InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HDAC4

Summary

InnateDB Protein

IDBP-84596.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HDAC4

Protein Name

histone deacetylase 4

Synonyms

AHO3; BDMR; HA6116; HD4; HDAC-4; HDAC-A; HDACA;

Species

Homo sapiens

Ensembl Protein

ENSP00000264606

InnateDB Gene

IDBG-84594 (HDAC4)

Protein Structure

UniProt Annotation

Function

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. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269PubMed:10523670, ECO:0000269PubMed:24413532}.

Subcellular Localization

Nucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation.

Disease Associations

Brachydactyly-mental retardation syndrome (BDMR) [MIM:600430]: A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism. {ECO:0000269PubMed:20691407}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 253 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	253 [view]
Protein-Protein	182 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	67 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001047	core promoter binding
GO:0003677	DNA binding
GO:0003714	transcription corepressor activity
GO:0004407	histone deacetylase activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0019901	protein kinase binding
GO:0030955	potassium ion binding
GO:0032041	NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0033558	protein deacetylase activity
GO:0033613	activating transcription factor binding
GO:0042826	histone deacetylase binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046969	NAD-dependent histone deacetylase activity (H3-K9 specific)
GO:0046970	NAD-dependent histone deacetylase activity (H4-K16 specific)
GO:0070491	repressing transcription factor binding
GO:0097372	NAD-dependent histone deacetylase activity (H3-K18 specific)

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0001501	skeletal system development
GO:0002076	osteoblast development
GO:0006338	chromatin remodeling
GO:0006351	transcription, DNA-templated
GO:0006954	inflammatory response
GO:0007399	nervous system development
GO:0008284	positive regulation of cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0010832	negative regulation of myotube differentiation
GO:0010882	regulation of cardiac muscle contraction by calcium ion signaling
GO:0014894	response to denervation involved in regulation of muscle adaptation
GO:0014898	cardiac muscle hypertrophy in response to stress
GO:0016568	chromatin modification
GO:0016575	histone deacetylation
GO:0030183	B cell differentiation
GO:0033235	positive regulation of protein sumoylation
GO:0034983	peptidyl-lysine deacetylation
GO:0042113	B cell activation
GO:0042493	response to drug
GO:0043393	regulation of protein binding
GO:0043433	negative regulation of sequence-specific DNA binding transcription factor activity
GO:0045668	negative regulation of osteoblast differentiation
GO:0045820	negative regulation of glycolytic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048742	regulation of skeletal muscle fiber development
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051153	regulation of striated muscle cell differentiation
GO:0070555	response to interleukin-1
GO:0070932	histone H3 deacetylation
GO:0070933	histone H4 deacetylation

Cellular Component

GO:0000118	histone deacetylase complex
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0017053	transcriptional repressor complex
GO:0030017	sarcomere
GO:0030018	Z disc
GO:0031594	neuromuscular junction
GO:0031672	A band
GO:0042641	actomyosin
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000286 Histone deacetylase superfamily
IPR017320 Histone deacetylase class II, eukaryotic
IPR019154 Arb2 domain
IPR023801 Histone deacetylase domain
IPR024643 Histone deacetylase, glutamine rich N-terminal domain

PFAM

PF09757
PF00850
PF12203

PRINTS

PR01270

PIRSF

PIRSF037911

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt