Histone deacetylase 5

Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.^[5][6][7]

HDAC5
Identifiers
Aliases	HDAC5, HD5, NY-CO-9, histone deacetylase 5
External IDs	OMIM: 605315; MGI: 1333784; HomoloGene: 3995; GeneCards: HDAC5; OMA:HDAC5 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.31 Start 44,076,746 bp[1] End 44,123,702 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 D Start 102,194,432 bp[2] End 102,230,166 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of leg skin of abdomen ganglionic eminence muscle of thigh right frontal lobe popliteal artery tibial arteries right hemisphere of cerebellum apex of heart gastric mucosa Top expressed in neural layer of retina perirhinal cortex entorhinal cortex CA3 field primary visual cortex dentate gyrus of hippocampal formation granule cell superior frontal gyrus lip muscle of thigh central gray substance of midbrain More reference expression data BioGPS More reference expression data
Gene ontology Molecular function NAD-dependent histone deacetylase activity (H3-K14 specific) protein deacetylase activity histone deacetylase binding chromatin binding metal ion binding protein binding hydrolase activity protein kinase C binding histone deacetylase activity transcription factor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component Golgi apparatus histone deacetylase complex cytoplasm nucleus nucleoplasm cytosol nuclear speck protein-containing complex Biological process histone H3 deacetylation chromatin remodeling regulation of myotube differentiation regulation of transcription, DNA-templated regulation of gene expression, epigenetic positive regulation of DNA-binding transcription factor activity regulation of histone H3-K9 acetylation response to activity transcription, DNA-templated protein deacetylation negative regulation of cell migration involved in sprouting angiogenesis B cell activation neuron differentiation negative regulation of myotube differentiation cellular response to insulin stimulus B cell differentiation inflammatory response regulation of protein binding negative regulation of transcription, DNA-templated cellular response to lipopolysaccharide positive regulation of transcription by RNA polymerase II response to cocaine negative regulation of transcription by RNA polymerase II histone deacetylation chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10014 15184 Ensembl ENSG00000108840 ENSMUSG00000008855 UniProt Q9UQL6 Q9Z2V6 RefSeq (mRNA) NM_001015053 NM_005474 NM_139205 NM_001382393 NM_001077696 NM_001284248 NM_001284249 NM_001284250 NM_010412 NM_001361596 RefSeq (protein) NP_001015053 NP_005465 NP_001369322 n/a Location (UCSC) Chr 17: 44.08 – 44.12 Mb Chr 11: 102.19 – 102.23 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 chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the class II histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. It coimmunoprecipitates only with HDAC3 family member and might form multicomplex proteins. It also interacts with myocyte enhancer factor-2 (MEF2) proteins, resulting in repression of MEF2-dependent genes. This gene is thought to be associated with colon cancer. Two transcript variants encoding different isoforms have been found for this gene.^[7]

AMP-activated protein kinase regulation of the glucose transporter GLUT4 occurs by phosphorylation of HDAC5.^[8]

HDAC5 is involved in memory consolidation and suggests that development of more selective HDAC inhibitors for the treatment of Alzheimer's disease should avoid targeting HDAC5.^[9] Its function can be effectively examined by siRNA knockdown based on an independent validation.^[10]

HDAC5 overexpression in urothelial carcinoma cell lines inhibits long-term proliferation but can promote epithelial-to-mesenchymal transition (EMT)^[11]

Interactions

Histone deacetylase 5 has been shown to interact with:

• BCL6,^[12]
• CBX5,^[13]
• GATA1,^[14]
• HDAC3,^{[5][15][16][17]}
• IKZF1,^[18]
• MEF2A,^[19]
• NRIP1,^[20]
• NCOR1,^[15][21]
• NCOR2,^[21]
• YWHAQ,^[22] and
• ZBTB16.^[12][23]

See also

• Histone deacetylase

References

1. GRCh38: Ensembl release 89: ENSG00000108840 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000008855 – 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 (April 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proceedings of the National Academy of Sciences of the United States of America. 96 (9): 4868–73. Bibcode:1999PNAS...96.4868G. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385.
6. Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, et al. (May 1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". International Journal of Cancer. 76 (5): 652–8. doi:10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P. PMID 9610721. S2CID 916155.
7. "Entrez Gene: HDAC5 histone deacetylase 5".
8. McGee SL, van Denderen BJ, Howlett KF, Mollica J, Schertzer JD, Kemp BE, Hargreaves M (April 2008). "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5". Diabetes. 57 (4): 860–7. doi:10.2337/db07-0843. PMID 18184930. S2CID 17274354.
9. Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A (January 2013). "Loss of HDAC5 impairs memory function: implications for Alzheimer's disease". Journal of Alzheimer's Disease. 33 (1): 35–44. doi:10.3233/JAD-2012-121009. hdl:2434/223089. PMID 22914591.
10. Munkácsy G, Sztupinszki Z, Herman P, Bán B, Pénzváltó Z, Szarvas N, Győrffy B (September 2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy: Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. PMC 5056990. PMID 27673562.
11. Jaguva Vasudevan AA, Hoffmann MJ, Beck ML, Poschmann G, Petzsch P, Wiek C, et al. (April 2019). "HDAC5 Expression in Urothelial Carcinoma Cell Lines Inhibits Long-Term Proliferation but Can Promote Epithelial-to-Mesenchymal Transition". International Journal of Molecular Sciences. 20 (9): 2135. doi:10.3390/ijms20092135. PMC 6539474. PMID 31052182.
12. Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry. 277 (24): 22045–52. doi:10.1074/jbc.M201736200. PMID 11929873.
13. Zhang CL, McKinsey TA, Olson EN (October 2002). "Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation". Molecular and Cellular Biology. 22 (20): 7302–12. doi:10.1128/MCB.22.20.7302-7312.2002. PMC 139799. PMID 12242305.
14. Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, et al. (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene. 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. PMID 14668799. S2CID 24491249.
15. Zhang J, Kalkum M, Chait BT, Roeder RG (March 2002). "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2". Molecular Cell. 9 (3): 611–23. doi:10.1016/S1097-2765(02)00468-9. PMID 11931768.
16. Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell. 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. hdl:11858/00-001M-0000-002C-9FF9-9. PMID 11804585.
17. Grozinger CM, Schreiber SL (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7835–40. Bibcode:2000PNAS...97.7835G. doi:10.1073/pnas.140199597. PMC 16631. PMID 10869435.
18. Koipally J, Georgopoulos K (August 2002). "A molecular dissection of the repression circuitry of Ikaros". The Journal of Biological Chemistry. 277 (31): 27697–705. doi:10.1074/jbc.M201694200. PMID 12015313.
19. Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000). "mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity". The Journal of Biological Chemistry. 275 (20): 15594–9. doi:10.1074/jbc.M908437199. PMID 10748098.
20. Castet A, Boulahtouf A, Versini G, Bonnet S, Augereau P, Vignon F, et al. (2004). "Multiple domains of the Receptor-Interacting Protein 140 contribute to transcription inhibition". Nucleic Acids Research. 32 (6): 1957–66. doi:10.1093/nar/gkh524. PMC 390375. PMID 15060175.
21. Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development. 14 (1): 45–54. doi:10.1101/gad.14.1.45. PMC 316335. PMID 10640275.
22. Vega RB, Harrison BC, Meadows E, Roberts CR, Papst PJ, Olson EN, McKinsey TA (October 2004). "Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5". Molecular and Cellular Biology. 24 (19): 8374–85. doi:10.1128/MCB.24.19.8374-8385.2004. PMC 516754. PMID 15367659.
23. Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, et al. (November 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. S2CID 26092755.

Further reading

• Verdin E, Dequiedt F, Kasler HG (May 2003). "Class II histone deacetylases: versatile regulators" (PDF). Trends in Genetics. 19 (5): 286–93. doi:10.1016/S0168-9525(03)00073-8. hdl:2268/80861. PMID 12711221.
• Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes & Development. 14 (1): 45–54. doi:10.1101/gad.14.1.45. PMC 316335. PMID 10640275.
• Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000). "mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity". The Journal of Biological Chemistry. 275 (20): 15594–9. doi:10.1074/jbc.M908437199. PMID 10748098.
• Grozinger CM, Schreiber SL (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 7835–40. Bibcode:2000PNAS...97.7835G. doi:10.1073/pnas.140199597. PMC 16631. PMID 10869435.
• Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000). "BCoR, a novel corepressor involved in BCL-6 repression". Genes & Development. 14 (14): 1810–23. doi:10.1101/gad.14.14.1810. PMC 316791. PMID 10898795.
• Mahlknecht U, Schnittger S, Ottmann OG, Schoch C, Mosebach M, Hiddemann W, Hoelzer D (October 2000). "Chromosomal organization and localization of the human histone deacetylase 5 gene (HDAC5)". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1493 (3): 342–8. doi:10.1016/S0167-4781(00)00191-3. PMID 11018260.
• Zhang CL, McKinsey TA, Lu JR, Olson EN (January 2001). "Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor". The Journal of Biological Chemistry. 276 (1): 35–9. doi:10.1074/jbc.M007364200. PMID 11022042.
• McKinsey TA, Zhang CL, Lu J, Olson EN (November 2000). "Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation". Nature. 408 (6808): 106–11. Bibcode:2000Natur.408..106M. doi:10.1038/35040593. PMC 4459600. PMID 11081517.
• McKinsey TA, Zhang CL, Olson EN (December 2000). "Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5". Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14400–5. Bibcode:2000PNAS...9714400M. doi:10.1073/pnas.260501497. PMC 18930. PMID 11114197.
• Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E (September 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". The Journal of Biological Chemistry. 276 (38): 35826–35. doi:10.1074/jbc.M104935200. PMID 11466315.
• McKinsey TA, Zhang CL, Olson EN (September 2001). "Identification of a signal-responsive nuclear export sequence in class II histone deacetylases". Molecular and Cellular Biology. 21 (18): 6312–21. doi:10.1128/MCB.21.18.6312-6321.2001. PMC 87361. PMID 11509672.
• Ozawa Y, Towatari M, Tsuzuki S, Hayakawa F, Maeda T, Miyata Y, et al. (October 2001). "Histone deacetylase 3 associates with and represses the transcription factor GATA-2". Blood. 98 (7): 2116–23. doi:10.1182/blood.V98.7.2116. PMID 11567998.
• Potter GB, Beaudoin GM, DeRenzo CL, Zarach JM, Chen SH, Thompson CC (October 2001). "The hairless gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor". Genes & Development. 15 (20): 2687–701. doi:10.1101/gad.916701. PMC 312820. PMID 11641275.
• Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Molecular Cell. 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. hdl:11858/00-001M-0000-002C-9FF9-9. PMID 11804585.
• Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". The Journal of Biological Chemistry. 277 (24): 22045–52. doi:10.1074/jbc.M201736200. PMID 11929873.
• Huang Y, Tan M, Gosink M, Wang KK, Sun Y (May 2002). "Histone deacetylase 5 is not a p53 target gene, but its overexpression inhibits tumor cell growth and induces apoptosis". Cancer Research. 62 (10): 2913–22. PMID 12019172.

External links

• HDAC5+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.