Tchem KDM4A Lysine-specific demethylase 4A

Protein Summary

Description

Histone demethylase that specifically demethylates 'Lys-9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:26741168). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. Isoform 2: Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain. This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein containing a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor. [provided by RefSeq, Apr 2009]

Uniprot Accession IDs

• O75164
• Q5VVB1

Gene Name

• KDM4A

Ensembl ID

• ENST00000372396
• ENSP00000361473
• ENSG00000066135

Symbol

• JHDM3A
• JMJD2
• JMJD2A
• KIAA0677
• JMJD2
• JHDM3A
• JMJD2A
• TDRD14A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.85
cell type or tissue	0.78
transcription factor binding site profile	0.76
biological process	0.75
molecular function	0.73

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Zinc Finger Transcription Factor / Lysine-specific Demethylase 4a

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 176.48   (req: < 5)

Gene RIFs: 55   (req: <= 3)

Antibodies: 387   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 176.48   (req: >= 5)

Gene RIFs: 55   (req: > 3)

Antibodies: 387   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 129

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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GlyGen

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ARCHS4

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Approved Drugs (0)

No approved drugs found

Active Ligands (129)

Explore Active Ligands

1 – 10 of 129

CHEMBL3786952

KDM4ATchem Epigenetic

pIC50 : 8.7

2,4-pyridine dicarboxylic acid

KDM4ATchem Epigenetic

pKi : 8.66

2-(2-Aminothiazol-4-yl)isonicotinic Acid

KDM4ATchem Epigenetic

pIC50 : 7.92

CHEMBL4216044

KDM4ATchem Epigenetic

pEC50 : 8.89

3-(((3-Methylthiophen-2-yl)methyl)amino)isonicotinic Acid

KDM4ATchem Epigenetic

pIC50 : 7.3

3-((Furan-2-ylmethyl)amino)isonicotinic Acid

KDM4ATchem Epigenetic

pIC50 : 7.4

CHEMBL4287561

KDM4ATchem Epigenetic

pIC50 : 7

CHEMBL3770740

KDM4ATchem Epigenetic

pIC50 : 6.9

CHEMBL3771180,CHEMBL3771198

KDM4ATchem Epigenetic

pIC50 : 7.2

CHEMBL3769724

KDM4ATchem Epigenetic

pIC50 : 6.9

Protein-Protein Interactions (163)

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1 – 10 of 163

• See Interactions on String-DB

ZNF414

Tdark

Novelty:  1.29024829

p_int:  0.999999501

p_ni:  4.95e-7

p_wrong:  4e-9

Score:  0.58

Data Source:  BioPlex,STRINGDB

CCL19

Tbio

Novelty:  0.00169711

p_int:  0.999999406

p_ni:  5.77e-7

p_wrong:  1.7e-8

Data Source:  BioPlex

CCL22

Tbio

Novelty:  0.00245992

p_int:  0.99999937

p_ni:  3.2e-8

p_wrong:  5.97e-7

Score:  0.169

Data Source:  BioPlex,STRINGDB

STK11

Tchem

Family:  Kinase

Novelty:  0.00073247

p_int:  0.999998658

p_ni:  0.000001342

p_wrong:  1e-9

Score:  0.246

Data Source:  BioPlex,STRINGDB

KDM4B

Tchem

Family:  Epigenetic

Novelty:  0.01615072

p_int:  0.999896731

p_ni:  1.1e-8

p_wrong:  0.000103259

Score:  0.968

Data Source:  BioPlex,STRINGDB

AFAP1L1

Tbio

Novelty:  0.2636613

p_int:  0.999406597

p_ni:  0.000252683

p_wrong:  0.00034072

Data Source:  BioPlex

ABHD5

Tbio

Family:  Enzyme

Novelty:  0.00806614

p_int:  0.757873857

p_ni:  0.000169951

p_wrong:  0.241956192

Score:  0.232

Data Source:  BioPlex,STRINGDB

HIST3H3

Tbio

Novelty:  0.04915012

Score:  0.992

Data Source:  Reactome,STRINGDB

RNF8

Tbio

Family:  Enzyme

Novelty:  0.01189548

Score:  0.967

Data Source:  Reactome,STRINGDB

RNF168

Tbio

Family:  Enzyme

Novelty:  0.01827754

Score:  0.967

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (8)

Reactome (7)

WikiPathways (1)

Chromatin modifying enzymes (R-HSA-3247509)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509
Reactome	Chromatin organization	238 targets	R-HSA-4839726
Reactome	DNA Double Strand Break Response	58 targets	R-HSA-5693606
Reactome	DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
Reactome	DNA Repair	306 targets	R-HSA-73894

Name	Explore in Pharos	Explore in Source
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
DNA Double Strand Break Response	58 targets	R-HSA-5693606
DNA Double-Strand Break Repair	146 targets	R-HSA-5693532
DNA Repair	306 targets	R-HSA-73894

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (29)

Functions (9)

Components (6)

Processes (14)

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1 – 9 of 9

GO Term	Evidence	Assigned by
histone demethylase activity (H3-K36 specific)	Inferred from Direct Assay (IDA)	UniProtKB
methylated histone binding	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
histone demethylase activity (H3-K9 specific)	Inferred from Mutant Phenotype (IMP)	UniProtKB
chromatin binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
histone demethylase activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Disease Associations ()

No disease associations found

GWAS Traits (27)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
self reported educational attainment	EFO_0004784	5	5	6		95.1
mathematical ability	EFO_0004875	4	2	4		90.9
smoking initiation	EFO_0005670	3	3	3		89.7
alkaline phosphatase measurement	EFO_0004533	2	2	1	7.3	89
schizophrenia	EFO_0000692	7	4	2	1.1	81.5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
self reported educational attainment	EFO_0004784	6		95.1
mathematical ability	EFO_0004875	4		90.9
smoking initiation	EFO_0005670	3		89.7
alkaline phosphatase measurement	EFO_0004533	1	7.3	89
schizophrenia	EFO_0000692	2	1.1	81.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Chromatin regulator
Complete proteome
Dioxygenase
Host-virus interaction
Iron
Metal-binding
Nucleus

GWAS Trait Find Similar Targets

No Header	No Header
age at menarche
alkaline phosphatase measurement
attention deficit hyperactivity disorder
autism spectrum disorder
bipolar disorder
BMI-adjusted hip circumference
C-reactive protein measurement
Cannabis use
cigarettes per day measurement
cognitive function measurement

MGI Phenotype Find Similar Targets

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cardiovascular system phenotype
homeostasis/metabolism phenotype
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	lysine demethylase 4A	VGNC:8061	456829
Macaque	lysine demethylase 4A		701272
Mouse	lysine (K)-specific demethylase 4A	MGI:2446210	230674
Rat	lysine demethylase 4A	RGD:1306378	313539
Dog	lysine demethylase 4A	VGNC:42324	482530

Species	Name	OMA	EggNOG	Inparanoid
Chimp	lysine demethylase 4A
Macaque	lysine demethylase 4A
Mouse	lysine (K)-specific demethylase 4A
Rat	lysine demethylase 4A
Dog	lysine demethylase 4A

Publication Statistics

PubMed Score 176.48

PubMed score by year

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PubTator Score 105.69

PubTator score by year

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Related Publications

Text Mined References (76)

GeneRif Annotations (55)

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PMID	Year	Title