HDAC6

هیستون دِاَستیلاز ۶ (انگلیسی: Histone deacetylase 6‎) یک پروتئین است که در انسان توسط ژن «HDAC6» کُدگذاری می‌شود.[5][6]

HDAC6
ساختارهای موجود PDB Ortholog search: PDBe RCSB List of PDB id codes 3C5K, 3GV4, 3PHD, 5EDU, 5KH7
معین‌کننده‌ها
نام‌های دیگر	HDAC6, CPBHM, HD6, PPP1R90, JM21, histone deacetylase 6
شناسه‌های بیرونی	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]
الگوی گسترش RNA More reference expression data
هستی‌شناسی ژن عملکرد ملکولی • 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 پیوند پروتئینی • 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 ترکیبات سلولی • سیتوزول • perinuclear region of cytoplasm • حفره غشایی • ریزلوله • هسته یاخته • multivesicular body • cell projection • microtubule associated complex • aggresome • dynein complex • histone deacetylase complex • پریکاریون • آسه • Inclusion bodies • دندریت • cell leading edge • cytoplasmic microtubule • cell body • neuron projection • نوکلئوپلاسم • سیتوپلاسم • protein-containing complex فرایند زیستی • 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 • regulation of signaling 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 • regulation of gene expression, epigenetic • negative regulation of protein-containing complex disassembly • خودخواری • negative regulation of microtubule depolymerization • lysosome localization • histone deacetylation • cellular response to hydrogen peroxide • covalent chromatin modification • collateral sprouting • dendritic spine morphogenesis • cilium assembly • 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 • protein-containing complex disassembly • positive regulation of peptidyl-serine phosphorylation • polyamine deacetylation • spermidine deacetylation Sources:آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
گونه‌ها	انسان	موش
Entrez	10013	15185
آنسامبل	ENSG00000094631	ENSMUSG00000031161
یونی‌پروت	Q9UBN7	Q9Z2V5
RefSeq (mRNA)	XR_246712، NM_001321225، NM_001321226، NM_001321227، NM_001321228، NM_001321229، NM_001321230، NM_001321231، NR_135591، NR_135592، NR_135593، XM_017029187، XR_001755632، XR_002958755، XR_002958756، XR_002958757 NM_006044، XR_246712، NM_001321225، NM_001321226، NM_001321227، NM_001321228، NM_001321229، NM_001321230، NM_001321231، NR_135591، NR_135592، NR_135593، XM_017029187، XR_001755632، XR_002958755، XR_002958756، XR_002958757	NM_010413، XM_006527567، XM_017318389، XM_017318390 NM_001130416، NM_010413، XM_006527567، XM_017318389، XM_017318390
RefSeq (پروتئین)	NP_001308155، NP_001308156، NP_001308157، NP_001308158، NP_001308159، NP_001308160، NP_006035، XP_016884676 NP_001308154، NP_001308155، NP_001308156، NP_001308157، NP_001308158، NP_001308159، NP_001308160، NP_006035، XP_016884676	NP_034543، XP_006527630، XP_017173878، XP_036017717 NP_001123888، NP_034543، XP_006527630، XP_017173878، XP_036017717
موقعیت (UCSC)	Chr X: 48.8 – 48.82 Mb	Chr X: 7.93 – 7.95 Mb
جستجوی PubMed	[3]	[4]
ویکی‌داده
مشاهده/ویرایش Human View/Edit Mouse

این پروتئین نقش بسیار مهمی در تنظیم رونویسی ژن‌ها، پیشرفتِ چرخهٔ سلولی و وقایع تکاملی سلول دارد.

این آنزیم موجب جمع‌شدگی مژک سلول‌ها می‌شود که برای انجام میتوز ضروری است.[7] علاوه بر آن، هیستون دِاَستیلاز ۶ موجب افزایش مهاجرت سلول شده و فرایند دِاستیلاسیونِ آلفا توبولین را تسهیل می‌کند.[8]

اهمیت بالینی

جهش در ژن «HDAC6» با بیماری آلزایمر در ارتباط است.[9]

همچنین ساخت بیش از حد این پروتئین با سرطان‌زایی و زنده‌ماندن سلول‌ها مرتبط است و موجب افزایش متاستاز سرطان‌ها هم می‌شود.[10]

منابع

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. 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.
8. 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.
9. 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.
10. 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.

• مشارکت‌کنندگان ویکی‌پدیا. «HDAC6». در دانشنامهٔ ویکی‌پدیای انگلیسی، بازبینی‌شده در ۹ مارس ۲۰۲۰.

برای مطالعهٔ بیشتر

• 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.

پیوند به بیرون

• HDAC6 protein, human در سرعنوان‌های موضوعی پزشکی (MeSH) در کتابخانهٔ ملی پزشکی ایالات متحدهٔ آمریکا
• مکان ژن انسانی HDAC6 در مرورگر ژنومی UCSC.
• جزئیات ژن انسانی HDAC6 در مرورگر ژنومی UCSC.