JMJD2A: Human jumonji domain containing 2A
Ng, S.S., Pilka, E.S., Kavanagh, K.L., McDonough, M.A., Savitsky, P., von Delft, F., Gileadi, O., Lee, W.H., Muller, S., Marsden, B.D., Schofield, C.J., Oppermann, U.
Datapack version: 2 (built on 14.Jul.08)
Quick Facts
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SGC
target ID
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JMJD2AA
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QUICK FACTS
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JMJD2A, jumonji domain containing 2A, JHDM3A, jumonji C (JmjC)-domaincontaining histone demethylase 3A, KIAA0677
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Updated
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27.Sep.2006
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Protein Size
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120.66 kDa
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#residues
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1064 aa
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Contact info.
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Name: Udo Oppermann
Contact us
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Entrez Gene
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JMJD2A
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cDNA available?
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MGC
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Gene sequence
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NM_014663.1
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Protein sequence
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NP_055478.2
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Biochemical function
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oxidative trimethylation-specific demethylase, converting specific trimethylated histone residues (H3 lysine 9 and H3 lysine 36) to the dimethylated form
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Biological function
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JMJD2A is a transcriptional co-repressor
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It antagonizes methylated H3K9 nucleated events.
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Has been suggested to play a role in development, cell proliferation and oncogenesis.
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Human mutations
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OMIM:
609764
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Mouse models
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No mouse model is available yet but
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siRNA-mediated knockdown of JMJD2A have confirmed its role as transcriptional repressor as it leads to increased levels of H3K9 methylation and upregulation of a JMJD2A target gene, ASCL2
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Summary role in disease
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no disease has been directly linked to JMJD2A yet
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Associates with pRb and HDACs and potentiates pRb-mediated repression of E2F-regulated promoters implying an important role for this protein in cell proliferation and oncogenesis
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Closest
sequence
Matches
(10 or less)
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27.Sep.2006
Name
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%ID
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Description
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gi|
12803467|
gb|AAH
02558.1|
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100.00
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Jumonji domain containing 2A [Homo sapiens]
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gi|
40788326|
dbj|BAA
31652.2|
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100.00
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KIAA0677 protein [Homo sapiens]
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gi|
109157946|
pdb|
2GP5|B
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100.00
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Chain B, Crystal Structure Of Catalytic Core Domain Of Jmjd2a Complexed With Alpha-Ketoglutarate
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NP_055478.2|
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99.91
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jumonji domain containing 2A [Homo sapiens]
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gi|
55727024|
emb|CAH
90269.1|
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99.44
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hypothetical protein [Pongo pygmaeus]
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XP_
513098.1|
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96.85
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PREDICTED: similar to Jumonji domain containing protein 2A [Pan troglodytes]
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XP_
001096047.1|
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96.52
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PREDICTED: jumonji domain containing 2A isoform 3 [Macaca mulatta]
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XP_
851005.1|
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96.43
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PREDICTED: similar to Jumonji domain containing protein 2A isoform 2 [Canis familiaris]
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XP_
539647.2|
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96.43
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PREDICTED: similar to Jumonji domain containing protein 2A isoform 1 [Canis familiaris]
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XP_
862943.1|
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96.05
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PREDICTED: similar to Jumonji domain containing protein 2A isoform 4 [Canis familiaris]
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Closest match in
PDB
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27.Sep.2006
Name
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%ID
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Description
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2gp5
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100.00
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jumonji domain-containing protein 2a; chain: a, b; engineered: yes
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2gp3
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100.00
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jumonji domain-containing protein 2a; chain: a, b; engineered: yes
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2gfa
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98.32
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jumonji domain-containing protein 2a; chain: a, b; fragment: double tudor domain; engineered: yes; mol_id: 2; molecule: peptide; chain: c, d; engineered: yes
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2gf7
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98.32
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jumonji domain-containing protein 2a; chain: a, b, c, d; fragment: double tudor domain; engineered: yes
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1mm2
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26.23
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mi2-beta; chain: a; fragment: mi2-beta (residues 446-501); synonym: chromodomain helicase-dna-binding protein 4; engineered: yes
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2fui
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19.35
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bromodomain phd finger transcription factor; chain: a; fragment: phd finger domain (residues 2583-2639); engineered: yes
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2fuu
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19.35
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bromodomain phd finger transcription factor; chain: a; fragment: phd finger domain (residues 2583-2639); engineered: yes; mol_id: 2; molecule: histone h3; chain: b; fragment: h3(1-15)k4me3; engineered: yes; mutation: yes
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1mm3
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27.87
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mi2-beta(chromodomain helicase-dna-binding protein 4) and transcription factor wstf; chain: a; fragment: residues 1-61; engineered: yes; other_details: the c-terminal loop (residue 37-49) was replaced by corresponding loop from wstf.
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1wem
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18.42
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death associated transcription factor 1; chain: a; fragment: phd domain; synonym: death inducer-obliterator-1, dio-1; engineered: yes
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1weq
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22.35
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phd finger protein 7; chain: a; fragment: phd domain; engineered: yes
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Splice forms and/or domain structure
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6 alternative spliced forms are predicted
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ProSite hits
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Accession
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Description
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PS51183
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JmjN domain profile
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PS51184
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JmjC domain profile
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Protein, expression/ Localization
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A full length protein but also a half-sized protein fragment have been detected; the shorter form is up-regulated in THP-1 cells during the G2/M phase of the cell cycle
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Primarily nuclear
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Also cytoplasmic
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Gene expression
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Widely expressed; expression has been described in ovary, kidney, heart, brain, lung, liver, skeletal muscle, pancreas, spleen, thymus and testis
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Substrates/ cofactors/ inhibitors
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Cofactors:
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Fe(II)
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alpha-ketoglutarate (a-KG)
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Interacting proteins
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Histone H3; the double tudor domain (JmjN and JmjC domains) of JMJD2A are required for demethylase activity; can directly remove methyl groups from modified H3K9 and H3K36 as well as H3-K4 and H4-K20
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class I histone deacetylases (HDACs): HDAC1, HDAC2, and HDAC3
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retinoblastoma protein (pRb); interaction results in enhanced pRb-mediated repression of E2F-regulated promoters
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viral Tax protein
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Corepressor N-CoR (nuclear receptor corepressor); interaction occurs between the N-terminal region of N-CoR and a small NID (N-CoR interaction domain) in the middle portion of JMJD2A (aa 597-637) and results in repression of the ASCL2 gene
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Posttsranslational modification
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Phosphorylated at Tyr 547
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Key references
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PMID:
16732292
,
16601153
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16603238
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15927959
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16677698
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16024779
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Other comments
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JMJD2A is a member of the Jumonji domain 2 (JMJD2) family. It encodes a protein with a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers.
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