Histone deacetylase 8

Details

Name
Histone deacetylase 8
Synonyms
  • 3.5.1.98
  • HD8
  • HDACL1
Gene Name
HDAC8
Organism
Humans
Amino acid sequence
>lcl|BSEQ0003191|Histone deacetylase 8
MEEPEEPADSGQSLVPVYIYSPEYVSMCDSLAKIPKRASMVHSLIEAYALHKQMRIVKPK
VASMEEMATFHTDAYLQHLQKVSQEGDDDHPDSIEYGLGYDCPATEGIFDYAAAIGGATI
TAAQCLIDGMCKVAINWSGGWHHAKKDEASGFCYLNDAVLGILRLRRKFERILYVDLDLH
HGDGVEDAFSFTSKVMTVSLHKFSPGFFPGTGDVSDVGLGKGRYYSVNVPIQDGIQDEKY
YQICESVLKEVYQAFNPKAVVLQLGADTIAGDPMCSFNMTPVGIGKCLKYILQWQLATLI
LGGGGYNLANTARCWTYLTGVILGKTLSSEIPDHEFFTAYGPDYVLEITPSCRPDRNEPH
RIQQILNYIKGNLKHVV
Number of residues
377
Molecular Weight
41757.29
Theoretical pI
5.37
GO Classification
Functions
histone deacetylase activity / metal ion binding / NAD-dependent histone deacetylase activity (H3-K14 specific) / transcription factor binding
Processes
chromatin assembly or disassembly / chromatin modification / chromatin organization / mitotic cell cycle / negative regulation of transcription from RNA polymerase II promoter / regulation of cohesin localization to chromatin / sister chromatid cohesion / transcription, DNA-templated
Components
cytoplasm / cytosol / histone deacetylase complex / nuclear chromosome / nucleoplasm / nucleus / plasma membrane
General Function
Transcription factor binding
Specific Function
Responsible for 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0016492|Histone deacetylase 8 (HDAC8)
ATGGAGGAGCCGGAGGAACCGGCGGACAGTGGGCAGTCGCTGGTCCCGGTTTATATCTAT
AGTCCCGAGTATGTCAGTATGTGTGACTCCCTGGCCAAGATCCCCAAACGGGCCAGTATG
GTGCATTCTTTGATTGAAGCATATGCACTGCATAAGCAGATGAGAGATGAAGCATCTGGT
TTTTGTTATCTCAATGATGCTGTCCTGGGAATATTACGATTGCGACGGAAATTTGAGCGT
ATTCTCTACGTGGATTTGGATCTGCACCATGGAGATGGTGTAGAAGACGCATTCAGTTTC
ACCTCCAAAGTCATGACCGTGTCCCTGCACAAATTCTCCCCAGGATTTTTCCCAGGAACA
GGTGACGTGTCTGATGTTGGCCTAGGGAAGGGACGGTACTACAGTGTAAATGTGCCCATT
CAGGATGGCATACAAGATGAAAAATATTACCAGATCTGTGAAAGTGTACTAAAGGAAGTA
TACCAAGCCTTTAATCCCAAAGCAGTGGTCTTACAGCTGGGAGCTGACACAATAGCTGGG
GATCCCATGTGCTCCTTTAACATGACTCCAGTGGGAATTGGCAAGTGTCTTAAGTACATC
CTTCAATGGCAGTTGGCAACACTCATTTTGGGAGGAGGAGGCTATAACCTTGCCAACACG
GCTCGATGCTGGACATACTTGACCGGGGTCATCCTAGGGAAAACACTATCCTCTGAGATC
CCAGATCATGAGTTTTTCACAGCATATGGTCCTGATTATGTGCTGGAAATCACGCCAAGC
TGCCGGCCAGACCGCAATGAGCCCCACCGAATCCAACAAATCCTCAACTACATCAAAGGG
AATCTGAAGCATGTGGTCTAG
Chromosome Location
X
Locus
Xq13
External Identifiers
ResourceLink
UniProtKB IDQ9BY41
UniProtKB Entry NameHDAC8_HUMAN
GenBank Protein ID8118721
GenBank Gene IDAF230097
GenAtlas IDHDAC8
HGNC IDHGNC:13315
General References
  1. Hu E, Chen Z, Fredrickson T, Zhu Y, Kirkpatrick R, Zhang GF, Johanson K, Sung CM, Liu R, Winkler J: Cloning and characterization of a novel human class I histone deacetylase that functions as a transcription repressor. J Biol Chem. 2000 May 19;275(20):15254-64. [PubMed:10748112]
  2. Buggy JJ, Sideris ML, Mak P, Lorimer DD, McIntosh B, Clark JM: Cloning and characterization of a novel human histone deacetylase, HDAC8. Biochem J. 2000 Aug 15;350 Pt 1:199-205. [PubMed:10926844]
  3. Van den Wyngaert I, de Vries W, Kremer A, Neefs J, Verhasselt P, Luyten WH, Kass SU: Cloning and characterization of human histone deacetylase 8. FEBS Lett. 2000 Jul 28;478(1-2):77-83. [PubMed:10922473]
  4. 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: Characterization of a highly complex region in Xq13 and mapping of three isodicentric breakpoints associated with preleukemia. Genomics. 2000 Mar 15;64(3):221-9. [PubMed:10756090]
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  9. Amann JM, Nip J, Strom DK, Lutterbach B, Harada H, Lenny N, Downing JR, Meyers S, Hiebert SW: ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol Cell Biol. 2001 Oct;21(19):6470-83. [PubMed:11533236]
  10. Durst KL, Lutterbach B, Kummalue T, Friedman AD, Hiebert SW: The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain. Mol Cell Biol. 2003 Jan;23(2):607-19. [PubMed:12509458]
  11. Lee H, Rezai-Zadeh N, Seto E: Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A. Mol Cell Biol. 2004 Jan;24(2):765-73. [PubMed:14701748]
  12. Waltregny D, Glenisson W, Tran SL, North BJ, Verdin E, Colige A, Castronovo V: Histone deacetylase HDAC8 associates with smooth muscle alpha-actin and is essential for smooth muscle cell contractility. FASEB J. 2005 Jun;19(8):966-8. Epub 2005 Mar 16. [PubMed:15772115]
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  17. Somoza JR, Skene RJ, Katz BA, Mol C, Ho JD, Jennings AJ, Luong C, Arvai A, Buggy JJ, Chi E, Tang J, Sang BC, Verner E, Wynands R, Leahy EM, Dougan DR, Snell G, Navre M, Knuth MW, Swanson RV, McRee DE, Tari LW: Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure. 2004 Jul;12(7):1325-34. [PubMed:15242608]
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  19. Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW: Structural studies of human histone deacetylase 8 and its site-specific variants complexed with substrate and inhibitors. Biochemistry. 2008 Dec 23;47(51):13554-63. doi: 10.1021/bi801610c. [PubMed:19053282]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB025654-Dimethylamino-N-(6-Hydroxycarbamoyethyl)Benzamide-N-Hydroxy-7-(4-Dimethyla Minobenzoyl)AminoheptanamideexperimentalunknownDetails
DB02917N-Hydroxy-4-(Methyl{[5-(2-Pyridinyl)-2-Thienyl]Sulfonyl}Amino)BenzamideexperimentalunknownDetails
DB042977-[4-(Dimethylamino)Phenyl]-N-Hydroxy-4,6-Dimethyl-7-Oxo-2,4-HeptadienamideexperimentalunknownDetails
DB02546Vorinostatapproved, investigationalunknownDetails
DB07350(2E)-N-hydroxy-3-[1-methyl-4-(phenylacetyl)-1H-pyrrol-2-yl]prop-2-enamideexperimentalunknownDetails
DB075865-(4-METHYL-BENZOYLAMINO)-BIPHENYL-3,4'-DICARBOXYLIC ACID 3-DIMETHYLAMIDE-4'-HYDROXYAMIDEexperimentalunknownDetails
DB081687-AMINO-4-METHYL-CHROMEN-2-ONEexperimentalunknownDetails
DB01592IronapprovedunknowncofactorDetails
DB01593Zincapproved, investigationalunknowncofactorDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14488Ferrous gluconateapprovedunknownDetails
DB14489Ferrous succinateapprovedunknownDetails
DB14490Ferrous ascorbateapprovedunknownDetails
DB14491Ferrous fumarateapprovedunknownDetails
DB14501Ferrous glycine sulfateapprovedunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails
DB05015Belinostatapproved, investigationalyesinhibitorDetails
DB06603Panobinostatapproved, investigationalyesinhibitorDetails