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 04-NOV-2026, entry version 238. DE RecName: Full=Histone deacetylase 5 {ECO:0000303|PubMed:11018260, ECO:0000303|PubMed:11114197}; DE Short=HD5; DE EC=3.5.1.98 {ECO:0000269|PubMed:10220385}; DE AltName: Full=Antigen NY-CO-9; GN Name=HDAC5 {ECO:0000303|PubMed:10220385, ECO:0000303|PubMed:11018260, GN ECO:0000312|HGNC:HGNC:14068}; GN Synonyms=KIAA0600 {ECO:0000312|HGNC:HGNC:14068}; 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), TISSUE SPECIFICITY, FUNCTION, RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. 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; DOI=10.1101/gad.14.14.1810; 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: In vitro, it deacetylates lysine residues on the N-terminal CC part of the core histones (H2A, H2B, H3 and H4) (PubMed:10220385). CC Histone deacetylation gives a tag for epigenetic repression and plays CC an 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:10220385, ECO:0000269|PubMed:24413532, CC ECO:0000269|PubMed:28167758}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + CC acetate; 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 Evidence={ECO:0000269|PubMed:10220385}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197; CC Evidence={ECO:0000305|PubMed:10220385}; CC -!- ACTIVITY REGULATION: Inhibited by trichostatin A. CC {ECO:0000269|PubMed:10220385}. 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=5; 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: Widely expressed. Expressed in the heart, brain, CC kidney, pancreas, liver, skeletal muscle, placenta (PubMed:10220385). CC {ECO:0000269|PubMed:10220385}. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_001015053.2. [Q9UQL6-3] DR RefSeq; NP_001369322.1; NM_001382393.1. [Q9UQL6-1] DR RefSeq; NP_005465.2; NM_005474.5. [Q9UQL6-1] DR RefSeq; XP_047291003.1; XM_047435047.1. [Q9UQL6-3] DR PDB; 5UWI; X-ray; 2.14 A; D=1078-1095. DR PDB; 8Q9P; X-ray; 2.20 A; X=179-195. DR AlphaFoldDB; Q9UQL6; -. DR SASBDB; Q9UQL6; -. DR SMR; Q9UQL6; -. DR BioGRID; 115331; 371. DR CORUM; Q9UQL6; -. DR DIP; DIP-38260N; -. DR ELM; Q9UQL6; -. DR FunCoup; Q9UQL6; 2922. DR IntAct; Q9UQL6; 43. DR NDEx; IQUERY-CP-HDAC5; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000225983; -. DR BindingDB; Q9UQL6; -. DR ChEMBL; CHEMBL2563; -. DR DrugBank; DB12565; Abexinostat. DR DrugBank; DB05015; Belinostat. DR DrugBank; DB01262; Decitabine. DR DrugBank; DB11841; Entinostat. DR DrugBank; DB12645; Givinostat. DR DrugBank; DB14979; Martinostat. DR DrugBank; DB06603; Panobinostat. DR DrugBank; DB06819; Phenylbutyric acid. DR DrugBank; DB03766; Propanoic acid. DR DrugBank; DB12847; Pyroxamide. DR DrugBank; DB06176; Romidepsin. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB02546; Vorinostat. DR DrugCentral; Q9UQL6; -. DR GuidetoPHARMACOLOGY; 2660; -. DR GlyGen; Q9UQL6; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9UQL6; -. DR PhosphoSitePlus; Q9UQL6; -. DR BioMuta; HDAC5; -. DR DMDM; 296434519; -. DR jPOST; Q9UQL6; -. DR MassIVE; Q9UQL6; -. DR PaxDb; 9606-ENSP00000225983; -. DR PeptideAtlas; Q9UQL6; -. DR ProteomicsDB; 85556; -. [Q9UQL6-1] DR ProteomicsDB; 85557; -. [Q9UQL6-2] DR ProteomicsDB; 85558; -. [Q9UQL6-3] DR Pumba; Q9UQL6; -. DR Antibodypedia; 3425; 861 antibodies from 47 providers. DR DNASU; 10014; -. DR Ensembl; ENST00000225983.10; ENSP00000225983.5; ENSG00000108840.18. [Q9UQL6-3] DR Ensembl; ENST00000336057.9; ENSP00000337290.4; ENSG00000108840.18. [Q9UQL6-2] DR Ensembl; ENST00000586802.5; ENSP00000468004.1; ENSG00000108840.18. [Q9UQL6-1] DR Ensembl; ENST00000682912.1; ENSP00000507606.1; ENSG00000108840.18. [Q9UQL6-1] DR Ensembl; ENST00000715273.1; ENSP00000520442.1; ENSG00000108840.18. [Q9UQL6-1] DR Ensembl; ENST00000864902.1; ENSP00000534961.1; ENSG00000108840.18. [Q9UQL6-3] DR Ensembl; ENST00000864918.1; ENSP00000534977.1; ENSG00000108840.18. [Q9UQL6-3] DR Ensembl; ENST00000864923.1; ENSP00000534982.1; ENSG00000108840.18. [Q9UQL6-2] 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 AGR; HGNC:14068; -. DR ClinPGx; PA29230; -. 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 OpenTargets; ENSG00000108840; -. DR VEuPathDB; HostDB:ENSG00000108840; -. DR eggNOG; KOG1343; Eukaryota. DR GeneTree; ENSGT00940000160534; -. DR HOGENOM; CLU_006530_2_0_1; -. DR InParanoid; Q9UQL6; -. DR OrthoDB; 424012at2759; -. DR PAN-GO; Q9UQL6; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9UQL6; -. 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 Reactome; R-HSA-9976102; Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells). DR SignaLink; Q9UQL6; -. DR SIGNOR; Q9UQL6; -. DR Agora; ENSG00000108840; -. DR BioGRID-ORCS; 10014; 20 hits in 1176 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 164 other cell types or tissues. DR ExpressionAtlas; Q9UQL6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; 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:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0001216; F:DNA-binding transcription activator activity; IMP:ARUK-UCL. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB. DR GO; GO:0141221; F:histone deacetylase activity, hydrolytic mechanism; IEA:UniProtKB-EC. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0040029; P:epigenetic regulation of gene expression; IBA:GO_Central. 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:0045892; P:negative regulation of DNA-templated transcription; TAS:UniProtKB. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; NAS:UniProtKB. 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:BHF-UCL. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR CDD; cd10164; ClassIIa_HDAC5_Gln-rich-N; 1. DR CDD; cd10007; HDAC5; 1. DR FunFam; 3.40.800.20:FF:000002; Histone deacetylase; 1. DR Gene3D; 6.10.250.1550; -; 1. DR Gene3D; 3.40.800.20; Histone deacetylase domain; 1. DR InterPro; IPR046949; HDAC4/5/7/9. DR InterPro; IPR000286; HDACs. DR InterPro; IPR023801; His_deacetylse_dom. DR InterPro; IPR037138; His_deacetylse_dom_sf. DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N. DR InterPro; IPR023696; Ureohydrolase_dom_sf. DR PANTHER; PTHR45364:SF12; HISTONE DEACETYLASE; 1. DR PANTHER; PTHR45364; HISTONE DEACETYLASE 9-RELATED; 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; Arginase/deacetylase; 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; Proteomics identification; Reference proteome; Repressor; KW Transcription; 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 247..258 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 272..281 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 312..327 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 328..340 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 494..504 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 581..621 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1104..1113 FT /note="Basic and 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 STRAND 180..182 FT /evidence="ECO:0007829|PDB:8Q9P" FT HELIX 183..192 FT /evidence="ECO:0007829|PDB:8Q9P" 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 //