HDAC5_HUMAN
ID HDAC5_HUMAN Reviewed; 1122 AA.
AC Q9UQL6; C9JFV9; O60340; O60528; Q96DY4;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Histone deacetylase 5;
DE Short=HD5;
DE EC=3.5.1.98;
DE AltName: Full=Antigen NY-CO-9;
GN Name=HDAC5; Synonyms=KIAA0600;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10220385; DOI=10.1073/pnas.96.9.4868;
RA Grozinger C.M., Hassig C.A., Schreiber S.L.;
RT "Three proteins define a class of human histone deacetylases related to
RT yeast Hda1p.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-176 (ISOFORM 3).
RC TISSUE=Neuroblastoma;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 189-1122 (ISOFORM 1).
RC TISSUE=Colon carcinoma;
RX PubMed=9610721;
RX DOI=10.1002/(sici)1097-0215(19980529)76:5<652::aid-ijc7>3.0.co;2-p;
RA Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E.,
RA Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J.;
RT "Characterization of human colon cancer antigens recognized by autologous
RT antibodies.";
RL Int. J. Cancer 76:652-658(1998).
RN [8]
RP GENE ORGANIZATION.
RX PubMed=11018260; DOI=10.1016/s0167-4781(00)00191-3;
RA Mahlknecht U., Schnittger S., Ottmann O.G., Schoch C., Mosebach M.,
RA Hiddemann W., Hoelzer D.;
RT "Chromosomal organization and localization of the human histone deacetylase
RT 5 gene (HDAC5).";
RL Biochim. Biophys. Acta 1493:342-348(2000).
RN [9]
RP INTERACTION WITH BCOR.
RX PubMed=10898795;
RA Huynh K.D., Fischle W., Verdin E., Bardwell V.J.;
RT "BCoR, a novel corepressor involved in BCL-6 repression.";
RL Genes Dev. 14:1810-1823(2000).
RN [10]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-259; SER-279;
RP SER-498; SER-661 AND SER-713.
RX PubMed=11081517; DOI=10.1038/35040593;
RA McKinsey T.A., Zhang C.-L., Lu J., Olson E.N.;
RT "Signal-dependent nuclear export of a histone deacetylase regulates muscle
RT differentiation.";
RL Nature 408:106-111(2000).
RN [11]
RP INTERACTION WITH 14-3-3, AND PHOSPHORYLATION AT SER-259 AND SER-498.
RX PubMed=11114197; DOI=10.1073/pnas.260501497;
RA McKinsey T.A., Zhang C.-L., Olson E.N.;
RT "Activation of the myocyte enhancer factor-2 transcription factor by
RT calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to
RT histone deacetylase 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14400-14405(2000).
RN [12]
RP NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF VAL-1086 AND LEU-1092.
RX PubMed=11509672; DOI=10.1128/mcb.21.18.6312-6321.2001;
RA McKinsey T.A., Zhang C.-L., Olson E.N.;
RT "Identification of a signal-responsive nuclear export sequence in class II
RT histone deacetylases.";
RL Mol. Cell. Biol. 21:6312-6321(2001).
RN [13]
RP UBIQUITINATION.
RX PubMed=12354939; DOI=10.1073/pnas.172511699;
RA Hook S.S., Orian A., Cowley S.M., Eisenman R.N.;
RT "Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ
RT domain) and copurifies with deubiquitinating enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002).
RN [14]
RP INTERACTION WITH BCL6.
RX PubMed=12504096; DOI=10.1016/s0006-291x(02)02873-5;
RA Mascle X., Albagli O., Lemercier C.;
RT "Point mutations in BCL6 DNA-binding domain reveal distinct roles for the
RT six zinc fingers.";
RL Biochem. Biophys. Res. Commun. 300:391-396(2003).
RN [15]
RP INTERACTION WITH KDM5B.
RX PubMed=17373667; DOI=10.1002/ijc.22673;
RA Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K.,
RA Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., Freemont P.,
RA Taylor-Papadimitriou J.;
RT "Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts
RT directly with histone deacetylases.";
RL Int. J. Cancer 121:265-275(2007).
RN [16]
RP INTERACTION WITH DDIT3.
RX PubMed=17872950; DOI=10.1074/jbc.m703735200;
RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.;
RT "Critical and functional regulation of CHOP (C/EBP homologous protein)
RT through the N-terminal portion.";
RL J. Biol. Chem. 282:35687-35694(2007).
RN [17]
RP PHOSPHORYLATION AT SER-259 AND SER-498, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF SER-259 AND SER-498.
RX PubMed=18184930; DOI=10.2337/db07-0843;
RA McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., Schertzer J.D.,
RA Kemp B.E., Hargreaves M.;
RT "AMP-activated protein kinase regulates GLUT4 transcription by
RT phosphorylating histone deacetylase 5.";
RL Diabetes 57:860-867(2008).
RN [18]
RP PHOSPHORYLATION AT SER-259 AND SER-498.
RX PubMed=18332134; DOI=10.1074/jbc.m800264200;
RA Ha C.H., Wang W., Jhun B.S., Wong C., Hausser A., Pfizenmaier K.,
RA McKinsey T.A., Olson E.N., Jin Z.G.;
RT "Protein kinase D-dependent phosphorylation and nuclear export of histone
RT deacetylase 5 mediates vascular endothelial growth factor-induced gene
RT expression and angiogenesis.";
RL J. Biol. Chem. 283:14590-14599(2008).
RN [19]
RP INTERACTION WITH BAHD1.
RX PubMed=19666599; DOI=10.1073/pnas.0901259106;
RA Bierne H., Tham T.N., Batsche E., Dumay A., Leguillou M.,
RA Kerneis-Golsteyn S., Regnault B., Seeler J.S., Muchardt C., Feunteun J.,
RA Cossart P.;
RT "Human BAHD1 promotes heterochromatic gene silencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:13826-13831(2009).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-533, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [21]
RP PHOSPHORYLATION AT THR-292, AND MUTAGENESIS OF SER-259; SER-291 AND
RP THR-292.
RX PubMed=20188095; DOI=10.1016/j.febslet.2010.02.057;
RA Harrison B.C., Huynh K., Lundgaard G.L., Helmke S.M., Perryman M.B.,
RA McKinsey T.A.;
RT "Protein kinase C-related kinase targets nuclear localization signals in a
RT subset of class IIa histone deacetylases.";
RL FEBS Lett. 584:1103-1110(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP INTERACTION WITH ANKRA2.
RX PubMed=22649097; DOI=10.1126/scisignal.2002979;
RA Xu C., Jin J., Bian C., Lam R., Tian R., Weist R., You L., Nie J.,
RA Bochkarev A., Tempel W., Tan C.S., Wasney G.A., Vedadi M., Gish G.D.,
RA Arrowsmith C.H., Pawson T., Yang X.J., Min J.;
RT "Sequence-specific recognition of a PxLPxI/L motif by an ankyrin repeat
RT tumbler lock.";
RL Sci. Signal. 5:RA39-RA39(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-611; SER-661 AND SER-1108,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP FUNCTION, AND INTERACTION WITH EP300.
RX PubMed=24413532; DOI=10.1158/0008-5472.can-13-2020;
RA Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y.,
RA Kim Y.N., Seong J.K., Lee M.O.;
RT "Differential regulation of estrogen receptor alpha expression in breast
RT cancer cells by metastasis-associated protein 1.";
RL Cancer Res. 74:1484-1494(2014).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [27]
RP INTERACTION WITH CUL7.
RX PubMed=25752541; DOI=10.1016/j.str.2015.02.001;
RA Nie J., Xu C., Jin J., Aka J.A., Tempel W., Nguyen V., You L., Weist R.,
RA Min J., Pawson T., Yang X.J.;
RT "Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome
RT protein CCDC8.";
RL Structure 23:700-712(2015).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-35, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [29]
RP FUNCTION, AND INTERACTION WITH RARA.
RX PubMed=28167758; DOI=10.1073/pnas.1621425114;
RA Lee D.Y., Lin T.E., Lee C.I., Zhou J., Huang Y.H., Lee P.L., Shih Y.T.,
RA Chien S., Chiu J.J.;
RT "MicroRNA-10a is crucial for endothelial response to different flow
RT patterns via interaction of retinoid acid receptors and histone
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:2072-2077(2017).
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone
CC deacetylation gives a tag for epigenetic repression and plays an
CC important role in transcriptional regulation, cell cycle progression
CC and developmental events. Histone deacetylases act via the formation of
CC large multiprotein complexes. Involved in muscle maturation by
CC repressing transcription of myocyte enhancer MEF2C. During muscle
CC differentiation, it shuttles into the cytoplasm, allowing the
CC expression of myocyte enhancer factors. Involved in the MTA1-mediated
CC epigenetic regulation of ESR1 expression in breast cancer. Serves as a
CC corepressor of RARA and causes its deacetylation (PubMed:28167758). In
CC association with RARA, plays a role in the repression of microRNA-10a
CC and thereby in the inflammatory response (PubMed:28167758).
CC {ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:28167758}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-
CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-
CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; EC=3.5.1.98;
CC -!- SUBUNIT: Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C,
CC NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6,
CC DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts with EP300 in the presence
CC of TFAP2C. Interacts with ANKRA2. Interacts with CUL7 (as part of the
CC 3M complex); negatively regulated by ANKRA2. Interacts with ZBTB7B; the
CC interaction allows the recruitment of HDAC4 on CD8 loci for
CC deacetylation and possible inhibition of CD8 genes expression (By
CC similarity). Interacts with RARA (PubMed:28167758).
CC {ECO:0000250|UniProtKB:Q9Z2V6, ECO:0000269|PubMed:10898795,
CC ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12504096,
CC ECO:0000269|PubMed:17373667, ECO:0000269|PubMed:17872950,
CC ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:22649097,
CC ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:25752541,
CC ECO:0000269|PubMed:28167758}.
CC -!- INTERACTION:
CC Q9UQL6; Q9H9E1: ANKRA2; NbExp=2; IntAct=EBI-715576, EBI-10215533;
CC Q9UQL6; Q9HCU9: BRMS1; NbExp=2; IntAct=EBI-715576, EBI-714781;
CC Q9UQL6; P23771: GATA3; NbExp=4; IntAct=EBI-715576, EBI-6664760;
CC Q9UQL6; Q9UQL6: HDAC5; NbExp=3; IntAct=EBI-715576, EBI-715576;
CC Q9UQL6; P25791-3: LMO2; NbExp=3; IntAct=EBI-715576, EBI-11959475;
CC Q9UQL6; Q06413: MEF2C; NbExp=3; IntAct=EBI-715576, EBI-2684075;
CC Q9UQL6; Q13761: RUNX3; NbExp=5; IntAct=EBI-715576, EBI-925990;
CC Q9UQL6; P31947: SFN; NbExp=3; IntAct=EBI-715576, EBI-476295;
CC Q9UQL6; P63104: YWHAZ; NbExp=3; IntAct=EBI-715576, EBI-347088;
CC Q9UQL6; Q8VEB1: Grk5; Xeno; NbExp=2; IntAct=EBI-715576, EBI-8367081;
CC Q9UQL6; P08393: ICP0; Xeno; NbExp=3; IntAct=EBI-715576, EBI-6148881;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the
CC nucleus and the cytoplasm. In muscle cells, it shuttles into the
CC cytoplasm during myocyte differentiation. The export to cytoplasm
CC depends on the interaction with a 14-3-3 chaperone protein and is due
CC to its phosphorylation at Ser-259 and Ser-498 by AMPK, CaMK1 and SIK1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9UQL6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UQL6-2; Sequence=VSP_002081;
CC Name=3;
CC IsoId=Q9UQL6-3; Sequence=VSP_039180;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between the
CC nucleus and the cytoplasm. {ECO:0000250}.
CC -!- PTM: Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and Ser-
CC 498. The phosphorylation is required for the export to the cytoplasm
CC and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2,
CC impairing nuclear import. Phosphorylated by GRK5, leading to nuclear
CC export of HDAC5 and allowing MEF2-mediated transcription (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Polyubiquitination however does not lead to its
CC degradation. {ECO:0000269|PubMed:12354939}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC18040.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA25526.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF132608; AAD29047.1; -; mRNA.
DR EMBL; AB011172; BAA25526.2; ALT_INIT; mRNA.
DR EMBL; AC023855; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013140; AAH13140.1; ALT_TERM; mRNA.
DR EMBL; BC051824; AAH51824.1; -; mRNA.
DR EMBL; BX458255; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF039691; AAC18040.1; ALT_FRAME; mRNA.
DR EMBL; BK000028; DAA00017.1; -; Genomic_DNA.
DR CCDS; CCDS32663.1; -. [Q9UQL6-3]
DR CCDS; CCDS45696.1; -. [Q9UQL6-1]
DR RefSeq; NP_001015053.1; NM_001015053.1. [Q9UQL6-3]
DR RefSeq; NP_005465.2; NM_005474.4. [Q9UQL6-1]
DR RefSeq; XP_005256963.1; XM_005256906.4.
DR PDB; 5UWI; X-ray; 2.14 A; D=1078-1095.
DR PDBsum; 5UWI; -.
DR AlphaFoldDB; Q9UQL6; -.
DR SMR; Q9UQL6; -.
DR BioGRID; 115331; 363.
DR CORUM; Q9UQL6; -.
DR DIP; DIP-38260N; -.
DR ELM; Q9UQL6; -.
DR IntAct; Q9UQL6; 40.
DR MINT; Q9UQL6; -.
DR STRING; 9606.ENSP00000225983; -.
DR BindingDB; Q9UQL6; -.
DR ChEMBL; CHEMBL2563; -.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB06603; Panobinostat.
DR DrugCentral; Q9UQL6; -.
DR GuidetoPHARMACOLOGY; 2660; -.
DR iPTMnet; Q9UQL6; -.
DR PhosphoSitePlus; Q9UQL6; -.
DR BioMuta; HDAC5; -.
DR DMDM; 296434519; -.
DR EPD; Q9UQL6; -.
DR jPOST; Q9UQL6; -.
DR MassIVE; Q9UQL6; -.
DR MaxQB; Q9UQL6; -.
DR PaxDb; Q9UQL6; -.
DR PeptideAtlas; Q9UQL6; -.
DR PRIDE; Q9UQL6; -.
DR ProteomicsDB; 85556; -. [Q9UQL6-1]
DR ProteomicsDB; 85557; -. [Q9UQL6-2]
DR ProteomicsDB; 85558; -. [Q9UQL6-3]
DR Antibodypedia; 3425; 777 antibodies from 44 providers.
DR DNASU; 10014; -.
DR Ensembl; ENST00000225983.10; ENSP00000225983.5; ENSG00000108840.16. [Q9UQL6-3]
DR Ensembl; ENST00000336057.9; ENSP00000337290.4; ENSG00000108840.16. [Q9UQL6-2]
DR Ensembl; ENST00000586802.5; ENSP00000468004.1; ENSG00000108840.16. [Q9UQL6-1]
DR Ensembl; ENST00000682912.1; ENSP00000507606.1; ENSG00000108840.16. [Q9UQL6-1]
DR GeneID; 10014; -.
DR KEGG; hsa:10014; -.
DR MANE-Select; ENST00000682912.1; ENSP00000507606.1; NM_005474.5; NP_005465.2.
DR UCSC; uc002ifd.2; human. [Q9UQL6-1]
DR CTD; 10014; -.
DR DisGeNET; 10014; -.
DR GeneCards; HDAC5; -.
DR HGNC; HGNC:14068; HDAC5.
DR HPA; ENSG00000108840; Low tissue specificity.
DR MIM; 605315; gene.
DR neXtProt; NX_Q9UQL6; -.
DR OpenTargets; ENSG00000108840; -.
DR PharmGKB; PA29230; -.
DR VEuPathDB; HostDB:ENSG00000108840; -.
DR eggNOG; KOG1343; Eukaryota.
DR GeneTree; ENSGT00940000160534; -.
DR HOGENOM; CLU_006530_2_0_1; -.
DR InParanoid; Q9UQL6; -.
DR OMA; SKCWGAH; -.
DR OrthoDB; 1484694at2759; -.
DR PhylomeDB; Q9UQL6; -.
DR TreeFam; TF106174; -.
DR PathwayCommons; Q9UQL6; -.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR SignaLink; Q9UQL6; -.
DR SIGNOR; Q9UQL6; -.
DR BioGRID-ORCS; 10014; 10 hits in 1096 CRISPR screens.
DR ChiTaRS; HDAC5; human.
DR GeneWiki; Histone_deacetylase_5; -.
DR GenomeRNAi; 10014; -.
DR Pharos; Q9UQL6; Tclin.
DR PRO; PR:Q9UQL6; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UQL6; protein.
DR Bgee; ENSG00000108840; Expressed in cortical plate and 162 other tissues.
DR ExpressionAtlas; Q9UQL6; baseline and differential.
DR Genevisible; Q9UQL6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IMP:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; NAS:BHF-UCL.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; TAS:ProtInc.
DR GO; GO:0031507; P:heterochromatin assembly; TAS:ProtInc.
DR GO; GO:0016575; P:histone deacetylation; IDA:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006476; P:protein deacetylation; IMP:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IMP:BHF-UCL.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N.
DR InterPro; IPR017320; Histone_deAcase_II_euk.
DR InterPro; IPR030703; Histone_deacetylase_5.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR PANTHER; PTHR45364; PTHR45364; 1.
DR PANTHER; PTHR45364:SF2; PTHR45364:SF2; 1.
DR Pfam; PF12203; HDAC4_Gln; 1.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037911; HDAC_II_euk; 1.
DR PRINTS; PR01270; HDASUPER.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator;
KW Cytoplasm; Hydrolase; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..1122
FT /note="Histone deacetylase 5"
FT /id="PRO_0000114701"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 41..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 302..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 536..625
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..1028
FT /note="Histone deacetylase"
FT REGION 1097..1122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1081..1122
FT /note="Nuclear export signal"
FT COMPBIAS 228..242
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..281
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..617
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 833
FT /evidence="ECO:0000250"
FT BINDING 696
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 698
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 704
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 259
FT /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT /evidence="ECO:0000269|PubMed:11114197,
FT ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18332134"
FT MOD_RES 292
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000269|PubMed:20188095"
FT MOD_RES 498
FT /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT /evidence="ECO:0000269|PubMed:11114197,
FT ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18332134"
FT MOD_RES 533
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 7
FT /note="S -> SA (in isoform 3)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_039180"
FT VAR_SEQ 684..768
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9628581"
FT /id="VSP_002081"
FT VARIANT 137
FT /note="R -> Q (in dbSNP:rs438096)"
FT /id="VAR_055903"
FT VARIANT 565
FT /note="G -> A (in dbSNP:rs33916560)"
FT /id="VAR_055904"
FT MUTAGEN 259
FT /note="S->A: Reduces AMPK- and caMK-dependent
FT phosphorylation and the subsequent nuclear export.
FT Abolishes nuclear export; when associated with A-498. Does
FT not affect phosphorylation by PKN1 and PKN2."
FT /evidence="ECO:0000269|PubMed:11081517,
FT ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20188095"
FT MUTAGEN 279
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:11081517"
FT MUTAGEN 291
FT /note="S->A: Does not affect phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:20188095"
FT MUTAGEN 292
FT /note="T->A: Abolishes phosphorylation by PKC."
FT /evidence="ECO:0000269|PubMed:20188095"
FT MUTAGEN 498
FT /note="S->A: Reduces AMPK- and CaMK-dependent
FT phosphorylation and the subsequent nuclear export.
FT Abolishes nuclear export; when associated with A-259."
FT /evidence="ECO:0000269|PubMed:11081517,
FT ECO:0000269|PubMed:18184930"
FT MUTAGEN 661
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:11081517"
FT MUTAGEN 713
FT /note="S->A: No effect."
FT /evidence="ECO:0000269|PubMed:11081517"
FT MUTAGEN 1086
FT /note="V->A: Reduces CaMK-dependent nuclear export."
FT /evidence="ECO:0000269|PubMed:11509672"
FT MUTAGEN 1092
FT /note="L->A: Reduces CaMK-dependent nuclear export."
FT /evidence="ECO:0000269|PubMed:11509672"
FT CONFLICT 37
FT /note="V -> L (in Ref. 6; BX458255)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="Q -> R (in Ref. 6; BX458255)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="R -> G (in Ref. 6; BX458255)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="D -> E (in Ref. 1; AAD29047, 5; AAH51824 and 7;
FT AAC18040)"
FT /evidence="ECO:0000305"
FT CONFLICT 671
FT /note="S -> N (in Ref. 7; AAC18040)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="G -> S (in Ref. 7; AAC18040)"
FT /evidence="ECO:0000305"
FT CONFLICT 1026
FT /note="E -> K (in Ref. 7; AAC18040)"
FT /evidence="ECO:0000305"
FT CONFLICT 1074
FT /note="E -> G (in Ref. 7; AAC18040)"
FT /evidence="ECO:0000305"
FT CONFLICT 1093
FT /note="S -> L (in Ref. 7; AAC18040)"
FT /evidence="ECO:0000305"
FT HELIX 1083..1090
FT /evidence="ECO:0007829|PDB:5UWI"
SQ SEQUENCE 1122 AA; 121978 MW; CF4BE774E3588FEC CRC64;
MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR
GALVGSVDPT LREQQLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ
QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS
TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL
PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI
TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSPNQ
FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST
SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS
MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE
LPRQPTTHPE ETEEELTEQQ EVLLGEGALT MPREGSTESE STQEDLEEED EEDDGEEEED
CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ
SSPAAPGGMK SPPDQPVKHL FTTGVVYDTF MLKHQCMCGN THVHPEHAGR IQSIWSRLQE
TGLLSKCERI RGRKATLDEI QTVHSEYHTL LYGTSPLNRQ KLDSKKLLGP ISQKMYAVLP
CGGIGVDSDT VWNEMHSSSA VRMAVGCLLE LAFKVAAGEL KNGFAIIRPP GHHAEESTAM
GFCFFNSVAI TAKLLQQKLN VGKVLIVDWD IHHGNGTQQA FYNDPSVLYI SLHRYDNGNF
FPGSGAPEEV GGGPGVGYNV NVAWTGGVDP PIGDVEYLTA FRTVVMPIAH EFSPDVVLVS
AGFDAVEGHL SPLGGYSVTA RCFGHLTRQL MTLAGGRVVL ALEGGHDLTA ICDASEACVS
ALLSVELQPL DEAVLQQKPN INAVATLEKV IEIQSKHWSC VQKFAAGLGR SLREAQAGET
EEAETVSAMA LLSVGAEQAQ AAAAREHSPR PAEEPMEQEP AL
