HDAC8

HDAC8
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1T64, 1T67, 1T69, 1VKG, 1W22, 2V5W, 2V5X, 3EW8, 3EWF, 3EZP, 3EZT, 3F06, 3F07, 3F0R, 3MZ3, 3MZ4, 3MZ6, 3MZ7, 3RQD, 3SFF, 3SFH, 4QA0, 4QA1, 4QA2, 4QA3, 4QA4, 4QA5, 4QA6, 4QA7, 4RN0, 4RN1, 4RN2, 5DC7, 5D1D, 5D1C, 5DC8, 5D1B, 5DC5, 5DC6, 5BWZ
Identifiers
Aliases	HDAC8, CDLS5, HD8, HDACL1, MRXS6, RPD3, WTS, CDA07, histone deacetylase 8, KDAC8
External IDs	OMIM: 300269; MGI: 1917565; HomoloGene: 41274; GeneCards: HDAC8; OMA:HDAC8 - orthologs
Gene location (Human)
Chr.	X chromosome (human)
End	72,573,101 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	101,548,965 bp
RNA expression pattern
	Top expressed in
	epithelium of colon; ; left adrenal gland; ; left adrenal cortex; ; right adrenal gland; ; tendon of biceps brachii; ; right adrenal cortex; ; gonad; ; Achilles tendon; ; cerebellar hemisphere; ; anterior pituitary;
	Top expressed in
	wall of esophagus; ; mucosa of esophagus; ; epithelium of esophagus; ; ventricular zone; ; Rathke's pouch; ; dentate gyrus of hippocampal formation granule cell; ; lumbar subsegment of spinal cord; ; right kidney; ; zygote; ; embryo;
	More reference expression data
	n/a
Gene ontology
Molecular function	Hsp90 protein binding; NAD-dependent histone deacetylase activity (H3-K14 specific); histone deacetylase activity; metal ion binding; Hsp70 protein binding; protein binding; hydrolase activity; chromatin binding; transcription factor binding; deacetylase activity;
Cellular component	cytoplasm; histone deacetylase complex; cytosol; plasma membrane; nucleoplasm; nuclear chromosome; nucleus;
Biological process	histone H3 deacetylation; regulation of transcription, DNA-templated; regulation of protein stability; regulation of telomere maintenance; negative regulation of transcription by RNA polymerase II; transcription, DNA-templated; sister chromatid cohesion; regulation of cohesin loading; negative regulation of protein ubiquitination; histone deacetylation; negative regulation of gene expression; cellular response to trichostatin A; negative regulation of osteoblast differentiation; cellular response to forskolin; negative regulation of histone H3-K9 acetylation; chromatin organization; positive regulation of transcription by RNA polymerase II; histone H4 deacetylation;
	Sources:Amigo / QuickGO
Orthologs
	55869
	70315
	ENSG00000147099
	ENSMUSG00000067567
	Q9BY41
	Q8VH37
NM_001166418; NM_001166419; NM_001166420; NM_001166422; NM_001166448;
	NM_018486
	NM_027382; NM_001313742
NP_001159890; NP_001159891; NP_001159892; NP_001159894; NP_001159920;
	NP_060956
	NP_001300671; NP_081658
	Wikidata
View/Edit Human	View/Edit Mouse

Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene.^[5]^[6]^[7]

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation / deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter.^[7]

Histone deacetylase 8 is involved in skull morphogenesis^[8] and metabolic control of the ERR-alpha / PGC1-alpha transcriptional complex.^[9]

Clinical significance

HDAC8 has been linked to number of disease states notably to acute myeloid leukemia and is related to actin cytoskeleton in smooth muscle cells. siRNA targeting HDAC8 showed anticancer effects.^[10] Inhibition of HDAC8 induced apoptosis has been observed in T cell lymphomas.^[11] In addition the HDAC8 enzyme has been implicated in the pathogenesis of neuroblastoma.^[12] Therefore, there has been interest in developing HDAC8 selective inhibitors.^[13]^[14]

Interactions

ERR-alpha.^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000147099 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000067567 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ McDonell N, Ramser J, Francis F, Vinet MC, Rider S, Sudbrak R, Riesselman L, Yaspo ML, Reinhardt R, Monaco AP, Ross F, Kahn A, Kearney L, Buckle V, Chelly J (May 2000). "Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia". Genomics. 64 (3): 221–9. doi:10.1006/geno.2000.6128. PMID 10756090.
^ Van den Wyngaert I, de Vries W, Kremer A, Neefs J, Verhasselt P, Luyten WH, Kass SU (Aug 2000). "Cloning and characterization of human histone deacetylase 8". FEBS Lett. 478 (1–2): 77–83. doi:10.1016/S0014-5793(00)01813-5. PMID 10922473.
^ ^a ^b "Entrez Gene: HDAC8 histone deacetylase 8".
^ Haberland M, Mokalled MH, Montgomery RL, Olson EN (July 2009). "Epigenetic control of skull morphogenesis by histone deacetylase 8". Genes Dev. 23 (14): 1625–30. doi:10.1101/gad.1809209. PMC 2714711. PMID 19605684.
^ ^a ^b Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V (July 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol. 24 (7): 1349–58. doi:10.1210/me.2009-0441. PMC 5417470. PMID 20484414.
^ Gallinari P, Di Marco S, Jones P, Pallaoro M, Steinkühler C (March 2007). "HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics". Cell Res. 17 (3): 195–211. doi:10.1038/sj.cr.7310149. PMID 17325692.
^ Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ (May 2008). "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas". Leukemia. 22 (5): 1026–34. doi:10.1038/leu.2008.9. PMID 18256683.
^ Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M, Witt O (January 2009). "Histone deacetylase 8 in neuroblastoma tumorigenesis". Clin. Cancer Res. 15 (1): 91–9. doi:10.1158/1078-0432.CCR-08-0684. PMID 19118036.
^ Patil V, Sodji QH, Kornacki JR, Mrksich M, Oyelere AK (May 2013). "3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition". Journal of Medicinal Chemistry. 56 (9): 3492–506. doi:10.1021/jm301769u. PMC 3657749. PMID 23547652.
^ Suzuki T, Ota Y, Ri M, Bando M, Gotoh A, Itoh Y, Tsumoto H, Tatum PR, Mizukami T, Nakagawa H, Iida S, Ueda R, Shirahige K, Miyata N (November 2012). "Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries". Journal of Medicinal Chemistry. 55 (22): 9562–75. doi:10.1021/jm300837y. PMID 23116147.

External links

HDAC8+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000147099 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000067567 – 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.

[pmid10756090-5] McDonell N, Ramser J, Francis F, Vinet MC, Rider S, Sudbrak R, Riesselman L, Yaspo ML, Reinhardt R, Monaco AP, Ross F, Kahn A, Kearney L, Buckle V, Chelly J (May 2000). "Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia". Genomics. 64 (3): 221–9. doi:10.1006/geno.2000.6128. PMID 10756090.

[pmid10922473-6] Van den Wyngaert I, de Vries W, Kremer A, Neefs J, Verhasselt P, Luyten WH, Kass SU (Aug 2000). "Cloning and characterization of human histone deacetylase 8". FEBS Lett. 478 (1–2): 77–83. doi:10.1016/S0014-5793(00)01813-5. PMID 10922473.

[entrez-7] "Entrez Gene: HDAC8 histone deacetylase 8".

[pmid19605684-8] Haberland M, Mokalled MH, Montgomery RL, Olson EN (July 2009). "Epigenetic control of skull morphogenesis by histone deacetylase 8". Genes Dev. 23 (14): 1625–30. doi:10.1101/gad.1809209. PMC 2714711. PMID 19605684.

[pmid20484414-9] Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V (July 2010). "An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha". Mol. Endocrinol. 24 (7): 1349–58. doi:10.1210/me.2009-0441. PMC 5417470. PMID 20484414.

[pmid17325692-10] Gallinari P, Di Marco S, Jones P, Pallaoro M, Steinkühler C (March 2007). "HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics". Cell Res. 17 (3): 195–211. doi:10.1038/sj.cr.7310149. PMID 17325692.

[pmid18256683-11] Balasubramanian S, Ramos J, Luo W, Sirisawad M, Verner E, Buggy JJ (May 2008). "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas". Leukemia. 22 (5): 1026–34. doi:10.1038/leu.2008.9. PMID 18256683.

[pmid19118036-12] Oehme I, Deubzer HE, Wegener D, Pickert D, Linke JP, Hero B, Kopp-Schneider A, Westermann F, Ulrich SM, von Deimling A, Fischer M, Witt O (January 2009). "Histone deacetylase 8 in neuroblastoma tumorigenesis". Clin. Cancer Res. 15 (1): 91–9. doi:10.1158/1078-0432.CCR-08-0684. PMID 19118036.

[pmid23547652-13] Patil V, Sodji QH, Kornacki JR, Mrksich M, Oyelere AK (May 2013). "3-Hydroxypyridin-2-thione as novel zinc binding group for selective histone deacetylase inhibition". Journal of Medicinal Chemistry. 56 (9): 3492–506. doi:10.1021/jm301769u. PMC 3657749. PMID 23547652.

[pmid23116147-14] Suzuki T, Ota Y, Ri M, Bando M, Gotoh A, Itoh Y, Tsumoto H, Tatum PR, Mizukami T, Nakagawa H, Iida S, Ueda R, Shirahige K, Miyata N (November 2012). "Rapid discovery of highly potent and selective inhibitors of histone deacetylase 8 using click chemistry to generate candidate libraries". Journal of Medicinal Chemistry. 55 (22): 9562–75. doi:10.1021/jm300837y. PMID 23116147.

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v t e Hydrolases: carbon-nitrogen non-peptide (EC 3.5)
3.5.1: Linear amides / Amidohydrolases	Asparaginase Glutaminase Urease Biotinidase Aminoacylase ACY1 Aspartoacylase(ACY2) ACY3 Ceramidase Aspartylglucosaminidase Fatty acid amide hydrolase Histone deacetylase Sirtuin
3.5.2: Cyclic amides/ Amidohydrolases	Barbiturase Beta-lactamase Dihydroorotase
3.5.3: Linear amidines/ Ureohydrolases	Arginase Agmatinase Protein-arginine deiminase
3.5.4: Cyclic amidines/ Aminohydrolases	Guanine deaminase Adenosine deaminase AMP deaminase Inosine monophosphate synthase DCMP deaminase GTP cyclohydrolase I Cytidine deaminase AICDA Activation-induced cytidine deaminase
3.5.5: Nitriles/ Aminohydrolases	Nitrilase
3.5.99: Other	Riboflavinase Thiaminase II

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)