Histone deacetylase 4

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. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1.

Classification

Family (Pfam)

PF12203 HDAC4_Gln, PF00850 Hist_deacetyl

InterPro

HDAC4/5/7/9, HDACs, His_deacetylse_dom, His_deacetylse_dom_sf, Hist_deacetylase_Gln_rich_N, Ureohydrolase_dom_sf

Functional cluster

Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 19

• 2H8N X-ray 2.60A
• 2O94 X-ray 3.00A
• 2VQJ X-ray 2.10A
• 2VQM X-ray 1.80A
• 2VQO X-ray 2.15A
• 2VQQ X-ray 1.90A
• 2VQV X-ray 3.30A
• 2VQW X-ray 3.00A
• 3UXG X-ray 1.85A
• 3UZD X-ray 1.86A
• 3V31 X-ray 1.57A
• 4CBT X-ray 3.03A
• … and 7 more

A predicted model is available from AlphaFold.

Gene Ontology · 43

• GO:0000785 chromatin
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0000118 histone deacetylase complex
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0017053 transcription repressor complex
• GO:0001216 DNA-binding transcription activator activity
• GO:0140297 DNA-binding transcription factor binding
• GO:0004407 histone deacetylase activity
• GO:0141221 histone deacetylase activity, hydrolytic mechanism
• GO:0042826 histone deacetylase binding
• GO:0042802 identical protein binding
• GO:0060090 molecular adaptor activity
• GO:0030955 potassium ion binding
• GO:0033558 protein lysine deacetylase activity
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
• GO:0019789 SUMO transferase activity
• GO:0008270 zinc ion binding
• GO:0042113 B cell activation
• GO:0030183 B cell differentiation
• GO:0014898 cardiac muscle hypertrophy in response to stress
• GO:0006338 chromatin remodeling
• GO:0006351 DNA-templated transcription
• GO:0040029 epigenetic regulation of gene expression
• GO:0006954 inflammatory response
• GO:0045814 negative regulation of gene expression, epigenetic
• GO:0045820 negative regulation of glycolytic process
• GO:0010832 negative regulation of myotube differentiation
• GO:0061084 negative regulation of protein refolding
• GO:0010944 negative regulation of transcription by competitive promoter binding
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0007399 nervous system development
• GO:0008284 positive regulation of cell population proliferation
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0033235 positive regulation of protein sumoylation
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0016925 protein sumoylation
• GO:0014894 response to denervation involved in regulation of muscle adaptation
• GO:0070555 response to interleukin-1
• GO:0060337 type I interferon-mediated signaling pathway

Disease associations

• neurodevelopmental disorder with central hypotonia and dysmorphic facies MONDO:0859232

Drugs targeting this protein · 10

• ABEXINOSTAT inhibitor
• QUISINOSTAT inhibitor
• TACEDINALINE inhibitor
• ENTINOSTAT inhibitor
• ROMIDEPSIN inhibitor
• PANOBINOSTAT LACTATE inhibitor
• FIMEPINOSTAT inhibitor
• BELINOSTAT inhibitor
• CUDC-101 inhibitor
• GIVINOSTAT HYDROCHLORIDE inhibitor

Related proteins · sequence + function similarity

• Histone deacetylase 4 0.99
• Histone deacetylase 4 0.99
• Histone deacetylase 4 0.96
• Histone deacetylase 9 0.93
• Histone deacetylase 5 0.92
• Histone deacetylase 5 0.92
• Histone deacetylase 5 0.92
• Histone deacetylase 5 0.92
• Histone deacetylase 9 0.82
• Histone deacetylase 9 0.82
• Forkhead box protein P4 0.81
• Histone deacetylase 7 0.81

Co-cited proteins · studied together in the literature

• Histone deacetylase 5 6 shared papers
• ATPase MORC2 1 shared papers
• Calcium/calmodulin-dependent protein kinase type II subunit delta 1 shared papers
• Nuclear receptor subfamily 2 group C member 1 1 shared papers
• Histone deacetylase 9 3 shared papers
• 14-3-3 protein beta/alpha 1 shared papers
• Dedicator of cytokinesis protein 8 1 shared papers
• Ankyrin repeat family A protein 2 2 shared papers
• Histone deacetylase 7 1 shared papers
• Protein deacetylase HDAC6 3 shared papers
• Amine oxidase [flavin-containing] A 1 shared papers
• DNA-binding protein RFXANK 2 shared papers

Literature · 31 cited papers

• Missense substitutions at a conserved 14-3-3 binding site in HDAC4 cause a novel intellectual disability syndrome. HGG Adv. · 2021
• NP220 mediates silencing of unintegrated retroviral DNA. Nature · 2018
• ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation. Nat. Commun. · 2016
• Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8. Structure · 2015
• Haploinsufficiency of HDAC4 does not cause intellectual disability in all affected individuals. Am. J. Med. Genet. A · 2014
• Differential regulation of estrogen receptor alpha expression in breast cancer cells by metastasis-associated protein 1. Cancer Res. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• 20 ans apres: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition. Eur. J. Hum. Genet. · 2014
• Phenotypic variant of Brachydactyly-mental retardation syndrome in a family with an inherited interstitial 2q37.3 microdeletion including HDAC4. Eur. J. Hum. Genet. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat tumbler lock. Sci. Signal. · 2012
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• … and 19 more in the literature graph