Tclin HDAC6 Histone deacetylase 6

Protein Summary

Description

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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 (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy. 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 class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains which appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q9UBN7
• O94975
• Q6NT75
• Q7L3E5
• Q96CY0
• HD6

Gene Name

• HDAC6

Ensembl ID

• ENST00000334136
• ENSP00000334061
• ENSG00000094631
• ENST00000376619
• ENSP00000365804
• ENST00000426196
• ENSP00000402189
• ENST00000643374
• ENSP00000496046
• ENST00000644068
• ENSP00000496013

Symbol

• KIAA0901
• HD6
• JM21
• CPBHM
• PPP1R90

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	1
histone modification site profile	0.9
interacting protein	0.89
hub protein	0.88

Protein Classes

DTO Classes

Protein / Epigenetic Regulator / Eraser / Histone Deacetylase / Hdac Class Iib / Histone Deacetylase 6

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: 1023.43   (req: < 5)

Gene RIFs: 214   (req: <= 3)

Antibodies: 978   (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: 1023.43   (req: >= 5)

Gene RIFs: 214   (req: > 3)

Antibodies: 978   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 68

Tchem

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

Active Ligands: 2329

Tclin

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

Active Drugs: 6

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 (6)

Explore Approved Drugs

1 – 6 of 6

celecoxib

HDAC6Tclin Epigenetic

INHIBITOR pIC50 : 7.24

vorinostat

HDAC6Tclin Epigenetic

INHIBITOR pKi : 9

romidepsin

HDAC6Tclin Epigenetic

INHIBITOR pKi : 5.96

belinostat

HDAC6Tclin Epigenetic

INHIBITOR pIC50 : 7.57

panobinostat

HDAC6Tclin Epigenetic

INHIBITOR pKi : 8.46

ruxolitinib

HDAC6Tclin Epigenetic

INHIBITOR pKd : 10.44

Active Ligands (2329)

Explore Active Ligands

1 – 10 of 2329

fimepinostat

HDAC6Tclin Epigenetic

pIC50 : 9.44

trichostatin

HDAC6Tclin Epigenetic

pKi : 8.45

CUDC-101

HDAC6Tclin Epigenetic

pIC50 : 8.62

Belinosta

HDAC6Tclin Epigenetic

pKi : 7.66

CHEMBL1830424

HDAC6Tclin Epigenetic

pKi : 7.68

dacinostat

HDAC6Tclin Epigenetic

pKi : 8.85

KA1010

HDAC6Tclin Epigenetic

pIC50 : 8.1

pracinostat

HDAC6Tclin Epigenetic

pKi : 7.57

quisinostat

HDAC6Tclin Epigenetic

pKi : 7.51

scriptaid

HDAC6Tclin Epigenetic

pKi : 8.66

Protein-Protein Interactions (356)

Explore Interacting Targets

1 – 10 of 356

• See Interactions on String-DB

TUBA3C

Tchem

Novelty:  0.0187396

p_int:  0.99999557

p_ni:  0.00000443

Score:  0.174

Data Source:  BioPlex,STRINGDB

NCOA1

Tchem

Family:  Epigenetic

Novelty:  0.00344663

p_int:  0.999946969

p_ni:  0.000052888

p_wrong:  1.43e-7

Score:  0.21

Data Source:  BioPlex,STRINGDB

LPIN3

Tbio

Family:  Enzyme

Novelty:  0.01641336

p_int:  0.999903133

p_ni:  0.00009685

p_wrong:  1.7e-8

Score:  0.201

Data Source:  BioPlex,STRINGDB

UBL7

Tdark

Novelty:  0.20935024

p_int:  0.999675342

p_ni:  0.000324148

p_wrong:  5.1e-7

Score:  0.613

Data Source:  BioPlex,STRINGDB

TIMM50

Tbio

Family:  Enzyme

Novelty:  0.0238053

p_int:  0.999500946

p_ni:  0.000499054

p_wrong:  1e-9

Score:  0.199

Data Source:  BioPlex,STRINGDB

CHEK1

Tchem

Family:  Kinase

Novelty:  0.00066843

p_int:  0.999452122

p_ni:  0.000547878

Score:  0.256

Data Source:  BioPlex,STRINGDB

KCNAB3

Tbio

Family:  IC

Novelty:  0.10128237

p_int:  0.999265822

p_ni:  0.000734176

p_wrong:  2e-9

Score:  0.267

Data Source:  BioPlex,STRINGDB

NYAP2

Tdark

Family:  Enzyme

Novelty:  1.08965558

p_int:  0.998392308

p_ni:  0.001606304

p_wrong:  0.000001388

Data Source:  BioPlex

MCM7

Tbio

Novelty:  0.0017984

p_int:  0.998253088

p_ni:  0.001745688

p_wrong:  0.000001224

Score:  0.238

Data Source:  BioPlex,STRINGDB

TULP2

Tdark

Family:  TF

Novelty:  0.20144336

p_int:  0.998182874

p_ni:  0.001793295

p_wrong:  0.000023831

Score:  0.159

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

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

Pathways (39)

Reactome (24)

KEGG (2)

PathwayCommons (4)

WikiPathways (9)

Cellular response to heat stress (R-HSA-3371556)

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1 – 5 of 24

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cellular response to heat stress	100 targets	R-HSA-3371556
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Cellular responses to stress	392 targets	R-HSA-2262752
Reactome	Cilium Assembly	187 targets	R-HSA-5617833
Reactome	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	58 targets	R-HSA-2894862

Name	Explore in Pharos	Explore in Source
Cellular response to heat stress	100 targets	R-HSA-3371556
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Cellular responses to stress	392 targets	R-HSA-2262752
Cilium Assembly	187 targets	R-HSA-5617833
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	58 targets	R-HSA-2894862

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (85)

Functions (19)

Components (17)

Processes (49)

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Items per page:

10

1 – 10 of 19

GO Term	Evidence	Assigned by
misfolded protein binding	Inferred from Experiment (EXP)	Reactome
alpha-tubulin binding	Inferred from Direct Assay (IDA)	BHF-UCL
dynein complex binding	Inferred from Direct Assay (IDA)	BHF-UCL
histone deacetylase activity	Inferred from Direct Assay (IDA)	BHF-UCL
Hsp90 protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
microtubule binding	Inferred from Direct Assay (IDA)	BHF-UCL
polyubiquitin modification-dependent protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
tau protein binding	Inferred from Direct Assay (IDA)	BHF-UCL
tubulin deacetylase activity	Inferred from Direct Assay (IDA)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (5)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	1	2	2		90
eosinophil percentage of leukocytes	EFO_0007991	1	1	1		82.8
platelet count	EFO_0004309	1	1	1		57.8
mean platelet volume	EFO_0004584	1	1	1		15.5
type II diabetes mellitus	EFO_0001360	1	1	0	1.1	2.4

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	2		90
eosinophil percentage of leukocytes	EFO_0007991	1		82.8
platelet count	EFO_0004309	1		57.8
mean platelet volume	EFO_0004584	1		15.5
type II diabetes mellitus	EFO_0001360	0	1.1	2.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Actin-binding
Alternative splicing
Autophagy
Cell projection
Chromatin regulator
Complete proteome
Cytoplasm
Hydrolase
Metal-binding

GWAS Trait Find Similar Targets

No Header	No Header
eosinophil count
eosinophil percentage of leukocytes
mean platelet volume
platelet count
type II diabetes mellitus

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cellular phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	histone deacetylase 6		711363
Mouse	histone deacetylase 6	MGI:1333752	15185
Rat	histone deacetylase 6	RGD:619981	84581
Rat	histone deacetylase 6	RGD:11442569	108348065
Dog	histone deacetylase 6	VGNC:50630	480907

Species	Name	OMA	EggNOG	Inparanoid
Macaque	histone deacetylase 6
Mouse	histone deacetylase 6
Rat	histone deacetylase 6
Rat	histone deacetylase 6
Dog	histone deacetylase 6

Publication Statistics

PubMed Score 1023.43

PubMed score by year

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PubTator Score 517.11

PubTator score by year

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Related Publications

Text Mined References (262)

GeneRif Annotations (214)

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PMID	Year	Title