chlorprothixene
kcaDRD4D(4) dopamine receptor25060.5368Nature11159Akathisia
Amenorrhoea
Dyskinesia
Dystonia
Ejaculation disorder
Electrocardiogram change
Extrapyramidal disorder
Galactorrhoea
Hypercholesterolaemia
Hyperprolactinaemia
Hyperthermia
Hypothermia
Lipid metabolism disorder
Menstrual disorder
Mydriasis
Nasal congestion
Neuroleptic malignant syndrome
Orthostatic hypotension
Parkinsonism
Tardive dyskinesia
G-protein coupled receptor 1Parkinson's disease
Psychiatric illness
Respiratory diseases
This is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase. Dopamine receptor agonist: Ergoloid, Pergolide
Dopamine receptor antagonist: Amoxapine, Pimozide
kcaDRD5D(1B) dopamine receptor8090.5365Neuron-specific, localized primarily within limbic regions of the brain. <a class="attribution" href="P21918#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>Akathisia
Amenorrhoea
Dyskinesia
Dystonia
Electrocardiogram change
Extrapyramidal disorder
Galactorrhoea
Hypothermia
Nasal congestion
Neuroleptic malignant syndrome
Parkinsonism
Tardive dyskinesia
G-protein coupled receptor 1Respiratory diseases This is one of the five types (D1 to D5) of receptors for dopamine, and the activity of this receptor is mediated by g proteins which activate adenylyl cyclase.
kcaDUTDeoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial1400.7785Found in a variety of tissues. Isoform 3 expression is constitutive, while isoform 2 expression correlates with the onset of DNA replication (at protein level). Isoform 2 degradation coincides with the cessation of nuclear DNA replication (at protein level).dUTPaseThis enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
kcaDYN1Dynamin-11680.7659TRAFAC class dynamin-like GTPaseMicrotubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes. Involved in receptor-mediated endocytosis.
kcaDYR1ADual specificity tyrosine-phosphorylation-regulated kinase 1A17710.5846Ubiquitous. Highest levels in skeletal muscle, testis, fetal lung and fetal kidney.protein kinaseMental retardation, autosomal dominant 7 (MRD7) [MIM:614104]: A disease characterized by primary microcephaly, severe mental retardation without speech, anxious autistic behavior, and dysmorphic features, including bitemporal narrowing, deep-set eyes, large simple ears, and a pointed nasal tip. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Note=The disease is caused by mutations affecting the gene represented in this entry.May play a role in a signaling pathway regulating nuclear functions of cell proliferation. Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Phosphorylates serine, threonine and tyrosine residues in its sequence and in exogenous substrates such as CRY2, FOXO1, SRSF6 and SIRT1.
kcaDYRK4Dual specificity tyrosine-phosphorylation-regulated kinase 45410.5845protein kinasePossible non-essential role in spermiogenesis (By similarity).
kcaE2AK1Eukaryotic translation initiation factor 2-alpha kinase 11090.5493Expressed predominantly in erythroid cells. At much lower levels, expressed in hepatocytes (at protein level).protein kinaseInhibits protein synthesis at the translation initiation level, in response to various stress conditions, including oxidative stress, heme deficiency, osmotic shock and heat shock. Exerts its function through the phosphorylation of EIF2S1 at 'Ser- 48' and 'Ser-51', thus preventing its recycling. Binds hemin forming a 1:1 complex through a cysteine thiolate and histidine nitrogenous coordination. This binding occurs with moderate affinity, allowing it to sense the heme concentration within the cell. Thanks to this unique heme-sensing capacity, plays a crucial role to shut off protein synthesis during acute heme-deficient conditions. In red blood cells (RBCs), controls hemoglobin synthesis ensuring a coordinated regulation of the synthesis of its heme and globin moieties. Thus plays an essential protective role for RBC survival in anemias of iron deficiency. Similarly, in hepatocytes, involved in heme-mediated translational control of CYP2B and CYP3A and possibly other hepatic P450 cytochromes. May also contain ER stress during acute heme-deficient conditions (By similarity).
kcaE2AK3Eukaryotic translation initiation factor 2-alpha kinase 31940.9284Ubiquitous. A high level expression is seen in secretory tissues.protein kinaseWolcott-Rallison syndrome (WRS) [MIM:226980]: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities. Note=The disease is caused by mutations affecting the gene represented in this entry.Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity).
kcaEAA2Excitatory amino acid transporter 2780.7812sodium:dicarboxylateTransports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
kcaEAA3Excitatory amino acid transporter 3810.5512Expressed in all tissues tested including liver, muscle, testis, ovary, retinoblastoma cell line, neurons and brain (in which there was dense expression in substantia nigra, red nucleus, hippocampus and in cerebral cortical layers).sodium:dicarboxylateSchizophrenia 18 (SCZD18) [MIM:615232]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A deletion at the chromosome 9p24.2 locus, including SLC1A1, has been identified in patients with psychotic disorders (PubMed:21982423). This 84 kb deletion is immediately upstream of the SLC1A1 gene in a regulatory region that contains the full native promoter sequence, extends through exon 1 of the SLC1A1 mRNA, co-segregates with disease in an extended 5-generation pedigree and increases disease risk more than 18-fold for family members (PubMed:23341099).Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium. Negatively regulated by ARL6IP5 (By similarity).
kcaEBP3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase1830.6495EBPChondrodysplasia punctata 2, X-linked dominant (CDPX2) [MIM:302960]: A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)- en-3-beta-ol in the plasma and tissues. Note=The disease is caused by mutations affecting the gene represented in this entry.Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
kcaECE1Endothelin-converting enzyme 14660.5226All isoforms are expressed in umbilical vein endothelial cells, polynuclear neutrophils, fibroblasts, atrium cardiomyocytes and ventricles. Isoforms A, B and C are also expressed in placenta, lung, heart, adrenal gland and phaeochromocytoma; isoforms A and C in liver, testis and small intestine; isoform <a href="#P42892" onclick="ensureIsoformSequenceVisible('P42892'); return true;">B</a>, C and D in endothelial cells and umbilical vein smooth muscle cells; isoforms C and D in saphenous vein cells, and isoform <a href="#P42892-3" onclick="ensureIsoformSequenceVisible('P42892-3'); return true;">C</a> in kidney. <a class="attribution" href="P42892#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a> <a class="attribution" href="P42892#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>peptidase M13Alzheimer's disease
Cardiovascular disease, unspecified
Converts big endothelin-1 to endothelin-1.
kcaEDNRAEndothelin-1 receptor25000.6355Nature11159Isoform <a href="#P25101" onclick="ensureIsoformSequenceVisible('P25101'); return true;">1</a>, isoform <a href="#P25101-3" onclick="ensureIsoformSequenceVisible('P25101-3'); return true;">3</a> and isoform <a href="#P25101-4" onclick="ensureIsoformSequenceVisible('P25101-4'); return true;">4</a> are expressed in a variety of tissues, with highest levels in the aorta and cerebellum, followed by lung, atrium and cerebral cortex, lower levels in the placenta, kidney, adrenal gland, duodenum, colon, ventricle and liver but no expression in umbilical vein endothelial cells. Within the placenta, isoform <a href="#P25101" onclick="ensureIsoformSequenceVisible('P25101'); return true;">1</a>, isoform <a href="#P25101-2" onclick="ensureIsoformSequenceVisible('P25101-2'); return true;">2</a>, isoform <a href="#P25101-3" onclick="ensureIsoformSequenceVisible('P25101-3'); return true;">3</a> and isoform <a href="#P25101-4" onclick="ensureIsoformSequenceVisible('P25101-4'); return true;">4</a> are expressed in the villi and stem villi vessels. <a class="attribution" href="P25101#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="P25101#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a>G-protein coupled receptor 1Atopic asthma
Cardiovascular disease, unspecified
Chronic renal failure
Hypertension
Ovarian cancer
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
kcaEDNRBEndothelin B receptor18330.4201Nature11159Expressed in placental stem villi vessels, but not in cultured placental villi smooth muscle cells. <a class="attribution" href="P24530#ref19" onclick="ensureReferenceVisible('ref19')">Ref.19</a>G-protein coupled receptor 1Atopic asthma
Glial proliferation
Melanoma
Neuronal injury
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Endothelin receptor, ET-A/ET-B antagonist: Ambrisentan, Bosentan
kcaEF2KEukaryotic elongation factor 2 kinase4490.5002protein kinaseThreonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.
kcaEGFREpidermal growth factor receptor52680.7063Ubiquitously expressed. Isoform <a href="#P00533-2" onclick="ensureIsoformSequenceVisible('P00533-2'); return true;">2</a> is also expressed in ovarian cancers. <a class="attribution" href="P00533#ref48" onclick="ensureReferenceVisible('ref48')">Ref.48</a>Decreased appetiteprotein kinaseBreast cancer
Cancer, unspecific
Colorectal cancer
Glioblastoma multiforme
Head and neck tumors
Lymphangiomatosis
Nonsmall cell lung cancer
Ovarian cancer
Pancreatic cancer
Solid tumor
Squamous cell carcinoma
Tumors
HCV infection
Receptor for egf, but also for other members of the egf family, as tgf-alpha, amphiregulin, betacellulin, heparin-binding egf-like growth factor, gp30 and vaccinia virus growth factor. Is involved in the control of cell growth and differentiation. Epidermal growth factor receptor erbB1 inhibitor: Cetuximab, Erlotinib, Gefitinib, Lapatinib, Panitumumab
kcaEGLN1Egl nine homolog 12860.8161According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. Note=The disease is caused by mutations affecting the gene represented in this entry.Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferencially recognized via a LXXLAP motif.
kcaEGLN2Egl nine homolog 2670.9113Expressed in adult and fetal heart, brain, liver, lung, skeletal muscle, and kidney. Also expressed in testis and placenta. Highest levels in adult brain, placenta, lung, kidney, and testis. Expressed in hormone responsive tissues, including normal and cancerous mammary, ovarian and prostate epithelium. <a class="attribution" href="Q96KS0#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>Anemia
Kidney Disease
kcaEGLN3Egl nine homolog 3580.5731Widely expressed at low levels. Expressed at higher levels in adult heart (cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle), lung and placenta, and in fetal spleen, heart and skeletal muscle. Also expressed in pancreas. Localized to pancreatic acini and islet cells.Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway. Target proteins are preferencially recognized via a LXXLAP motif.
kcaEHMT2Histone-lysine N-methyltransferase EHMT2780.6511Expressed in all tissues examined, with high levels in fetal liver, thymus, lymph node, spleen and peripheral blood leukocytes and lower level in bone marrow.class V-like SAM-binding methyltransferaseHistone methyltransferase that specifically mono- and dimethylates 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. H3K9me represents a specific tag for epigenetic transcriptional repression by recruiting HP1 proteins to methylated histones. Also mediates monomethylation of 'Lys-56' of histone H3 (H3K56me1) in G1 phase, leading to promote interaction between histone H3 and PCNA and regulating DNA replication. Also weakly methylates 'Lys-27' of histone H3 (H3K27me). Also required for DNA methylation, the histone methyltransferase activity is not required for DNA methylation, suggesting that these 2 activities function independently. Probably targeted to histone H3 by different DNA-binding proteins like E2F6, MGA, MAX and/or DP1. May also methylate histone H1. In addition to the histone methyltransferase activity, also methylates non-histone proteins: mediates dimethylation of 'Lys- 373' of p53/TP53. Also methylates CDYL, WIZ, ACIN1, DNMT1, HDAC1, ERCC6, KLF12 and itself.
kcaELNENeutrophil elastase14480.7112Bone marrow cells.peptidase S1Adult respiratory distress syndrome
Allergic rhinitis, unspecified
Asthma
Attenuated coronary flow reserve and myocardial dysfunction
Chronic bronchitis
Chronic obstructive pulmonary disease, unspecified
Cystic fibrosis
Emphysema
Intestinal ischemia-reperfusion associated with lung injury and the acute respiratory distress syndrome
Mucociliary dysfunction
Pulmonary edema (thrombin-induced)
Medullasin modifies the functions of natural killer cells, monocytes and granulocytes.
kcaEPHB4Ephrin type-B receptor 45260.5362Abundantly expressed in placenta but also detected in kidney, liver, lung, pancreas, skeletal muscle and heart. Expressed in primitive and myeloid, but not lymphoid, hematopoietic cells. Also observed in cell lines derived from liver, breast, colon, lung, melanocyte and cervix. <a class="attribution" href="P54760#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>protein kinaseLung Cancer
Solid tumors
kcaERBB2Receptor tyrosine-protein kinase erbB-223510.7099Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth. <a class="attribution" href="P04626#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a>protein kinaseNot Available Receptor protein-tyrosine kinase erbB-2 inhibitor: Lapatinib, Pertuzumab, Trastuzumab, Trastuzumab Emtansine
kcaERBB4Receptor tyrosine-protein kinase erbB-47870.6384Expressed at highest levels in brain, heart, kidney, in addition to skeletal muscle, parathyroid, cerebellum, pituitary, spleen, testis and breast. Lower levels in thymus, lung, salivary gland, and pancreas. Isoform JM-A CYT-1 and isoform JM-B CYT-1 are expressed in cerebellum, but only the isoform JM-B is expressed in the heart. <a class="attribution" href="Q15303#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q15303#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q15303#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a> <a class="attribution" href="Q15303#ref48" onclick="ensureReferenceVisible('ref48')">Ref.48</a>protein kinaseDermatologic Complications
Ependymoma
Metastatic (Stage IV) Breast Cancer
Specifically binds and is activated by neuregulins, nrg- 2, nrg-3, heparin-binding egf-like growth factor, betacellulin and ntak. Interaction with these factors induces cell differenciation. Not activated by egf, tgf-a, and amphiregulin.
kcaERCC5DNA repair protein complementing XP-G cells640.9278XPG/RAD2 endonucleaseXeroderma pigmentosum complementation group G (XP-G) [MIM:278780]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-G patients present features of Cockayne syndrome, cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex. Note=The disease is caused by mutations affecting the gene represented in this entry.Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3'incision in DNA nucleotide excision repair (NER). Acts as a cofactor for a DNA glycosylase that removes oxidized pyrimidines from DNA. May also be involved in transcription-coupled repair of this kind of damage, in transcription by RNA polymerase II, and perhaps in other processes too.
kcaERG1Squalene monooxygenase1220.543squalene monooxygenaseFungal diseases
Hypercholesterolemia
Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
kcaERG7Lanosterol synthase1750.5147terpene cyclase/mutaseHypercholesterolemia Catalyzes the cyclization of (s)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus.
kcaERN1Serine/threonine-protein kinase/endoribonuclease IRE1740.5116Ubiquitously expressed. High levels observed in pancreatic tissue.protein kinaseSenses unfolded proteins in the lumen of the endoplasmic reticulum via its N-terminal domain which leads to enzyme auto- activation. The active endoribonuclease domain splices XBP1 mRNA to generate a new C-terminus, converting it into a potent unfolded-protein response transcriptional activator and triggering growth arrest and apoptosis.
kcaESR1Estrogen receptor27420.6716Nature11159
VirtualToxLab
Acne
Blood urea increased
Bone disorder
Breast pain
Chloasma
Depression
Electrolyte imbalance
Embolism arterial
Endometrial cancer
Endometrial hyperplasia
Epiphyses premature fusion
Erythema multiforme
Fibrocystic breast disease
Gynaecomastia
Hepatic function abnormal
Hypercalcaemia
Jaundice
Menstrual disorder
Metrorrhagia
Neoplasm
Oedema
Porphyria non-acute
Sodium retention
Urticaria
Uterine inflammation
Weight increased
nuclear hormone receptorBrain injury
Breast cancer
Cardiovascular disease, unspecified
Coronary atherosclerosis
Endocrine independent cancer
Neurodegenerative diseases
Osteoporosis, unspecified
Postmenopausal symptoms
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
kcaESR2Estrogen receptor beta24100.519Nature11159
VirtualToxLab
Isoform beta-1 is expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors. Isoform beta-2 is expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus. Isoform beta-3 is found in testis. Isoform beta-4 is expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus. Isoform beta-5 is expressed in testis, placenta, skeletal muscle, spleen and leukocytes, and at a lower level in heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland and uterus. Not expressed in brain.Acne
Blood urea increased
Bone disorder
Breast pain
Chloasma
Depression
Electrolyte imbalance
Endometrial cancer
Endometrial hyperplasia
Epiphyses premature fusion
Erythema multiforme
Fibrocystic breast disease
Gynaecomastia
Hepatic function abnormal
Hypercalcaemia
Jaundice
Menstrual disorder
Metrorrhagia
Neoplasm
Oedema
Porphyria non-acute
Sodium retention
Urticaria
Uterine inflammation
Weight increased
nuclear hormone receptorBreast cancer
Cardiovascular disease, unspecified
ER beta-positive prostate tumors
Neurodegenerative diseases
Vascular injury response
Nuclear hormone receptor. binds estrogens with an affinity similar to that of esr1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability. Estrogen receptor beta: Estramustine Phosphate
Estrogen receptor beta modulator: Chlorotrianisene, Raloxifene
kcaEST1Liver carboxylesterase 14370.5718Expressed predominantly in liver with lower levels in heart and lung. <a class="attribution" href="P23141#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a>type-B carboxylesterase/lipaseAlzheimer's disease
Atherosclerosis
Cardiovascular disease, unspecified
Cocaine overdose
Hypercholesterolaemia
Protection against chemical weapons like Sarin, Soman and VX gas
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl coa ester.
kcaEST2Cocaine esterase1490.5426Preferentially expressed in intestine with moderate expression in liver. Within the intestine, highest expression is found in small intestine with lower expression in colon and rectum.type-B carboxylesterase/lipaseInvolved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
kcaF16P1Fructose-1,6-bisphosphatase 14100.735FBPase class 1Diabetes Mellitus Type 2
kcaFA10Coagulation factor X51970.7581Plasma; synthesized in the liver. <a class="attribution" href="P00742#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>peptidase S1Thrombosis
Thrombotic disease
Factor xa is a vitamin k-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor va, calcium and phospholipid during blood clotting. Coagulation factor X inhibitor: Apixaban, Rivaroxaban
kcaFA11Coagulation factor XI1070.6044Isoform <a href="#P03951-2" onclick="ensureIsoformSequenceVisible('P03951-2'); return true;">2</a> is produced by platelets and megakaryocytes but absent from other blood cells.peptidase S1Clotting Disorders Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX.
kcaFA12Coagulation factor XII8250.5161peptidase S1Factor XII deficiency (FA12D) [MIM:234000]: An asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. Factor XII deficiency is divided into two categories, a cross-reacting material (CRM)- negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection). Note=The disease is caused by mutations affecting the gene represented in this entry. Hereditary angioedema 3 (HAE3) [MIM:610618]: An hereditary angioedema occurring only in women. Hereditary angioedema is an autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema type 3 differs from types 1 and 2 in that both concentration and function of C1 esterase inhibitor are normal. Hereditary angioedema type 3 is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). Note=The disease is caused by mutations affecting the gene represented in this entry.Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta- factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa.
kcaFA7Coagulation factor VII6800.6063Plasma.peptidase S1Coagulative disorders Circulates in the blood in a zymogen form. Factor vii is converted to factor viia by factor xa, factor xiia, factor ixa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor viia then converts factor x to factor xa.
kcaFA9Coagulation factor IX2040.7046Synthesized primarily in the liver and secreted in plasma.peptidase S1Blood, Blood Forming Organ Disorders, Unspecified
Cardiac Surgery
Coronary Artery Disease
Thrombosis
Vascular Diseases
Venous Thromboembolism
Factor ix is a vitamin k-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor x to its active form in the presence of ca(2+) ions, phospholipids, and factor viiia.
kcaFAAH1Fatty-acid amide hydrolase 120320.6569Highly expressed in the brain, small intestine, pancreas, skeletal muscle and testis. Also expressed in the kidney, liver, lung, placenta and prostate. <a class="attribution" href="O00519#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>amidaseAnalgesics
Anesthetic
Anxiety disorder, unspecified
Pain
Sedation
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Anandamide amidohydrolase inhibitor: Acetaminophen
kcaFABP4Fatty acid-binding protein, adipocyte1440.6641calycinAtherosclerosis Lipid transport protein in adipocytes. Binds both long chain fatty acid and retinoic acid.
kcaFABPHFatty acid-binding protein, heart650.5224calycinFABP are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters.
kcaFAK1Focal adhesion kinase 111950.5136Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous.protein kinaseNote=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
kcaFAK2Protein-tyrosine kinase 2-beta7790.5535Most abundant in the brain, with highest levels in amygdala and hippocampus. Low levels in kidney (at protein level). Also expressed in spleen and lymphocytes.protein kinaseNote=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T- cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2.
kcaFASFatty acid synthase11870.5076Ubiquitous. Prominent expression in brain, lung, and liver. <a class="attribution" href="P49327#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P49327#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>Endometrial carcinoma
Leukemia, unspecified
Malaria
Mesothelioma
Metastatic osteosarcoma in the lung
Obesity
Prostate cancer
Tumors
Fatty acid synthetase catalyzes the formation of long- chain fatty acids from acetyl-coa, malonyl-coa and nadph. This multifunctional protein has 7 catalytic activities and an acyl carrier protein. Fatty acid synthase inhibitor: Orlistat
kcaFCGRNIgG receptor FcRn large subunit p511740.5531immunoglobulinAutoimmune diseases Binds to the fc region of monomeric immunoglobulins gamma. Mediates the uptake of igg from milk. Possible role in transfer of immunoglobulin g from mother to fetus.
kcaFDFTSqualene synthase7420.6067phytoene/squalene synthaseHypercholesterolemia
Hyperlipidemia
Hypocholesterolemia
kcaFEN1Flap endonuclease 1610.9362XPG/RAD2 endonucleaseStructure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double- stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
kcaFGF1Fibroblast growth factor 1660.8582Predominantly expressed in kidney and brain. Detected at much lower levels in heart and skeletal muscle. <a class="attribution" href="P05230#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P05230#ref22" onclick="ensureReferenceVisible('ref22')">Ref.22</a>heparin-binding growth factorsHepatic fibrosis The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.
kcaFGF2Fibroblast growth factor 2560.6046Expressed in granulosa and cumulus cells. Expressed in hepatocellular carcinoma cells, but not in non-cancerous liver tissue. <a class="attribution" href="P09038#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a> <a class="attribution" href="P09038#ref18" onclick="ensureReferenceVisible('ref18')">Ref.18</a>heparin-binding growth factorsHepatic fibrosis
Rheumatoid arthritis, unspecified
The heparin-binding growth factors are angiogenic agents in vivo and are potent mitogens for a variety of cell types in vitro. There are differences in the tissue distribution and concentration of these 2 growth factors.
kcaFGFR1Fibroblast growth factor receptor 120280.6781Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform <a href="#P11362-16" onclick="ensureIsoformSequenceVisible('P11362-16'); return true;">17</a>, isoform <a href="#P11362-18" onclick="ensureIsoformSequenceVisible('P11362-18'); return true;">18</a> and isoform <a href="#P11362-19" onclick="ensureIsoformSequenceVisible('P11362-19'); return true;">19</a> are not detected in these cells. <a class="attribution" href="P11362#ref19" onclick="ensureReferenceVisible('ref19')">Ref.19</a>protein kinasePeripheral Vascular Disease
Severe Coronary Heart Disease
Solid tumors
Ulcers
Fibroblast growth factor receptor 1 inhibitor: Pazopanib, Regorafenib
kcaFGFR2Fibroblast growth factor receptor 23070.6protein kinaseAngiogenesis in metastatic and atherosclerotic processes Receptor for acidic and basic fibroblast growth factors. Fibroblast growth factor receptor 2 agonist: Palifermin
Fibroblast growth factor receptor 2 inhibitor: Regorafenib
kcaFGFR3Fibroblast growth factor receptor 39120.5651Expressed in brain, kidney and testis. Very low or no expression in spleen, heart, and muscle. In 20- to 22-week old fetuses it is expressed at high level in kidney, lung, small intestine and brain, and to a lower degree in spleen, liver, and muscle. Isoform <a href="#P22607-2" onclick="ensureIsoformSequenceVisible('P22607-2'); return true;">2</a> is detected in epithelial cells. Isoform <a href="#P22607" onclick="ensureIsoformSequenceVisible('P22607'); return true;">1</a> is not detected in epithelial cells. Isoform <a href="#P22607" onclick="ensureIsoformSequenceVisible('P22607'); return true;">1</a> and isoform <a href="#P22607-2" onclick="ensureIsoformSequenceVisible('P22607-2'); return true;">2</a> are detected in fibroblastic cells. <a class="attribution" href="P22607#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>protein kinaseAchondroplasia
Multiple Myeloma
Osteopenic disorders
Skeletal disorders
Solid tumors
T(4;14) myeloma
Receptor for acidic and basic fibroblast growth factors. Preferentially binds fgf1. Fibroblast growth factor receptor 3 inhibitor: Pazopanib
kcaFGFR4Fibroblast growth factor receptor 42620.7867Expressed in gastrointestinal epithelial cells, pancreas, and gastric and pancreatic cancer cell lines. <a class="attribution" href="P22455#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>protein kinaseObesity Receptor for acidic fibroblast growth factor. Does not bind to basic fibroblast growth factor. Binds FGF19.
kcaFKB1APeptidyl-prolyl cis-trans isomerase FKBP1A5270.6084FKBP-type PPIase
kcaFKBP5Peptidyl-prolyl cis-trans isomerase FKBP5940.5738Widely expressed, enriched in testis compared to other tissues.Immunophilin protein with PPIase and co-chaperone activities. Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded.
kcaFLT3Receptor-type tyrosine-protein kinase FLT319490.6633Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia. <a class="attribution" href="P36888#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P36888#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P36888#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P36888#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a>protein kinaseAcute myeloid leukemia
Autoimmune diseases
MLL-rearranged acute lymphoblastic leukemias
Receptor for the fl cytokine, and has a tyrosine-protein kinase activity. Tyrosine-protein kinase receptor FLT3 inhibitor: Sorafenib, Sunitinib
kcaFNTAProtein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha19300.6828protein prenyltransferase subunit alphaAcute myeloid leukemia (AML)
Amebiasis
Bladder cancer
Breast cancer
Cancer, unspecific
Colorectal Cancer
Malaria
Non-small cell lung cancer (NSCLC)
Pancreatic Cancer
Solid tumors
Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the c-terminus of several proteins having the c-terminal sequence cys-aliphatic-aliphatic-x.
kcaFNTBProtein farnesyltransferase subunit beta18900.691protein prenyltransferase subunit betaCancer, unspecific Catalyzes the transfer of a farnesyl moiety from farnesyl pyrophosphate to a cysteine at the fourth position from the c-terminus of several proteins. The beta subunit is responsible for peptide-binding.
kcaFOSProto-oncogene c-Fos620.5969bZIPBreast cancer
Neurological symptom
Nuclear phosphoprotein which forms a tight but non- covalently linked complex with the c-jun/ap-1 transcription factor. C-fos has a critical function in regulating the development of cells destined to form and maintain the skeleton.
kcaFPPSFarnesyl pyrophosphate synthase1900.5058FPP/GGPP synthaseCancer, unspecific
Chagas' disease
Hypercholesterolemia
Leishmania infections
Myeloma disease
Osteoporosis, unspecified
Skeletal disorders
Toxoplasma infections
Trypanosomatid infections
Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.
kcaFPR1fMet-Leu-Phe receptor2510.5942Neutrophils.G-protein coupled receptor 1Gastric ulcer High affinity receptor for n-formyl-methionyl peptides, which are powerful neutrophils chemotactic factors. Binding of fmlp to the receptor causes activation of neutrophils. This response is mediated via a g-protein that activates a phosphatidylinositol.
kcaFUCOTissue alpha-L-fucosidase1000.5064glycosyl hydrolase 29Fucosidosis (FUCA1D) [MIM:230000]: An autosomal recessive lysosomal storage disease characterized by accumulation of fucose- containing glycolipids and glycoproteins in various tissues. Clinical signs include facial dysmorphism, dysostosis multiplex, moderate hepatomegaly, severe intellectual deficit, deafness, and according to age, angiokeratomas. Note=The disease is caused by mutations affecting the gene represented in this entry.Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N- acetylglucosamine of the carbohydrate moieties of glycoproteins.
kcaFURINFurin4130.6307Seems to be expressed ubiquitously.peptidase S8Furin is likely to represent the ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RX(K/R)R consensus motif.
kcaG6PDGlucose-6-phosphate 1-dehydrogenase6600.5423Isoform <a href="#P11413-2" onclick="ensureIsoformSequenceVisible('P11413-2'); return true;">Long</a> is found in lymphoblasts, granulocytes and sperm.glucose-6-phosphate dehydrogenaseSystemic lupus erythematosus Produces pentose sugars for nucleic acid synthesis and main producer of nadph reducing power.
kcaGABR1Gamma-aminobutyric acid type B receptor subunit 11750.5396Highly expressed in brain and weakly in heart, small intestine and uterus. Isoform 1A is mostly expressed in granular cell and molecular layer. Isoform 1B is mostly expressed in Purkinje cells. Isoform 1E is predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland.G-protein coupled receptor 3Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen. Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
kcaGALR1Galanin receptor type 1730.7585G-protein coupled receptor 1Convulsions
Obesity
Receptor for the hormone galanin. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity.
kcaGALR2Galanin receptor type 21450.854Expressed abundantly within the central nervous system in both hypothalamus and hippocampus. In peripheral tissues, the strongest expression was observed in heart, kidney, liver, and small intestine.G-protein coupled receptor 1Alzheimer's disease
Central nervous system diseases
Cerebral hemorrhage
Diabetes mellitus
Diarrhea
Eating disorders
Obesity
Receptor for the hormone galanin and for galp. The activity of this receptor is mediated by G proteins that activate the phospholipase c/protein kinase c pathway (via gq) and that inhibit adenylyl cyclase (via gi).
kcaGASRGastrin/cholecystokinin type B receptor21780.4732Nature11159Isoform <a href="#P32239" onclick="ensureIsoformSequenceVisible('P32239'); return true;">1</a> is expressed in brain, pancreas, stomach, the colon cancer cell line LoVo and the T-lymphoblastoma Jurkat, but not in heart, placenta, liver, lung, skeletal muscle, kidney or the stomach cancer cell line AGS. Expressed at high levels in the small cell lung cancer cell line NCI-H510, at lower levels in NCI-H345, NCI-H69 and GLC-28 cell lines, not expressed in GLC-19 cell line. Within the stomach, expressed at high levels in the mucosa of the gastric fundus and at low levels in the antrum and duodenum. Isoform <a href="#P32239-2" onclick="ensureIsoformSequenceVisible('P32239-2'); return true;">2</a> is present in pancreatic cancer cells and colorectal cancer cells, but not in normal pancreas or colonic mucosa. Isoform <a href="#P32239-3" onclick="ensureIsoformSequenceVisible('P32239-3'); return true;">3</a> is expressed in brain, pancreas, stomach, the stomach cancer cell line AGS and the colon cancer cell line LoVo. <a class="attribution" href="P32239#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="P32239#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="P32239#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a> <a class="attribution" href="P32239#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P32239#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="P32239#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>G-protein coupled receptor 1Acid-related diseases
Anxiety disorder, unspecified
Cocaine dependence
Gastrin sensitive tumours
Gastrointestinal adenocarcinomas
Gastrointestinal motility disorders
Malignant gliomas
Medullary thyroid cancer
Neuroendocrine tumors
Small cell lung cancer
Stromal ovarian tumors
Receptor for gastrin and cholecystokinin, and the ckk-b receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. this receptor mediates its action by association with G proteins.
kcaGBA2Non-lysosomal glucosylceramidase540.7965Widely expressed. Highly expressed in brain, heart, skeletal muscle, kidney and placenta and expressed at lower level in liver.non-lysosomal glucosylceramidaseSpastic paraplegia 46, autosomal recessive (SPG46) [MIM:614409]: A neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging. Note=The disease is caused by mutations affecting the gene represented in this entry.Non-lysosomal glucosylceramidase that catalyzes the conversion of glucosylceramide (GlcCer) to free glucose and ceramide. Involved in sphingomyelin generation and prevention of glycolipid accumulation. May also catalyze the hydrolysis of bile acid 3-O-glucosides, however, the relevance of such activity is unclear in vivo. Plays a role in central nevous system development. Required for proper formation of motor neuron axons.
kcaGBRA1Gamma-aminobutyric acid receptor subunit alpha-133590.6969Nature11159Agitation
Amnesia
Apnoea
Ataxia
Cholestasis
Confusional state
Dependence
Dermatitis exfoliative
Dysarthria
Erythema multiforme
Folate deficiency
Gangrene
Hiccups
Hypoprothrombinaemia
Hypotension
Incontinence
Irritability
Jaundice
Laryngospasm
Libido disorder
Necrosis
Nystagmus
Respiratory depression
Respiratory disorder
Salivary gland disorder
Somnolence
Speech disorder
Thrombophlebitis
Urinary retention
ligand-gated ion channelAnxiety disorders
Insomnia
kcaGBRA2Gamma-aminobutyric acid receptor subunit alpha-232190.6869Agitation
Amnesia
Apnoea
Ataxia
Bone marrow disorder
Cholestasis
Confusional state
Dependence
Dermatitis exfoliative
Dysarthria
Erythema multiforme
Folate deficiency
Gangrene
Hypoprothrombinaemia
Hypotension
Incontinence
Irritability
Jaundice
Laryngospasm
Libido disorder
Nystagmus
Respiratory depression
Respiratory disorder
Salivary gland disorder
Somnolence
Urinary retention
Vertigo
ligand-gated ion channelAnxiety disorder, unspecified
Disorders of initiating and maintaining sleep [insomnias]
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRA3Gamma-aminobutyric acid receptor subunit alpha-332410.6989Agitation
Amnesia
Apnoea
Ataxia
Bone marrow disorder
Cholestasis
Confusional state
Dependence
Dermatitis exfoliative
Dysarthria
Erythema multiforme
Folate deficiency
Gangrene
Hypoprothrombinaemia
Hypotension
Incontinence
Irritability
Jaundice
Laryngospasm
Libido disorder
Nystagmus
Respiratory depression
Respiratory disorder
Salivary gland disorder
Somnolence
Speech disorder
Urinary retention
ligand-gated ion channelAnxiety disorder, unspecified
Disorders of initiating and maintaining sleep [insomnias]
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRA4Gamma-aminobutyric acid receptor subunit alpha-426780.6874ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRA5Gamma-aminobutyric acid receptor subunit alpha-532720.7081Agitation
Amnesia
Apnoea
Ataxia
Bone marrow disorder
Cholestasis
Confusional state
Dependence
Dermatitis exfoliative
Dysarthria
Erythema multiforme
Folate deficiency
Gangrene
Hypoprothrombinaemia
Hypotension
Incontinence
Irritability
Jaundice
Laryngospasm
Libido disorder
Nystagmus
Respiratory depression
Respiratory disorder
Salivary gland disorder
Somnolence
Speech disorder
Urinary retention
ligand-gated ion channelAlzheimer's Disease
Central nervous system diseases
Cognitive deficits
Delirium
Dementia
Gaba, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the gaba/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRA6Gamma-aminobutyric acid receptor subunit alpha-627660.6704ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRB1Gamma-aminobutyric acid receptor subunit beta-126430.6882ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRB2Gamma-aminobutyric acid receptor subunit beta-228110.6977Isoform <a href="#P47870" onclick="ensureIsoformSequenceVisible('P47870'); return true;">1</a> and isoform <a href="#P47870-1" onclick="ensureIsoformSequenceVisible('P47870-1'); return true;">2</a> show reduced expression in schizophrenic brain. Isoform <a href="#P47870-3" onclick="ensureIsoformSequenceVisible('P47870-3'); return true;">3</a> shows increased expression in schizophrenic and bipolar disorder brains while isoform <a href="#P47870-4" onclick="ensureIsoformSequenceVisible('P47870-4'); return true;">4</a> shows reduced expression. <a class="attribution" href="P47870#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="P47870#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Agitation
Amnesia
Ataxia
Bone marrow disorder
Confusional state
Dependence
Hypotension
Incontinence
Jaundice
Libido disorder
Respiratory depression
Somnolence
Urinary retention
ligand-gated ion channelInsomnia
kcaGBRB3Gamma-aminobutyric acid receptor subunit beta-334410.7182ligand-gated ion channelEpilepsy, childhood absence 5 (ECA5) [MIM:612269]: A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRDGamma-aminobutyric acid receptor subunit delta26420.688ligand-gated ion channelGeneralized epilepsy with febrile seizures plus 5 (GEFS+5) [MIM:613060]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Epilepsy, idiopathic generalized 10 (EIG10) [MIM:613060]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Juvenile myoclonic epilepsy 7 (EJM7) [MIM:613060]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBREGamma-aminobutyric acid receptor subunit epsilon26200.6925Expressed in many tissues. Highest levels of expression in adult heart and placenta.ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRG1Gamma-aminobutyric acid receptor subunit gamma-126430.6878ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRG2Gamma-aminobutyric acid receptor subunit gamma-235480.7243Agitation
Amnesia
Ataxia
Blood disorder
Bone marrow disorder
Confusional state
Dependence
Jaundice
Libido disorder
Respiratory depression
Somnolence
Urinary retention
ligand-gated ion channelBrain injury
kcaGBRG3Gamma-aminobutyric acid receptor subunit gamma-326420.688ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
kcaGBRPGamma-aminobutyric acid receptor subunit pi26420.688Most abundant in the uterus, also expressed in lung, thymus and prostate.ligand-gated ion channelGABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
kcaGCRGlucocorticoid receptor20270.7217Nature11159
VirtualToxLab
Widely expressed. In the heart, detected in left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole adult and fetal heart. <a class="attribution" href="P04150#ref21" onclick="ensureReferenceVisible('ref21')">Ref.21</a>Acne
Adrenal disorder
Adrenal insufficiency
Adrenal suppression
Amenorrhoea
Bone disorder
Calcium metabolism disorder
Cataract
Cushingoid
Depression
Dysphonia
Embolism arterial
Endocrine disorder
Epidural lipomatosis
Epistaxis
Euphoric mood
Fluid retention
Foot and mouth disease
Fracture
Fungal infection
Glaucoma
Growth retardation
Hyperglycaemia
Hypertension
Hypertrichosis
Hypokalaemia
Impaired healing
Increased appetite
Intracranial pressure increased
Menstrual disorder
Muscular weakness
Nitrogen balance negative
Oedema
Oral candidiasis
Osteonecrosis
Osteoporosis
Pancreatic disorder
Pancreatitis acute
Peptic ulcer
Phosphorus metabolism disorder
Sepsis
Skin atrophy
Skin striae
Superinfection
Telangiectasia
nuclear hormone receptorCocaine dependence
Drug dependence
Major depressive disorder
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (gre) and as a modulator of other transcription factors. Affects inflammatory responses and cellular proliferation. Glucocorticoid receptor agonist: Alclometasone Dipropionate, Amcinonide, Beclomethasone Dipropionate, Betamethasone, Betamethasone Acetate, Betamethasone Benzoate, Betamethasone Dipropionate, Betamethasone Phosphoric Acid, Betamethasone Valerate, Budesonide, Ciclesonide, Clobetasol Propionate, Clocortolone Pivalate, Cortisone Acetate, Desonide, Desoximetasone, Dexamethasone, Dexamethasone Acetate, Dexamethasone Phosphoric Acid, Diflorasone Diacetate, Difluprednate, Flumethasone Pivalate, Flunisolide, Fluocinolone Acetonide, Fluocinonide, Fluorometholone, Fluorometholone Acetate, Fluprednisolone, Flurandrenolide, Fluticasone Furoate, Fluticasone Propionate, Halcinonide, Halobetasol Propionate, Hydrocortamate, Hydrocortisone, Hydrocortisone Acetate, Hydrocortisone Butyrate, Hydrocortisone Cypionate, Hydrocortisone Hemisuccinate, Hydrocortisone Phosphoric Acid, Hydrocortisone Probutate, Hydrocortisone Valerate, Loteprednol Etabonate, Medrysone, Meprednisone, Methylprednisolone, Methylprednisolone Hemisuccinate, Mometasone Furoate, Paramethasone Acetate, Prednicarbate, Prednisolone, Prednisolone Acetate, Prednisolone Phosphoric Acid, Prednisolone Tebutate, Prednisone, Rimexolone, Triamcinolone, Triamcinolone Acetonide, Triamcinolone Diacetate, Triamcinolone Hexacetonide
Glucocorticoid receptor antagonist: Mifepristone
kcaGHRLAppetite-regulating hormone520.5429Highest level in stomach. All forms are found in serum as well. Other tissues compensate for the loss of ghrelin synthesis in the stomach following gastrectomy. <a class="attribution" href="Q9UBU3#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>motilinAnorexia nervosa
Cachexia
Noninsulin-dependent diabetes mellitus
Obesity
Specific ligand for the growth hormone secretagogue receptor type 1 (ghsr) inducing the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation.
kcaGHSRGrowth hormone secretagogue receptor type 113040.5766Nature11159Pituitary and hypothalamus.G-protein coupled receptor 1Anorexia
Cachexia
Cardiovascular disease, unspecified
Gastrointestinal Diseases and Disorders, miscellaneous
Gastroparesis
Ileus
Noninsulin-dependent diabetes mellitus
Receptor for ghrelin, coupled to g-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (ghrp) (e.g. Met-enkephalin and ghrp-6) as well as non-peptide, low molecular weight secretagogues.
kcaGLCMGlucosylceramidase3700.5669glycosyl hydrolase 30Metabolic Disease
kcaGLP1RGlucagon-like peptide 1 receptor2710.8582G-protein coupled receptor 2Central nervous system diseases
Diabetic neuropathy
Noninsulin-dependent diabetes mellitus
Obesity
This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Glucagon-like peptide 1 receptor agonist: Exenatide, Liraglutide
kcaGLRA1Glycine receptor subunit alpha-1830.6441Respiratory depressionligand-gated ion channelConvulsions
Depression
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
kcaGNRHRGonadotropin-releasing hormone receptor17620.6824Pituitary, ovary, testis, breast and prostate but not in liver and spleen.FlushingG-protein coupled receptor 1Cancer, unspecific
Hypogonadotropic hypogonadism
Reproductive disorder
Receptor for gonadotropin releasing hormone (gnrh) that mediate the action of gnrh to stimulate the secretion of the gonadotropic hormones (lh and fsh). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol. Gonadotropin-releasing hormone receptor agonist: Gonadorelin, Goserelin, Histrelin, Leuprolide, Nafarelin, Triptorelin
Gonadotropin-releasing hormone receptor antagonist: Abarelix, Cetrorelix, Degarelix, Ganirelix Acetate
kcaGPBARG-protein coupled bile acid receptor 13750.5932Ubiquitously expressed. Expressed at higher level in spleen and placenta. Expressed at lower level in other tissues. In digestive tissues, it is expressed in stomach, duodenum, ileocecum, ileum, jejunum, ascending colon, transverse colon, descending colon, cecum and liver, but not in esophagus and rectum. <a class="attribution" href="Q8TDU6#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q8TDU6#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q8TDU6#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>G-protein coupled receptor 1Type 2 Diabetes Receptor for bile acid. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids.
kcaGPR35G-protein coupled receptor 354310.6717Predominantly expressed in immune and gastrointestinal tissues.G-protein coupled receptor 1Acts as a receptor for kynurenic acid, an intermediate in the tryptophan metabolic pathway. The activity of this receptor is mediated by G-proteins that elicit calcium mobilization and inositol phosphate production through G(qi/o) proteins.
kcaGRB2Growth factor receptor-bound protein 22820.5364GRB2/sem-5/DRKAdapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.
kcaGRIA1Glutamate receptor 112030.6063Widely expressed in brain.glutamate-gated ion channelSchizophrenia Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist.
kcaGRIA2Glutamate receptor 212950.582glutamate-gated ion channelReceptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
kcaGRIA3Glutamate receptor 310980.5738glutamate-gated ion channelMental retardation, X-linked 94 (MRX94) [MIM:300699]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non- syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. MRX94 patients have moderate mental retardation. Other variable features are macrocephaly, seizures, myoclonic jerks, autistic behavior, asthenic body habitus, distal muscle weakness and hyporeflexia. Note=The disease is caused by mutations affecting the gene represented in this entry.Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
kcaGRIA4Glutamate receptor 411880.5682glutamate-gated ion channelReceptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
kcaGRIK1Glutamate receptor ionotropic, kainate 16590.5206Most abundant in the cerebellum and the suprachiasmatic nuclei (SCN) of the hypothalamus.glutamate-gated ion channelAnalgesics
Epilepsy
Pain
L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of glu are mediated by a variety of receptors that are named according to their selective agonists.
kcaGRIK2Glutamate receptor ionotropic, kainate 25560.6188Expression is higher in cerebellum than in cerebral cortex.glutamate-gated ion channelMental retardation, autosomal recessive 6 (MRT6) [MIM:611092]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. In contrast to syndromic or specific mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic mental retardation. MRT6 patients display mild to severe mental retardation and psychomotor development delay in early childhood. Patients do not have neurologic problems, congenital malformations, or facial dysmorphism. Body height, weight, and head circumference are normal. Note=The disease is caused by mutations affecting the gene represented in this entry.Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L- glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity).
kcaGRIK3Glutamate receptor ionotropic, kainate 34490.5082glutamate-gated ion channelReceptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.
kcaGRIK4Glutamate receptor ionotropic, kainate 43950.5537glutamate-gated ion channelReceptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
kcaGRIK5Glutamate receptor ionotropic, kainate 54290.535glutamate-gated ion channelReceptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > domoate > L- glutamate >> AMPA >> NMDA = 1S,3R-ACPD.
kcaGRK7G protein-coupled receptor kinase 7740.6495Retinal cones, outer and inner segments.protein kinaseRetina-specific kinase involved in the shutoff of the photoresponse and adaptation to changing light conditions via cone opsin phosphorylation, including rhodopsin (RHO).
kcaGRM1Metabotropic glutamate receptor 18520.6862Detected in brain.G-protein coupled receptor 3Analgesics
Convulsions
Neuronal injury
Pain
Receptor for glutamate. The activity of this receptor is mediated by a g-protein that activates a phosphatidylinositol- calcium second messenger system. May participate in the central action of glutamate in the cns, such as long-term potentiation.
kcaGRM2Metabotropic glutamate receptor 29250.6568Detected in brain cortex (at protein level). Widely expressed in different regions of the adult brain as well as in fetal brain. <a class="attribution" href="Q14416#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>G-protein coupled receptor 3Alzheimer's disease
Analgesics
Anxiety disorder, unspecified
Epilepsy
Pain, unspecified
Traumatic brain injury
Receptor for glutamate. The activity of this receptor is mediated by a g-protein that inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.
kcaGRM3Metabotropic glutamate receptor 31880.6567Detected in brain cortex, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, hippocampus, corpus callosum, caudate nucleus and amygdala. <a class="attribution" href="Q14832#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>G-protein coupled receptor 3Alzheimer's disease
Analgesics
Epilepsy
Pain
Psychosis
Schizophrenia and Schizoaffective Disorders
Traumatic brain injury
Receptor for glutamate. The activity of this receptor is mediated by a g-protein that inhibits adenylate cyclase activity.
kcaGRM5Metabotropic glutamate receptor 527290.5092G-protein coupled receptor 3Analgesics
Anxiety Disorders
Convulsions
Depression
Drug dependence
Gastroesophageal Reflux Disease (GERD)
Inflammatory pain
Migraine and Cluster Headaches
Neuronal injury
Parkinson's disease
Receptor for glutamate. The activity of this receptor is mediated by a g-protein that activates a phosphatidylinositol- calcium second messenger system and generates a calcium-activated chloride current.
kcaGRM7Metabotropic glutamate receptor 7770.7123Expressed in many areas of the brain, especially in the cerebral cortex, hippocampus, and cerebellum. Expression of GRM7 isoforms in non-neuronal tissues appears to be restricted to isoform <a href="#Q14831-3" onclick="ensureIsoformSequenceVisible('Q14831-3'); return true;">3</a> and isoform <a href="#Q14831-4" onclick="ensureIsoformSequenceVisible('Q14831-4'); return true;">4</a>. <a class="attribution" href="Q14831#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q14831#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>G-protein coupled receptor 3Convulsions Receptor for glutamate. The activity of this receptor is mediated by a g-protein that inhibits adenylate cyclase activity.
kcaGRPRGastrin-releasing peptide receptor1550.6957Highly expressed in pancreas. Also expressed in stomach, adrenal cortex and brain. <a class="attribution" href="P30550#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>G-protein coupled receptor 1Small cell lung cancer Receptor for gastrin releasing peptide (grp). This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaGSHRGlutathione reductase, mitochondrial1130.5238class-I pyridine nucleotide-disulfide oxidoreductaseMaintains high levels of reduced glutathione in the cytosol.
kcaGSK3AGlycogen synthase kinase-3 alpha15630.6565protein kinaseNot Available
kcaGSK3BGlycogen synthase kinase-3 beta34070.6297Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. Colocalizes with EIF2AK2/PKR and TAU in the Alzheimer's disease (AD) brain. <a class="attribution" href="P49841#ref38" onclick="ensureReferenceVisible('ref38')">Ref.38</a>protein kinaseAlzheimer's disease
Bipolar affective disorder
Brain injury
Immunodeficiency
Ischemia
Noninsulin-dependent diabetes mellitus
Participates in the wnt signaling pathway. Implicated in the hormonal control of several regulatory proteins including glycogen synthase, myb, and the transcription factor c-jun. Phosphorylates c-jun at sites proximal to its dna-binding domain. Glycogen synthase kinase-3 inhibitor: Lithium Carbonate, Lithium Citrate
kcaGSTP1Glutathione S-transferase P750.8415GSTConjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
kcaHCAR2Hydroxycarboxylic acid receptor 25690.5602G-protein coupled receptor 1Type IV and V hyperlipidemia Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (d)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through g(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils.
kcaHDA10Histone deacetylase 106150.6386Ubiquitous. High expression in liver, spleen, pancreas and kidney.histone deacetylaseResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.
kcaHDA11Histone deacetylase 115780.6662Weakly expressed in most tissues. Strongly expressed in brain, heart, skeletal muscle, kidney and testis.histone deacetylaseResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.
kcaHDAC3Histone deacetylase 39830.5989Widely expressed.histone deacetylaseResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys- 27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation.
kcaHDAC4Histone deacetylase 48760.6728Ubiquitous.histone deacetylaseAcne
Basal cell carcinoma
Bladder cancer
Colorectal Cancer
Cutaneous T-Cell Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Liver Cancer
Lymphoma, Unspecified
Melanoma; Prostate cancer
Mesothelioma
Multiple Myeloma
Myelodysplastic Syndrome
Ovarian cancer
Pancreatic Cancer
Prostate cancer
Prostate cancer (hormone refractory)
Renal Cell Carcinoma
Sarcoma
Skin cancer
Solid tumors
Responsible for the deacetylation of lysine residues on the n-terminal part of the core histones (h2a, h2b, h3 and h4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation.
kcaHDAC5Histone deacetylase 56630.6397Ubiquitous.histone deacetylaseResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors.
kcaHDAC6Histone deacetylase 615240.6636histone deacetylaseMultiple myeloma Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Plays a central role in microtubuldependent cell motility via deacetylation of tubulin. Histone deacetylase 6 inhibitor: Vorinostat
kcaHDAC7Histone deacetylase 76760.6544histone deacetylaseResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors (By similarity). May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene.
kcaHDAC8Histone deacetylase 811550.551Weakly expressed in most tissues. Expressed at higher level in heart, brain, kidney and pancreas and also in liver, lung, placenta, prostate and kidney.histone deacetylaseCornelia de Lange syndrome 5 (CDLS5) [MIM:300882]: A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Note=The disease is caused by mutations affecting the gene represented in this entry. Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. Note=The disease is caused by mutations affecting the gene represented in this entry.Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility.
kcaHDAC9Histone deacetylase 95970.672Broadly expressed, with highest levels in brain, heart, muscle and testis. Isoform 3 is present in human bladder carcinoma cells (at protein level).histone deacetylaseNote=A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein.Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription. Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.
kcaHMDH3-hydroxy-3-methylglutaryl-coenzyme A reductase9100.5569MyalgiaHMG-CoA reductaseAtherosclerosis
Cardiovascular disease, unspecified
Cervical cancer
Coronary heart disease
Dyslipidemia
Head and neck squamous cell carcinomas
Hypercholesterolemia
Hypertriglyceridemia
Myocardial infarction
This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis. HMG-CoA reductase inhibitor: Atorvastatin, Cerivastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin, Simvastatin
kcaHMOX1Heme oxygenase 11210.644Expressed at higher levels in renal cancer tissue than in normal tissue (at protein level). <a class="attribution" href="P09601#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>heme oxygenaseAtherosclerosis
Cardiovascular disease, unspecified
Cerebral vasospasm
Chronic myeloid leukemia
Crohn's Disease
Ischemic injury of the liver
Kaposi's sarcoma
Neonatal Hyperbilirubinemia, jaundice
Oxidative tissue injuries
Ulcerative colitis
Vascular disease
Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen.
kcaHNF4AHepatocyte nuclear factor 4-alpha2390.782nuclear hormone receptorNoninsulin-dependent diabetes mellitus Transcriptionally controlled transcription factor. Binds to dna sites required for the transcription of alpha 1- antitrypsin, apolipoprotein ciii, transthyretin genes and hnf1- alpha. May be essential for development of the liver, kidney and intestine.
kcaHPSEHeparanase2180.6228Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle's and Huxley's layers of inner the root sheath (IRS) at anagen phase. <a class="attribution" href="Q9Y251#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q9Y251#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a> <a class="attribution" href="Q9Y251#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="Q9Y251#ref29" onclick="ensureReferenceVisible('ref29')">Ref.29</a> <a class="attribution" href="Q9Y251#ref38" onclick="ensureReferenceVisible('ref38')">Ref.38</a>glycosyl hydrolase 79Hepatocellular Cancer Following Curative Resection
Lung Cancer
Prostate cancer
kcaHRH1Histamine H1 receptor17350.7452Nature11159Agranulocytosis
Akathisia
Anticholinergic syndrome
Ataxia
Bladder disorder
Bone marrow disorder
Central nervous system stimulation
Chest discomfort
Conduction disorder
Constipation
Convulsion
Cycloplegia
Dermatitis allergic
Diabetic eye disease
Dry mouth
Dystonia
Dysuria
Euphoric mood
Extrapyramidal disorder
Galactorrhoea
Haemolytic anaemia
Hypercholesterolaemia
Hyperthermia
Hyporeflexia
Increased appetite
Increased viscosity of bronchial secretion
Insomnia
Muscular weakness
Myopathy
Nervousness
Parkinsonism
Photosensitivity reaction
Sedation
Skin sensitisation
Somnolence
Tachycardia
Tardive dyskinesia
Tinnitus
Tremor
Urinary retention
Urinary tract disorder
Vision blurred
Weight increased
G-protein coupled receptor 1Acute lymphoblastic leukaemia (therapy-refractory)
Allergic diseases
Allergic rhinitis, unspecified
Anxiety disorder, unspecified
Chronic rhinitis
Chronic urticaria
Epidermal hyperplasia
Epilepsy
Hypotension
Intimal hyperplasia
Ischemia
Motion sickness
Nausea and vomiting
Seasonal allergic rhinitis
Systemic arterial vasodilation
In peripheral tissues, the h1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neuro. Histamine H1 receptor agonist: Histamine, Tolazoline
Histamine H1 receptor antagonist: Acrivastine, Alcaftadine, Antazoline, Azatadine, Azelastine, Bepotastine, Bromodiphenhydramine, Brompheniramine, Buclizine, Carbinoxamine, Cetirizine, Chlorpheniramine, Chlorpheniramine Polistirex, Clemastine, Cyclizine, Cyproheptadine, Desloratadine, Dexbrompheniramine, Dexchlorpheniramine, Dimenhydrinate, Diphenhydramine, Diphenylpyraline, Doxylamine, Emedastine, Epinastine, Fexofenadine, Hydroxyzine, Ketotifen, Levocabastine, Levocetirizine, Loratadine, Meclizine, Methdilazine, Methylpromazine, Olopatadine, Orphenadrine, Pheniramine, Promethazine, Propiomazine, Pyrilamine, Trimipramine, Tripelennamine, Triprolidine
kcaHRH2Histamine H2 receptor6290.6716Nature11159Anticholinergic syndrome
Cycloplegia
G-protein coupled receptor 1Epidermal hyperplasia
Lasting tachycardia
Peptic ulcer
Systemic arterial vasodilation
Zollinger-Ellison syndrome
The H2 subclass of histamine receptors mediates gastric acid secretion and also appears to regulate gastrointestinal motility and intestinal secretion., and it plays possible role in regulating cell growth and differentiation. Histamine H2 receptor agonist: Betazole, Tolazoline
Histamine H2 receptor antagonist: Cimetidine, Famotidine, Methantheline, Nizatidine, Ranitidine
kcaHRH3Histamine H3 receptor37470.6587Nature11159Expressed predominantly in the CNS, with the greatest expression in the thalamus and caudate nucleus. The various isoforms are mainly coexpressed in brain, but their relative expression level varies in a region-specific manner. Isoform <a href="#Q9Y5N1-3" onclick="ensureIsoformSequenceVisible('Q9Y5N1-3'); return true;">3</a> and isoform <a href="#Q9Y5N1-7" onclick="ensureIsoformSequenceVisible('Q9Y5N1-7'); return true;">7</a> are highly expressed in the thalamus, caudate nucleus and cerebellum while isoform <a href="#Q9Y5N1-5" onclick="ensureIsoformSequenceVisible('Q9Y5N1-5'); return true;">5</a> and isoform <a href="#Q9Y5N1-6" onclick="ensureIsoformSequenceVisible('Q9Y5N1-6'); return true;">6</a> show a poor expression. Isoform <a href="#Q9Y5N1-5" onclick="ensureIsoformSequenceVisible('Q9Y5N1-5'); return true;">5</a> and isoform <a href="#Q9Y5N1-6" onclick="ensureIsoformSequenceVisible('Q9Y5N1-6'); return true;">6</a> show a high expression in the amygdala, substantia nigra, cerebral cortex and hypothalamus. Isoform <a href="#Q9Y5N1-7" onclick="ensureIsoformSequenceVisible('Q9Y5N1-7'); return true;">7</a> is not found in hypothalamus or substantia nigra.G-protein coupled receptor 1Acid-related diseases
Allergic rhinitis, unspecified
Alzheimer's disease
Attention-deficit hyperactivity disorder
Central nervous system diseases
Inflammatory diseases
Schizophrenia
The h3 subclass of histamine receptors could mediate the histamine signals in cns and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist).
kcaHRH4Histamine H4 receptor9730.513Expressed primarily in the bone marrow and eosinophils. Shows preferential distribution in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils. Also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver and lymph node. <a class="attribution" href="Q9H3N8#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Anticholinergic syndromeG-protein coupled receptor 1Allergic diseases
Allergy, unspecified
Asthma
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues and display a significant level of constitutive activity (spontaneous activity in the absence of agonist).
kcaHS90AHeat shock protein HSP 90-alpha8510.6651heat shock protein 90Breast cancer
Chronic Myelogenous Leukemia (CML)
Gastrointestinal Stromal Tumors (GIST)
Hematological Malignancies
HER2-positive Metastatic Breast Cancer
Melanoma
Multiple Myeloma
Non-small Cell Lung Cancer
Ovarian cancer
Prostate cancer
Refractory Hematological Malignancies
Solid tumors
kcaHS90BHeat shock protein HSP 90-beta7770.7395heat shock protein 90Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.
kcaHSP7CHeat shock cognate 71 kDa protein540.8122Ubiquitous.heat shock protein 70Bacterial infections Chaperone. Isoform 2 may function as an endogenous inhibitory regulator of hsc70 by competing the cochaperones.
kcaHYESBifunctional epoxide hydrolase 213320.6246AB hydrolaseCardiovascular disease, unspecified
Hypertension
Renal diseases
This enzyme acts on epoxides (alkene oxides, oxiranes) and arene oxides. plays a role in xenobiotic metabolism by degrading potential toxic epoxides. also determines steady- state levels of physiological mediators.
kcaI23O1Indoleamine 2,3-dioxygenase 12820.5806indoleamine 2,3-dioxygenaseDepression Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.
kcaICAM1Intercellular adhesion molecule 16100.666immunoglobulinAsthma
Autoimmune diseases
Inflammation
Multiple sclerosis
Icam proteins are ligands for the leukocyte adhesion lfa-1 protein (integrin alpha-l/beta-2).
kcaICMTProtein-S-isoprenylcysteine O-methyltransferase2500.6504Ubiquitously expressed. Expressed at higher levels in the cerebellum and putamen than in other brain regions. Abundant expression seen in the Purkinje cells and pontine neurons.class VI-like SAM-binding methyltransferaseCatalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.
kcaIDEInsulin-degrading enzyme3680.5284peptidase M16Alzheimer's disease May play a role in the cellular processing of insulin. May be involved in intercellular peptide signaling.
kcaIGF1RInsulin-like growth factor 1 receptor21050.7654Found as a hybrid receptor with INSR in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Expressed in a variety of tissues. Overexpressed in tumors, including melanomas, cancers of the colon, pancreas prostate and kidney. <a class="attribution" href="P08069#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a> <a class="attribution" href="P08069#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a> <a class="attribution" href="P08069#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a> <a class="attribution" href="P08069#ref24" onclick="ensureReferenceVisible('ref24')">Ref.24</a>protein kinaseCancer, unspecific
Colorectal cancer
Ewing's sarcoma
Medulloblastoma
Peripheral neuroectodermal tumor
Tumors
This receptor binds insulin-like growth factor I (IGF I) with a high affinity and igf ii with a lower affinity. It has a tyrosine-protein kinase activity. Insulin-like growth factor I receptor agonist: Mecasermin, Mecasermin Rinfabate
kcaIKBANF-kappa-B inhibitor alpha510.6279NF-kappa-B inhibitorEctodermal dysplasia, anhidrotic, with T-cell immunodeficiency autosomal dominant (ADEDAID) [MIM:612132]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. Note=The disease is caused by mutations affecting the gene represented in this entry.Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.
kcaIKKAInhibitor of nuclear factor kappa-B kinase subunit alpha7140.5597Widely expressed.protein kinaseAsthma Phosphorylates inhibitors of nf-kappa-b thus leading to the dissociation of the inhibitor/nf-kappa-b complex and ultimately the degradation of the inhibitor. Also phosphorylates ncoa3.
kcaIKKBInhibitor of nuclear factor kappa-B kinase subunit beta13020.7185Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.protein kinaseAsthma
Autoimmune diseases
Fibrosing alveolitis
Inflammation
Inflammatory lung disease
Rheumatoid arthritis, unspecified
Transplant failure or rejection
Phosphorylates inhibitors of nf-kappa-b thus leading to the dissociation of the inhibitor/nf-kappa-b complex and ultimately the degradation of the inhibitor. Also phosphorylates ncoa3 (by similarity).
kcaIKKEInhibitor of nuclear factor kappa-B kinase subunit epsilon4540.5322protein kinaseAnalgesics
Herpes virus infection
Inflammation
Inflammatory diseases
Pain, unspecified
Rheumatoid arthritis, unspecified
kcaIL8Interleukin-81790.6518intercrine alphaAngiogenesis in metastatic and atherosclerotic processes
Arthritis
Human cytomegalovirus infections
Inflammation
Mechanical nociceptor hypersensitivity
Meningitis
Il-8 is a chemotactic factor that attracts neutrophils, basophils, and t-cells, but not monocytes. It is also involved in neutrophil activation. It is released from several cell types in response to an inflammatory stimulus.
kcaIMDH1Inosine-5'-monophosphate dehydrogenase 11490.5583IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor.IMPDH/GMPRInflammatory bowel disease Inosine-5'-monophosphate dehydrogenase 1 inhibitor: Ribavirin
kcaIMDH2Inosine-5'-monophosphate dehydrogenase 27390.6069IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor.IMPDH/GMPRLeukemia, unspecified Imp is the rate limiting enzyme in the de novo synthesis of guanine nucleotides and therefore is involved in the regulation of cell growth. It may also have a role in the development of malignancy and the growth progression of some tumors. Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor: Mycophenolate Mofetil, Mycophenolic Acid, Thioguanine
kcaINSRInsulin receptor16380.6862Isoform <a href="#P06213" onclick="ensureIsoformSequenceVisible('P06213'); return true;">Long</a> and isoform <a href="#P06213-2" onclick="ensureIsoformSequenceVisible('P06213-2'); return true;">Short</a> are predominantly expressed in tissue targets of insulin metabolic effects: liver, adipose tissue and skeletal muscle but are also expressed in the peripheral nerve, kidney, pulmonary alveoli, pancreatic acini, placenta vascular endothelium, fibroblasts, monocytes, granulocytes, erythrocytes and skin. Isoform <a href="#P06213-2" onclick="ensureIsoformSequenceVisible('P06213-2'); return true;">Short</a> is preferentially expressed in fetal cells such as fetal fibroblasts, muscle, liver and kidney. Found as a hybrid receptor with IGF1R in muscle, heart, kidney, adipose tissue, skeletal muscle, hepatoma, fibroblasts, spleen and placenta (at protein level). Overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas. <a class="attribution" href="P06213#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a> <a class="attribution" href="P06213#ref28" onclick="ensureReferenceVisible('ref28')">Ref.28</a> <a class="attribution" href="P06213#ref32" onclick="ensureReferenceVisible('ref32')">Ref.32</a> <a class="attribution" href="P06213#ref33" onclick="ensureReferenceVisible('ref33')">Ref.33</a>protein kinaseDiabetes mellitus This receptor binds insulin and has a tyrosine-protein kinase activity. Insulin receptor agonist: Insulin Aspart, Insulin Aspart Protamine Recombinant, Insulin Detemir, Insulin Glargine, Insulin Glulisine, Insulin Human, Insulin Lispro, Insulin Lispro Protamine Recombinant, Insulin Pork, Insulin Purified Beef, Insulin Purified Pork, Insulin Susp Isophane Beef, Insulin Susp Isophane Beef/Pork, Insulin Susp Isophane Purified Beef, Insulin Susp Isophane Purified Pork, Insulin Susp Isophane Recombinant Human, Insulin Susp Isophane Semisynthetic Purified Human, Insulin Susp Protamine Zinc Beef/Pork, Insulin Susp Protamine Zinc Purified Beef, Insulin Susp Protamine Zinc Purified Pork, Insulin Zinc Susp Beef, Insulin Zinc Susp Extended Beef, Insulin Zinc Susp Extended Purified Beef, Insulin Zinc Susp Extended Recombinant Human, Insulin Zinc Susp Prompt Beef, Insulin Zinc Susp Prompt Purified Pork, Insulin Zinc Susp Purified Beef, Insulin Zinc Susp Purified Beef/Pork, Insulin Zinc Susp Purified Pork, Insulin Zinc Susp Recombinant Human, Insulin Zinc Susp Semisynthetic Purified Human
kcaIRAK1Interleukin-1 receptor-associated kinase 16540.5037Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2.protein kinaseSerine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways. Is rapidly recruited by MYD88 to the receptor- signaling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.
kcaIRAK4Interleukin-1 receptor-associated kinase 49580.5992protein kinaseAutoimmune diseases
Inflammation
Sepsis
kcaITA2BIntegrin alpha-IIb19320.6717Isoform 1 and isoform 2 were identified in platelets and megakaryocytes, but not in reticulocytes or in Jurkat and U-937 white blood cell line. Isoform 3 is expressed by leukemia, prostate adenocarcinoma and melanoma cells but not by platelets or normal prostate or breast epithelial cells.integrin alpha chainGlanzmann thrombasthenia (GT) [MIM:273800]: A common inherited disease of platelet aggregation. It is characterized by mucocutaneous bleeding of mild-to-moderate severity. GT has been classified clinically into types I and II. In type I, platelets show absence of the glycoprotein IIb-IIIa complexes at their surface and lack fibrinogen and clot retraction capability. In type II, the platelets express the GPIIb-IIIa complex at reduced levels, have detectable amounts of fibrinogen, and have low or moderate clot retraction capability. Note=The disease is caused by mutations affecting the gene represented in this entry. Bleeding disorder, platelet-type 16 (BDPLT16) [MIM:187800]: An autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities. Note=The disease is caused by mutations affecting the gene represented in this entry.Integrin alpha-IIb/beta-3 is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. It recognizes the sequence R-G-D in a wide array of ligands. It recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha- IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial cell surface.
kcaITA4Integrin alpha-414930.5747integrin alpha chainNot Available Integrin alpha-4/beta-7 inhibitor: Natalizumab
kcaITA5Integrin alpha-52470.6123integrin alpha chainMacular Degeneration
kcaITALIntegrin alpha-L5840.7116integrin alpha chainInflammatory diseases
kcaITAVIntegrin alpha-V15510.6878integrin alpha chainBrain tumors The alpha-v integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and von willebrand factor. They recognize the sequence r-g-d. Integrin alpha-V/beta-3 inhibitor: Abciximab
kcaITB1Integrin beta-114860.5727Isoform beta-1A is widely expressed, other isoforms are generally coexpressed with a more restricted distribution. Isoform beta-1B is expressed in skin, liver, skeletal muscle, cardiac muscle, placenta, umbilical vein endothelial cells, neuroblastoma cells, lymphoma cells, hepatoma cells and astrocytoma cells. Isoform beta-1C and isoform beta-1C-2 are expressed in muscle, kidney, liver, placenta, cervical epithelium, umbilical vein endothelial cells, fibroblast cells, embryonal kidney cells, platelets and several blood cell lines. Isoform beta-C-2, rather than isoform beta-1C, is selectively expressed in peripheral T-cells. Isoform beta-1C is expressed in non-proliferating and differentiated prostate gland epithelial cells and in platelets, on the surface of erythroleukemia cells and in various hematopoietic cell lines. Isoform beta-1D is expressed specifically in striated muscle (skeletal and cardiac muscle). <a class="attribution" href="P05556#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P05556#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a> <a class="attribution" href="P05556#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a> <a class="attribution" href="P05556#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a> <a class="attribution" href="P05556#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="P05556#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a>integrin beta chainAsthma
Macular Degeneration
Rheumatoid arthritis
Tumors
Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta- 1 and alpha-11/beta-1 are receptors for collagen, and integrins alpha- 1/beta-1 and alpha-2/beta-2 recognize the proline-hydroxylated sequence g-f-p-g-e-r in collagen. Integrin alpha-4/beta-1 inhibitor: Natalizumab
kcaITB2Integrin beta-24730.6994integrin beta chainIschemic stroke Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins alpha-M/beta-2 and alpha-X/beta-2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin alpha-X/beta-2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin alpha-M/beta-2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin alpha-M/beta-2 is also a receptor for factor X. Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1.
kcaITB3Integrin beta-326950.6113Isoform beta-3A and isoform beta-3C are widely expressed. Isoform beta-3A is specifically expressed in osteoblast cells; isoform beta-3C is specifically expressed in prostate and testis.integrin beta chainPlatelet adhesion Integrin alpha-v/beta-3 is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von willebrand factor. Integrin alpha-iib/beta-3 is a receptor for fibronectin.
kcaITB5Integrin beta-52700.7313integrin beta chainIntegrin alpha-V/beta-5 is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligand.
kcaITB6Integrin beta-61280.5682integrin beta chainIntegrin alpha-V/beta-6 is a receptor for fibronectin and cytotactin. It recognizes the sequence R-G-D in its ligands. Internalisation of integrin alpha-V/beta-6 via clathrin-mediated endocytosis promotes carcinoma cell invasion.
kcaITB7Integrin beta-74270.5306Expressed in a variety of leukocyte lines.integrin beta chainRheumatoid arthritis
kcaITKTyrosine-protein kinase ITK/TSK12590.6403T-cell lines and natural killer cell lines.protein kinaseAsthma Plays a role in t cell proliferation and differentiation. Tyrosine-protein kinase ITK/TSK inhibitor: Pazopanib
kcaJAK1Tyrosine-protein kinase JAK15640.7014Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue.protein kinaseTyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
kcaJAK2Tyrosine-protein kinase JAK220620.6966Ubiquitously expressed throughout most tissues. <a class="attribution" href="O60674#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a>protein kinaseHodgkin's disease, unspecified
Leukemia, unspecified
Vascular disease
Tyrosine kinase of the non-receptor type, involved in interleukin 3 signal transduction. Tyrosine-protein kinase JAK2 inhibitor: Ruxolitinib
kcaJAK3Tyrosine-protein kinase JAK316410.6013In NK cells and an NK-like cell line but not in resting T-cells or in other tissues. The S-form is more commonly seen in hematopoietic lines, whereas the B-form is detected in cells both of hematopoietic and epithelial origins. <a class="attribution" href="P52333#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>protein kinaseAcute graft-versus-host disease
Chronic graft-versus-host disease
Immunosuppression
Rheumatoid-arthritis
Tyrosine kinase of the non-receptor type, involved in the interleukin-2 and interleukin-4 signaling pathway. Phosphorylates stat6, irs1, irs2 and pi3k.
kcaKAPCAcAMP-dependent protein kinase catalytic subunit alpha16460.5851Isoform <a href="#P17612" onclick="ensureIsoformSequenceVisible('P17612'); return true;">1</a> is ubiquitous. Isoform <a href="#P17612-2" onclick="ensureIsoformSequenceVisible('P17612-2'); return true;">2</a> is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids. <a class="attribution" href="P17612#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a> <a class="attribution" href="P17612#ref28" onclick="ensureReferenceVisible('ref28')">Ref.28</a>protein kinaseNot Available
kcaKAPCBcAMP-dependent protein kinase catalytic subunit beta5050.5445Isoform 1 is most abundant in the brain, with low level expression in kidney. Isoform 2 is predominantly expressed in thymus, spleen and kidney. Isoform 3 and isoform 4 are only expressed in the brain.protein kinaseMediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis.
kcaKAPCGcAMP-dependent protein kinase catalytic subunit gamma4250.5712Testis specific. But important tissues such as brain and ovary have not been analyzed for the content of transcript.protein kinasePhosphorylates a large number of substrates in the cytoplasm and the nucleus.
kcaKC1DCasein kinase I isoform delta9070.67Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. However, kinase activity is not uniform, with highest kinase activity in splenocytes. In blood, highly expressed in hemopoietic cells and mature granulocytes. Also found in monocytes and lymphocytes.protein kinaseAdvanced sleep phase syndrome, familial, 2 (FASPS2) [MIM:615224]: A disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. Note=The disease is caused by mutations affecting the gene represented in this entry.Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phospohorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.
kcaKC1ECasein kinase I isoform epsilon1480.5951Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.protein kinaseCasein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phospohorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine- induced granuloytic differentiation.
kcaKC1G2Casein kinase I isoform gamma-27050.5746Testis.protein kinaseSerine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates COL4A3BP/CERT, MTA1 and SMAD3. Involved in brain development and vesicular trafficking and neurotransmitter releasing from small synaptic vesicles. Regulates fast synaptic transmission mediated by glutamate. SMAD3 phosphorylation promotes its ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Hyperphosphorylation of the serine-repeat motif of COL4A3BP/CERT leads to its inactivation by dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis. Triggers PER1 proteasomal degradation probably through phosphorylation.
kcaKC1G3Casein kinase I isoform gamma-35930.5349protein kinaseSerine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity).
kcaKCC1DCalcium/calmodulin-dependent protein kinase type 1D3970.5044Widely expressed. Highly and mostly expressed in polymorphonuclear leukocytes (neutrophilic and eosinophilic granulocytes) while little or no expression is observed in monocytes and lymphocytes.protein kinaseCalcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine- induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta.
kcaKCC2BCalcium/calmodulin-dependent protein kinase type II subunit beta7490.5035Widely expressed. Expressed in adult and fetal brain. Expression is slightly lower in fetal brain. Expressed in skeletal muscle.protein kinaseCalcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in dendritic spine and synapse formation, neuronal plasticity and regulation of sarcoplasmic reticulum Ca(2+) transport in skeletal muscle. In neurons, plays an essential structural role in the reorganization of the actin cytoskeleton during plasticity by binding and bundling actin filaments in a kinase-independent manner. This structural function is required for correct targeting of CaMK2A, which acts downstream of NMDAR to promote dendritic spine and synapse formation and maintain synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In developing hippocampal neurons, promotes arborization of the dendritic tree and in mature neurons, promotes dendritic remodeling. Participates in the modulation of skeletal muscle function in response to exercise. In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of triadin, a ryanodine receptor-coupling factor, and phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2.
kcaKCNE1Potassium voltage-gated channel subfamily E member 1610.6139Expressed in heart, lung, kidney, testis, ovaries, small intestine, peripheral blood leukocytes. Not detected in pancreas, spleen, prostate and colon. Restrictively localized in the apical membrane portion of epithelial cells.potassium channel KCNEJervell and Lange-Nielsen syndrome 2 (JLNS2) [MIM:612347]: An autosomal recessive disorder characterized by congenital deafness, prolongation of the QT interval, syncopal attacks due to ventricular arrhythmias, and a high risk of sudden death. Note=The disease is caused by mutations affecting the gene represented in this entry. Long QT syndrome 5 (LQT5) [MIM:613695]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Note=The disease is caused by mutations affecting the gene represented in this entry.Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).
kcaKCNH2Potassium voltage-gated channel subfamily H member 262230.6249Nature11159
VirtualToxLab
Highly expressed in heart and brain. Isoforms USO are frequently overexpressed in cancer cells. <a class="attribution" href="Q12809#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>Electrocardiogram QT prolongedpotassium channelCardiac arrhythmias Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. channel properties are modulated by camp and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (ikr). HERG blocker: Amiodarone, Dofetilide, Dronedarone, Ibutilide, Sotalol
kcaKCNN1Small conductance calcium-activated potassium channel protein 11100.7171potassium channel KCNNForms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin (By similarity).
kcaKCNN2Small conductance calcium-activated potassium channel protein 21150.7061Expressed in atrial myocytes (at protein level). Widely expressed.potassium channel KCNNForms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
kcaKCNN3Small conductance calcium-activated potassium channel protein 32480.7053potassium channel KCNNForms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
kcaKCNQ1Potassium voltage-gated channel subfamily KQT member 11660.5531Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries.potassium channelCardiac arrhythmias Probably important in cardiac repolarization. associates with kcne1 (mink) to form the i(ks) cardiac potassium current. elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorinem strongly suppresses kcnq1/kcne1.
kcaKDM5ALysine-specific demethylase 5A640.7524JARID1 histone demethylaseHistone demethylase that specifically demethylates 'Lys- 4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May stimulate transcription mediated by nuclear receptors. May be involved in transcriptional regulation of Hox proteins during cell differentiation. May participate in transcriptional repression of cytokines such as CXCL12.
kcaKIF11Kinesin-like protein KIF118750.5924TRAFAC class myosin-kinesin ATPaseLiver cancers Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.
kcaKISSRKiSS-1 receptor1770.538Most highly expressed in the pancreas, placenta and spinal cord, with lower-level of expression in peripheral blood leukocytes, kidney, lung, fetal liver, stomach, small intestine, testes, spleen, thymus, adrenal glands and lymph nodes. In the adult brain, expressed in the superior frontal gyrus, putamen, caudate nucleus, cingulate gyrus, nucleus accumbens, hippocampus, pons and amygdala, as well as the hypothalamus and pituitary. Expression levels are higher in early (7-9 weeks) than term placentas. Expression levels were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells. Expressed at higher levels in first trimester trophoblasts than at term of gestation. Also found in the extravillous trophoblast suggesting endocrine/paracrine activation mechanism. <a class="attribution" href="Q969F8#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q969F8#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q969F8#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="Q969F8#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a> <a class="attribution" href="Q969F8#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="Q969F8#ref17" onclick="ensureReferenceVisible('ref17')">Ref.17</a>G-protein coupled receptor 1Human reproductive syndromes
kcaKITMast/stem cell growth factor receptor Kit14050.5865Isoform <a href="#P10721" onclick="ensureIsoformSequenceVisible('P10721'); return true;">1</a> and isoform <a href="#P10721-2" onclick="ensureIsoformSequenceVisible('P10721-2'); return true;">2</a> are detected in spermatogonia and Leydig cells. Isoform <a href="#P10721-3" onclick="ensureIsoformSequenceVisible('P10721-3'); return true;">3</a> is detected in round spermatids, elongating spermatids and spermatozoa (at protein level). Widely expressed. Detected in the hematopoietic system, the gastrointestinal system, in melanocytes and in germ cells. <a class="attribution" href="P10721#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P10721#ref28" onclick="ensureReferenceVisible('ref28')">Ref.28</a>protein kinaseCancer, unspecific
Gastrointestinal stromal tumors
Inflammation
Malignant phyllodes tumours
Ovarian cancer
Phyllodes tumours
Renal cell carcinoma
Small cell lung cancer
This is the receptor for stem cell factor (mast cell growth factor). It has a tyrosine-protein kinase activity. binding of the ligands leads to the autophosphorylation of kit and its association with substrates such as phosphatidylinositol 3-kinase (pi3k). Stem cell growth factor receptor inhibitor: Dasatinib, Imatinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib
kcaKLK1Kallikrein-11240.6656Isoform 2 is expressed in pancreas, salivary glands, kidney, colon, prostate gland, testis, spleen and the colon adenocarcinoma cell line T84.peptidase S1Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
kcaKLKB1Plasma kallikrein1990.7391peptidase S1Hereditary Angioedema (HAE) Plasma kallikrein inhibitor: Aprotinin, Ecallantide
kcaKPCAProtein kinase C alpha type16450.7412protein kinaseLeukemia, unspecified
Prostate cancer
This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme.pkc is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. Pkc also serves as the receptor for phorbol esters.
kcaKPCBProtein kinase C beta type9260.733protein kinaseB-lineage malignancies
Diabetes mellitus
Diabetic retinopathy
Macular edema
This is a calcium-activated, phospholipid-dependent, serine- and threonine-specific enzyme. Pkc is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. Pkc also serves as the receptor for phorbol esters.
kcaKPCDProtein kinase C delta type19020.7497protein kinaseNot Available
kcaKPCD1Serine/threonine-protein kinase D15120.7837protein kinaseSerine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenic protein 2 (BMP2)- induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa- B. May be involved in pain transmission by directly modulating TRPV1 receptor.
kcaKPCEProtein kinase C epsilon type9070.6433protein kinaseNot Available
kcaKPCIProtein kinase C iota type8570.6669Predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. Highly expressed in non-small cell lung cancers.protein kinaseCalcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non- small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis.
kcaKPCLProtein kinase C eta type7870.7166Most abundant in lung, less in heart and skin. <a class="attribution" href="P24723#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>protein kinaseNot Available
kcaKPCTProtein kinase C theta type13890.7583Expressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets. <a class="attribution" href="Q04759#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>protein kinaseNot Available
kcaLATS1Serine/threonine-protein kinase LATS1790.5647Expressed in all adult tissues examined except for lung and kidney.protein kinaseNegative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in maintenance of ploidy through its actions in both mitotic progression and the G1 tetraploidy checkpoint. Negatively regulates G2/M transition by down-regulating CDK1 kinase activity. Involved in the control of p53 expression. Affects cytokinesis by regulating actin polymerization through negative modulation of LIMK1. May also play a role in endocrine function.
kcaLATS2Serine/threonine-protein kinase LATS2790.5325Expressed at high levels in heart and skeletal muscle and at lower levels in all other tissues examined.protein kinaseNegative regulator of YAP1 in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Acts as a tumor suppressor which plays a critical role in centrosome duplication, maintenance of mitotic fidelity and genomic stability. Negatively regulates G1/S transition by down-regulating cyclin E/CDK2 kinase activity. Negative regulator of the androgen receptor. Phosphorylates SNAI1 in the nucleus leading to its nuclear retention and stabilization, which enhances its epithelial-mesenchymal transition and tumor cell invasion/migration activities. This tumor-promoting activity is independent of its effects upon YAP1 or WWTR1/TAZ.
kcaLCKTyrosine-protein kinase Lck27630.5094Expressed specifically in lymphoid cells.protein kinasePhiladelphia-positive leukemia Tyrosine-protein kinase LCK inhibitor: Dasatinib, Pazopanib
kcaLDHAL-lactate dehydrogenase A chain920.5707LDH/MDHGlycogen storage disease 11 (GSD11) [MIM:612933]: A metabolic disorder that results in exertional myoglobinuria, pain, cramps and easy fatigue. Note=The disease is caused by mutations affecting the gene represented in this entry.
kcaLDHBL-lactate dehydrogenase B chain590.5387LDH/MDH
kcaLGULLactoylglutathione lyase660.7601glyoxalase ITumors Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to s-lactoylglutathione.
kcaLIMK2LIM domain kinase 21490.7755Highest expression in the placenta; moderate level in liver, lung, kidney, and pancreas. LIMK2a is found to be more abundant then LIMK2b in liver, colon, stomach, and spleen, while in brain, kidney, and placenta LIMK2b is the dominant form. In adult lung, both LIMK2a and LIMK2b is nearly equally observed.protein kinaseDisplays serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP) in vitro.
kcaLKHA4Leukotriene A-4 hydrolase5690.5128Isoform <a href="#P09960" onclick="ensureIsoformSequenceVisible('P09960'); return true;">1</a> and isoform <a href="#P09960-2" onclick="ensureIsoformSequenceVisible('P09960-2'); return true;">2</a> are expressed in monocytes, lymphocytes, neutrophils, reticulocytes, platelets and fibroblasts.peptidase M1Inflammation
Leukemia, Myeloid
Myocardial infarction
Oesophageal cancer
Solid tumors
Hydrolyzes an epoxide moiety of leukotriene a4 (lta-4) to form leukotriene b4 (ltb-4). The enzyme also has some peptidase activity.
kcaLMBL1Lethal(3)malignant brain tumor-like protein 1870.8315Widely expressed. Expression is reduced in colorectal cancer cell line SW480 and promyelocytic leukemia cell line HL-60.Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post- translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.
kcaLMBL3Lethal(3)malignant brain tumor-like protein 3740.7731Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Required for normal maturation of myeloid progenitor cells (By similarity).
kcaLMBL4Lethal(3)malignant brain tumor-like protein 4750.9412Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility (By similarity).
kcaLOX15Arachidonate 15-lipoxygenase4760.7051Detected in monocytes and eosinophils (at protein level). Expressed in airway epithelial cells.lipoxygenaseNote=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD) (PubMed:17959182).Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12- hydroperoxyeicosatetraenoic acid/12-HPETE and 15- hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. Beside its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.
kcaLOX5Arachidonate 5-lipoxygenase29140.5606lipoxygenaseNot Available Arachidonate 5-lipoxygenase inhibitor: Balsalazide, Meclofenamic Acid, Mesalamine, Olsalazine, Sulfasalazine, Zileuton
kcaLPAR2Lysophosphatidic acid receptor 21050.5038Expressed most abundantly in testes and peripheral blood leukocytes with less expression in pancreas, spleen, thymus and prostate. Little or no expression in heart, brain, placenta, lung, liver, skeletal muscle, kidney, ovary, small intestine, or colon.G-protein coupled receptor 1Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Seems to be coupled to the G(i)/G(o), G(12)/G(13), and G(q) families of heteromeric G proteins. Plays a key role in phospholipase C-beta (PLC-beta) signaling pathway. Stimulates phospholipase C (PLC) activity in a manner that is independent of RALA activation.
kcaLPAR3Lysophosphatidic acid receptor 31800.6406Most abundantly expressed in prostate, testes, pancreas, and heart, with moderate levels in lung and ovary. No detectable expression in brain, placenta, liver, skeletal muscle, kidney, spleen, thymus, small intestine, colon, or peripheral blood leukocytes.G-protein coupled receptor 1Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. May play a role in the development of ovarian cancer. Seems to be coupled to the G(i)/G(o) and G(q) families of heteromeric G proteins.
kcaLRRK2Leucine-rich repeat serine/threonine-protein kinase 25590.5664Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.protein kinaseParkinson disease 8 (PARK8) [MIM:607060]: A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients. Note=The disease is caused by mutations affecting the gene represented in this entry.May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May also have GTPase activity. Positively regulates autophagy through a calcium- dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes.
kcaLT4R1Leukotriene B4 receptor 15610.5746Expressed at highest levels in heart, skeletal muscle and at lower levels in brain and liver. High level of expression in lymphoid tissues.G-protein coupled receptor 1Adverse Effects, Chemotherapy
Asthma
Cancer
Chronic Obstructive Pulmonary Disease (COPD)
Cystic Fibrosis
Immunological disorders
Inflammation
Renal Cell Carcinoma
Rheumatoid arthritis
Receptor for extracellular atp > utp and adp. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac p2y receptor involved in the regulation of cardiac muscle control.
kcaLT4R2Leukotriene B4 receptor 22810.6837Widely expressed.G-protein coupled receptor 1Immunological disorders
Inflammation
Low-affinity receptor for leukotrienes including leukotriene b4. Mediates chemotaxis of granulocytes and macrophages. The response is mediated via g-proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaLX15BArachidonate 15-lipoxygenase B790.8162Expressed in hair, prostate, lung, ovary, lymph node, spinal cord and cornea.lipoxygenaseNon-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid to 15S- hydroperoxyeicosatetraenoic acid/(15S)-HPETE. Also acts on linoleic acid to produce 13-hydroxyoctadecadienoic acid/13-HPODE. Has no detectable 8S-lipoxygenase activity but reacts with (8S)- HPETE to produce (8S,15S)-diHPETE. May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophage differentiation into proatherogenic foam cells.
kcaLYAM2E-selectin2010.6535selectin/LECAMAsthma
Atopic Dermatitis
Chronic Obstructive Pulmonary Disease (COPD)
Inflammatory skin disorder
Ischemic stroke
Psoriasis and Psoriatic Disorders
Expressed on cytokine induced endothelial cells and mediates their binding to leukocytes. The ligand recognized by elam-1 is sialyl-lewis x (alpha(1->3)fucosylated derivatives of polylactosamine that are found at the nonreducing termini of glycolipids).
kcaLYNTyrosine-protein kinase Lyn9410.5337Detected in monocytes (at protein level). Detected in placenta, and in fetal brain, lung, liver and kidney. Widely expressed in a variety of organs, tissues, and cell types such as epidermoid, hematopoietic, and neuronal cells. Expressed in primary neuroblastoma tumors.protein kinaseNote=Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down- regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down- regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3- kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr- 72'.
kcaM3K10Mitogen-activated protein kinase kinase kinase 101150.5363Expressed in brain and skeletal muscle.protein kinaseCancer, unspecific
kcaM3K11Mitogen-activated protein kinase kinase kinase 111400.7763Expressed in a wide variety of normal and neoplastic tissues including fetal lung, liver, heart and kidney, and adult lung, liver, heart, kidney, placenta, skeletal muscle, pancreas and brain.protein kinaseActivates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.
kcaM3K15Mitogen-activated protein kinase kinase kinase 15730.8216Isoform 2 and isoform 3 are widely expressed. Isoform 2 highest levels are observed in fetal brain, and isoform 3 highest levels in pancreas, peripheral blood leukocytes, fetal brain and spleen.protein kinaseMay function in a signal transduction pathway that is activated by various cell stresses and leads to apoptosis.
kcaM3K5Mitogen-activated protein kinase kinase kinase 51620.7037Abundantly expressed in heart and pancreas.protein kinaseCardiac diseases
Malignant fibrous histiocytomas
Phosphorylates and activates two different subgroups of map kinase kinases, mkk4/sek1 and mkk3/mapkk6 (or mkk6), which in turn activates stress-activated protein kinase (sapk, also known as jnk; c-jun amino-terminal kinase) and p38 subgroups of map kinase.
kcaM3K6Mitogen-activated protein kinase kinase kinase 6740.6823protein kinaseComponent of a protein kinase signal transduction cascade. Activates the JNK, but not ERK or p38 kinase pathways.
kcaM3K8Mitogen-activated protein kinase kinase kinase 82800.5411Expressed in several normal tissues and human tumor-derived cell lines.protein kinaseNot Available
kcaM3K9Mitogen-activated protein kinase kinase kinase 91440.5768Expressed in epithelial tumor cell lines of colonic, breast and esophageal origin. <a class="attribution" href="P80192#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>protein kinaseCancer, unspecific
kcaM4K5Mitogen-activated protein kinase kinase kinase kinase 57310.5285Ubiquitously expressed in all tissues examined, with high levels in the ovary, testis and prostate.protein kinaseMay play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
kcaMAP11Methionine aminopeptidase 12310.7279peptidase M24ACotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.
kcaMAP2Methionine aminopeptidase 24900.7311peptidase M24ABacterial infections
Cancer, unspecific
Mesothelioma
Removes the amino-terminal methionine from nascent proteins.
kcaMAPK2MAP kinase-activated protein kinase 217290.7981Expressed in all tissues examined.protein kinaseStress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat- shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3.
kcaMBTD1MBT domain-containing protein 1750.9196Note=A chromosomal aberration involving MBTD1 is a cause of acute poorly differentiated myeloid leukemia. Translocation (10;17)(p15;q21) with ZMYND11.Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility (By similarity). Specifically binds to monomethylated and dimethylated 'Lys-20' on histone H4.
kcaMC3RMelanocortin receptor 310790.3812Nature11159Brain, placental, and gut tissues.G-protein coupled receptor 1Chronic inflammatory diseases
Gouty arthritis
Obesity
Receptor for msh (alpha, beta and gamma) and acth. This receptor is mediated by G proteins which activate adenylate cyclase.
kcaMC4RMelanocortin receptor 431130.7309Nature11159Brain, placental, and gut tissues.G-protein coupled receptor 1Erectile Dysfunction
Obesity
Sexual Dysfunction, Female
Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-msh. This receptor is mediated by G proteins that stimulates adenylate cyclase.
kcaMCHR1Melanin-concentrating hormone receptor 132270.5848Highest level in brain, particularly in the frontal cortex and hypothalamus, lower levels in the liver and heart.G-protein coupled receptor 1Obesity
Social anxiety disorder
Vitiligo
Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
kcaMCHR2Melanin-concentrating hormone receptor 22050.6115Specifically expressed in the brain, with highest levels in cerebral cortex, hippocampus and amygdala. No expression detected in the cerebellum, thalamus or hypothalamus.G-protein coupled receptor 1Obesity
Social anxiety disorder
Receptor for melanin-concentrating hormone, coupled to G proteins that activate phosphoinositide hydrolysis.
kcaMCRMineralocorticoid receptor6650.5141VirtualToxLabUbiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes. <a class="attribution" href="P08235#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P08235#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>Acne
Adrenal insufficiency
Amenorrhoea
Cushingoid
Depression
Embolism arterial
Endocrine disorder
Euphoric mood
Hyperglycaemia
Hypokalaemia
Menstrual disorder
Muscular weakness
Oedema
Osteoporosis
Peptic ulcer
nuclear hormone receptorAutoimmune and sudden sensorineural hearing loss
Brain injury
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion. Mineralocorticoid receptor agonist: Desoxycorticosterone Acetate, Desoxycorticosterone Pivalate, Fludrocortisone Acetate
Mineralocorticoid receptor antagonist: Drospirenone, Eplerenone, Felodipine, Nimodipine, Spironolactone
kcaMDM2E3 ubiquitin-protein ligase Mdm28550.5645Ubiquitous. Isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-A, isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-B, isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-C, isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-D, isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-E, isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-F and isoform <a href="#Q00987" onclick="ensureIsoformSequenceVisible('Q00987'); return true;">Mdm2</a>-G are observed in a range of cancers but absent in normal tissues.MDM2/MDM4Not Available
kcaMDR1Multidrug resistance protein 112870.6822Expressed in liver, kidney, small intestine and brain.Alopecia
Angioedema
Azoospermia
Bone marrow failure
Hyperlipidaemia
Mucosal inflammation
Oligomenorrhoea
Stomatitis
ABC transporterCancer, unspecific Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
kcaMDR1BMultidrug resistance protein 1B1010.514ABC transporterEnergy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
kcaMETHepatocyte growth factor receptor26640.7729Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. <a class="attribution" href="P08581#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a> <a class="attribution" href="P08581#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a>protein kinaseGastric Cancer
Hepatocellular carcinoma
Lung cancer
Pancreatic Cancer
Prostate cancer (metastatic)
Renal Cell Carcinoma
Small cell lung cancer
Solid tumors
Receptor for hepatocyte growth factor. Has a tyrosine- protein kinase activity. Hepatocyte growth factor receptor inhibitor: Cabozantinib, Crizotinib
kcaMGLLMonoglyceride lipase3860.5263Detected in adipose tissue, lung, liver, kidney, brain and heart.AB hydrolaseConverts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.
kcaMK01Mitogen-activated protein kinase 112560.5374protein kinaseNeurodegenerative diseases
Proliferative diseases
Phosphorylates microtubule-associated protein-2 (map2). Myelin basic protein (mbp), and elk-1; may promote entry in the cell cycle. Mitogen-activated protein kinase; ERK1/ERK2 inhibitor: Lithium Carbonate, Lithium Citrate
kcaMK03Mitogen-activated protein kinase 32330.5222protein kinaseNeurodegenerative diseases
Proliferative diseases
Traumatic brain injury
Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as elk-1. Phosphorylates eif4ebp1; required for initiation of translation.
kcaMK08Mitogen-activated protein kinase 820040.6498protein kinaseCancer, unspecific
Crohn's disease, unspecified
Hearing Loss
Inflammatory Disorders, Unspecified
Insulin resistance
Obesity
Responds to activation by environmental stress and pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of ap-1 such as c-jun and atf2 and thus regulates ap-1 transcriptional activity.
kcaMK09Mitogen-activated protein kinase 916150.6632protein kinaseNot Available
kcaMK10Mitogen-activated protein kinase 1014320.7148Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.protein kinaseIschemic stroke
Neurological diseases
Responds to activation by environmental stress and pro- inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of ap-1 such as c-jun and atf2 and thus regulates ap-1 transcriptional activity.
kcaMK11Mitogen-activated protein kinase 117780.6394Highest levels in the brain and heart. Also expressed in the placenta, lung, liver, skeletal muscle, kidney and pancreas.protein kinaseInflammation
Psoriasis
Rheumatoid arthritis, unspecified
Kinase involved in a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment, by cytokines, or by environmental stress. Phosphorylates preferentially transcription factor atf2. MAP kinase p38 beta inhibitor: Regorafenib
kcaMK12Mitogen-activated protein kinase 1213210.785Highly expressed in skeletal muscle and heart. <a class="attribution" href="P53778#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P53778#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>protein kinaseAnalgesics
Cancer, unspecific
Cardiovascular Disorders
Coronary Artery Disease
Inflammatory Bowel Disease
Inflammatory Disorders, Unspecified
Neurologic Disorders
Oral Facial Pain
Pain, Acute or Chronic
Psoriasis and Psoriatic Disorders
Rheumatoid arthritis
kcaMK13Mitogen-activated protein kinase 1313560.7705Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.protein kinaseSerine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.
kcaMK14Mitogen-activated protein kinase 1445440.5685Brain, heart, placenta, pancreas and skeletal muscle. Expressed to a lesser extent in lung, liver and kidney.Abdominal pain upperprotein kinaseAdult respiratory distress syndrome
Alzheimer's disease
Crescentic glomerulonephritis
Crohn's disease, unspecified
Cytokine-mediated diseases
Endotoxemia
Inflammation
Insulin resistance
Multiple myeloma
Psoriasis
Rheumatoid arthritis, unspecified
Skin diseases
Thrombosis
Responds to activation by environmental stress, pro- inflammatory cytokines and lipopolysaccharide (lps) by phosphorylating a number of transcription factors, such as elk-1 and atf2 and several downstream kinases, such as mapkapk2 and mapkapk5.
kcaMKNK1MAP kinase-interacting serine/threonine-protein kinase 11260.5255Ubiquitous.protein kinaseMay play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7- methylguanosine-containing mRNA cap.
kcaMMP1Interstitial collagenase34860.7162peptidase M10ACancer, unspecific
Chondrosarcoma
Emphysema
Hormone-refractory Prostate cancer
Kaposi's Sarcoma
Lung Cancer
Myocardial infarction (MI)
Non-small Cell Lung Cancer
Osteoarthritis
Pancreatic Cancer
Cleaves collagens of types i, ii, and iii at one site in the helical domain. Also cleaves collagens of types vii and x. Matrix metalloproteinase-1 inhibitor: Doxycycline
kcaMMP12Macrophage metalloelastase5010.7162Found in alveolar macrophages but not in peripheral blood monocytes.peptidase M10AAtherosclerosis
Crohn's disease, unspecified
Emphysema
Gastro-intestinal ulcers
Non-small Cell Lung Cancer (NSCLC)
Prostate cancer
Renal Cell Carcinoma
Ulcerative colitis
May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the p1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the p1 site.
kcaMMP13Collagenase 325710.6851Seems to be specific to breast carcinomas.peptidase M10ABrain Cancer
Hormone-refractory Prostate cancer
Kaposi's Sarcoma
Lung Cancer
Myocardial infarction (MI)
Non-small Cell Lung Cancer
Osteoarthritis
Prostate cancer
Squamous cell carcinoma
Degrades collagen type i. Does not act on gelatin or casein. Could have a role in tumoral process. Matrix metalloproteinase 13 inhibitor: Doxycycline
kcaMMP14Matrix metalloproteinase-148150.6083Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors. <a class="attribution" href="P50281#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a>peptidase M10ABrain Cancer
Hormone-refractory Prostate cancer
Kaposi's Sarcoma
Lung Cancer
Myocardial infarction (MI)
Non-small Cell Lung Cancer
Osteoarthritis
Pancreatic Cancer
Prostate cancer
kcaMMP272 kDa type IV collagenase37570.7432Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. <a class="attribution" href="P08253#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a>peptidase M10ABrain Cancer
Breast cancer
Cancer, unspecific
Hepatocellular carcinoma
Hormone-refractory Prostate cancer
Kaposi's Sarcoma
Lung Cancer
Non-small Cell Lung Cancer
Osteoarthritis
Pancreatic Cancer
Prostate cancer
Renal Cell Carcinoma
Smooth muscle hyperplasia
kcaMMP3Stromelysin-119790.6351peptidase M10ABrain Cancer
Cancer, unspecific
Lung Cancer
Myocardial infarction (MI)
Osteoarthritis
Osteoarthritis
Ovarian cancer
Pancreatic Cancer
Prostate cancer
Can degrade fibronectin, laminin, gelatins of type i, iii, iv, and v; collagens iii, iv, x, and ix, and cartilage proteoglycans. Activates procollagenase.
kcaMMP7Matrilysin6220.6205peptidase M10ACancer, unspecific
Inflammation
Degrades casein, gelatins of types i, iii, iv, and v, and fibronectin. Activates procollagenase. Matrix metalloproteinase 7 inhibitor: Doxycycline
kcaMMP8Neutrophil collagenase10520.6827Neutrophils.peptidase M10AInflammatory diseases
Osteoarthritis
Osteoporosis, unspecified
Rheumatoid arthritis, unspecified
Tumors
Can degrade fibrillar type i, ii, and iii collagens. Matrix metalloproteinase 8 inhibitor: Doxycycline
kcaMMP9Matrix metalloproteinase-927650.7103Produced by normal alveolar macrophages and granulocytes.peptidase M10AAdvanced lung cancer
Atherosclerosis
Brain Cancer
Guillain-Barre syndrome
Hormone-refractory Prostate cancer
Kaposi's Sarcoma
Lung Cancer
Multiple sclerosis
Non-small Cell Lung Cancer
Osteoarthritis
Pancreatic Cancer
Prostate cancer
Renal Cell Carcinoma
Restenosis
Rheumatoid arthritis, unspecified
Could play a role in bone osteoclastic resorption.
kcaMP2K1Dual specificity mitogen-activated protein kinase kinase 110040.6609Widely expressed, with extremely low levels in brain. <a class="attribution" href="Q02750#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>protein kinaseBreast cancer
Prostate cancer
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a thr-glu-tyr sequence located in map kinases. Activates erk1 and erk2 map kinases. Dual specificity mitogen-activated protein kinase kinase 1 inhibitor: Trametinib
kcaMPIP2M-phase inducer phosphatase 24560.54MPI phosphataseCancer, unspecific Functions as a dosage-dependent inducer in mitotic control. It is a tyrosine protein phosphatase required for progression of the cell cycle. It directly dephosphorylates cdc2 and activate its kinase activity.
kcaMRP1Multidrug resistance-associated protein 13250.7627Lung, testis and peripheral blood mononuclear cells.ABC transporterCystic fibrosis
Streptococcus pneumoniae infections
May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly.
kcaMSHRMelanocyte-stimulating hormone receptor11370.637Melanocytes and corticoadrenal tissue.G-protein coupled receptor 1Melanoma
Obesity
Receptor for msh (alpha, beta and gamma) and acth. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
kcaMTAPS-methyl-5'-thioadenosine phosphorylase740.6545Ubiquitously expressed.PNP/MTAP phosphorylaseT cell leukemias Plays a major role in polyamine metabolism and is important for the salvage of both adenine and methionine.
kcaMTLRMotilin receptor2910.5998Expressed only in thyroid, stomach, and bone marrow.G-protein coupled receptor 1Eating disorders
Gastroesophageal Reflux Disease (GERD)
Gastrointestinal Diseases and Disorders, miscellaneous
Gastrointestinal reflux disorders
Gastroparesis
Irritable Bowel Syndrome (IBS)
Obesity
Receptor for motilin.
kcaMTORSerine/threonine-protein kinase mTOR15980.8221Expressed in numerous tissues, with highest levels in testis. <a class="attribution" href="P42345#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="P42345#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a>PI3/PI4-kinaseCancer, unspecific
Immunosuppression
Acts as the target for the cell-cycle arrest and immunosuppressive effects of the fkbp12-rapamycin complex.
kcaMTPMicrosomal triglyceride transfer protein large subunit1810.6394Liver and small intestine. Also found in ovary, testis and kidney. <a class="attribution" href="P55157#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>Atherosclerosis
Cardiovascular disease, unspecified
Hyperlipidemia
Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein b.
kcaMTR1AMelatonin receptor type 1A8830.587Expressed in hypophyseal pars tuberalis and hypothalamic suprachiasmatic nuclei (SCN). Hippocampus.G-protein coupled receptor 1Chronic Primary Insomnia
Insomnia
Major Depressive Disorder
kcaMTR1BMelatonin receptor type 1B7730.5366Expressed in retina and less in brain and hippocampus.G-protein coupled receptor 1Insomnia Melatonin receptor agonist: Ramelteon
kcaNCEH1Neutral cholesterol ester hydrolase 11250.6532Expressed in monocyte-derived macrophages. Up- regulated in invasive melanoma and breast carcinoma cell lines.'GDXG' lipolytic enzymeHydrolyzes 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. May be responsible for cholesterol ester hydrolysis in macrophages, thereby contributing to the development of atherosclerosis. Also involved in organ detoxification by hydrolyzing exogenous organophosphorus compounds. May contribute to cancer pathogenesis by promoting tumor cell migration.
kcaNCOA3Nuclear receptor coactivator 39880.6568Widely expressed. High expression in heart, skeletal muscle, pancreas and placenta. Low expression in brain, and very low in lung, liver and kidney.SRC/p160 nuclear receptor coactivatorBreast cancer Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Plays a central role in creating a multisubunit coactivator complex.
kcaNCOR2Nuclear receptor corepressor 22890.5207Ubiquitous. High levels of expression are detected in lung, spleen and brain.N-CoR nuclear receptor corepressorsTranscriptional corepressor. Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors. Involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival.
kcaNEK2Serine/threonine-protein kinase Nek210570.5093Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up- regulated in various cancer cell lines, as well as primary breast tumors.protein kinaseRetinitis pigmentosa 67 (RP67) [MIM:615565]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note=The disease is caused by mutations affecting the gene represented in this entry.Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S- arrested cells. Isoform 2, which is not present in the nucleolus, does not.
kcaNEK6Serine/threonine-protein kinase Nek61100.6372Ubiquitous, with highest expression in heart and skeletal muscle. Up-regulated in a variety of malignant cancers, such as breast, colon, lung, and gastric cancers.protein kinaseProtein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved in G2/M phase cell cycle arrest induced by DNA damage. Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence.
kcaNEPNeprilysin10900.551peptidase M13Congestive Heart Failure
Hypertension
Prostate cancer (early stage hormone sensitive)
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as met- and leu-enkephalins by cleavage of a gly-phe bond.
kcaNICANicastrin3020.6457Widely expressed.nicastrinAcne inversa, familial, 1 (ACNINV1) [MIM:142690]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Note=The disease is caused by mutations affecting the gene represented in this entry.Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta- amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex.
kcaNK1RSubstance-P receptor27060.6853Nature11159G-protein coupled receptor 1Analgesics
Asthma
Mood [affective] disorders
Neuropathic pain
Visceral pain
This is a receptor for the tachykinin neuropeptide substance p. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. Neurokinin 1 receptor antagonist: Aprepitant, Fosaprepitant
kcaNK2RSubstance-K receptor9680.7169G-protein coupled receptor 1Analgesics
Anxiety Disorders
Asthma
Depression
Generalized Anxiety Disorders (GAD)
Pain, Acute or Chronic
Urinary incontinence
This is a receptor for the tachykinin neuropeptide substance k (neurokinin a). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaNK3RNeuromedin-K receptor7010.75G-protein coupled receptor 1Arterial hypertension
Depression
Irritable Bowel Syndrome (IBS)
Parkinson's disease
Schizophrenia and Schizoaffective Disorders
Schizophrenia and Schizoaffective Disorders
This is a receptor for the tachykinin neuropeptide neuromedin k (neurokinin b). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
kcaNMBRNeuromedin-B receptor1770.7732Expressed in epididymis (at protein level).G-protein coupled receptor 1Receptor for neuromedin-B.
kcaNMD3AGlutamate receptor ionotropic, NMDA 3A26320.629glutamate-gated ion channel
kcaNMD3BGlutamate receptor ionotropic, NMDA 3B26120.6298glutamate-gated ion channelNMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
kcaNMDE1Glutamate receptor ionotropic, NMDA 2A29790.6448Respiratory depressionglutamate-gated ion channelAnalgesics
Pain (anesthesia, neuropathic)
Nmda receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium and is mediated by glycine. Glutamate [NMDA] receptor antagonist: Acamprosate, Amantadine, Felbamate, Orphenadrine
Glutamate [NMDA] receptor negative allosteric modulator: Ketamine, Memantine
Glutamate [NMDA] receptor subunit epsilon 1 antagonist: Dextromethorphan, Dextromethorphan Polistirex
kcaNMDE2Glutamate receptor ionotropic, NMDA 2B33360.6405Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells, lower expression in the basal ganglia. <a class="attribution" href="Q13224#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>glutamate-gated ion channelAlcohol dependence
Alcoholism
Analgesics
Chronic pain
Convulsions
Dementia
Drug-induced dyskinesias
Pain (anesthesia, neuropathic)
Parkinson's disease
Stroke
Traumatic head injury
Nmda receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium, and mediated by glycine.
kcaNMDE3Glutamate receptor ionotropic, NMDA 2C30430.6385Mainly expressed in brain with predominant expression is in the cerebellum, also present in the hippocampus, amygdala, caudate nucleus, corpus callosum, subthalamic nuclei and thalamus. Detected in the heart, skeletal muscle and pancreas.glutamate-gated ion channelNMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
kcaNMDE4Glutamate receptor ionotropic, NMDA 2D27040.627glutamate-gated ion channelNMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
kcaNMDZ1Glutamate receptor ionotropic, NMDA 137110.6358Respiratory depressionglutamate-gated ion channelAnalgesics
Pain, unspecific
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors.
kcaNMT1Glycylpeptide N-tetradecanoyltransferase 11460.579Heart, gut, kidney, liver and placenta.NMTAdds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
kcaNMT2Glycylpeptide N-tetradecanoyltransferase 21120.6366NMTAdds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins.
kcaNOD1Nucleotide-binding oligomerization domain-containing protein 13470.7797Highly expressed in adult heart, skeletal muscle, pancreas, spleen and ovary. Also detected in placenta, lung, liver, kidney, thymus, testis, small intestine and colon.Enhances caspase-9-mediated apoptosis. Induces NF-kappa- B activity via RIPK2 and IKK-gamma. Confers responsiveness to intracellular bacterial lipopolysaccharides (LPS). Forms an intracellular sensing system along with ARHGEF2 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIPK2 dependent NF-kappa-B signaling pathway activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides but also in the activation of NF-kappa-B by Shigella effector proteins IpgB2 and OspB. Recruits NLRP10 to the cell membrane following bacterial infection.
kcaNOS1Nitric oxide synthase, brain12340.5173Isoform <a href="#P29475" onclick="ensureIsoformSequenceVisible('P29475'); return true;">1</a> is ubiquitously expressed: detected in skeletal muscle and brain, also in testis, lung and kidney, and at low levels in heart, adrenal gland and retina. Not detected in the platelets. Isoform <a href="#P29475-3" onclick="ensureIsoformSequenceVisible('P29475-3'); return true;">3</a> is expressed only in testis. Isoform <a href="#P29475-4" onclick="ensureIsoformSequenceVisible('P29475-4'); return true;">4</a> is detected in testis, skeletal muscle, lung, and kidney, at low levels in the brain, but not in the heart and adrenal gland.NOSHelminth infection
Migraine and Cluster Headaches
Schizophrenia
Produces nitric oxide (no) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, no displays many properties of a neurotransmitter.
kcaNOS2Nitric oxide synthase, inducible13190.6396Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets.NOSIschemia reperfusion injuries Produces nitric oxide (no) which is a messenger molecule with diverse functions throughout the body. In macrophages, no mediates tumoricidal and bactericidal actions.
kcaNOX1NADPH oxidase 11940.5429NOH-1L is detected in colon, uterus, prostate, and colon carcinoma, but not in peripheral blood leukocytes. NOH- 1S is detected only in colon and colon carcinoma cells.NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.
kcaNOX4NADPH oxidase 41100.6395Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma, endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells.Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity. Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
kcaNPBW1Neuropeptides B/W receptor type 14940.6933Found in cerebellum and frontal cortex. Detected at high levels in hippocampus, amygdala and trachea; at moderate levels in fetal brain, pituitary gland and prostate. Not in caudate, accumbens, kidney or liver. Also detected at high levels in lung carcinoma.G-protein coupled receptor 1Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals. Has a higher affinity for neuropeptide B.
kcaNPCL1Niemann-Pick C1-like protein 11230.5601Widely expressed. Expressed in liver. Also expressed in small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach and muscle. <a class="attribution" href="Q9UHC9#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q9UHC9#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q9UHC9#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>patchedHypercholesterolemia
Sitosterolemia
Niemann-Pick C1-like protein 1 inhibitor: Ezetimibe
kcaNPFF2Neuropeptide FF receptor 2660.523Isoform 1 is abundant in placenta. Relatively highly expressed in thymus, testis, and small intestine. Expressed at low levels in several tissues including spleen, prostate, brain, heart, ovary, colon, kidney, lung, liver and pancreas and not expressed in skeletal muscle and leukocytes. Isoform 2 expression is highest in placenta (but at relatively low level compared to isoform 1). Very low level of expression in numerous tissues including adipose tissue and many brain regions. Isoform 3 is expressed in brain and heart and, at lower levels, in kidney, liver, lung and pancreas.G-protein coupled receptor 1Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system.
kcaNPY1RNeuropeptide Y receptor type 111040.466Nature11159G-protein coupled receptor 1Analgesics
Anxiety disorder, unspecified
Cardiovascular disease, unspecified
Convulsions
Drug dependence
Metabolic disorder, unspecified
Obesity
Pain, unspecified
Rhinitis
Receptor for neuropeptide y and peptide yy. The rank order of affinity of this receptor for pancreatic polypeptides is npy > [pro-34] pyy, pyy and [leu-31, pro-34] npy > npy (2-36) > [ile-31, gln-34] pp and pyy (3-36) > pp > npy free acid.
kcaNPY2RNeuropeptide Y receptor type 27320.6465Nature11159High levels in amygdala, corpus callosum, hippocampus and subthalamic nucleus. Also detectable in caudate nucleus, hypothalamus and substantia nigra.G-protein coupled receptor 1Obesity
kcaNPY4RNeuropeptide Y receptor type 41170.6696Highest levels found in brain, coronary artery and ileum. Low levels in pancreas and kidney. Detected in colon and small intestine.G-protein coupled receptor 1Obesity
Schizophrenia and Schizoaffective Disorders
kcaNPY5RNeuropeptide Y receptor type 514060.5067Brain; hypothalamus.G-protein coupled receptor 1Epilepsy
Obesity
Opioid dependence
Temporal lobe epilepsy
Receptor for neuropeptide y and peptide yy. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.
kcaNQO1NAD(P)H dehydrogenase [quinone] 11020.677NADCancer, unspecific
Nonsmall cell lung cancer
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin k-dependent gamma-carboxylation of glutamate residues.
kcaNQO2Ribosyldihydronicotinamide dehydrogenase [quinone]2660.7656NADCancer, unspecific
Malaria
Tumors
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin k-dependent gamma-carboxylation of glutamate residues.
kcaNR1H2Oxysterols receptor LXR-beta7180.7021VirtualToxLabUbiquitous.nuclear hormone receptorAtherosclerosis
Dyslipidemia
Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-aggtca-3' and 4-nt spacing (dr-4).
kcaNR1H3Oxysterols receptor LXR-alpha6400.6613VirtualToxLabVisceral organs specific expression. Strong expression was found in liver, kidney and intestine followed by spleen and to a lesser extent the adrenals.nuclear hormone receptorAtherosclerosis
Cancer, unspecific
Orphan receptor. Interaction with rxr shifts rxr from its role as a silent dna-binding partner to an active ligand- binding subunit in mediating retinoid responses through target genes defined by lxres. Lxres are dr4-type response elements.
kcaNR1H4Bile acid receptor5380.6831nuclear hormone receptorCancer, unspecific
Hypercholesterolemia
Intrahepatic cholestasis
Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. repress the transcription of the cholesterol 7-alpha-hydroxylase gene (cyp7a1) and activates the intestinal bile acid-binding protein (ibabp). Bile acid receptor FXR agonist: Chenodiol, Ursodiol
kcaNR1I2Nuclear receptor subfamily 1 group I member 22190.735Nature11159Expressed in liver, colon and small intestine.Hepatitisnuclear hormone receptorAnxiety disorder, unspecified
Depression
Eye inflammation
Multiple Sclerosis
Orphan receptor; Its natural ligand is probably pregnane. Binds to a response element in the cyp3a4 gene promoter. activates its expression in response to a wide variety of endobiotics and xenobiotics.
kcaNRP1Neuropilin-1570.5219The expression of isoforms 1 and 2 does not seem to overlap. Isoform <a href="#O14786" onclick="ensureIsoformSequenceVisible('O14786'); return true;">1</a> is expressed by the blood vessels of different tissues. In the developing embryo it is found predominantly in the nervous system. In adult tissues, it is highly expressed in heart and placenta; moderately in lung, liver, skeletal muscle, kidney and pancreas; and low in adult brain. Isoform <a href="#O14786-2" onclick="ensureIsoformSequenceVisible('O14786-2'); return true;">2</a> is found in liver hepatocytes, kidney distal and proximal tubules.neuropilinCancer, unspecific The membrane-bound isoform 1 is a receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system.
kcaNTCP2Ileal sodium/bile acid cotransporter2380.6019Hypokalaemia
Pancreatitis
bile acid:sodium symporterCrohn's disease, unspecified Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine.
kcaNTR1Neurotensin receptor type 14450.7728Nature11159Expressed in prostate (at protein level). Detected in colon and peripheral blood mononuclear cells. Detected at very low levels in brain. <a class="attribution" href="P30989#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P30989#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>G-protein coupled receptor 1Analgesics
Colorectal Cancer
Depression
Lung Cancer
NTR-positive tumors
Pain, Acute or Chronic
Pancreatic cancer
Prostate cancer
Psychosis
Schizophrenia and Schizoaffective Disorders
Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol- calcium second messenger system.
kcaNTR2Neurotensin receptor type 21090.8696Expressed in prostate (at protein level).G-protein coupled receptor 1Receptor for the tridecapeptide neurotensin. It is associated with G proteins that activate a phosphatidylinositol- calcium second messenger system.
kcaNTRK1High affinity nerve growth factor receptor12120.6252Isoform TrkA-I is found in most non-neuronal tissues. Isoform TrkA-II is primarily expressed in neuronal cells. TrkA-III is specifically expressed by pluripotent neural stem and neural crest progenitors. <a class="attribution" href="P04629#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a> <a class="attribution" href="P04629#ref18" onclick="ensureReferenceVisible('ref18')">Ref.18</a>protein kinaseAcute myeloid leukemia (AML)
Analgesics
Cancer, unspecific
Neurodegenerative diseases
Pain, unspecified
Pancreatic Cancer
Prostate cancer
Required for high-affinity binding to nerve growth factor (ngf), neurotrophin-3 and neurotrophin-4/5 but not brain- derived neurotrophic factor (bdnf). Known substrates for the trk receptors are shc, pi-3 kinase, and plc-gamma-1.
kcaOPRDDelta-type opioid receptor68650.7328Nature11159Biliary colic
Bladder disorder
Bradycardia
Cerebrovascular disorder
Constipation
Death
Dependence
Dermatitis contact
Drug tolerance
Dysuria
Euphoric mood
Hyperhidrosis
Hypothermia
Injection site irritation
Injection site pain
Intracranial pressure increased
Mental disorder
Miosis
Mood altered
Muscle spasms
Oliguria
Orthostatic hypotension
Pruritus
Respiratory depression
Restlessness
Shock
Somnolence
Ureteral spasm
Urticaria
Withdrawal syndrome
G-protein coupled receptor 1Analgesics
Cough
Dyspnea
Ischemia
Pain, unspecified
Parkinson's disease
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective and receptor for enkephalins. Opioid receptors; mu/kappa/delta agonist: Codeine, Codeine Polistirex, Hydrocodone, Hydrocodone Polistirex, Nalbuphine, Oxymorphone
Opioid receptors; mu/kappa/delta antagonist: Nalmefene, Naloxone, Naltrexone
kcaOPRKKappa-type opioid receptor61440.7168Nature11159Detected in brain and placenta. <a class="attribution" href="P41145#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P41145#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>Biliary colic
Bladder disorder
Bradycardia
Cerebrovascular disorder
Coma
Constipation
Death
Dependence
Dermatitis contact
Drug tolerance
Dysphoria
Dysuria
Euphoric mood
Hyperhidrosis
Hypothermia
Injection site irritation
Injection site pain
Intracranial pressure increased
Mental disorder
Miosis
Mood altered
Muscle spasms
Oliguria
Orthostatic hypotension
Pruritus
Respiratory depression
Respiratory disorder
Restlessness
Shock
Somnolence
Ureteral spasm
Withdrawal syndrome
G-protein coupled receptor 1Alcohol dependence
Analgesics
Behcet's disease
Diarrhea
Dyspnea
Focal ischemia
Immune disease
Neurodegenerative diseases
Pain, unspecified
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. The receptor for dynorphins and may play a role in arousal and regulation of autonomic and neuroendocrine functions. Kappa opioid receptor agonist: Anileridine, Buprenorphine
Kappa opioid receptor antagonist: Dezocine
Kappa opioid receptor partial agonist: Butorphanol, Levallorphan
kcaOPRMMu-type opioid receptor83890.7311Nature11159Expressed in brain. Isoform <a href="#P35372-16" onclick="ensureIsoformSequenceVisible('P35372-16'); return true;">16</a> and isoform <a href="#P35372-17" onclick="ensureIsoformSequenceVisible('P35372-17'); return true;">17</a> are detected in brain. <a class="attribution" href="P35372#ref32" onclick="ensureReferenceVisible('ref32')">Ref.32</a>Biliary colic
Biliary tract disorder
Bladder disorder
Bradycardia
Cerebrovascular disorder
Coma
Constipation
Death
Dependence
Dermatitis contact
Disorientation
Drug tolerance
Dry mouth
Dysphoria
Dysuria
Euphoric mood
Hyperhidrosis
Hypothermia
Injection site irritation
Injection site pain
Intracranial pressure increased
Mental disorder
Miosis
Mood altered
Muscle rigidity
Muscle spasms
Oliguria
Orthostatic hypotension
Pruritus
Respiratory depression
Respiratory disorder
Restlessness
Shock
Somnolence
Ureteral spasm
Urticaria
Withdrawal syndrome
G-protein coupled receptor 1Analgesics
Cough
Diarrhea
Dyspnea
Opioid-induced bowel dysfunction
Pain, unspecified
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. The receptor for beta-endorphin. Mu opioid receptor agonist: Alfentanil, Anileridine, Buprenorphine, Difenoxin, Dihydrocodeine, Diphenoxylate, Fentanyl, Hydromorphone, Levomethadyl Acetate, Levorphanol, Loperamide, Meperidine, Methadone, Morphine, Oxycodone, Propoxyphene, Remifentanil, Sufentanil, Tapentadol, Tramadol
Mu opioid receptor antagonist: Alvimopan, Levallorphan, Methylnaltrexone
Mu opioid receptor partial agonist: Butorphanol, Dezocine
kcaOPRXNociceptin receptor14580.5819HyperhidrosisG-protein coupled receptor 1Analgesics
Anorexia nervosa
Anxiety disorder, unspecified
Cerebral ischemia
Depression
Drug dependence
Epilepsy
Erectile dysfunction
Hypertension
Neurogenic bladder
Neuropathic pain
Pain, unspecified
Receptor for the neuropeptide nocipeptin/orphanin fq. Has a potential role in modulating a number of brain functions, including instinctive behaviors and emotions. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase.
kcaOX2ROrexin receptor type 27470.6427G-protein coupled receptor 1Gastrointestinal motility disorders
Nausea and vomiting
Nonselective, high-affinity receptor for both orexin-a and orexin-b neuropeptides.
kcaOXYROxytocin receptor10670.68G-protein coupled receptor 1Cancer, unspecific Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol- calcium second messenger system. Oxytocin receptor agonist: Oxytocin
kcaP2RX1P2X purinoceptor 1530.5069P2X receptorLigand-gated ion channel with relatively high calcium permeability. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle. Seems to be linked to apoptosis, by increasing the intracellular concentration of calcium in the presence of ATP, leading to programmed cell death (By similarity).
kcaP2RX2P2X purinoceptor 21610.6021P2X receptorDeafness, autosomal dominant, 41 (DFNA41) [MIM:608224]: A form of non-syndromic deafness characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies. Note=The disease is caused by mutations affecting the gene represented in this entry.Ion channel gated by extracellular ATP involved in a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis. In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling. Mediates synaptic transmission between neurons and from neurons to smooth muscle.
kcaP2Y12P2Y purinoceptor 129730.799Highly expressed in the platelets, lower levels in the brain. Lowest levels in the lung, appendix, pituitary and adrenal gland. Expressed in the spinal cord and in the fetal brain.G-protein coupled receptor 1Aggregation and activation of platelets
Cardiovascular disease, unspecified
Thrombosis
Receptor for adp and atp coupled to g-proteins that inhibit the adenylyl cyclase second messenger system, which is not activated by udp and utp. Involved in platelets aggregation. Purinergic receptor P2Y12 antagonist: Clopidogrel, Prasugrel, Ticlopidine
Purinergic receptor P2Y12 negative allosteric modulator: Ticagrelor
kcaP3C2BPhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta880.6045Expressed in columnar and transitional epithelia, mononuclear cells, and ganglion cells (at protein level). Widely expressed, with highest levels in thymus and placenta and lowest in peripheral blood, skeletal muscle and kidney.PI3/PI4-kinasePhosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades.
kcaP4K2APhosphatidylinositol 4-kinase type 2-alpha530.5829Widely expressed. Highest expression is observed in kidney, brain, heart, skeletal muscle, and placenta and lowest expression is observed in colon, thymus, and small intestine.PI3/PI4-kinaseTogether with PI4K2B and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells (By similarity). This lipid kinase is the major phosphatidylinositol 4-phosphate (PI4P) producer in the Golgi apparatus, it generates more than 50% of this molecule which is essential for the identity of the organelle, protein sorting and membrane trafficking.
kcaP4K2BPhosphatidylinositol 4-kinase type 2-beta530.5829Widely expressed.PI3/PI4-kinaseTogether with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells and is likely to be involved in the regulation of vesicular trafficking.
kcaP53Cellular tumor antigen p533620.633Ubiquitous. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform <a href="#P04637-2" onclick="ensureIsoformSequenceVisible('P04637-2'); return true;">2</a> is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform <a href="#P04637-3" onclick="ensureIsoformSequenceVisible('P04637-3'); return true;">3</a> is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform <a href="#P04637-7" onclick="ensureIsoformSequenceVisible('P04637-7'); return true;">7</a> is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform <a href="#P04637-8" onclick="ensureIsoformSequenceVisible('P04637-8'); return true;">8</a> is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform <a href="#P04637-9" onclick="ensureIsoformSequenceVisible('P04637-9'); return true;">9</a> is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine. <a class="attribution" href="P04637#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>p53Bladder cancer
Cancer, unspecific
Hepatocellular carcinoma
Kidney Cancer
Prostate cancer
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division.
kcaP85APhosphatidylinositol 3-kinase regulatory subunit alpha1450.6397Isoform 2 is expressed in skeletal muscle and brain, and at lower levels in kidney and cardiac muscle. Isoform 2 and isoform 4 are present in skeletal muscle (at protein level).PI3K p85 subunitAgammaglobulinemia 7, autosomal recessive (AGM7) [MIM:615214]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. Note=The disease is caused by mutations affecting the gene represented in this entry. SHORT syndrome (SHORTS) [MIM:269880]: A rare, multisystem disease characterized by short stature, anomalies of the anterior chamber of the eye, characteristic facial features such as triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella, partial lipodystrophy, hernias, hyperextensibility, and delayed dentition. The clinical phenotype can include insulin resistance, nephrocalcinosis, and hearing deficits. Developmental milestones and cognition are normal. Note=The disease is caused by mutations affecting the gene represented in this entry.Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling.
kcaPA21BPhospholipase A25520.6055phospholipase A2Arthritis
Eicosanoid-mediated disorders
Inflammation
Pa2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
kcaPA24ACytosolic phospholipase A22740.6975Expressed in various tissues such as macrophages, platelets, neutrophils, fibroblasts and lung endothelium.Atherosclerosis
Cancer, unspecific
Diabetes mellitus
Lipid metabolic disorders
Neurodegenerative diseases
Obesity
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
kcaPA2GXGroup 10 secretory phospholipase A2740.6656Found in spleen, thymus, peripheral blood leukocytes, pancreas, lung, and colon.phospholipase A2PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides. Has a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.
kcaPAFAPlatelet-activating factor acetylhydrolase3150.7335Plasma.AB hydrolaseAtherosclerosis
Cardiovascular Disorders
Coronary atherosclerosis
Modulates the action of platelet-activating factor (paf) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-paf. Has a specificity for substrates with a short residue at the sn-2 position.
kcaPAK1Serine/threonine-protein kinase PAK 18410.6417protein kinaseProtein kinase involved in intracellular signaling pathways downstream of integrins and receptor-type kinases that plays an important role in cytoskeleton dynamics, in cell adhesion, migration, proliferation, apoptosis, mitosis, and in vesicle-mediated transport processes. Can directly phosphorylate BAD and protects cells against apoptosis. Activated by interaction with CDC42 and RAC1. Functions as GTPase effector that links the Rho-related GTPases CDC42 and RAC1 to the JNK MAP kinase pathway. Phosphorylates and activates MAP2K1, and thereby mediates activation of downstream MAP kinases. Involved in the reorganization of the actin cytoskeleton, actin stress fibers and of focal adhesion complexes. Phosphorylates the tubulin chaperone TBCB and thereby plays a role in the regulation of microtubule biogenesis and organization of the tubulin cytoskeleton. Plays a role in the regulation of insulin secretion in response to elevated glucose levels. Part of a ternary complex that contains PAK1, DVL1 and MUSK that is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2. Phosphorylates MYL9/MLC2. Phosphorylates RAF1 at 'Ser-338' and 'Ser-339' resulting in: activation of RAF1, stimulation of RAF1 translocation to mitochondria, phosphorylation of BAD by RAF1, and RAF1 binding to BCL2. Phosphorylates SNAI1 at 'Ser-246' promoting its transcriptional repressor activity by increasing its accumulation in the nucleus. In podocytes, promotes NR3C2 nuclear localization. Required for atypical chemokine receptor ACKR2- induced phosphorylation of LIMK1 and cofilin (CFL1) and for the up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F- actin cluster formation performed by SHANK3, maybe through CFL1 phosphorylation and inactivation.
kcaPAK4Serine/threonine-protein kinase PAK 411580.6639Highest expression in prostate, testis and colon.protein kinaseSerine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN.
kcaPAR1Proteinase-activated receptor 16440.5333Platelets and vascular endothelial cells.G-protein coupled receptor 1Acute Coronary Syndrome
Analgesics
Cardiovascular Disorders
Inflammation
Ischemic Stroke
Pain, unspecified
Vascular disease
High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development.
kcaPARP1Poly [ADP-ribose] polymerase 114590.6802Asthma
Cancer, unspecific
Chronic obstructive pulmonary disease
Diabetic cardiovascular dysfunction
Diabetic endothelial dysfunction
Multiple sclerosis
Traumatic brain injury
Tumors
Involved in the base excision repair (ber) pathway, by catalysing the poly(adp-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in dna metabolism. This modification follows DNA damages.
kcaPARP2Poly [ADP-ribose] polymerase 2950.9004Widely expressed, mainly in actively dividing tissues. The highest levels are in the brain, heart, pancreas, skeletal muscle and testis; also detected in kidney, liver, lung, placenta, ovary and spleen; levels are low in leukocytes, colon, small intestine, prostate and thymus.Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
kcaPCPLysosomal Pro-X carboxypeptidase3030.6346Highest levels in placenta, lung and liver. Also present in heart, brain, pancreas and kidney.peptidase S28Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.
kcaPD2RProstaglandin D2 receptor6710.7799Expressed in retinal choroid, ciliary epithelium, longitudinal and circular ciliary muscles, iris, small intestine and platelet membranes. <a class="attribution" href="Q13258#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a> <a class="attribution" href="Q13258#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>G-protein coupled receptor 1Allergic diseases Receptor for prostaglandin d2 (pgd2). The activity of this receptor is mainly mediated by g(s) proteins that stimulates adenylate cyclase, resulting in an elevation of intracellular camp. A mobilization of calcium is also observed.
kcaPD2R2Prostaglandin D2 receptor 213060.5118Widespread expression. High expression in stomach, small intestine, heart and thymus. Intermediate expression in colon, spinal cord and peripheral blood and low expression in brain, skeletal muscle and spleen. Expressed also on Th2- and Tc2- type cells, eosinophils and basophils. <a class="attribution" href="Q9Y5Y4#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q9Y5Y4#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="Q9Y5Y4#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a> <a class="attribution" href="Q9Y5Y4#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>G-protein coupled receptor 1Asthma
Chronic obstructive pulmonary disease
Orphan receptor.
kcaPDE10cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A9230.5902Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.cyclic nucleotide phosphodiesterasePlays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.
kcaPDE11Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A1230.7372Isoform 1 is present in prostate, pituitary, heart and liver. It is however not present in testis nor in penis, suggesting that weak inhibition by Tadalafil (Cialis) is not relevant (at protein level). Isoform 2 may be expressed in testis. Isoform 4 is expressed in adrenal cortex.cyclic nucleotide phosphodiesterasePrimary pigmented nodular adrenocortical disease 2 (PPNAD2) [MIM:610475]: A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Note=The disease is caused by mutations affecting the gene represented in this entry.Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP. Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'- GMP, respectively.
kcaPDE1ACalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A4130.662Flushingcyclic nucleotide phosphodiesteraseCardiovascular disease, unspecified
Erectile dysfunction
Has a higher affinity for cgmp than for camp.
kcaPDE1BCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B4940.62Flushingcyclic nucleotide phosphodiesteraseCardiovascular disease, unspecified
Erectile dysfunction
Has a higher affinity for cgmp than for camp.
kcaPDE1CCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C5060.6711Flushingcyclic nucleotide phosphodiesteraseCardiovascular disease, unspecified
Erectile dysfunction
Has a higher affinity for cgmp than for camp.
kcaPDE2AcGMP-dependent 3',5'-cyclic phosphodiesterase2940.896Expressed in brain and to a lesser extent in heart, placenta, lung, skeletal muscle, kidney and pancreas.Dyspepsia
Flushing
Headache
cyclic nucleotide phosphodiesteraseColorectal cancer
Erectile dysfunction
Hydrolyzes both cyclic amp (camp) and cyclic gmp (cgmp).
kcaPDE3AcGMP-inhibited 3',5'-cyclic phosphodiesterase A11880.7818Nature11159Dyspepsia
Palpitations
cyclic nucleotide phosphodiesteraseBronchial asthma
Chronic myeloid leukemia
Vascular disease
Hydrolyzes both cyclic amp (camp) and cyclic gmp (cgmp) (by similarity). Phosphodiesterase 3A inhibitor: Cilostazol, Dyphylline, Inamrinone, Milrinone, Theophylline
kcaPDE3BcGMP-inhibited 3',5'-cyclic phosphodiesterase B9920.8001Abundant in adipose tissues.cyclic nucleotide phosphodiesteraseCyclic nucleotide phosphodiesterase with a dual- specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes. May play a role in fat metabolism. Regulates cAMP binding of RAPGEF3. Through simultaneous binding to RAPGEF3 and PIK3R6 assembles a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis.
kcaPDE4AcAMP-specific 3',5'-cyclic phosphodiesterase 4A17610.7093Isoform <a href="#P27815" onclick="ensureIsoformSequenceVisible('P27815'); return true;">1</a> is widely expressed. Isoform <a href="#P27815-2" onclick="ensureIsoformSequenceVisible('P27815-2'); return true;">2</a> is abundant in liver, stomach, testis, thyroid and adrenal glands. It is also found in placenta, kidney, pancreas, ovary, uterus, skin, monocytes, mast cells, macrophages, as well as in bronchial smooth muscle. Isoform <a href="#P27815-6" onclick="ensureIsoformSequenceVisible('P27815-6'); return true;">6</a> is expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes. Isoform <a href="#P27815-7" onclick="ensureIsoformSequenceVisible('P27815-7'); return true;">7</a> is expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Isoform <a href="#P27815-7" onclick="ensureIsoformSequenceVisible('P27815-7'); return true;">7</a> is expressed in the brain. Found in specific neuronal subpopulations in cortex, spinal cord and cerebellum (at protein level). <a class="attribution" href="P27815#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="P27815#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a> <a class="attribution" href="P27815#ref7" onclick="ensureReferenceVisible('ref7')">Ref.7</a>Diarrhoea
Dyspepsia
Flushing
Palpitations
cyclic nucleotide phosphodiesteraseChronic lymphocytic leukemia Phosphodiesterase 4A inhibitor: Theophylline
kcaPDE4BcAMP-specific 3',5'-cyclic phosphodiesterase 4B20070.6857Expressed in brain, heart, lung and skeletal muscle.Diarrhoea
Dyspepsia
Flushing
Palpitations
cyclic nucleotide phosphodiesteraseAsthma
Chronic lymphocytic leukemia
May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents. Phosphodiesterase 4 inhibitor: Amlexanox, Dyphylline, Flavoxate, Roflumilast, Theophylline, Theophylline Glycinate
kcaPDE4CcAMP-specific 3',5'-cyclic phosphodiesterase 4C13560.6546Expressed in various tissues but not in cells of the immune system.cyclic nucleotide phosphodiesteraseHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
kcaPDE4DcAMP-specific 3',5'-cyclic phosphodiesterase 4D17510.6995Nature11159Widespread; most abundant in skeletal muscle. Isoform <a href="#Q08499-8" onclick="ensureIsoformSequenceVisible('Q08499-8'); return true;">6</a> is detected in brain. Isoform <a href="#Q08499-9" onclick="ensureIsoformSequenceVisible('Q08499-9'); return true;">8</a> is detected in brain, placenta, lung and kidney. Isoform <a href="#Q08499-11" onclick="ensureIsoformSequenceVisible('Q08499-11'); return true;">7</a> is detected in heart and skeletal muscle. <a class="attribution" href="Q08499#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>Dyspepsia
Flushing
cyclic nucleotide phosphodiesteraseAsthma Regulates the levels of camp in the cell.
kcaPDE5AcGMP-specific 3',5'-cyclic phosphodiesterase15370.8366Expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung.Diarrhoea
Dyspepsia
Flushing
Palpitations
cyclic nucleotide phosphodiesteraseErectile dysfunction
Injury to spine and spinal cord
Pulmonary hypertension
Vascular disease
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides, and this phosphodiesterase catalyzes the specific hydrolysis of cgmp to 5'-GMP. Phosphodiesterase 5A inhibitor: Avanafil, Dipyridamole, Sildenafil, Tadalafil, Vardenafil
kcaPDE7AHigh affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A3450.6994PDE7A1 is found at high levels in skeletal muscle and at low levels in a variety of tissues including brain and heart. It is expressed as well in two T-cell lines. PDE7A2 is found abundantly in skeletal muscle and at low levels in heart.cyclic nucleotide phosphodiesteraseHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May have a role in muscle signal transduction.
kcaPDE9AHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A1140.7673Expressed in all tissues examined (testis, brain, small intestine, skeletal muscle, heart, lung, thymus, spleen, placenta, kidney, liver, pancreas, ovary and prostate) except blood. Highest levels in brain, heart, kidney, spleen, prostate and colon. Isoform PDE9A12 is found in prostate.cyclic nucleotide phosphodiesteraseHydrolyzes the second messenger cGMP, which is a key regulator of many important physiological processes.
kcaPDK1[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial2560.5645Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas.PDK/BCKDK protein kinaseSerine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress.
kcaPDK2[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial1630.5288Expressed in many tissues, with the highest level in heart and skeletal muscle, intermediate levels in brain, kidney, pancreas and liver, and low levels in placenta and lung.PDK/BCKDK protein kinaseSerine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis.
kcaPDK3[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial1100.7161Expressed in heart, skeletal muscle, spinal cord, as well as fetal and adult brain.PDK/BCKDK protein kinaseCharcot-Marie-Tooth disease, X-linked dominant, 6 (CMTX6) [MIM:300905]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. Note=The disease is caused by mutations affecting the gene represented in this entry.Inhibits pyruvate dehydrogenase activity by phosphorylation of the E1 subunit PDHA1, and thereby regulates glucose metabolism and aerobic respiration. Can also phosphorylate PDHA2. Decreases glucose utilization and increases fat metabolism in response to prolonged fasting, and as adaptation to a high-fat diet. Plays a role in glucose homeostasis and in maintaining normal blood glucose levels in function of nutrient levels and under starvation. Plays a role in the generation of reactive oxygen species.
kcaPDK4[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial1650.5342Ubiquitous; highest levels of expression in heart and skeletal muscle.PDK/BCKDK protein kinaseSerine/threonine kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.
kcaPDPK13-phosphoinositide-dependent protein kinase 110470.5083Appears to be expressed ubiquitously. The Tyr-9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast. <a class="attribution" href="O15530#ref34" onclick="ensureReferenceVisible('ref34')">Ref.34</a>protein kinaseCancer, unspecific
Diabetes mellitus
Phosphorylates and activates not only pkb/akt, but also pka, pkc-zeta, p70s6k and p90s6k/rsk. May play a general role in signaling processes and in development (by similarity). Isoform 3 is catalytically inactive.
kcaPE2R1Prostaglandin E2 receptor EP1 subtype6690.7751Abundant in kidney. Lower level expression in lung, skeletal muscle and spleen, lowest expression in testis and not detected in liver brain and heart.G-protein coupled receptor 1Analgesics
Visceral pain
Receptor for prostaglandin e2 (pge2). The activity of this receptor is mediated by g(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Prostanoid EP1 receptor agonist: Alprostadil
kcaPE2R2Prostaglandin E2 receptor EP2 subtype6120.7217Placenta and lung.FlushingG-protein coupled receptor 1Cerebral oxidative damage Receptor for prostaglandin e2 (pge2). The activity of this receptor is mediated by g(s) proteins that stimulates adenylate cyclase. The subsequent raise in intracellular camp is responsible for the relaxing effect of this receptor on smooth muscle. Prostanoid EP2 receptor agonist: Alprostadil
kcaPE2R3Prostaglandin E2 receptor EP3 subtype9820.8377Expressed in small intestine, heart, pancreas, gastric fundic mucosa, mammary artery and pulmonary vessels. <a class="attribution" href="P43115#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>DiarrhoeaG-protein coupled receptor 1Peripheral Vascular Disease Prostanoid EP3 receptor agonist: Misoprostol
kcaPE2R4Prostaglandin E2 receptor EP4 subtype7470.8474High in intestine and in peripheral blood mononuclear cells; low in lung, kidney, thymus, uterus, vasculature and brain. Not found in liver, heart, retina oe skeletal muscle.DiarrhoeaG-protein coupled receptor 1Dry eye
Osteoporosis, unspecified
Renal failure
Ulcerative colitis
Receptor for prostaglandin e2 (pge2). The activity of this receptor is mediated by g(s) proteins that stimulates adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics and intestinal epithelial.
kcaPEN2Gamma-secretase subunit PEN-23050.6434Widely expressed. Expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, skeletal muscle, heart and brain.PEN-2Acne inversa, familial, 2 (ACNINV2) [MIM:613736]: A chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Note=The disease is caused by mutations affecting the gene represented in this entry.Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta- amyloid precursor protein). Probably represents the last step of maturation of gamma-secretase, facilitating endoproteolysis of presenilin and conferring gamma-secretase activity.
kcaPEPAPepsin A-12260.6543peptidase A1Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.
kcaPERFPerforin-11380.516complement C6/C7/C8/C9Familial hemophagocytic lymphohistiocytosis 2 (FHL2) [MIM:603553]: A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. Note=The disease is caused by mutations affecting the gene represented in this entry.Plays a key role in secretory granule-dependent cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by facilitating the uptake of cytotoxic granzymes.
kcaPERMMyeloperoxidase830.696peroxidaseAlzheimer's disease
Atherosclerosis
Lung cancer
Multiple sclerosis
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated pmn, mpo catalyzes the production of hypohalous acids, primarily hypochlorous acid.
kcaPF2RProstaglandin F2-alpha receptor2070.6093G-protein coupled receptor 1Bone disorders
Dysmenorrhea, unspecified
Glaucoma
Inflammatory diseases
Ocular hypertension
Receptor for prostaglandin f2-alpha (pgf2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (by similarity). Prostanoid FP receptor agonist: Bimatoprost, Carboprost, Dinoprost, Lanatoprost, Tafluprost, Travoprost
kcaPGFRAPlatelet-derived growth factor receptor alpha12090.5373Detected in platelets (at protein level). Widely expressed. Detected in brain, fibroblasts, smooth muscle, heart, and embryo. Expressed in primary and metastatic colon tumors and in normal colon tissue. <a class="attribution" href="P16234#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P16234#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="P16234#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a>Adrenal disorder
Adrenal insufficiency
Amenorrhoea
Bone disorder
Cushingoid
Endocrine disorder
Euphoric mood
Hyperglycaemia
Hypertension
Hypertrichosis
Hypokalaemia
Intracranial pressure increased
Menstrual disorder
Muscular weakness
Oedema
Osteonecrosis
Osteoporosis
Pancreatitis acute
Peptic ulcer
Skin atrophy
Skin striae
Superinfection
Telangiectasia
protein kinaseHypereosinophilic syndrome
Lung cancer
Receptor that binds both pdgfa and pdgfb and has a tyrosine-protein kinase activity.
kcaPGFRBPlatelet-derived growth factor receptor beta22290.6365Adrenal disorder
Adrenal insufficiency
Amenorrhoea
Bone disorder
Cushingoid
Endocrine disorder
Euphoric mood
Hyperglycaemia
Hypertension
Hypertrichosis
Hypokalaemia
Intracranial pressure increased
Menstrual disorder
Muscular weakness
Oedema
Osteonecrosis
Osteoporosis
Pancreatitis acute
Peptic ulcer
Skin atrophy
Skin striae
Superinfection
Telangiectasia
protein kinaseChronic myeloproliferative diseases
Ewing's sarcoma
Receptor that binds specifically to pdgfb and has a tyrosine-protein kinase activity. Phosphorylates tyr residues at the c-terminus of ptpn11 creating a binding site for the sh2 domain of grb2. Platelet-derived growth factor receptor agonist: Becaplermin
Platelet-derived growth factor receptor beta inhibitor: Dasatinib, Imatinib, Sorafenib
Platelet-derived growth factor receptor inhibitor: Pazopanib, Regorafenib, Sunitinib
kcaPGH1Prostaglandin G/H synthase 138980.4979Nature11159Abdominal pain upper
Aplastic anaemia
Asthma
Dyspepsia
Erythema multiforme
Gastrointestinal haemorrhage
Haematuria
Haemorrhagic diathesis
Hepatitis
Nephropathy
Oedema
Peptic ulcer
Pruritus
Rash
Renal failure
Renal tubular disorder
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
prostaglandin G/H synthaseCardiovascular disease, unspecified
Chronic inflammatory diseases
May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
kcaPGH2Prostaglandin G/H synthase 243690.5607Nature11159Abdominal pain upper
Aplastic anaemia
Dyspepsia
Erythema multiforme
Flatulence
Gastrointestinal haemorrhage
Haematuria
Haemorrhagic diathesis
Hepatitis
Nephropathy
Oedema
Oliguria
Peptic ulcer
Pruritus
Renal failure
Thrombocytopenia
Tinnitus
prostaglandin G/H synthaseAbdominal aortic aneurysm
Adenomatous polyposis
Alzheimer's disease
Analgesics
Arthritis
Bladder cancer
Breast cancer
Cancer, unspecific
Carcinoma in situ, unspecified
Carpal tunnel syndrome
Colorectal cancer
Dysmenorrhea, unspecified
Endometriosis
Genitourinary tumors
Gestational hypertension
Inflammation
Inflammatory diseases
Lung cancer
Malignant mesothelioma
Meningioma
Myocardial infarction
Oropharyngeal squamous cell carcinoma
Osteoarthritis
Pain, unspecified
Pathological angiogenesis
Peutz-Jeghers syndrome
Prostate cancer
Pyresis
Renal cell carcinoma
Rheumatoid arthritis, unspecified
Stroke
Vascular lesion regression
May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity. Cyclooxygenase inhibitor: Acetaminophen, Aminosalicylic Acid, Aspirin, Balsalazide, Bismuth Subsalicylate, Bromfenac, Diclofenac, Diflunisal, Fenoprofen, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Ketorolac, Meclofenamic Acid, Mefenamic Acid, Mesalamine, Naproxen, Nepafenac, Olsalazine, Oxaprozin, Oxyphenbutazone, Phenylbutazone, Piroxicam, Sulfasalazine, Sulindac, Suprofen, Tolmetin
Cyclooxygenase-2 inhibitor: Carprofen, Celecoxib, Etodolac, Meloxicam, Nabumetone, Rofecoxib, Valdecoxib
kcaPGTB1Geranylgeranyl transferase type-1 subunit beta6060.67protein prenyltransferase subunit betaCatalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. Known substrates include RAC1, RAC2, RAP1A and RAP1B.
kcaPHKG1Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform820.6422protein kinaseCatalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43 and NRGN/RC3 (By similarity).
kcaPI2RProstacyclin receptor3470.6232G-protein coupled receptor 1Analgesics
Diabetes mellitus
Inflammatory pain
Receptor for prostacyclin (prostaglandin i2 or pgi2). The activity of this receptor is mediated by g(s) proteins which activate adenylate cyclase. Prostanoid IP receptor agonist: Epoprostenol, Iloprost, Treprostinil
kcaPI4KAPhosphatidylinositol 4-kinase alpha600.5246Expressed ubiquitously. Highest levels in placenta and brain. Little or no expression in lung, liver, pancreas, testis or leukocytes.PI3/PI4-kinaseActs on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol- 1,4,5,-trisphosphate.
kcaPIM1Serine/threonine-protein kinase pim-119440.7655Expressed primarily in cells of the hematopoietic and germline lineages. Isoform 1 and isoform 2 are both expressed in prostate cancer cell lines.protein kinaseProto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl- X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post- translational levels. Phosphorylation of CDKN1B,induces 14-3-3- proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.
kcaPIM2Serine/threonine-protein kinase pim-211370.7145Highly expressed in hematopoietic tissues, in leukemic and lymphoma cell lines, testis, small intestine, colon and colorectal adenocarcinoma cells. Weakly expressed in normal liver, but highly expressed in hepatocellular carcinoma tissues.protein kinaseProto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression, the regulation of cap-dependent protein translation and through survival signaling by phosphorylation of a pro-apoptotic protein, BAD. Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase transcriptional activity. The stabilization of MYC exerted by PIM2 might explain partly the strong synergism between these 2 oncogenes in tumorigenesis. Regulates cap-dependent protein translation in a mammalian target of rapamycin complex 1 (mTORC1)-independent manner and in parallel to the PI3K-Akt pathway. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti- apoptotic protein Bcl-X(L)/BCL2L1. Promotes cell survival in response to a variety of proliferative signals via positive regulation of the I-kappa-B kinase/NF-kappa-B cascade; this process requires phosphorylation of MAP3K8/COT. Isoform 1 is less active in this respect. Promotes growth factor-independent proliferation by phosphorylation of cell cycle factors such as CDKN1A and CDKN1B. Involved in the positive regulation of chondrocyte survival and autophagy in the epiphyseal growth plate.
kcaPIM3Serine/threonine-protein kinase pim-38430.7605Detected in various tissues, including the heart, brain, lung, kidney, spleen, placenta, skeletal muscle, and peripheral blood leukocytes. Not found or barely expressed in the normal adult endoderm-derived organs such as colon, thymus, liver, or small intestine. However, expression is augmented in premalignant and malignant lesions of these organs.protein kinaseProto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth.
kcaPK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform26440.737PI3/PI4-kinaseColorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis. Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The gene represented in this entry may be involved in disease pathogenesis. Note=Most of the cancer-derived mutations are missense mutations and map to one of the three hotspots: Glu-542; Glu-545 and His-1047. Mutated isoforms participate in cellular transformation and tumorigenesis induced by oncogenic receptor tyrosine kinases (RTKs) and HRAS/KRAS. Interaction with HRAS/KRAS is required for Ras-driven tumor formation. Mutations increasing the lipid kinase activity are required for oncogenic signaling. The protein kinase activity may not be required for tumorigenesis. Keratosis, seborrheic (KERSEB) [MIM:182000]: A common benign skin tumor. Seborrheic keratoses usually begin with the appearance of one or more sharply defined, light brown, flat macules. The lesions may be sparse or numerous. As they initially grow, they develop a velvety to finely verrucous surface, followed by an uneven warty surface with multiple plugged follicles and a dull or lackluster appearance. Note=The disease is caused by mutations affecting the gene represented in this entry. Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) [MIM:602501]: A syndrome characterized by a spectrum of anomalies including primary megalencephaly, prenatal overgrowth, brain and body asymmetry, cutaneous vascular malformations, digital anomalies consisting of syndactyly with or without postaxial polydactyly, connective tissue dysplasia involving the skin, subcutaneous tissue, and joints, and cortical brain malformations, most distinctively polymicrogyria. Note=The disease is caused by mutations affecting the gene represented in this entry. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. Note=The disease is caused by mutations affecting the gene represented in this entry. Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE) [MIM:612918]: A sporadically occurring, non-hereditary disorder characterized by asymmetric somatic hypertrophy and anomalies in multiple organs. It is defined by four main clinical findings: congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal/spinal abnormalities. The presence of truncal overgrowth and characteristic patterned macrodactyly at birth differentiates CLOVE from other syndromic forms of overgrowth. Note=The disease is caused by mutations affecting the gene represented in this entry. Cowden syndrome 5 (CWS5) [MIM:615108]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid. Note=The disease is caused by mutations affecting the gene represented in this entry.Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4- phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5- bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation in breast cancer cells through the PDPK1- AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. Has also serine-protein kinase activity: phosphorylates PIK3R1 (p85alpha regulatory subunit), EIF4EBP1 and HRAS.
kcaPK3CBPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform11250.6639Expressed ubiquitously.PI3/PI4-kinaseNot Available
kcaPK3CDPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform12290.6574Isoform <a href="#O00329-2" onclick="ensureIsoformSequenceVisible('O00329-2'); return true;">2</a> is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform <a href="#O00329" onclick="ensureIsoformSequenceVisible('O00329'); return true;">1</a> and isoform <a href="#O00329-2" onclick="ensureIsoformSequenceVisible('O00329-2'); return true;">2</a> are widely expressed. Isoform <a href="#O00329" onclick="ensureIsoformSequenceVisible('O00329'); return true;">1</a> is expressed predominantly in leukocytes. <a class="attribution" href="O00329#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>PI3/PI4-kinaseInflammatory diseases
kcaPK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform13060.6579Pancreas, skeletal muscle, liver and heart. <a class="attribution" href="P48736#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>PI3/PI4-kinaseAngioedema
Cancer, unspecific
Heart failure
Myocardial infarction
Solid tumors
3-phosphorylates the cellular phosphoinositide ptdins-4,5-biphosphate (ptdins(4,5)p2).
kcaPKN1Serine/threonine-protein kinase N1960.6754Found ubiquitously. Expressed in heart, brain, placenta, lung, skeletal muscle, kidney and pancreas. Expressed in numerous tumor cell lines, especially in breast tumor cells.protein kinasePKC-related serine/threonine-protein kinase involved in various processes such as regulation of the intermediate filaments of the actin cytoskeleton, cell migration, tumor cell invasion and transcription regulation. Regulates the cytoskeletal network by phosphorylating proteins such as VIM and neurofilament proteins NEFH, NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to bind to microtubules, resulting in disruption of tubulin assembly. Acts as a key coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for epigenetic transcriptional activation that promotes demethylation of histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5, HDAC7 and HDAC9, leading to impair their import in the nucleus. Phosphorylates 'Thr-38' of PPP1R14A, 'Ser- 159', 'Ser-163' and 'Ser-170' of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.
kcaPKN2Serine/threonine-protein kinase N27800.5355Ubiquitous. Expressed in numerous tumor cell lines, especially in bladder tumor cells.protein kinasePKC-related serine/threonine-protein kinase and Rho/Rac effector protein that participates in specific signal transduction responses in the cell. Plays a role in the regulation of cell cycle progression, actin cytoskeleton assembly, cell migration, cell adhesion, tumor cell invasion and transcription activation signaling processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and hence decreases CTTN ability to associate with filamentous actin. Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct RhoA target required for the regulation of the maturation of primordial junctions into apical junction formation in bronchial epithelial cells. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase activity that is required for establishment of skin cell-cell adhesion during keratinocytes differentiation. Regulates epithelial bladder cells speed and direction of movement during cell migration and tumor cell invasion. Inhibits Akt pro-survival-induced kinase activity. Mediates Rho protein-induced transcriptional activation via the c- fos serum response factor (SRF). Phosphorylates HCV NS5B leading to stimulation of HCV RNA replication.
kcaPLD1Phospholipase D11880.6292Expressed abundantly in the pancreas and heart and at high levels in brain, placenta, spleen, uterus and small intestine. <a class="attribution" href="Q13393#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>phospholipase DInflammation Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (by similarity).
kcaPLK1Serine/threonine-protein kinase PLK115540.5445Placenta and colon.protein kinaseAcute myeloid leukemia
Advanced or metastatic non-small cell lung cancer
Advanced solid tumor
Cancer, unspecific
Metastatic hormone refractory Prostate cancer
Non-Hodgkins Lymphoma
Pancreatic cancer
Pancreatic, prostate and a number of other cancers
May be required for cell division and may have a role during g1 or s phase.
kcaPLK2Serine/threonine-protein kinase PLK22000.6042Expressed at higher level in the fetal lung, kidney, spleen and heart.protein kinaseTumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.
kcaPLK3Serine/threonine-protein kinase PLK39310.6613Transcripts are highly detected in placenta, lung, followed by skeletal muscle, heart, pancreas, ovaries and kidney and weakly detected in liver and brain. May have a short half-live. In cells of hematopoietic origin, strongly and exclusively detected in terminally differentiated macrophages. Transcript expression appears to be down-regulated in primary lung tumor.protein kinaseSerine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.
kcaPLK4Serine/threonine-protein kinase PLK48250.5957protein kinaseSerine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.
kcaPLMNPlasminogen10100.6682Present in plasma and many other extracellular fluids. It is synthesized in the liver.peptidase S1Excessive postoperative bleeding
Hemorrhage
Plasminogen activator: Alteplase, Reteplase, Streptokinase, Tenecteplase, Urokinase
Plasminogen inhibitor: Aminocaproic Acid, Aprotinin, Tranexamic Acid
kcaPNPHPurine nucleoside phosphorylase2520.5754PNP/MTAP phosphorylaseB cell acute lymphoblastic leukemia (B-ALL)
Cutaneous T-cell Lymphoma
Malaria
Moderate to Severe Plaque Psoriasis
Psoriasis
Refractory Cutaneous T-cell Lymphoma (CTCL)
Schistosomiasis [bilharziasis]
T-cell proliferation
Trypanosomatid infections
Tumors
kcaPPARAPeroxisome proliferator-activated receptor alpha26240.6226Skeletal muscle, liver, heart and kidney. <a class="attribution" href="Q07869#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q07869#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a>Myalgianuclear hormone receptorHyperglycemia
Hyperinsulinemia
Insulin resistance
Lipid metabolic disorders
Obesity
Receptor that bind peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-coa oxidase and activates its transcription. It therefore controls the perox[UniProt] Peroxisome proliferator-activated receptor alpha agonist: Clofibrate, Fenofibrate, Fenofibric Acid, Gemfibrozil
kcaPPARDPeroxisome proliferator-activated receptor delta15200.7578Ubiquitous with maximal levels in placenta and skeletal muscle.nuclear hormone receptorAtherosclerosis
Hyperlipidemia
Inflammation
Metabolic Disease
Metabolic syndrome X
Noninsulin-dependent diabetes mellitus
Obesity
Skin diseases
Receptor that bind peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-coa oxidase and activates its transcription.
kcaPPARGPeroxisome proliferator-activated receptor gamma41500.7375VirtualToxLabHighest expression in adipose tissue. Lower in skeletal muscle, spleen, heart and liver. Also detectable in placenta, lung and ovary. <a class="attribution" href="P37231#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>Dyspepsianuclear hormone receptorNot Available Peroxisome proliferator-activated receptor gamma agonist: Balsalazide, Mesalamine, Olsalazine, Pioglitazone, Rosiglitazone, Troglitazone
kcaPPCEProlyl endopeptidase5950.6627peptidase S9ADementia
Neurological diseases
Cleaves peptide bonds on the c-terminal side of prolyl residues within peptides that are up to approximately 30 amino acids long.
kcaPRGRProgesterone receptor17830.7235Nature11159
VirtualToxLab
Acne
Amenorrhoea
Biliary tract disorder
Breast pain
Depression
Fibrocystic breast disease
Gynaecomastia
Hirsutism
Jaundice cholestatic
Libido disorder
Menstrual disorder
Metrorrhagia
Migraine
Oedema
Urticaria
Weight increased
nuclear hormone receptorBreast cancer The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor agonist: Danazol, Desogestrel, Drospirenone, Dydrogesterone, Ethynodiol Diacetate, Etonogestrel, Fluticasone Propionate, Hydroxyprogesterone Caproate, Levonorgestrel, Medroxyprogesterone Acetate, Megestrol Acetate, Norelgestromin, Norethindrone, Norethindrone Acetate, Norethynodrel, Norgestimate, Norgestrel, Progesterone
Progesterone receptor antagonist: Mifepristone
Progesterone receptor modulator: Ulipristal Acetate
kcaPRKDCDNA-dependent protein kinase catalytic subunit7900.6558PI3/PI4-kinaseLeukemia, unspecified Ser/thr kinase involved in dna double-stranded break repair, v(d)j recombination and modulation of transcription. Must be bound to dna to express its catalytic properties.
kcaPROCVitamin K-dependent protein C2140.5082Plasma; synthesized in the liver.peptidase S1Varicose and spider veins of the leg Protein c is a vitamin k-dependent serine protease that regulates blood coagulation by inactivating factors va and viiia in the presence of calcium ions and phospholipids.
kcaPSB2Proteasome subunit beta type-2510.6286peptidase T1BThe proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit has a trypsin-like activity.
kcaPSN1Presenilin-13280.6631Expressed in a wide range of tissues including various regions of the brain, liver, spleen and lymph nodes. <a class="attribution" href="P49768#ref13" onclick="ensureReferenceVisible('ref13')">Ref.13</a> <a class="attribution" href="P49768#ref27" onclick="ensureReferenceVisible('ref27')">Ref.27</a>peptidase A22AFamilial Alzheimer's disease Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as notch receptors and app (beta-amyloid precursor protein).
kcaPSN2Presenilin-23090.6519Isoform <a href="#P49810" onclick="ensureIsoformSequenceVisible('P49810'); return true;">1</a> is seen in the placenta, skeletal muscle and heart while isoform <a href="#P49810-2" onclick="ensureIsoformSequenceVisible('P49810-2'); return true;">2</a> is seen in the heart, brain, placenta, liver, skeletal muscle and kidney. <a class="attribution" href="P49810#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>peptidase A22AFamilial Alzheimer's disease Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as notch receptors and app (beta-amyloid precursor protein).
kcaPTAFRPlatelet-activating factor receptor13730.6928Expressed in the placenta, lung, left and right heart ventricles, heart atrium, leukocytes and differentiated HL-60 granulocytes. <a class="attribution" href="P25105#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P25105#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="P25105#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a>G-protein coupled receptor 1Ocular allergy Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G protein that activates a phosphatidylinositol-calcium second messenger system.
kcaPTGESProstaglandin E synthase4960.672MAPEGInflammation
Rheumatoid arthritis, unspecified
kcaPTK6Protein-tyrosine kinase 65560.6033Epithelia-specific. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues. Not expressed in breast or ovarian tissue but expressed in high percentage of breast and ovarian cancers. Also overexpressed in some metastatic melanomas, lymphomas, colon cancers, squamous cell carcinomas and prostate cancers. Also found in melanocytes. Not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform <a href="#Q13882-2" onclick="ensureIsoformSequenceVisible('Q13882-2'); return true;">2</a> is present in prostate epithelial cell lines derived from normal prostate and prostate adenocarcinomas, as well as in a variety of cell lines. <a class="attribution" href="Q13882#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a> <a class="attribution" href="Q13882#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a> <a class="attribution" href="Q13882#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a> <a class="attribution" href="Q13882#ref20" onclick="ensureReferenceVisible('ref20')">Ref.20</a>protein kinaseBreast cancer
Cancer, unspecific
Pancreatic cancer
Prostate tumor
May function as an intracellular signal transducer in epithelial tissues. Overexpression in mammary cells leads to mitogenically sensitization to egf, and results in a partially transformed phenotype. Tyrosine-protein kinase BRK inhibitor: Vandetanib
kcaPTN1Tyrosine-protein phosphatase non-receptor type 122210.7403protein-tyrosine phosphataseType 2 Diabetes May play an important role in CKII- and p60c-src-induced signal transduction cascades (By similarity).
kcaPTN2Tyrosine-protein phosphatase non-receptor type 24720.7971Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta.protein-tyrosine phosphataseNon-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3, STAT5A, STAT5B and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. Beside the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Plays also an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogenesis and liver glucose production through negative regulation of the IL6 signaling pathways. Finally, it negatively regulates prolactin-mediated signaling pathway through dephosphorylation of STAT5A and STAT5B. May also bind DNA.
kcaPTN22Tyrosine-protein phosphatase non-receptor type 225300.6117Both isoform 1 and 4 are predominantly expressed in lymphoid tissues and cells. Isoform 1 is expressed in thymocytes and both mature B and T-cells.protein-tyrosine phosphataseSystemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2.
kcaPTN6Tyrosine-protein phosphatase non-receptor type 61600.7057Isoform <a href="#P29350" onclick="ensureIsoformSequenceVisible('P29350'); return true;">1</a> is expressed in hematopoietic cells. Isoform <a href="#P29350-3" onclick="ensureIsoformSequenceVisible('P29350-3'); return true;">2</a> is expressed in non-hematopoietic cells.protein-tyrosine phosphataseSolid tumors
kcaPTPRAReceptor-type tyrosine-protein phosphatase alpha610.6075protein-tyrosine phosphatase
kcaPTPRCReceptor-type tyrosine-protein phosphatase C2680.6077protein-tyrosine phosphataseAlzheimer's disease Required for t-cell activation through the antigen receptor. The first ptpase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one.
kcaPTPRFReceptor-type tyrosine-protein phosphatase F1430.6225protein-tyrosine phosphatasePossible cell adhesion receptor. It possesses an intrinsic protein tyrosine phosphatase activity (PTPase) and dephosphorylates EPHA2 regulating its activity. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one.
kcaPYGMGlycogen phosphorylase, muscle form4420.6739glycogen phosphorylaseDiabetes Mellitus Type 2
Noninsulin-dependent diabetes mellitus
Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
kcaPYRDDihydroorotate dehydrogenase (quinone), mitochondrial6080.7347dihydroorotate dehydrogenasePostaxial acrofacial dysostosis (POADS) [MIM:263750]: POADS is characterized by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the posterior elements of the limbs, coloboma of the eyelids and supernumerary nipples. POADS is a very rare disorder: only 2 multiplex families, each consisting of 2 affected siblings born to unaffected, nonconsanguineous parents, have been described among a total of around 30 reported cases. Note=The disease is caused by mutations affecting the gene represented in this entry.Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
kcaQPCTGlutaminyl-peptide cyclotransferase1700.5113glutaminyl-peptide cyclotransferaseResponsible for the biosynthesis of pyroglutamyl peptides. Has a bias against acidic and tryptophan residues adjacent to the N-terminal glutaminyl residue and a lack of importance of chain length after the second residue. Also catalyzes N-terminal pyroglutamate formation. In vitro, catalyzes pyroglutamate formation of N-terminally truncated form of APP amyloid-beta peptides [Glu-3]-beta-amyloid. May be involved in the N-terminal pyroglutamate formation of several amyloid-related plaque-forming peptides.
kcaRAF1RAF proto-oncogene serine/threonine-protein kinase5350.5494In skeletal muscle, isoform <a href="#P04049" onclick="ensureIsoformSequenceVisible('P04049'); return true;">1</a> is more abundant than isoform <a href="#P04049-2" onclick="ensureIsoformSequenceVisible('P04049-2'); return true;">2</a>. <a class="attribution" href="P04049#ref9" onclick="ensureReferenceVisible('ref9')">Ref.9</a>protein kinaseCancer, unspecific Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the ras-dependent signaling pathway from receptors to the nucleus. Serine/threonine-protein kinase RAF inhibitor: Regorafenib, Sorafenib
kcaRARARetinoic acid receptor alpha2730.5222nuclear hormone receptorAcute promyelocytic leukemia Nuclear receptor for retinoic acid. This metabolite has profound effects on vertebrate development. retinoic acid is a morphogen and is a powerful teratogen. This receptor controls cells functions by directly regulating gene expression.
kcaRARGRetinoic acid receptor gamma2700.504nuclear hormone receptorAcne
Emphysema
Photoaging
Psoriasis
Retinoic acid receptor gamma agonist: Adapalene
kcaRASHGTPase HRas860.5854Widely expressed. <a class="attribution" href="P01112#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>small GTPaseNot Available
kcaRENIRenin26730.6895peptidase A1Cancer, unspecific
Hypertension
Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin i from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney. Renin inhibitor: Aliskiren
kcaRIOK1Serine/threonine-protein kinase RIO11210.6026protein kinase
kcaRIOK2Serine/threonine-protein kinase RIO21170.7041protein kinase
kcaRIR1Ribonucleoside-diphosphate reductase large subunit1070.6776ribonucleoside diphosphate reductase large chainProvides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
kcaRIR2Ribonucleoside-diphosphate reductase subunit M2830.5721ribonucleoside diphosphate reductase small chainCancers Ribonucleoside-diphosphate reductase RR1 inhibitor: Clofarabine, Fludarabine Phosphate, Gallium Nitrate, Gemcitabine, Hydroxyurea
kcaRIR2BRibonucleoside-diphosphate reductase subunit M2 B710.5682Widely expressed at a high level in skeletal muscle and at a weak level in thymus. Expressed in epithelial dysplasias and squamous cell carcinoma.ribonucleoside diphosphate reductase small chainMitochondrial DNA depletion syndrome 8A (MTDPS8A) [MIM:612075]: A disorder due to mitochondrial dysfunction characterized by various combinations of neonatal hypotonia, neurological deterioration, respiratory distress, lactic acidosis, and renal tubulopathy. Note=The disease is caused by mutations affecting the gene represented in this entry. Mitochondrial DNA depletion syndrome 8B (MTDPS8B) [MIM:612075]: A disease due to mitochondrial dysfunction and characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy. Note=The disease is caused by mutations affecting the gene represented in this entry. Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 5 (PEOA5) [MIM:613077]: A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. Note=The disease is caused by mutations affecting the gene represented in this entry.Plays a pivotal role in cell survival by repairing damaged DNA in a p53/TP53-dependent manner. Supplies deoxyribonucleotides for DNA repair in cells arrested at G1 or G2. Contains an iron-tyrosyl free radical center required for catalysis. Forms an active ribonucleotide reductase (RNR) complex with RRM1 which is expressed both in resting and proliferating cells in response to DNA damage.
kcaRN5A2-5A-dependent ribonuclease770.6193Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes.protein kinaseProstate cancer, hereditary, 1 (HPC1) [MIM:601518]: A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress- response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. Might play a central role in the regulation of mRNA turnover.
kcaROCK2Rho-associated protein kinase 216190.5442protein kinaseProtein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.
kcaRORGNuclear receptor ROR-gamma2080.6244Isoform 1 is widely expressed in many tissues, including liver and adipose, and highly expressed in skeletal muscle. Isoform 2 is primarily expressed in immature thymocytes.nuclear hormone receptorNuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25- hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue- selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC- mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1. Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR- J(alpha) locus.
kcaRXRARetinoic acid receptor RXR-alpha4900.7054Highly expressed in liver, also found in lung, kidney and heart.Arthralgianuclear hormone receptorProstate cancer Nuclear hormone receptor. Involved in retinoic acid response pathway. Binds 9-cis retinoic acid (9c-ra).
kcaRXRBRetinoic acid receptor RXR-beta1950.5018Expressed in a variety of tumor cell lines.nuclear hormone receptorReceptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
kcaS1PR1Sphingosine 1-phosphate receptor 112490.6748Endothelial cells, and to a lesser extent, in vascular smooth muscle cells, fibroblasts, melanocytes, and cells of epithelioid origin.G-protein coupled receptor 1Autoimmune diseases Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. This inducible epithelial cell G-protein-coupled receptor may be involved in the processes that regulate the differentiation of endothelial cells. Seems to be coupled to the G(i) subclass of heteromeric G proteins.
kcaS1PR2Sphingosine 1-phosphate receptor 24930.7844G-protein coupled receptor 1Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.
kcaS1PR3Sphingosine 1-phosphate receptor 38820.6126Expressed in all tissues, but most abundantly in heart, placenta, kidney, and liver.G-protein coupled receptor 1Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. When expressed in rat HTC4 hepatoma cells, is capable of mediating S1P-induced cell proliferation and suppression of apoptosis.
kcaS1PR4Sphingosine 1-phosphate receptor 45680.6472Specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. Considerable level of expression in adult and fetal spleen as well as adult peripheral leukocytes and lung. Lower expression in adult thymus, lymph node, bone marrow, and appendix as well as in fetal liver, thymus, and lung.G-protein coupled receptor 1Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.
kcaS1PR5Sphingosine 1-phosphate receptor 52830.6417Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes.G-protein coupled receptor 1Receptor for the lysosphingolipid sphingosine 1- phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By similarity). May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells.
kcaS29A1Equilibrative nucleoside transporter 12550.6424Nature11159SLC29A/ENT transporterMalaria Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (nbmpr) and is sodium-independent.
kcaS5A13-oxo-5-alpha-steroid 4-dehydrogenase 16800.6227Liver and prostate (at a low level).steroid 5-alpha reductaseAcne
Alopecia, unspecified
Benign prostate hyperplasia
Hirsutism
Prostate cancer
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5- alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
kcaS5A23-oxo-5-alpha-steroid 4-dehydrogenase 26350.7348Expressed in high levels in the prostate and many other androgen-sensitive tissues.Gynaecomastiasteroid 5-alpha reductaseAlopecia, unspecified
Androgen-dependent diseases
Benign prostate hyperplasia
Prostate cancer
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5- alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology. Steroid 5-alpha-reductase 2 inhibitor: Finasteride
kcaS6A11Sodium- and chloride-dependent GABA transporter 31320.6342Widespread distribution in the brain.sodium:neurotransmitter symporterTerminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
kcaS6A12Sodium- and chloride-dependent betaine transporter690.5552Liver, heart, skeletal muscle, placenta, and a widespread distribution in the brain.sodium:neurotransmitter symporterTransports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.
kcaS6A13Sodium- and chloride-dependent GABA transporter 21200.5878Expressed in brain, kidney, lung, liver and testis.sodium:neurotransmitter symporterSodium-dependent GABA and taurine transporter. In presynaptic terminals, regulates GABA signaling termination through GABA uptake. May also be involved in beta-alanine transport.
kcaSC5A1Sodium/glucose cotransporter 13300.5554Expressed mainly in intestine and kidney.sodium:solute symporterDiabetes Actively transports glucose into cells by Na+ cotransport with a Na+ to glucose coupling ratio of 2:1. Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na+/glucose cotransporter arranged in series along kidney proximal tubules.
kcaSC5A2Sodium/glucose cotransporter 28200.652sodium:solute symporterType 2 Diabetes Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules. Sodium/glucose cotransporter 2 inhibitor: Canagliflozin
kcaSC5A7High affinity choline transporter 19870.5694Expressed in putamen, spinal cord and medulla. Specific for cholinergic neurons.sodium:solute symporterNeuronopathy, distal hereditary motor, 7A (HMN7A) [MIM:158580]: A neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMN7A is characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve. Note=The disease is caused by mutations affecting the gene represented in this entry.Imports choline from the extracellular space to the neuron with high affinity. Choline uptake is the rate-limiting step in acetylcholine synthesis. Sodium ion- and chloride ion- dependent.
kcaSC6A1Sodium- and chloride-dependent GABA transporter 13270.6974sodium:neurotransmitter symporterConvulsions
Psychosis
Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals. GABA transporter 1 inhibitor: Tiagabine
kcaSC6A2Sodium-dependent noradrenaline transporter28290.5966Nature11159Anticholinergic syndrome
Blood glucose abnormal
Conduction disorder
Cycloplegia
Dry mouth
Ejaculation disorder
Erectile dysfunction
Hyperhidrosis
Hypomania
Insomnia
Mania
Orthostatic hypotension
Palpitations
Psychotic disorder
Schizophrenia
Sexual dysfunction
Sleep disorder
Tremor
Weight decreased
sodium:neurotransmitter symporterDepression Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals. Norepinephrine transporter inhibitor: Amitriptyline, Amoxapine, Atomoxetine, Bupropion, Desipramine, Desvenlafaxine, Dexmethylphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Orphenadrine, Phendimetrazine, Phenmetrazine, Protriptyline, Tapentadol, Trimipramine, Venlafaxine
Norepinephrine transporter releasing agent: Amphetamine, Benzphetamine, Dextroamphetamine, Lisdexamfetamine, Phentermine, Phenylpropanolamine, Phenylpropanolamine Polistirex, Pseudoephedrine, Pseudoephedrine Polistirex
Norepinephrine transporter substrate: Bethanidine, Bretylium, Guanadrel, Guanethidine
kcaSC6A3Sodium-dependent dopamine transporter53670.6584Nature11159Dry mouth
Ejaculation disorder
Hyperhidrosis
Insomnia
Mydriasis
Nervousness
Palpitations
Restlessness
Tachycardia
Tremor
sodium:neurotransmitter symporterParkinson's disease Amine transporter, terminating the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals. Dopamine transporter inhibitor: Armodafinil, Bupropion, Dexmethylphenidate, Diethylpropion, Methylphenidate, Modafinil, Phendimetrazine, Phenmetrazine
Dopamine transporter releasing agent: Amphetamine, Dextroamphetamine, Lisdexamfetamine
kcaSC6A4Sodium-dependent serotonin transporter69860.7028Nature11159Expressed in platelets (at protein level). <a class="attribution" href="P31645#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>Anticholinergic syndrome
Blood glucose abnormal
Conduction disorder
Cycloplegia
Dependence
Dry mouth
Erectile dysfunction
Extrapyramidal disorder
Galactorrhoea
Hyperhidrosis
Hypomania
Insomnia
Libido disorder
Mania
Nervousness
Orthostatic hypotension
Palpitations
Psychotic disorder
Schizophrenia
Sexual dysfunction
Sleep disorder
Tachycardia
Tremor
Urinary retention
Weight decreased
sodium:neurotransmitter symporterSchizophrenia Terminates the action of serotonin by its high affinity sodium-dependent reuptake into presynaptic terminals. Serotonin transporter inhibitor: Amitriptyline, Amoxapine, Citalopram, Clomipramine, Desvenlafaxine, Duloxetine, Escitalopram, Fluoxetine, Fluvoxamine, Imipramine, Milnacipran, Nefazodone, Nortriptyline, Paroxetine, Protriptyline, Sertraline, Trazodone, Venlafaxine, Vilazodone
Serotonin transporter substrate: Chlorphentermine
kcaSC6A5Sodium- and chloride-dependent glycine transporter 24700.7479Expressed in medulla, and to a lesser extent in spinal cord and cerebellum.sodium:neurotransmitter symporterHyperekplexia 3 (HKPX3) [MIM:614618]: A neurologic disorder characterized by neonatal hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life- threatening neonatal apnea episodes. Notably, in some cases, symptoms resolved in the first year of life. Note=The disease is caused by mutations affecting the gene represented in this entry.Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses.
kcaSC6A9Sodium- and chloride-dependent glycine transporter 17260.5377Isoform GlyT-1A and isoform GlyT-1B can be found in brain, kidney, pancreas, lung, placenta and liver but isoform GlyT-1C is only found in brain.sodium:neurotransmitter symporterDisorders associated with NMDAR hypofunction Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May play a role in regulation of glycine levels in nmda receptor-mediated neurotransmission.
kcaSCN1ASodium channel protein type 1 subunit alpha2880.6434Agitation
Apnoea
Cardiac arrest
Central nervous system stimulation
Coma
Convulsion
Corneal disorder
Death
Dysarthria
Encephalopathy
Foetal damage
Hypoaesthesia oral
Impaired healing
Keratitis
Loss of consciousness
Methaemoglobinaemia
Muscle twitching
Myocardial depression
Nervousness
Presyncope
Respiratory failure
Sensitisation
Tinnitus
Tremor
Vasodilatation
Vision blurred
Visual pathway disorder
sodium channelAnalgesics
Local anesthesia
Pain
Seizures
kcaSCN2ASodium channel protein type 2 subunit alpha4450.5514sodium channelSeizures, benign familial infantile 3 (BFIS3) [MIM:607745]: An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae. Note=The disease is caused by mutations affecting the gene represented in this entry. Epileptic encephalopathy, early infantile, 11 (EIEE11) [MIM:613721]: An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. Note=The disease is caused by mutations affecting the gene represented in this entry.Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
kcaSCN3ASodium channel protein type 3 subunit alpha2920.6035Agitation
Apnoea
Cardiac arrest
Central nervous system stimulation
Coma
Convulsion
Corneal disorder
Death
Dysarthria
Encephalopathy
Foetal damage
Hypoaesthesia oral
Impaired healing
Keratitis
Loss of consciousness
Methaemoglobinaemia
Muscle twitching
Myocardial depression
Nervousness
Presyncope
Respiratory failure
Sensitisation
Tinnitus
Tremor
Vasodilatation
Vision blurred
Visual pathway disorder
sodium channelAnalgesics
Pain, unspecific
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na+ ions may pass in accordance with their electrochemical gradient.
kcaSCN5ASodium channel protein type 5 subunit alpha3900.6813Nature11159Found in jejunal circular smooth muscle cells (at protein level). Expressed in human atrial and ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. Isoform <a href="#Q14524-4" onclick="ensureIsoformSequenceVisible('Q14524-4'); return true;">4</a> is expressed in brain. <a class="attribution" href="Q14524#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q14524#ref15" onclick="ensureReferenceVisible('ref15')">Ref.15</a>Apnoea
Cardiac arrest
Central nervous system stimulation
Coma
Corneal disorder
Death
Diplopia
Dysarthria
Foetal damage
Hypoaesthesia oral
Impaired healing
Keratitis
Loss of consciousness
Methaemoglobinaemia
Muscle twitching
Myocardial depression
Nervousness
Nystagmus
Presyncope
Respiratory failure
Sensitisation
Tinnitus
Tremor
Ventricular fibrillation
Vision blurred
sodium channelAnalgesics
Cardiac dysrhythmias
Epileptic seizures
Pain
Refractory partial epilepsy
Sustained ventricular tachycardia
Sodium channel protein type V alpha subunit blocker: Dibucaine, Flecainide, Ranolazine
kcaSEPRSeprase4720.6963Fibroblast specific.peptidase S9BAtherogenesis
Inflammatory diseases
Thrombosis
May have a role in tissue remodeling during development and wound healing, and may contribute to invasiveness in malignant cancers.
kcaSGK1Serine/threonine-protein kinase Sgk11350.6886Expressed in most tissues with highest levels in the pancreas, followed by placenta, kidney and lung. Isoform <a href="#O00141-2" onclick="ensureIsoformSequenceVisible('O00141-2'); return true;">2</a> is strongly expressed in brain and pancreas, weaker in heart, placenta, lung, liver and skeletal muscle. <a class="attribution" href="O00141#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="O00141#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>protein kinaseLeukemia, Myeloid
Myelodysplastic Syndrome
Solid tumors
kcaSGMR1Sigma non-opioid intracellular receptor 140170.6092Widely expressed with higher expression in liver, colon, prostate, placenta, small intestine, heart and pancreas. Expressed in the retina by retinal pigment epithelial cells. <a class="attribution" href="Q99720#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q99720#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q99720#ref16" onclick="ensureReferenceVisible('ref16')">Ref.16</a>Biliary colic
Bladder disorder
Cerebrovascular disorder
Dependence
Dermatitis contact
Drug tolerance
Dry mouth
Hypothermia
Injection site irritation
Injection site pain
Intracranial pressure increased
Miosis
Mood altered
Oliguria
Respiratory depression
Shock
Ureteral spasm
Withdrawal syndrome
ERG2Neuropsychiatric disorders Sigma opioid receptor agonist: Dextromethorphan, Dextromethorphan Polistirex
Sigma opioid receptor modulator: Pentazocine
kcaSHHSonic hedgehog protein1620.5823Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues.hedgehogMicrophthalmia, isolated, with coloboma, 5 (MCOPCB5) [MIM:611638]: A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Note=The disease is caused by mutations affecting the gene represented in this entry. Holoprosencephaly 3 (HPE3) [MIM:142945]: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described. Note=The disease is caused by mutations affecting the gene represented in this entry. Solitary median maxillary central incisor (SMMCI) [MIM:147250]: Rare dental anomaly characterized by the congenital absence of one maxillary central incisor. Note=The disease is caused by mutations affecting the gene represented in this entry. Triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]: Autosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH expression. Preaxial polydactyly 2 (PPD2) [MIM:174500]: Polydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (PubMed:12837695).Intercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior- posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO (By similarity).
kcaSIR1NAD-dependent protein deacetylase sirtuin-13590.5829Widely expressed. <a class="attribution" href="Q96EB6#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>sirtuinDiabetes Mellitus Type 2
Neurologic Disorders
kcaSIR2NAD-dependent protein deacetylase sirtuin-23240.7661Isoform 1 is expressed in heart, liver and skeletal muscle, weakly expressed in the cortex. Isoform 2 is strongly expressed in the cortex, weakly expressed in heart and liver. Weakly expressed in several malignancies including breast, liver, brain, kidney and prostate cancers compared to normal tissues. Weakly expressed in glioma cell lines compared to normal brain tissues (at protein level). Widely expressed. Highly expressed in heart, brain and skeletal muscle, while it is weakly expressed in placenta and lung. Down-regulated in many gliomas suggesting that it may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network.sirtuinNAD-dependent protein deacetylase, which deacetylates internal lysines on histone and alpha-tubulin as well as many other proteins such as key transcription factors. Participates in the modulation of multiple and diverse biological processes such as cell cycle control, genomic integrity, microtubule dynamics, cell differentiation, metabolic networks, and autophagy. Plays a major role in the control of cell cycle progression and genomic stability. Functions in the antephase checkpoint preventing precocious mitotic entry in response to microtubule stress agents, and hence allowing proper inheritance of chromosomes. Positively regulates the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex activity by deacetylating CDC20 and FZR1, then allowing progression through mitosis. Associates both with chromatin at transcriptional start sites (TSSs) and enhancers of active genes. Plays a role in cell cycle and chromatin compaction through epigenetic modulation of the regulation of histone H4 'Lys-20' methylation (H4K20me1) during early mitosis. Specifically deacetylates histone H4 at 'Lys-16' (H4K16ac) between the G2/M transition and metaphase enabling H4K20me1 deposition by SETD8 leading to ulterior levels of H4K20me2 and H4K20me3 deposition throughout cell cycle, and mitotic S-phase progression. Deacetylates SETD8 modulating SETD8 chromatin localization during the mitotic stress response. Deacetylates also histone H3 at 'Lys- 57' (H3K56ac) during the mitotic G2/M transition. Upon bacterium Listeria monocytogenes infection, deacetylates 'Lys-18' of histone H3 in a receptor tyrosine kinase MET- and PI3K/Akt-dependent manner, thereby inhibiting transcriptional activity and promoting late stages of listeria infection. During oocyte meiosis progression, may deacetylate histone H4 at 'Lys-16' (H4K16ac) and alpha-tubulin, regulating spindle assembly and chromosome alignment by influencing microtubule dynamics and kinetochore function. Deacetylates alpha-tubulin at 'Lys-40' and hence controls neuronal motility, oligodendroglial cell arbor projection processes and proliferation of non-neuronal cells. Phosphorylation at Ser-368 by a G1/S-specific cyclin E-CDK2 complex inactivates SIRT2-mediated alpha-tubulin deacetylation, negatively regulating cell adhesion, cell migration and neurite outgrowth during neuronal differentiation. Deacetylates PARD3 and participates in the regulation of Schwann cell peripheral myelination formation during early postnatal development and during postinjury remyelination. Involved in several cellular metabolic pathways. Plays a role in the regulation of blood glucose homeostasis by deacetylating and stabilizing phosphoenolpyruvate carboxykinase PCK1 activity in response to low nutrient availability. Acts as a key regulator in the pentose phosphate pathway (PPP) by deacetylating and activating the glucose-6-phosphate G6PD enzyme, and therefore, stimulates the production of cytosolic NADPH to counteract oxidative damage. Maintains energy homeostasis in response to nutrient deprivation as well as energy expenditure by inhibiting adipogenesis and promoting lipolysis. Attenuates adipocyte differentiation by deacetylating and promoting FOXO1 interaction to PPARG and subsequent repression of PPARG-dependent transcriptional activity. Plays a role in the regulation of lysosome-mediated degradation of protein aggregates by autophagy in neuronal cells. Deacetylates FOXO1 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1- mediated autophagy. Deacetylates a broad range of transcription factors and co-regulators regulating target gene expression. Deacetylates transcriptional factor FOXO3 stimulating the ubiquitin ligase SCF(SKP2)-mediated FOXO3 ubiquitination and degradation. Deacetylates HIF1A and therefore promotes HIF1A degradation and inhibition of HIF1A transcriptional activity in tumor cells in response to hypoxia. Deacetylates RELA in the cytoplasm inhibiting NF-kappaB-dependent transcription activation upon TNF-alpha stimulation. Inhibits transcriptional activation by deacetylating p53/TP53 and EP300. Deacetylates also EIF5A. Functions as a negative regulator on oxidative stress-tolerance in response to anoxia-reoxygenation conditions. Plays a role as tumor suppressor. Isoform 1: Deacetylates EP300, alpha-tubulin and histone H3 and H4. Isoform 2: Deacetylates EP300, alpha-tubulin and histone H3 and H4. Isoform 5: Lacks deacetylation activity.
kcaSIR3NAD-dependent protein deacetylase sirtuin-3, mitochondrial640.7263Widely expressed.sirtuinNAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5O. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.
kcaSL9A1Sodium/hydrogen exchanger 15440.6272Kidney and intestine.monovalent cation:proton antiporter 1Heart failure
Myocardial ischemia and reperfusion injury
Involved in ph regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.
kcaSMOSmoothened homolog4640.6868G-protein coupled receptor Fz/SmoCancers G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7 and GLI3 in the cilia. Smoothened homolog inhibitor: Vismodegib
kcaSO1B1Solute carrier organic anion transporter family member 1B11020.5844Highly expressed in liver, at the basolateral membranes of centrilobular hepatocytes. Not detected in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocyte.organo anion transporterHyperbilirubinemia, Rotor type (HBLRR) [MIM:237450]: An autosomal recessive form of primary conjugated hyperbilirubinemia. Affected individuals develop mild jaundice not associated with hemolysis shortly after birth or in childhood. They have delayed plasma clearance of the unconjugated anionic dye bromsulphthalein and prominent urinary excretion of coproporphyrin I. Hepatic pigmentation is normal. Note=The disease is caused by mutations affecting the gene represented in this entry.Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. Involved in the clearance of bile acids and organic anions from the liver.
kcaSOAT1Sterol O-acyltransferase 112290.6556membrane-bound acyltransferaseCatalyzes the formation of fatty acid-cholesterol esters. Plays a role in lipoprotein assembly and dietary cholesterol absorption. In addition to its acyltransferase activity, it may act as a ligase.
kcaSOAT2Sterol O-acyltransferase 21260.7881membrane-bound acyltransferaseNot Available
kcaSPHK1Sphingosine kinase 11670.6026Widely expressed with highest levels in adult liver, kidney, heart and skeletal muscle. <a class="attribution" href="Q9NYA1#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>Late-Stage Ovarian cancer
Prostate cancer
kcaSRCProto-oncogene tyrosine-protein kinase Src37730.6387Expressed ubiquitously. Platelets, neurons and osteoclasts express 5-fold to 200-fold higher levels than most other tissues.Diarrhoeaprotein kinaseBreast cancer
Cancer, unspecific
Osteoporosis and other bone-related diseases
Osteoporosis, unspecified
Tyrosine-protein kinase SRC inhibitor: Bosutinib, Vandetanib
kcaSSR1Somatostatin receptor type 18050.5643Fetal kidney, fetal liver, and adult pancreas, brain, lung, jejunum and stomach.G-protein coupled receptor 1Cushing's disease
Neuroblastoma
Refractory Renal Cell Carcinoma
Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and na(+)/h(+) exchange. Somatostatin receptor 1 agonist: Pasireotide
kcaSSR3Somatostatin receptor type 37990.6333Brain, pituitary and pancreas. <a class="attribution" href="P32745#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>G-protein coupled receptor 1Cushing's disease Receptor for somatostatins-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. Somatostatin receptor 3 agonist: Pasireotide
kcaSSR4Somatostatin receptor type 47550.6992Specifically expressed in fetal and adult brain, lung tissue, stomach, and in lesser quantities in the kidney, pituitary and adrenals.G-protein coupled receptor 1Solid tumors
kcaSSR5Somatostatin receptor type 57890.6001Adult pituitary gland, heart, small intestine, adrenal gland, cerebellum and fetal hypothalamus. No expression in fetal or adult kidney, liver, pancreas, uterus, spleen, lung, thyroid or ovary. <a class="attribution" href="P35346#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P35346#ref3" onclick="ensureReferenceVisible('ref3')">Ref.3</a> <a class="attribution" href="P35346#ref4" onclick="ensureReferenceVisible('ref4')">Ref.4</a>G-protein coupled receptor 1Cushing's disease Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Somatostatin receptor 5 agonist: Lanreotide, Pasireotide
kcaSTK3Serine/threonine-protein kinase 38850.5553Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues.protein kinaseStress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38.
kcaSYKLysine--tRNA ligase1380.5503class-II aminoacyl-tRNA synthetaseCharcot-Marie-Tooth disease, recessive, intermediate type, B (CMTRIB) [MIM:613641]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. Note=The disease is caused by mutations affecting the gene represented in this entry. Deafness, autosomal recessive, 89 (DFNB89) [MIM:613916]: A form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies. Note=The disease is caused by mutations affecting the gene represented in this entry.Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.
kcaSYMCMethionine--tRNA ligase, cytoplasmic860.7087class-I aminoacyl-tRNA synthetaseBacterial infections
kcaT23OTryptophan 2,3-dioxygenase850.6561tryptophan 2,3-dioxygenaseIncorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).
kcaTA2RThromboxane A2 receptor11880.687Nature11159G-protein coupled receptor 1Platelet adhesion Receptor for thromboxane a2 (txa2), a potent stimulator of platelet aggregation. The activity of this receptor is mediated by a g-protein that activate a phosphatidylinositol-calcium second messenger system. In the kidney, the binding of txa2 to glomerula.
kcaTAB1TGF-beta-activated kinase 1 and MAP3K7-binding protein 1850.5248Ubiquitous.May be an important signaling intermediate between TGFB receptors and MAP3K7/TAK1. May play an important role in mammalian embryogenesis.
kcaTBK1Serine/threonine-protein kinase TBK14680.6177Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.protein kinaseGlaucoma 1, open angle, P (GLC1P) [MIM:177700]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. GLC1P is characterized by early onset, thin central corneas and low intraocular pressure. Note=The disease may be caused by mutations affecting the gene represented in this entry. A copy number variation on chromosome 12q14 consisting of a 300 kb duplication that includes TBK1, XPOT, RASSF3 and GNS has been found in individuals affected by glaucoma. TBK1 is the most likely candidate for the disorder (PubMed:21447600).Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser- 177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates and activates AKT1. Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein.
kcaTERATransitional endoplasmic reticulum ATPase2090.7255AAA ATPaseInclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1 (IBMPFD1) [MIM:167320]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. Note=The disease is caused by mutations affecting the gene represented in this entry. Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia (ALS14) [MIM:613954]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS14 may develop frontotemporal dementia. Note=The disease is caused by mutations affecting the gene represented in this entry.Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1L-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. Regulates E3 ubiquitin-protein ligase activity of RNF19A (By similarity). Component of the VCP/p97-AMFR/gp78 complex that participates in the final step of the sterol-mediated ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of HMGCR. Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites in a RNF8- and RNF168- dependent manner and promotes the recruitment of TP53BP1 at DNA damage sites. Recruited to stalled replication forks by SPRTN: may act by mediating extraction of DNA polymerase eta (POLH) to prevent excessive translesion DNA synthesis and limit the incidence of mutations induced by DNA damage.
kcaTERTTelomerase reverse transcriptase5820.6169Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes. <a class="attribution" href="O14746#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a> <a class="attribution" href="O14746#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>reverse transcriptaseCancer, unspecific
Lung cancer
Prostate carcinoma
Tumors
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. It elongates telomeres. It is a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence.
kcaTFTissue factor4150.7124Lung, placenta and pancreas. <a class="attribution" href="P13726#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>tissue factorAtherosclerosis
Coronary syndromes
Disseminated intravascular coagulation
Gliomas
Over-expression of TF
Sepsis
Thrombotic disease
Initiates blood coagulation by forming a complex with circulating factor vii or viia. The [tf:viia] complex activates factors ix or x by specific limited protolysis. Tf plays a role in normal hemostasis by initiating the cell-surface assembly.
kcaTGFR1TGF-beta receptor type-17080.5992Found in all tissues examined, most abundant in placenta and least abundant in brain and heart.protein kinaseCancer, unspecific
Fibrosis
Type i/type ii tgf-beta receptors form an heteromeric complex after binding tgf-beta at the cell surface and act as signal transducers.
kcaTHAThyroid hormone receptor alpha4680.7959VirtualToxLabnuclear hormone receptorThyrotoxicosis [hyperthyroidism] Nuclear hormone receptor. High affinity receptor for triiodothyronine. Thyroid hormone receptor agonist: Dextrothyroxine, Levothyroxine, Liothyronine
kcaTHBThyroid hormone receptor beta6330.838VirtualToxLabnuclear hormone receptorHyperlipidemia
Obesity
Thyroid hormone resistance syndrome
Thyrotoxicosis [hyperthyroidism]
High affinity receptor for triiodothyronine.
kcaTHRBProthrombin58210.7447Expressed by the liver and secreted in plasma.peptidase S1Coagulative disorders
Coronary atherosclerosis
Gliomas
Heparin-induced thrombocytopenia type II
Multiple organ failure
Thromboembolic disorders
Thrombosis
Thrombotic disease
Thrombin, which cleaves bonds after arg and lys, converts fibrinogen to fibrin and activates factors v, vii, viii, xiii, and, in complex with thrombomodulin, protein c. Thrombin inhibitor: Argatroban, Bivalirudin, Dabigatran Etexilate, Desirudin, Lepirudin
kcaTIE2Angiopoietin-1 receptor8280.6599Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney. <a class="attribution" href="Q02763#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q02763#ref8" onclick="ensureReferenceVisible('ref8')">Ref.8</a>Adrenal disorder
Adrenal insufficiency
Amenorrhoea
Bone disorder
Cushingoid
Endocrine disorder
Euphoric mood
Hyperglycaemia
Hypertension
Hypertrichosis
Hypokalaemia
Intracranial pressure increased
Menstrual disorder
Mental disorder
Muscular weakness
Oedema
Osteonecrosis
Osteoporosis
Pancreatitis acute
Peptic ulcer
Skin atrophy
Skin striae
Superinfection
Telangiectasia
protein kinaseTumors This protein is a protein tyrosine-kinase transmembrane receptor for angiopoietin 1. It may constitute the earliest mammalian endothelial cell lineage marker. Probably regulates endothelial cell proliferation, differentiation and guides the proper pattern. Tyrosine-protein kinase TIE-2 inhibitor: Regorafenib, Vandetanib
kcaTLK1Serine/threonine-protein kinase tousled-like 1790.5605Widely expressed. Present in fetal placenta, liver, kidney and pancreas but not heart or skeletal muscle. Also found in adult cell lines. Isoform 3 is ubiquitously expressed in all tissues examined.protein kinaseRapidly and transiently inhibited by phosphorylation following the generation of DNA double-stranded breaks during S- phase. This is cell cycle checkpoint and ATM-pathway dependent and appears to regulate processes involved in chromatin assembly. Isoform 3 phosphorylates and enhances the stability of the t-SNARE SNAP23, augmenting its assembly with syntaxin. Isoform 3 protects the cells from the ionizing radiation by facilitating the repair of DSBs. In vitro, phosphorylates histone H3 at 'Ser-10'.
kcaTLK2Serine/threonine-protein kinase tousled-like 2800.5513Ubiquitous. Detected in placenta, fetal liver, kidney, pancreas, heart and skeletal muscle. Highly expressed in testis. Detected in spleen, thymus, colon, ovary, small intestine, prostate and peripheral blood leukocytes.protein kinaseSerine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation. Phosphorylates the chromatin assembly factors ASF1A AND ASF1B. Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly. Negative regulator of amino acid starvation-induced autophagy.
kcaTLR4Toll-like receptor 4810.6655Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.Toll-like receptorLPS-induced left ventricular dysfunction Cooperates with ly96 and cd14 to mediate the innate immune response to bacterial lipopolysaccharide (lps). Acts via myd88, tirap and traf6, leading to nf-kappa-b activation, cytokine secretion and the inflammatory response.
kcaTLR7Toll-like receptor 71630.7027Detected in brain, placenta, spleen, stomach, small intestine, lung and in plasmacytoid pre-dendritic cells.Toll-like receptorBasal cell carcinoma
Hepatitis C
Skin cancer
Participates in the innate immune response to microbial agents. acts via myd88 and traf6, leading to nf-kappa-b activation, cytokine secretion and the inflammatory response (by similarity). Toll-like receptor 7 agonist: Imiquimod
Toll-like receptor 7 antagonist: Hydroxychloroquine
kcaTNFATumor necrosis factor4420.5612tumor necrosis factorAsthma
Behcet's disease
Chronic inflammatory diseases
Congestive heart failure
Crohn's disease, unspecified
Heart failure
Hyperimmunoglobulinemia D
Noninsulin-dependent diabetes mellitus
Periodic fever syndrome
Rheumatic diseases
Rheumatoid arthritis, unspecified
Rheumatoid arthritis, unspecified
Solid tumor
Cytokine that binds to tnfrsf1a/tnfr1 and tnfrsf1b/tnfbr. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin 1 secretion. TNF-alpha inhibitor: Adalimumab, Certolizumab Pegol, Etanercept, Golimumab, Infliximab
kcaTNKS1Tankyrase-1990.6109Ubiquitous; highest levels in testis.Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1. Stimulates 26S proteasome activity.
kcaTOP1DNA topoisomerase 13820.6072Alopecia
Anaemia
Stomatitis
type IB topoisomeraseBrain tumors
Breast cancer
Cancer, unspecific
Colorectal cancer
Esophageal squamous cell cancer
Fungal diseases
Gastric cancer
Lung cancer
Lymphoblast tumor
Ovarian cancer
The reaction catalyzed by topoisomerases leads to the conversion of one topological isomer of dna to another.
kcaTOP2ADNA topoisomerase 2-alpha3480.5086Alopecia
Angioedema
Bone marrow failure
Dysgeusia
Haemorrhage
Haemorrhagic diathesis
Mucosal inflammation
Stomatitis
type II topoisomeraseAcute promyelocytic leukemia
Bacterial infections
Cancer, unspecific
Fungal diseases
Herpes virus infection
Leishmania infections
Malaria
Trichomoniasis
kcaTOP2BDNA topoisomerase 2-beta2510.5386Alopecia
Anaemia
Bone marrow failure
Haemorrhagic diathesis
Mucosal inflammation
Stomatitis
type II topoisomeraseCancer, unspecific Control of topological states of dna by transient breakage and subsequent rejoining of dna strands. Topoisomerase II makes double-strand breaks.
kcaTPATissue-type plasminogen activator5250.5645Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk.peptidase S1Neurological diseases Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single arg-val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation and in cell migration. Tissue-type plasminogen activator inhibitor: Aminocaproic Acid
kcaTPP2Tripeptidyl-peptidase 2990.5246peptidase S8Eating disorders
Obesity
Psychiatric illness
kcaTRPA1Transient receptor potential cation channel subfamily A member 14300.6991Expressed at very low level. Expressed at very low level in human fibroblasts and at a moderate level in liposarcoma cells. <a class="attribution" href="O75762#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a>transient receptorAnalgesics
Irritation
Pain
Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes. Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (thc), the psychoactive component of marijuana. Transient receptor potential cation channel subfamily A member 1 opener: Menthol
kcaTRPV1Transient receptor potential cation channel subfamily V member 126460.616Widely expressed at low levels. Expression is elevated in dorsal root ganglia. In skin, expressed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands (at protein level). <a class="attribution" href="Q8NER1#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="Q8NER1#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a> <a class="attribution" href="Q8NER1#ref10" onclick="ensureReferenceVisible('ref10')">Ref.10</a>transient receptorAcute migraine
Analgesics
Chronic pathological pain
Osteoarthritis pain
Pain, Acute or Chronic
Urinary incontinence
Vanilloid receptor opener: Acetaminophen, Capsaicin
kcaTRPV2Transient receptor potential cation channel subfamily V member 22090.5908transient receptorCalcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH.
kcaTRPV4Transient receptor potential cation channel subfamily V member 42390.5374Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level). <a class="attribution" href="Q9HBA0#ref12" onclick="ensureReferenceVisible('ref12')">Ref.12</a>transient receptorAnalgesics
Neuropathic pain
kcaTRY1Trypsin-118690.7142peptidase S1Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Has activity against the synthetic substrates Boc-Phe- Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val- Pro-Arg-Mec. The single-chain form is more active than the two- chain form against all of these substrates.
kcaTRY2Trypsin-26260.7795Expressed in Paneth cells, at the base of small intestinal crypts.peptidase S1In the ileum, may be involved in defensin processing, including DEFA5.
kcaTRY3Trypsin-36040.7707Expressed in pancreas and brain. Also expressed in Paneth cells, at the base of small intestinal crypts.peptidase S1Digestive protease specialized for the degradation of trypsin inhibitors. In the ileum, may be involved in defensin processing, including DEFA5.
kcaTRYB1Tryptase alpha/beta-14690.5251peptidase S1Tryptase is the major neutral protease present in mast cells and is secreted upon the coupled activation-degranulation response of this cell type (By similarity).
kcaTSPOTranslocator protein 28490.5595TspO/BZRPBinds cholesterol and mediates its redistribution during erythropoiesis which may play a role in erythrocyte maturation.
kcaTTKDual specificity protein kinase TTK1750.6779Present in rapidly proliferating cell lines.protein kinaseCancer, unspecific Phosphorylates proteins on serine, threonine, and tyrosine. Probably associated with cell proliferation.
kcaTYDP2Tyrosyl-DNA phosphodiesterase 2860.6532Widely expressed.CCR4/nocturinDNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'- phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Has also 3'- tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'- tyrosyl-DNA phosphodiesterase in cells. Also acts as a 5'-tyrosyl- RNA phosphodiesterase following picornavirus infection: its activity is hijacked by picornavirus and acts by specifically cleaving the protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection, without impairing the integrity of viral RNA. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF- beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non- canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation. Acts as a regulator of ribosome biogenesis following stress.
kcaTYK2Non-receptor tyrosine-protein kinase TYK29620.6288Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines.protein kinaseProtein-tyrosine kinase 2 deficiency (TYK2 deficiency) [MIM:611521]: Consists of a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. Note=The disease is caused by mutations affecting the gene represented in this entry.Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
kcaTYPHThymidine phosphorylase1450.6842thymidine/pyrimidine-nucleoside phosphorylaseAngiogenesis
Breast cancer
Lung adenocarcinomas
Renal cell carcinoma
May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro.catalyzes the reversible phosphorolysis of thymidine.
kcaTYROTyrosinase620.6444tyrosinaseSkin diseases This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to dopa, dopa to dopa-quinone and possibly 5,6-dihydroxyindole to indole. Tyrosinase inhibitor: Avobenzone, Mequinol, Monobenzone
kcaTYSYThymidylate synthase9290.7079thymidylate synthaseBreast cancer
Colorectal cancer
Fungal diseases
Gastric cancer
Hepatocellular carcinoma
Malaria
Ovarian cancer
Pancreatic cancer
Proliferative diseases
kcaUFOTyrosine-protein kinase receptor UFO6230.5309Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.protein kinaseNote=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3- kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor.
kcaUROKUrokinase-type plasminogen activator10140.6598Expressed in the prostate gland and prostate cancers. <a class="attribution" href="P00749#ref23" onclick="ensureReferenceVisible('ref23')">Ref.23</a>peptidase S1Cancer, unspecific
Melanoma
Potent plasminogen activator and is clinically used for therapy of thrombolytic disorders.
kcaV1ARVasopressin V1a receptor15610.7247Nature11159G-protein coupled receptor 1Congestive heart failure
Dysmenorrhea, unspecified
Hypertension
Raynaud's syndrome
Renal diseases
Vasoconstriction
Water-retaining diseases
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Vasopressin V1a receptor agonist: Vasopressin Tannate
Vasopressin V1a receptor antagonist: Conivaptan
kcaV1BRVasopressin V1b receptor8100.8152G-protein coupled receptor 1Adrenocorticotrophic hormone-secreting tumors
Emotional diseases
Stress-related disorders
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl- inositol-calcium second messenger system. Vasopressin V1b receptor agonist: Vasopressin Tannate
kcaV2RVasopressin V2 receptor13200.8071Nature11159Kidney.G-protein coupled receptor 1Cerebral edema
Congestive heart failure
Diabetes insipidus
Glaucoma
Hydronephrosis
Hyponatremia
Liver cirrhosis
Nephrogenic diabetes insipidus
Ocular hypertension
Renal colic
Renal diseases
Syndrome of inappropriate secretion of antidiuretic hormone
Von Willebrand's disease
Water-retaining diseases
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Vasopressin V2 receptor agonist: Vasopressin Tannate
Vasopressin V2 receptor antagonist: Conivaptan, Tolvaptan
kcaVACHTVesicular acetylcholine transporter2510.5009Peripheral and central cholinergic nervous systems.major facilitatorInvolved in acetylcholine transport into synaptic vesicles.
kcaVCAM1Vascular cell adhesion protein 11860.6149Expressed on inflammed vascular endothelium, as well as on macrophage-like and dendritic cell types in both normal and inflammed tissue.Not Available
kcaVDRVitamin D3 receptor4440.9296nuclear hormone receptorBreast cancer
Colorectal cancer
Kaposi's sarcoma
Prostate cancer
Vitamin D deficiency
Nuclear hormone receptor. Vdr mediates the action of vitamin d3 by controlling the expression of hormone sensitive genes. Vitamin D receptor agonist: Calcifediol, Calcipotriene, Calcitriol, Cholecalciferol, Doxercalciferol, Ergocalciferol, Paricalcitol
kcaVGFR1Vascular endothelial growth factor receptor 119070.5548Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform <a href="#P17948-2" onclick="ensureIsoformSequenceVisible('P17948-2'); return true;">2</a> is strongly expressed in placenta. Isoform <a href="#P17948-3" onclick="ensureIsoformSequenceVisible('P17948-3'); return true;">3</a> is expressed in corneal epithelial cells (at protein level). Isoform <a href="#P17948-3" onclick="ensureIsoformSequenceVisible('P17948-3'); return true;">3</a> is expressed in vascular smooth muscle cells (VSMC). <a class="attribution" href="P17948#ref5" onclick="ensureReferenceVisible('ref5')">Ref.5</a> <a class="attribution" href="P17948#ref6" onclick="ensureReferenceVisible('ref6')">Ref.6</a>protein kinaseNeovascular Age-Related Macular Degeneration
Exudative age-related macular degeneration
Receptor for VEGF, VEGFB and PGF. Has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. Isoform SFlt1 may have an inhibitory role in angiogenesis. Vascular endothelial growth factor receptor inhibitor: Axitinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib, Vandetanib
kcaVGFR2Vascular endothelial growth factor receptor 260430.6799Detected in cornea (at protein level). Widely expressed. <a class="attribution" href="P35968#ref2" onclick="ensureReferenceVisible('ref2')">Ref.2</a>Adrenal disorder
Adrenal insufficiency
Amenorrhoea
Bone disorder
Cushingoid
Endocrine disorder
Euphoric mood
Hyperglycaemia
Hypertension
Hypertrichosis
Hypokalaemia
Intracranial pressure increased
Menstrual disorder
Muscular weakness
Oedema
Osteonecrosis
Osteoporosis
Pancreatitis acute
Peptic ulcer
Skin atrophy
Skin striae
Superinfection
Telangiectasia
protein kinaseAngiogenesis
Cancer, unspecific
Receptor for VEGF or VEGF-c, and has a tyrosine-protein kinase activity. the VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. Vascular endothelial growth factor receptor 2 inhibitor: Cabozantinib
kcaVGFR3Vascular endothelial growth factor receptor 312090.5905Detected in endothelial cells (at protein level). Widely expressed. Detected in fetal spleen, lung and brain. Detected in adult liver, muscle, thymus, placenta, lung, testis, ovary, prostate, heart, and kidney. <a class="attribution" href="P35916#ref1" onclick="ensureReferenceVisible('ref1')">Ref.1</a> <a class="attribution" href="P35916#ref14" onclick="ensureReferenceVisible('ref14')">Ref.14</a> <a class="attribution" href="P35916#ref28" onclick="ensureReferenceVisible('ref28')">Ref.28</a>protein kinaseAngiogenesis in metastatic and atherosclerotic processes Receptor for VEGF-c, and has a tyrosine-protein kinase activity.
kcaVMAT2Synaptic vesicular amine transporter1500.5203major facilitatorCocaine dependence
Neurodegenerative diseases
Involved in the atp-dependent vesicular transport of biogenic amine neurotransmitters. pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion. Synaptic vesicular amine transporter inhibitor: Benzphetamine, Deserpidine, Dextroamphetamine, Lisdexamfetamine, Rescinnamine, Reserpine, Tetrabenazine
kcaWEE1Wee1-like protein kinase4690.7271protein kinaseCancer May act as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDC2 before the onset of mitosis. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation. Specifically phosphorylates and inactivates cyclin B1-complexed CDC2 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDC2 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDC2 does not occur.
kcaWNT3Proto-oncogene Wnt-3810.7459WntTetraamelia, autosomal recessive (ARTTRA) [MIM:273395]: A rare human genetic disorder characterized by complete absence of all four limbs and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. Note=The disease is caused by mutations affecting the gene represented in this entry.Ligand for members of the frizzled family of seven transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube (By similarity).
kcaXBP1X-box-binding protein 19370.605bZIPMajor affective disorder 7 (MAFD7) [MIM:612371]: A major psychiatric disorder that is characterized by severe mood swings, with fluctuation between two abnormal mood states (manic or major depressive episode). Mania is accompanied by symptoms of euphoria, irritability, or excitation, whereas depression is associated with low mood and decreased motivation and energy. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.Transcription factor essential for hepatocyte growth, the differentiation of plasma cells, the immunoglobulin secretion, and the unfolded protein response (UPR). Acts during endoplasmic reticulum stress (ER) by activating unfolded protein response (UPR) target genes via direct binding to the UPR element (UPRE). Binds DNA preferably to the CRE-like element 5'- GATGACGTG[TG]N(3)[AT]T-3', and also to some TPA response elements (TRE). Binds to the HLA DR-alpha promoter. Binds to the Tax- responsive element (TRE) of HTLV-I.
kcaXDHXanthine dehydrogenase/oxidase2000.606Detected in milk (at protein level). <a class="attribution" href="P47989#ref11" onclick="ensureReferenceVisible('ref11')">Ref.11</a>xanthine dehydrogenaseGout This enzyme can be converted from the dehydrogenase form (d) to the oxidase form (o) irreversibly by proteolysis or reversibly through the oxidation of sulfhydryl groups. Xanthine dehydrogenase inhibitor: Allopurinol, Febuxostat
kcaXIAPE3 ubiquitin-protein ligase XIAP8170.746Ubiquitous, except peripheral blood leukocytes.IAPHepatocellular carcinoma
Neoplasms
Ovarian cancer
Apoptotic suppressor. Inhibitor of caspase-3, -7 and -9.
kcaZAP70Tyrosine-protein kinase ZAP-703400.6252Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells.protein kinaseSelective T-cell defect (STCD) [MIM:269840]: A form of severe combined immunodeficiency characterized by a selective absence of CD8+ T-cells. Note=The disease is caused by mutations affecting the gene represented in this entry.Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).

Copyright © 2020 Molsoft LLC.
All rights reserved.
Terms of Use
Privacy Policy