Tclin HDAC3 Histone deacetylase 3

Protein Summary

Description

Responsible 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 (PubMed:21444723, PubMed:23911289). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• O15379
• D3DQE1
• O43268
• Q9UEI5
• Q9UEV0
• HD3

Gene Name

• HDAC3

Ensembl ID

• ENST00000305264
• ENSP00000302967
• ENSG00000171720

Symbol

• HD3
• RPD3
• KDAC3
• RPD3-2

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
molecular function	0.98
histone modification site profile	0.87
cell type or tissue	0.8

Protein Classes

PANTHER Classes

Protein / Oxidoreductase / Reductase / Histone Deacetylase 3

Protein / Nucleic Acid Binding / Histone Deacetylase 3

Protein / Hydrolase / Deacetylase / Histone Deacetylase 3

DTO Classes

Protein / Epigenetic Regulator / Eraser / Histone Deacetylase / Hdac Class I / Histone Deacetylase 3

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: 194.01   (req: < 5)

Gene RIFs: 161   (req: <= 3)

Antibodies: 845   (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: 194.01   (req: >= 5)

Gene RIFs: 161   (req: > 3)

Antibodies: 845   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 28

Tchem

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

Active Ligands: 1005

Tclin

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

Active Drugs: 5

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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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (5)

Explore Approved Drugs

1 – 5 of 5

vorinostat

HDAC3Tclin Epigenetic

INHIBITOR pKi : 9

romidepsin

HDAC3Tclin Epigenetic

INHIBITOR pKi : 5.96

belinostat

HDAC3Tclin Epigenetic

INHIBITOR pIC50 : 7.57

panobinostat

HDAC3Tclin Epigenetic

INHIBITOR pKi : 8.46

chidamide

HDAC3Tclin Epigenetic

INHIBITOR pIC50 : 7.11

Active Ligands (1005)

Explore Active Ligands

1 – 10 of 1005

fimepinostat

HDAC3Tclin Epigenetic

pIC50 : 9.44

trichostatin

HDAC3Tclin Epigenetic

pKi : 8.45

CUDC-101

HDAC3Tclin Epigenetic

pIC50 : 8.62

Belinosta

HDAC3Tclin Epigenetic

pKi : 7.66

CHEMBL1830424

HDAC3Tclin Epigenetic

pKi : 7.68

dacinostat

HDAC3Tclin Epigenetic

pKi : 8.85

KA1010

HDAC3Tclin Epigenetic

pIC50 : 8.1

pracinostat

HDAC3Tclin Epigenetic

pKi : 7.57

quisinostat

HDAC3Tclin Epigenetic

pKi : 7.51

scriptaid

HDAC3Tclin Epigenetic

pKi : 8.66

Protein-Protein Interactions (468)

Explore Interacting Targets

1 – 10 of 468

• See Interactions on String-DB

GPS2

Tbio

Novelty:  0.00986158

p_int:  0.999990105

p_ni:  0.000009895

Score:  0.969

Data Source:  BioPlex,Reactome,STRINGDB

TBL1Y

Tbio

p_int:  0.999980819

p_ni:  0.000019181

Data Source:  BioPlex

ZSCAN5A

Tdark

Family:  TF

Novelty:  2.15267128

p_int:  0.983696316

p_ni:  0.016303684

Score:  0.244

Data Source:  BioPlex,STRINGDB

HNRNPLL

Tbio

Novelty:  0.0498467

p_int:  0.978655801

p_ni:  0.021344089

p_wrong:  1.1e-7

Score:  0.229

Data Source:  BioPlex,STRINGDB

CELA1

Tchem

Family:  Enzyme

Novelty:  0.00290708

p_int:  0.944434767

p_ni:  0.055550934

p_wrong:  0.000014299

Score:  0.169

Data Source:  BioPlex,STRINGDB

DGKG

Tbio

Family:  Enzyme

Novelty:  0.03666646

p_int:  0.942114844

p_ni:  0.057885155

p_wrong:  1e-9

Data Source:  BioPlex

CARD8

Tbio

Family:  Enzyme

Novelty:  0.0146799

p_int:  0.940935638

p_ni:  0.057414604

p_wrong:  0.001649758

Data Source:  BioPlex

CCT3

Tbio

Novelty:  0.01642521

p_int:  0.923828025

p_ni:  0.076170401

p_wrong:  0.000001574

Score:  0.918

Data Source:  BioPlex,STRINGDB

CDK2AP1

Tbio

Family:  Enzyme

Novelty:  0.01584718

p_int:  0.891059083

p_ni:  0.10893527

p_wrong:  0.000005647

Data Source:  BioPlex

RFPL4B

Tdark

Novelty:  2.42779597

p_int:  0.885292341

p_ni:  0.114707659

Score:  0.16

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

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

Pathways (65)

Reactome (50)

KEGG (3)

PathwayCommons (7)

WikiPathways (5)

Activation of HOX genes during differentiation (R-HSA-5619507)

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Items per page:

5

1 – 5 of 50

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Reactome	Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Reactome	Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471
Reactome	Chaperonin-mediated protein folding	96 targets	R-HSA-390466
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509

Name	Explore in Pharos	Explore in Source
Activation of HOX genes during differentiation	90 targets	R-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesis	90 targets	R-HSA-5617472
Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471
Chaperonin-mediated protein folding	96 targets	R-HSA-390466
Chromatin modifying enzymes	238 targets	R-HSA-3247509

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (37)

Functions (10)

Components (9)

Processes (18)

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1 – 10 of 10

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
protein deacetylase activity	Inferred from Direct Assay (IDA)	UniProtKB
transcription corepressor activity	Inferred from Direct Assay (IDA)	UniProtKB
cyclin binding	Inferred from Physical Interaction (IPI)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
histone deacetylase binding	Inferred from Physical Interaction (IPI)	UniProtKB
NF-kappaB binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
histone deacetylase activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
NAD-dependent histone deacetylase activity (H3-K14 specific)	Inferred from Electronic Annotation (IEA)	UniProtKB-EC

Disease Associations ()

No disease associations found

GWAS Traits (10)

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5

1 – 5 of 10

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	3	2	4		58.2
self reported educational attainment	EFO_0004784	1	2	2		53.6
mean platelet volume	EFO_0004584	2	2	2		53.1
triglyceride measurement	EFO_0004530	1	1	1		47.7
allergy	EFO_0003785	1	1	0	1	46.5

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 10

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mathematical ability	EFO_0004875	4		58.2
self reported educational attainment	EFO_0004784	2		53.6
mean platelet volume	EFO_0004584	2		53.1
triglyceride measurement	EFO_0004530	1		47.7
allergy	EFO_0003785	0	1	46.5

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Chromatin regulator
Complete proteome
Cytoplasm
Hydrolase
Nucleus
Phosphoprotein
Polymorphism
Reference proteome

GWAS Trait Find Similar Targets

No Header	No Header
age at first birth measurement
allergy
birth weight
cognitive function measurement
lifestyle measurement
mathematical ability
mean platelet volume
parental genotype effect measurement
self reported educational attainment
triglyceride measurement

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
muscle phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	histone deacetylase 3	VGNC:4032	738624
Macaque	histone deacetylase 3		704467
Mouse	histone deacetylase 3	MGI:1343091	15183
Rat	histone deacetylase 3	RGD:619977	84578
Dog	histone deacetylase 3	VGNC:50628	478040

Species	Name	OMA	EggNOG	Inparanoid
Chimp	histone deacetylase 3
Macaque	histone deacetylase 3
Mouse	histone deacetylase 3
Rat	histone deacetylase 3
Dog	histone deacetylase 3

Publication Statistics

PubMed Score 194.01

PubMed score by year

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PubTator Score 430.68

PubTator score by year

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Related Publications

Text Mined References (252)

GeneRif Annotations (161)

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PMID	Year	Title