2YBP
JMJD2A COMPLEXED WITH R-2-HYDROXYGLUTARATE AND HISTONE H3K36me3 PEPTIDE (30-41)
Domain Annotation: ECOD Classification ECOD Database Homepage
Chains | Family Name | Domain Identifier | Architecture | Possible Homology | Homology | Topology | Family | Provenance Source (Version) |
---|---|---|---|---|---|---|---|---|
A | JmjC | e2ybpA1 | A: beta sandwiches | X: jelly-roll | H: Double-stranded beta-helix (From Topology) | T: Double-stranded beta-helix | F: JmjC | ECOD (1.6) |
B | JmjC | e2ybpB1 | A: beta sandwiches | X: jelly-roll | H: Double-stranded beta-helix (From Topology) | T: Double-stranded beta-helix | F: JmjC | ECOD (1.6) |
Domain Annotation: CATH CATH Database Homepage
Chain | Domain | Class | Architecture | Topology | Homology | Provenance Source (Version) |
---|---|---|---|---|---|---|
A | 2.60.120.650 | Mainly Beta | Sandwich | Jelly Rolls | Cupin | CATH (4.3.0) |
B | 2.60.120.650 | Mainly Beta | Sandwich | Jelly Rolls | Cupin | CATH (4.3.0) |
Protein Family Annotation Pfam Database Homepage
Chains | Accession | Name | Description | Comments | Source |
---|---|---|---|---|---|
PF02373 | JmjC domain, hydroxylase (JmjC) | JmjC domain, hydroxylase | The JmjC domain belongs to the Cupin superfamily [3]. JmjC-domain proteins may be protein hydroxylases that catalyse a novel histone modification [4]. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the ... | Domain | |
PF02375 | jmjN domain (JmjN) | jmjN domain | - | Family | |
Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage
InterPro: Protein Family Classification InterPro Database Homepage
Chains | Accession | Name | Type |
---|---|---|---|
IPR001965 | Zinc finger, PHD-type | Domain | |
IPR002999 | Tudor domain | Domain | |
IPR047479 | Lysine-specific demethylase 4A, first Tudor domain | Domain | |
IPR003347 | JmjC domain | Domain | |
IPR003349 | JmjN domain | Domain | |
IPR019787 | Zinc finger, PHD-finger | Domain | |
IPR011011 | Zinc finger, FYVE/PHD-type | Homologous Superfamily | |
IPR047481 | Lysine-specific demethylase 4A, second Tudor domain | Domain | |
IPR047482 | Lysine-specific demethylase 4A, extended PHD finger | Domain | |
IPR034732 | Extended PHD (ePHD) domain | Domain | |
IPR013083 | Zinc finger, RING/FYVE/PHD-type | Homologous Superfamily | |
IPR040477 | Lysine-specific demethylase 4-like, Tudor domain | Domain | |
IPR009072 | Histone-fold | Homologous Superfamily | |
IPR007125 | Histone H2A/H2B/H3 | Domain | |
IPR000164 | Histone H3/CENP-A | Family |
Pharos: Disease Associations Pharos Homepage Annotation
Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage
Chains | Enzyme Name | Description | Catalytic Residues |
---|---|---|---|
lysine-specific [histone H3] demethylase M-CSA #370 | Jumonji Domain protein 2A (JMJD2A or lysine-specific demethylase 4A, KDM4A) is a 2-oxoglutarate dependent oxygenase which catalyses the hydroxylation of methyl groups present on lysine residues within histone protein 3, utilising a Fe(II) dependent redox reaction, with spontaneous deformylation to produce the demethylated lysine and formaldehyde. The enzyme catalyses the removal of methyl groups specifically from lysine residues K9 and K36. JMJD2A has been shown to be over-expressed relative to normal physiological levels in several cancers, and is of interest for its influence over epigenetic factors associated with cancer progression. The enzyme substrate specificity is determined by amino acids within the JMJD2A active site, and also the flexibility of residues positioned around the reactive lysine in the peptide backbone. The enzyme is most active with the tri-methyl substrate. Each of the three methyl groups binds in a discrete pocket, restricting rotation around the functional group and demethylation proceeds rapidly. In the presence of two methyl groups, the functional groups can flip between a more reactive and less reactive pocket, one which binds methyl groups weakly, but closer to the reactive Fe(II), and vice versa. JMJD2A is not active towards the mono-methyl lysine substrate. The single methyl group stays bound to the less reactive pocket, and cannot be demethylated. | Defined by 6 residues: GLY:A-192 [auth A-170]TYR:A-199 [auth A-177]HIS:A-210 [auth A-188]GLU:A-212 [auth A-190]HIS:A-298 [auth A-276]SER:A-310 [auth A-288] | EC: 1.14.11 (PDB Primary Data) EC: 1.14.11.66 (UniProt) EC: 1.14.11.69 (UniProt) |