2Q8E

Specificity and Mechanism of JMJD2A, a Trimethyllysine-Specific Histone Demethylase

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Protein Modification Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	JmjC	e2q8eB1	A: beta sandwiches	X: jelly-roll	H: Double-stranded beta-helix (From Topology)	T: Double-stranded beta-helix	F: JmjC	ECOD (1.6)
A	JmjC	e2q8eA1	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)
B	2.60.120.650	Mainly Beta	Sandwich	Jelly Rolls	Cupin	CATH (4.3.0)
A	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
A, B	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 ...	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 biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation [5].	Domain
A, B	PF02375	jmjN domain (JmjN)	jmjN domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	JmjC domain-containing histone demethylation protein 3A	histone H3K36 demethylase activity catalytic activity, acting on a protein protein demethylase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen histone demethylase activity demethylase activity dioxygenase activity oxidoreductase activity histone H3K36me2/H3K36me3 demethylase activity histone H3 demethylase activity histone modifying activity catalytic activity 2-oxoglutarate-dependent dioxygenase activity histone H3K9me2/H3K9me3 demethylase activity histone H3K36 demethylase activity catalytic activity, acting on a protein protein demethylase activity oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen histone demethylase activity demethylase activity dioxygenase activity oxidoreductase activity histone H3K36me2/H3K36me3 demethylase activity histone H3 demethylase activity histone modifying activity catalytic activity 2-oxoglutarate-dependent dioxygenase activity histone H3K9me2/H3K9me3 demethylase activity histone H3K9 demethylase activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding methylated histone binding modification-dependent protein binding histone binding methylation-dependent protein binding	regulation of cellular process negative regulation of biological process RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of cellular process negative regulation of biological process RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of DNA-templated transcription regulation of biological process negative regulation of metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process metabolic process cellular process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process multicellular organismal process cellular developmental process regulation of developmental process astrocyte differentiation cell development regulation of cell differentiation regulation of neurogenesis regulation of astrocyte differentiation regulation of gliogenesis regulation of cell development regulation of nervous system development multicellular organism development neurogenesis negative regulation of neurogenesis gliogenesis cell differentiation anatomical structure development regulation of multicellular organismal process negative regulation of nervous system development negative regulation of cell differentiation system development developmental process regulation of multicellular organismal development negative regulation of developmental process regulation of glial cell differentiation nervous system development negative regulation of astrocyte differentiation negative regulation of gliogenesis negative regulation of cell development negative regulation of glial cell differentiation central nervous system development glial cell differentiation negative regulation of multicellular organismal process positive regulation of biological process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of gene expression positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process positive regulation of neuron differentiation positive regulation of developmental process neuron differentiation positive regulation of cell differentiation generation of neurons regulation of neuron differentiation cellular component disassembly chromosome organization cell death cellular component organization execution phase of apoptosis organelle organization apoptotic chromosome condensation chromosome condensation cellular component disassembly involved in execution phase of apoptosis apoptotic nuclear changes apoptotic process cellular component organization or biogenesis programmed cell death negative regulation of catabolic process catabolic process autophagy regulation of catabolic process regulation of autophagy negative regulation of autophagy process utilizing autophagic mechanism response to nutrient levels response to stimulus negative regulation of gene expression muscle hypertrophy system process striated muscle adaptation striated muscle hypertrophy muscle system process muscle adaptation cardiac muscle adaptation response to stress cardiac muscle hypertrophy cardiac muscle hypertrophy in response to stress muscle hypertrophy in response to stress chromatin organization chromatin remodeling	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen membraneless organelle intracellular membraneless organelle chromatin chromosome pericentric heterochromatin heterochromatin chromosomal region chromosome, centromeric region nucleolus fibrillar center
C [auth F], D [auth G]	histone 3 peptide	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR001965	Zinc finger, PHD-type	Domain
A, B	IPR002999	Tudor domain	Domain
A, B	IPR047479	Lysine-specific demethylase 4A, first Tudor domain	Domain
A, B	IPR003347	JmjC domain	Domain
A, B	IPR003349	JmjN domain	Domain
A, B	IPR019787	Zinc finger, PHD-finger	Domain
A, B	IPR011011	Zinc finger, FYVE/PHD-type	Homologous Superfamily
A, B	IPR047481	Lysine-specific demethylase 4A, second Tudor domain	Domain
A, B	IPR047482	Lysine-specific demethylase 4A, extended PHD finger	Domain
A, B	IPR034732	Extended PHD (ePHD) domain	Domain
A, B	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A, B	IPR040477	Lysine-specific demethylase 4-like, Tudor domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: O75164	attention deficit hyperactivity disorder, inattentive type endogenous depression pancreatic intraductal papillary-mucinous carcinoma autism spectrum disorder medulloblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia bipolar disorder osteosarcoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C [auth F], D [auth G]	M3L	Parent Component: LYS RESID: AA0074 PSI-MOD : N6,N6,N6-trimethyl-L-lysine MOD:00083

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.