Histone deacetylase 5

Function

In vitro, it deacetylates 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 by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Serves as a corepressor of RARA and causes its deacetylation. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response.

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 · 2

• 5UWI X-ray 2.14A
• 8Q9P X-ray 2.20A

A predicted model is available from AlphaFold.

Gene Ontology · 37

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0000118 histone deacetylase complex
• GO:0016607 nuclear speck
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0003682 chromatin binding
• 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:0046872 metal ion binding
• GO:0005080 protein kinase C 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:0001222 transcription corepressor binding
• GO:0042113 B cell activation
• GO:0030183 B cell differentiation
• GO:0032869 cellular response to insulin stimulus
• GO:0071222 cellular response to lipopolysaccharide
• GO:0006351 DNA-templated transcription
• GO:0040029 epigenetic regulation of gene expression
• GO:0006954 inflammatory response
• GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
• GO:0045892 negative regulation of DNA-templated transcription
• GO:0045814 negative regulation of gene expression, epigenetic
• GO:0010832 negative regulation of myotube differentiation
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0030182 neuron differentiation
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0010830 regulation of myotube differentiation
• GO:0014823 response to activity
• GO:0042220 response to cocaine
• GO:0009410 response to xenobiotic stimulus

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 5 1.00
• Histone deacetylase 5 0.99
• Histone deacetylase 5 0.99
• Histone deacetylase 9 0.95
• Histone deacetylase 4 0.93
• Histone deacetylase 4 0.93
• Histone deacetylase 4 0.92
• Histone deacetylase 4 0.92
• Histone deacetylase 9 0.84
• Histone deacetylase 9 0.83
• Histone deacetylase 9-B 0.83
• Histone deacetylase 7 0.83

Co-cited proteins · studied together in the literature

• Histone deacetylase 4 6 shared papers
• Protein deacetylase HDAC6 4 shared papers
• Calcium/calmodulin-dependent protein kinase type 1 1 shared papers
• Serine/threonine-protein kinase D1 1 shared papers
• B-cell lymphoma 6 protein 1 shared papers
• Ankyrin repeat family A protein 2 2 shared papers
• Histone deacetylase 7 1 shared papers
• Histone deacetylase 7 3 shared papers
• Bromo adjacent homology domain-containing 1 protein 1 shared papers
• DNA-binding protein RFXANK 2 shared papers
• BCL-6 corepressor 1 shared papers
• Tribbles homolog 3 1 shared papers

Literature · 28 cited papers

• MicroRNA-10a is crucial for endothelial response to different flow patterns via interaction of retinoid acid receptors and histone deacetylases. Proc. Natl. Acad. Sci. U.S.A. · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome protein CCDC8. Structure · 2015
• 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
• 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
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Protein kinase C-related kinase targets nuclear localization signals in a subset of class IIa histone deacetylases. FEBS Lett. · 2010
• Human BAHD1 promotes heterochromatic gene silencing. Proc. Natl. Acad. Sci. U.S.A. · 2009
• Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science · 2009
• Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J. Biol. Chem. · 2008
• … and 16 more in the literature graph