Histone deacetylase 8

Function

Histone deacetylase that catalyzes 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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones.

Classification

Family (Pfam)

PF00850 Hist_deacetyl

InterPro

HDAC_I/II, HDACs, His_deacetylse_dom, His_deacetylse_dom_sf, Ureohydrolase_dom_sf

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 53

• 1T64 X-ray 1.90A
• 1T67 X-ray 2.31A
• 1T69 X-ray 2.91A
• 1VKG X-ray 2.20A
• 1W22 X-ray 2.50A
• 2V5W X-ray 2.00A
• 2V5X X-ray 2.25A
• 3EW8 X-ray 1.80A
• 3EWF X-ray 2.50A
• 3EZP X-ray 2.65A
• 3EZT X-ray 2.85A
• 3F06 X-ray 2.55A
• … and 41 more

A predicted model is available from AlphaFold.

Gene Ontology · 21

• GO:0005737 cytoplasm
• GO:0000118 histone deacetylase complex
• GO:0000228 nuclear chromosome
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0140297 DNA-binding transcription factor binding
• GO:0004407 histone deacetylase activity
• GO:0141221 histone deacetylase activity, hydrolytic mechanism
• GO:0160009 histone decrotonylase activity
• GO:0030544 Hsp70 protein binding
• GO:0051879 Hsp90 protein binding
• GO:0046872 metal ion binding
• GO:0033558 protein lysine deacetylase activity
• GO:0006325 chromatin organization
• GO:0006351 DNA-templated transcription
• GO:0031507 heterochromatin formation
• GO:0007064 mitotic sister chromatid cohesion
• GO:0031397 negative regulation of protein ubiquitination
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0031647 regulation of protein stability
• GO:0032204 regulation of telomere maintenance

Disease associations

• Cornelia de Lange syndrome 5 MONDO:0010471

Drugs targeting this protein · 11

• ABEXINOSTAT inhibitor
• QUISINOSTAT inhibitor
• TACEDINALINE inhibitor
• MOCETINOSTAT 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 8 0.99
• Histone deacetylase 8 0.99
• Histone deacetylase 8 0.99
• Histone deacetylase 8 0.94
• Histone deacetylase 8 0.94
• Histone deacetylase 8 0.86
• 4'-phosphopantetheine phosphatase 0.72
• 4'-phosphopantetheine phosphatase 0.71
• 4'-phosphopantetheine phosphatase 0.71
• 4'-phosphopantetheine phosphatase 0.71
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.68
• Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase 0.68

Co-cited proteins · studied together in the literature

• Structural maintenance of chromosomes protein 3 1 shared papers
• Histone deacetylase 8 1 shared papers
• Glutathione peroxidase 2 1 shared papers
• Tryptophan--tRNA ligase, cytoplasmic 1 shared papers
• YjeF N-terminal domain-containing protein 3 1 shared papers
• Actin-related protein 2/3 complex subunit 5-like protein 1 shared papers
• UV-stimulated scaffold protein A 1 shared papers
• Armadillo repeat-containing protein 2 1 shared papers
• Transmembrane protein 91 1 shared papers
• Protein Flattop 1 shared papers
• Nanos homolog 3 1 shared papers
• Serpin-like protein HMSD 1 shared papers

Literature · 20 cited papers

• Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res. · 2017
• X-exome sequencing identifies a HDAC8 variant in a large pedigree with X-linked intellectual disability, truncal obesity, gynaecomastia, hypogonadism and unusual face. J. Med. Genet. · 2012
• HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature · 2012
• Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry · 2008
• Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. EMBO Rep. · 2007
• Histone deacetylase 8 safeguards the human ever-shorter telomeres 1B (hEST1B) protein from ubiquitin-mediated degradation. Mol. Cell. Biol. · 2006
• Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus. Am. J. Surg. Pathol. · 2006
• The DNA sequence of the human X chromosome. Nature · 2005
• Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility. FASEB J. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• … and 8 more in the literature graph