HDAC6

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.[5][6]

HDAC6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3C5K, 3GV4, 3PHD, 5EDU, 5KH7
Identifiers
Aliases	HDAC6, CPBHM, HD6, PPP1R90, JM21, histone deacetylase 6
External IDs	OMIM: 300272 MGI: 1333752 HomoloGene: 31353 GeneCards: HDAC6
Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.23 Start 48,801,377 bp[1] End 48,824,982 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A1.1|X 3.58 cM Start 7,930,120 bp[2] End 7,947,889 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • histone deacetylase binding • misfolded protein binding • metal ion binding • enzyme binding • NAD-dependent histone deacetylase activity (H3-K14 specific) • beta-catenin binding • zinc ion binding • polyubiquitin modification-dependent protein binding • GO:0001948 protein binding • tau protein binding • dynein complex binding • Hsp90 protein binding • histone deacetylase activity • microtubule binding • alpha-tubulin binding • ubiquitin binding • beta-tubulin binding • actin binding • hydrolase activity • ubiquitin protein ligase binding • tubulin deacetylase activity • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • protein deacetylase activity • acetylspermidine deacetylase activity Cellular component • cytosol • perinuclear region of cytoplasm • caveola • microtubule • cell nucleus • multivesicular body • cell projection • microtubule associated complex • aggresome • dynein complex • histone deacetylase complex • perikaryon • axon • inclusion body • dendrite • cell leading edge • cytoplasmic microtubule • cell body • neuron projection • nucleoplasm • cytoplasm • macromolecular complex Biological process • Hsp90 deacetylation • protein quality control for misfolded or incompletely synthesized proteins • response to organic substance • cellular response to topologically incorrect protein • tubulin deacetylation • regulation of establishment of protein localization • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway • response to growth factor • intracellular protein transport • aggresome assembly • negative regulation of proteolysis • histone H3 deacetylation • positive regulation of signal transduction • peptidyl-lysine deacetylation • response to misfolded protein • regulation of transcription, DNA-templated • regulation of protein stability • ubiquitin-dependent protein catabolic process • mitochondrion localization • positive regulation of epithelial cell migration • regulation of fat cell differentiation • transcription, DNA-templated • regulation of autophagy of mitochondrion • polyubiquitinated misfolded protein transport • response to toxic substance • positive regulation of hydrogen peroxide-mediated programmed cell death • regulation of microtubule-based movement • positive regulation of receptor biosynthetic process • regulation of receptor activity • protein polyubiquitination • protein deacetylation • negative regulation of hydrogen peroxide metabolic process • regulation of autophagy • negative regulation of oxidoreductase activity • regulation of androgen receptor signaling pathway • negative regulation of transcription, DNA-templated • cellular response to misfolded protein • positive regulation of chaperone-mediated protein complex assembly • epigenetic regulation of gene expression • negative regulation of protein complex disassembly • autophagy • negative regulation of microtubule depolymerization • lysosome localization • histone deacetylation • cellular response to hydrogen peroxide • covalent chromatin modification • collateral sprouting • dendritic spine morphogenesis • cilium morphogenesis • regulation of macroautophagy • parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization • positive regulation of mitophagy in response to mitochondrial depolarization • chromatin organization • positive regulation of protein oligomerization • macromolecular complex disassembly • positive regulation of peptidyl-serine phosphorylation • polyamine deacetylation • spermidine deacetylation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10013	15185
Ensembl	ENSG00000094631	ENSMUSG00000031161
UniProt	Q9UBN7	Q9Z2V5
RefSeq (mRNA)	NM_006044 NM_001321225 NM_001321226 NM_001321227 NM_001321228 NM_001321229 NM_001321230 NM_001321231	NM_001130416 NM_010413
RefSeq (protein)	NP_001308154 NP_001308155 NP_001308156 NP_001308157 NP_001308158 NP_001308159 NP_001308160 NP_006035	NP_001123888 NP_034543
Location (UCSC)	Chr X: 48.8 – 48.82 Mb	Chr X: 7.93 – 7.95 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. 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 that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription.[7]

Clinical relevance

Mutations in this gene have been associated to Alzheimer's disease.[8]

Over expression of this protein correlates with tumorigenesis and cell survival. HDAC6 also encourages metastasis of cancer cells.[9]

Functions

Retracts the Cilium of the cell, which is necessary prior to mitosis of the cell.[10]

HDAC also encourages cell motility and catalyzes α-tubulin deacetylation.[11] As a result the enzyme also encourages cancer cell metastasis.[9]
HDAC6 also affects transcription and translation by regulating the heat-shock protein 90 (Hsp90) and stress granules (SGs), respectively.[9]

HDAC6 is also known to bond with high affinity to ubiquitinated proteins.[12] HDAC6 is also required in the formation of SG (Stress granule proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.

Interactions

HDAC6 has been shown to interact with HDAC11[13] and Zinc finger and BTB domain-containing protein 16.[14]

HDAC6 interacts with SG (Stress granule) protein G3BP1.[12]

See also

• Histone deacetylase

References

1. GRCh38: Ensembl release 89: ENSG00000094631 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031161 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Grozinger CM, Hassig CA, Schreiber SL (Jun 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc Natl Acad Sci U S A. 96 (9): 4868–73. Bibcode:1999PNAS...96.4868G. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
6. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (May 1999). "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (6): 355–64. doi:10.1093/dnares/5.6.355. PMID 10048485.
7. "Entrez Gene: HDAC6 histone deacetylase 6".
8. Cook C, Gendron TF, Scheffel K, Carlomagno Y, Dunmore J, DeTure M, Petrucelli L (5 April 2012). "Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation". Human Molecular Genetics. 21 (13): 2936–45. doi:10.1093/hmg/dds125. PMC 3373241. PMID 22492994.
9. Aldana-Masangkay GI, Sakamoto KM (2011). "The role of HDAC6 in cancer". J. Biomed. Biotechnol. 2011: 1–10. doi:10.1155/2011/875824. PMC 2975074. PMID 21076528.
10. Krishnamurthy K, Wang G, Silva J, Condie BG, Bieberich E (February 2007). "Ceramide regulates atypical PKCzeta/lambda-mediated cell polarity in primitive ectoderm cells. A novel function of sphingolipids in morphogenesis". J. Biol. Chem. 282 (5): 3379–90. doi:10.1074/jbc.M607779200. PMID 17105725. Lay summary – phys.org/news.
11. Gao YS, Hubbert CC, Lu J, Lee YS, Lee JY, Yao TP (2007). "Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis". Mol. Cell. Biol. 27 (24): 8637–47. doi:10.1128/MCB.00393-07. PMC 2169396. PMID 17938201.
12. Kwon S, Zhang Y, Matthias P (December 2007). "The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress response". Genes Dev. 21 (24): 3381–94. doi:10.1101/gad.461107. PMC 2113037. PMID 18079183.
13. Gao L, Cueto MA, Asselbergs F, Atadja P (Jul 2002). "Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family". J. Biol. Chem. 277 (28): 25748–55. doi:10.1074/jbc.M111871200. PMID 11948178.
14. Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A (Nov 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene. 23 (54): 8777–84. doi:10.1038/sj.onc.1208128. PMID 15467736.

Further reading

• Pazin MJ, Kadonaga JT (1997). "What's up and down with histone deacetylation and transcription?". Cell. 89 (3): 325–8. doi:10.1016/S0092-8674(00)80211-1. PMID 9150131.
• Wolffe AP (1997). "Transcriptional control. Sinful repression". Nature. 387 (6628): 16–7. doi:10.1038/387016a0. PMID 9139815.
• Huynh KD, Fischle W, Verdin E, Bardwell VJ (2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes Dev. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810 (inactive 2020-01-22). PMC 316791. PMID 10898795.
• Mahlknecht U, Schnittger S, Landgraf F, Schoch C, Ottmann OG, Hiddemann W, Hoelzer D (2001). "Assignment of the human histone deacetylase 6 gene (HDAC6) to X chromosome p11.23 by in situ hybridization". Cytogenet. Cell Genet. 93 (1–2): 135–6. doi:10.1159/000056967. PMID 11474198.
• Kao HY, Lee CH, Komarov A, Han CC, Evans RM (2002). "Isolation and characterization of mammalian HDAC10, a novel histone deacetylase". J. Biol. Chem. 277 (1): 187–93. doi:10.1074/jbc.M108931200. PMID 11677242.
• Seigneurin-Berny D, Verdel A, Curtet S, Lemercier C, Garin J, Rousseaux S, Khochbin S (2001). "Identification of Components of the Murine Histone Deacetylase 6 Complex: Link between Acetylation and Ubiquitination Signaling Pathways". Mol. Cell. Biol. 21 (23): 8035–44. doi:10.1128/MCB.21.23.8035-8044.2001. PMC 99970. PMID 11689694.
• Tong JJ, Liu J, Bertos NR, Yang XJ (2002). "Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain". Nucleic Acids Res. 30 (5): 1114–23. doi:10.1093/nar/30.5.1114. PMC 101247. PMID 11861901.
• Gao L, Cueto MA, Asselbergs F, Atadja P (2002). "Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family". J. Biol. Chem. 277 (28): 25748–55. doi:10.1074/jbc.M111871200. PMID 11948178.
• Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP (2002). "HDAC6 is a microtubule-associated deacetylase". Nature. 417 (6887): 455–8. Bibcode:2002Natur.417..455H. doi:10.1038/417455a. PMID 12024216.
• Kirsh O, Seeler JS, Pichler A, Gast A, Müller S, Miska E, Mathieu M, Harel-Bellan A, Kouzarides T, Melchior F, Dejean A (2002). "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase". EMBO J. 21 (11): 2682–91. doi:10.1093/emboj/21.11.2682. PMC 125385. PMID 12032081.
• Hook SS, Orian A, Cowley SM, Eisenman RN (2002). "Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes". Proc. Natl. Acad. Sci. U.S.A. 99 (21): 13425–30. Bibcode:2002PNAS...9913425H. doi:10.1073/pnas.172511699. PMC 129689. PMID 12354939.
• Westendorf JJ, Zaidi SK, Cascino JE, Kahler R, van Wijnen AJ, Lian JB, Yoshida M, Stein GS, Li X (2002). "Runx2 (Cbfa1, AML-3) Interacts with Histone Deacetylase 6 and Represses the p21CIP1/WAF1 Promoter". Mol. Cell. Biol. 22 (22): 7982–92. doi:10.1128/MCB.22.22.7982-7992.2002. PMC 134736. PMID 12391164.
• North BJ, Marshall BL, Borra MT, Denu JM, Verdin E (2003). "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase". Mol. Cell. 11 (2): 437–44. doi:10.1016/S1097-2765(03)00038-8. PMID 12620231.
• Voelter-Mahlknecht S, Mahlknecht U (2004). "Cloning and structural characterization of the human histone deacetylase 6 gene". Int. J. Mol. Med. 12 (1): 87–93. doi:10.3892/ijmm.12.1.87. PMID 12792815.
• Brush MH, Guardiola A, Connor JH, Yao TP, Shenolikar S (2004). "Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases". J. Biol. Chem. 279 (9): 7685–91. doi:10.1074/jbc.M310997200. PMID 14670976.
• Pandey UB, Batlevi Y, Baehrecke EH, Taylor JP (Nov–Dec 2007). "HDAC6 at the intersection of autophagy, the ubiquitin-proteasome system and neurodegeneration". Autophagy. 3 (6): 643–5. doi:10.4161/auto.5050. PMID 17912024.
• Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, Padmanabhan R, Hild M, Berry DL, Garza D, Hubbert CC, Yao TP, Baehrecke EH, Taylor JP (June 14, 2007). "HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS". Nature. 447 (7146): 859–63. Bibcode:2007Natur.447..860P. doi:10.1038/nature05853. PMID 17568747.

External links

• HDAC6+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• HDAC6 human gene location in the UCSC Genome Browser.
• HDAC6 human gene details in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.