HDAC4_HUMAN
ID HDAC4_HUMAN Reviewed; 1084 AA.
AC P56524; E9PGB9; F5GX36; Q86YH7; Q9UND6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Histone deacetylase 4;
DE Short=HD4;
DE EC=3.5.1.98;
GN Name=HDAC4; Synonyms=KIAA0288;
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).
RC TISSUE=Leukemia;
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 1).
RC TISSUE=Brain;
RX PubMed=9179496; DOI=10.1093/dnares/4.1.53;
RA Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N.,
RA Nomura N.;
RT "Construction and characterization of human brain cDNA libraries suitable
RT for analysis of cDNA clones encoding relatively large proteins.";
RL DNA Res. 4:53-59(1997).
RN [3]
RP SEQUENCE REVISION TO N-TERMINUS.
RA Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N.,
RA Nomura N.;
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=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 [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MEF2A.
RX PubMed=10487761; DOI=10.1093/emboj/18.18.5099;
RA Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T.;
RT "HDAC4 deacetylase associates with and represses the MEF2 transcription
RT factor.";
RL EMBO J. 18:5099-5107(1999).
RN [8]
RP FUNCTION, INTERACTION WITH MEF2C AND MEF2D, AND MUTAGENESIS OF HIS-803.
RX PubMed=10523670; DOI=10.1128/mcb.19.11.7816;
RA Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H.,
RA Th'ng J., Han J., Yang X.-J.;
RT "HDAC4, a human histone deacetylase related to yeast HDA1, is a
RT transcriptional corepressor.";
RL Mol. Cell. Biol. 19:7816-7827(1999).
RN [9]
RP PHOSPHORYLATION AT SER-246; SER-467 AND SER-632, MUTAGENESIS OF SER-246;
RP SER-467 AND SER-632, AND INTERACTION WITH 14-3-3 PROTEINS.
RX PubMed=10958686; DOI=10.1128/mcb.20.18.6904-6912.2000;
RA Wang A.H., Kruhlak M.J., Wu J., Bertos N.R., Vezmar M., Posner B.I.,
RA Bazett-Jones D.P., Yang X.-J.;
RT "Regulation of histone deacetylase 4 by binding of 14-3-3 proteins.";
RL Mol. Cell. Biol. 20:6904-6912(2000).
RN [10]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-467 AND
RP SER-632.
RX PubMed=11470791; DOI=10.1074/jbc.m105086200;
RA Zhao X., Ito A., Kane C.D., Liao T.-S., Bolger T.A., Lemrow S.M.,
RA Means A.R., Yao T.-P.;
RT "The modular nature of histone deacetylase HDAC4 confers phosphorylation-
RT dependent intracellular trafficking.";
RL J. Biol. Chem. 276:35042-35048(2001).
RN [11]
RP NUCLEAR EXPORT SIGNAL, AND MUTAGENESIS OF VAL-1056 AND LEU-1062.
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 [12]
RP INTERACTION WITH NR2C1.
RX PubMed=11463856; DOI=10.1210/mend.15.8.0682;
RA Franco P.J., Farooqui M., Seto E., Wei L.-N.;
RT "The orphan nuclear receptor TR2 interacts directly with both class I and
RT class II histone deacetylases.";
RL Mol. Endocrinol. 15:1318-1328(2001).
RN [13]
RP HOMODIMERIZATION, SUMOYLATION AT LYS-559, AND MUTAGENESIS OF LYS-559.
RX PubMed=12032081; DOI=10.1093/emboj/21.11.2682;
RA Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E.,
RA Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.;
RT "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4
RT deacetylase.";
RL EMBO J. 21:2682-2691(2002).
RN [14]
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 [15]
RP PHOSPHORYLATION BY CAMK2D.
RX PubMed=17179159; DOI=10.1074/jbc.m604281200;
RA Little G.H., Bai Y., Williams T., Poizat C.;
RT "Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially
RT transmits signals to histone deacetylase 4 in cardiac cells.";
RL J. Biol. Chem. 282:7219-7231(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632 AND SER-633, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP INVOLVEMENT IN BDMR.
RX PubMed=20691407; DOI=10.1016/j.ajhg.2010.07.011;
RA Williams S.R., Aldred M.A., Der Kaloustian V.M., Halal F., Gowans G.,
RA McLeod D.R., Zondag S., Toriello H.V., Magenis R.E., Elsea S.H.;
RT "Haploinsufficiency of HDAC4 causes brachydactyly mental retardation
RT syndrome, with brachydactyly type E, developmental delays, and behavioral
RT problems.";
RL Am. J. Hum. Genet. 87:219-228(2010).
RN [19]
RP INTERACTION WITH MORC2.
RX PubMed=20110259; DOI=10.1093/nar/gkq006;
RA Shao Y., Li Y., Zhang J., Liu D., Liu F., Zhao Y., Shen T., Li F.;
RT "Involvement of histone deacetylation in MORC2-mediated down-regulation of
RT carbonic anhydrase IX.";
RL Nucleic Acids Res. 38:2813-2824(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP INVOLVEMENT IN BDMR.
RX PubMed=23188045; DOI=10.1038/ejhg.2012.240;
RA Villavicencio-Lorini P., Klopocki E., Trimborn M., Koll R., Mundlos S.,
RA Horn D.;
RT "Phenotypic variant of Brachydactyly-mental retardation syndrome in a
RT family with an inherited interstitial 2q37.3 microdeletion including
RT HDAC4.";
RL Eur. J. Hum. Genet. 21:743-748(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, AND IDENTIFICATION BY
RP 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 [24]
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 [25]
RP INVOLVEMENT IN BDMR.
RX PubMed=24715439; DOI=10.1002/ajmg.a.36542;
RA Wheeler P.G., Huang D., Dai Z.;
RT "Haploinsufficiency of HDAC4 does not cause intellectual disability in all
RT affected individuals.";
RL Am. J. Med. Genet. A 164A:1826-1829(2014).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, AND IDENTIFICATION BY
RP 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 AND ANKRA2, AND MUTAGENESIS OF PRO-349 AND ILE-354.
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 FUNCTION, AND INTERACTION WITH HSPA1A AND HSPA1B.
RX PubMed=27708256; DOI=10.1038/ncomms12882;
RA Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K.,
RA Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H.,
RA Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.;
RT "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding
RT and degradation.";
RL Nat. Commun. 7:12882-12882(2016).
RN [29]
RP INTERACTION WITH ZNF638.
RX PubMed=30487602; DOI=10.1038/s41586-018-0750-6;
RA Zhu Y., Wang G.Z., Cingoez O., Goff S.P.;
RT "NP220 mediates silencing of unintegrated retroviral DNA.";
RL Nature 564:278-282(2018).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 343-359 IN COMPLEX WITH ANKRA2,
RP PHOSPHORYLATION AT SER-350, MOTIF, AND MUTAGENESIS OF LEU-345; TYR-346;
RP THR-347; SER-348; PRO-349; SER-350; LEU-351; PRO-352; ASN-353; ILE-354;
RP THR-355 AND LEU-356.
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 [31]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-727.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [32]
RP VARIANT ILE-754.
RX PubMed=24169519; DOI=10.1038/ejhg.2013.243;
RA Piton A., Poquet H., Redin C., Masurel A., Lauer J., Muller J.,
RA Thevenon J., Herenger Y., Chancenotte S., Bonnet M., Pinoit J.M., Huet F.,
RA Thauvin-Robinet C., Jaeger A.S., Le Gras S., Jost B., Gerard B., Peoc'h K.,
RA Launay J.M., Faivre L., Mandel J.L.;
RT "20 ans apres: a second mutation in MAOA identified by targeted high-
RT throughput sequencing in a family with altered behavior and cognition.";
RL Eur. J. Hum. Genet. 22:776-783(2014).
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 via its
CC interaction with the myocyte enhancer factors such as MEF2A, MEF2C and
CC MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1
CC expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77'
CC leading to their preferential binding to co-chaperone STUB1
CC (PubMed:27708256). {ECO:0000269|PubMed:10523670,
CC ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:27708256}.
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: Homodimer. Homodimerization via its N-terminal domain
CC (PubMed:12032081). Interacts with MEF2A (PubMed:10487761). Interacts
CC with MEF2C and MEF2D (PubMed:10523670). Interacts with AHRR (By
CC similarity). Interacts with NR2C1 (PubMed:11463856). Interacts with
CC HDAC7 (By similarity). Interacts with a 14-3-3 chaperone protein in a
CC phosphorylation dependent manner (PubMed:10958686). Interacts with
CC BTBD14B (By similarity). Interacts with KDM5B (PubMed:17373667).
CC Interacts with MYOCD (By similarity). Interacts with MORC2
CC (PubMed:20110259). Interacts (via PxLPxI/L motif) with ANKRA2 (via
CC ankyrin repeats). Interacts with CUL7 (as part of the 3M complex);
CC negatively regulated by ANKRA2 (PubMed:25752541). Interacts with EP300
CC in the presence of TFAP2C (PubMed:24413532). Interacts with HSPA1A and
CC HSPA1B leading to their deacetylation at 'Lys-77' (PubMed:27708256).
CC Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4
CC on CD8 loci for deacetylation and possible inhibition of CD8 genes
CC expression (By similarity). Interacts with DHX36 (By similarity).
CC Interacts with SIK3; this interaction leads to HDAC4 retention in the
CC cytoplasm (By similarity). Interacts with ZNF638 (PubMed:30487602).
CC {ECO:0000250|UniProtKB:Q6NZM9, ECO:0000250|UniProtKB:Q99P99,
CC ECO:0000269|PubMed:10487761, ECO:0000269|PubMed:10523670,
CC ECO:0000269|PubMed:10958686, ECO:0000269|PubMed:11463856,
CC ECO:0000269|PubMed:17373667, ECO:0000269|PubMed:20110259,
CC ECO:0000269|PubMed:22649097, ECO:0000269|PubMed:24413532,
CC ECO:0000269|PubMed:25752541, ECO:0000269|PubMed:27708256,
CC ECO:0000269|PubMed:30487602}.
CC -!- INTERACTION:
CC P56524; Q9H9E1: ANKRA2; NbExp=4; IntAct=EBI-308629, EBI-10215533;
CC P56524; P10275: AR; NbExp=4; IntAct=EBI-308629, EBI-608057;
CC P56524; P15336: ATF2; NbExp=2; IntAct=EBI-308629, EBI-1170906;
CC P56524; P41182: BCL6; NbExp=3; IntAct=EBI-308629, EBI-765407;
CC P56524; Q9HCU9: BRMS1; NbExp=2; IntAct=EBI-308629, EBI-714781;
CC P56524; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-308629, EBI-10171416;
CC P56524; Q01850: CDR2; NbExp=3; IntAct=EBI-308629, EBI-1181367;
CC P56524; O95967: EFEMP2; NbExp=3; IntAct=EBI-308629, EBI-743414;
CC P56524; Q08379: GOLGA2; NbExp=3; IntAct=EBI-308629, EBI-618309;
CC P56524; P56524: HDAC4; NbExp=4; IntAct=EBI-308629, EBI-308629;
CC P56524; Q15323: KRT31; NbExp=3; IntAct=EBI-308629, EBI-948001;
CC P56524; O76015: KRT38; NbExp=3; IntAct=EBI-308629, EBI-1047263;
CC P56524; Q6A162: KRT40; NbExp=3; IntAct=EBI-308629, EBI-10171697;
CC P56524; O95751: LDOC1; NbExp=3; IntAct=EBI-308629, EBI-740738;
CC P56524; A9UHW6: MIF4GD; NbExp=4; IntAct=EBI-308629, EBI-373498;
CC P56524; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-308629, EBI-742948;
CC P56524; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-308629, EBI-302345;
CC P56524; Q6NUQ1: RINT1; NbExp=3; IntAct=EBI-308629, EBI-726876;
CC P56524; Q13761: RUNX3; NbExp=9; IntAct=EBI-308629, EBI-925990;
CC P56524; P31947: SFN; NbExp=4; IntAct=EBI-308629, EBI-476295;
CC P56524; P63279: UBE2I; NbExp=3; IntAct=EBI-308629, EBI-80168;
CC P56524; P31946: YWHAB; NbExp=3; IntAct=EBI-308629, EBI-359815;
CC P56524; P62258: YWHAE; NbExp=4; IntAct=EBI-308629, EBI-356498;
CC P56524; P61981: YWHAG; NbExp=8; IntAct=EBI-308629, EBI-359832;
CC P56524; Q04917: YWHAH; NbExp=5; IntAct=EBI-308629, EBI-306940;
CC P56524; P27348: YWHAQ; NbExp=3; IntAct=EBI-308629, EBI-359854;
CC P56524; P63104: YWHAZ; NbExp=6; IntAct=EBI-308629, EBI-347088;
CC P56524; O54946-2: Dnajb6; Xeno; NbExp=2; IntAct=EBI-308629, EBI-13941040;
CC P56524; Q8AZK7: EBNA-LP; Xeno; NbExp=5; IntAct=EBI-308629, EBI-1185167;
CC P56524; P08393: ICP0; Xeno; NbExp=3; IntAct=EBI-308629, EBI-6148881;
CC P56524-2; Q8WXK1: ASB15; NbExp=3; IntAct=EBI-11953488, EBI-12809012;
CC P56524-2; Q9BUH8: BEGAIN; NbExp=3; IntAct=EBI-11953488, EBI-742722;
CC P56524-2; Q8TD16-2: BICD2; NbExp=3; IntAct=EBI-11953488, EBI-11975051;
CC P56524-2; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-11953488, EBI-2548012;
CC P56524-2; A2RRN7: CADPS; NbExp=3; IntAct=EBI-11953488, EBI-10179719;
CC P56524-2; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-11953488, EBI-739580;
CC P56524-2; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-11953488, EBI-11977221;
CC P56524-2; O95273: CCNDBP1; NbExp=3; IntAct=EBI-11953488, EBI-748961;
CC P56524-2; Q6NVV7: CDPF1; NbExp=3; IntAct=EBI-11953488, EBI-2802782;
CC P56524-2; Q01850: CDR2; NbExp=3; IntAct=EBI-11953488, EBI-1181367;
CC P56524-2; Q86X02: CDR2L; NbExp=3; IntAct=EBI-11953488, EBI-11063830;
CC P56524-2; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-11953488, EBI-739624;
CC P56524-2; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-11953488, EBI-740680;
CC P56524-2; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-11953488, EBI-2349927;
CC P56524-2; O94868-3: FCHSD2; NbExp=3; IntAct=EBI-11953488, EBI-11958845;
CC P56524-2; A1L4K1: FSD2; NbExp=3; IntAct=EBI-11953488, EBI-5661036;
CC P56524-2; Q08379: GOLGA2; NbExp=3; IntAct=EBI-11953488, EBI-618309;
CC P56524-2; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-11953488, EBI-5916454;
CC P56524-2; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-11953488, EBI-717919;
CC P56524-2; P54257: HAP1; NbExp=3; IntAct=EBI-11953488, EBI-712814;
CC P56524-2; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-11953488, EBI-10961706;
CC P56524-2; O75031: HSF2BP; NbExp=3; IntAct=EBI-11953488, EBI-7116203;
CC P56524-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11953488, EBI-6509505;
CC P56524-2; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-11953488, EBI-3044087;
CC P56524-2; Q15323: KRT31; NbExp=3; IntAct=EBI-11953488, EBI-948001;
CC P56524-2; Q14525: KRT33B; NbExp=3; IntAct=EBI-11953488, EBI-1049638;
CC P56524-2; O76011: KRT34; NbExp=3; IntAct=EBI-11953488, EBI-1047093;
CC P56524-2; Q92764: KRT35; NbExp=3; IntAct=EBI-11953488, EBI-1058674;
CC P56524-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-11953488, EBI-10171697;
CC P56524-2; O95751: LDOC1; NbExp=3; IntAct=EBI-11953488, EBI-740738;
CC P56524-2; Q02078-5: MEF2A; NbExp=3; IntAct=EBI-11953488, EBI-12232917;
CC P56524-2; Q02080: MEF2B; NbExp=3; IntAct=EBI-11953488, EBI-6427785;
CC P56524-2; Q06413: MEF2C; NbExp=5; IntAct=EBI-11953488, EBI-2684075;
CC P56524-2; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-11953488, EBI-10172526;
CC P56524-2; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-11953488, EBI-11522433;
CC P56524-2; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-11953488, EBI-10271199;
CC P56524-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11953488, EBI-79165;
CC P56524-2; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-11953488, EBI-2212028;
CC P56524-2; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-11953488, EBI-1105213;
CC P56524-2; Q08117-2: TLE5; NbExp=3; IntAct=EBI-11953488, EBI-11741437;
CC P56524-2; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-11953488, EBI-492476;
CC P56524-2; P14373: TRIM27; NbExp=3; IntAct=EBI-11953488, EBI-719493;
CC P56524-2; Q9BZW7: TSGA10; NbExp=3; IntAct=EBI-11953488, EBI-744794;
CC P56524-2; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-11953488, EBI-2799833;
CC P56524-2; P62258: YWHAE; NbExp=3; IntAct=EBI-11953488, EBI-356498;
CC P56524-2; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-11953488, EBI-12030590;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between the
CC nucleus and the cytoplasm. Upon muscle cells differentiation, it
CC accumulates in the nuclei of myotubes, suggesting a positive role of
CC nuclear HDAC4 in muscle 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-246, Ser-467 and Ser-632 by CaMK4 and
CC SIK1. The nuclear localization probably depends on sumoylation.
CC Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:Q6NZM9}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56524-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56524-2; Sequence=VSP_057290, VSP_057291;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between the
CC nucleus and the cytoplasm.
CC -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin repeats of
CC ANKRA2. {ECO:0000269|PubMed:22649097}.
CC -!- PTM: Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632.
CC Phosphorylation at other residues by CaMK2D is required for the
CC interaction with 14-3-3. Phosphorylation at Ser-350, within the
CC PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-
CC affinity docking site for 14-3-3. {ECO:0000269|PubMed:10958686,
CC ECO:0000269|PubMed:22649097}.
CC -!- PTM: Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase
CC RANBP2, and prevented by phosphorylation by CaMK4.
CC {ECO:0000269|PubMed:12032081}.
CC -!- DISEASE: Note=HDAC4 point mutations and chromosomal microdeletions
CC encompassing this gene have been found in patients with brachydactyly
CC and intellectual disability syndrome (PubMed:20691407, PubMed:24715439,
CC PubMed:23188045). However, HDAC4 haploinsufficiency is not fully
CC penetrant and multiple genes may contribute to manifestation of the
CC full phenotypic spectrum (PubMed:24715439, PubMed:23188045).
CC {ECO:0000269|PubMed:20691407, ECO:0000269|PubMed:23188045,
CC ECO:0000269|PubMed:24715439}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA22957.2; Type=Erroneous initiation; 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; AF132607; AAD29046.1; -; mRNA.
DR EMBL; AB006626; BAA22957.2; ALT_INIT; mRNA.
DR EMBL; AC017028; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC062017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF510800; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF510801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW71165.1; -; Genomic_DNA.
DR EMBL; BC039904; AAH39904.1; -; mRNA.
DR CCDS; CCDS2529.1; -. [P56524-1]
DR RefSeq; NP_006028.2; NM_006037.3. [P56524-1]
DR PDB; 2H8N; X-ray; 2.60 A; A/B/C/D=62-153.
DR PDB; 2O94; X-ray; 3.00 A; A/B/C/D=62-153.
DR PDB; 2VQJ; X-ray; 2.10 A; A=648-1057.
DR PDB; 2VQM; X-ray; 1.80 A; A=648-1057.
DR PDB; 2VQO; X-ray; 2.15 A; A/B=648-1057.
DR PDB; 2VQQ; X-ray; 1.90 A; A/B=648-1057.
DR PDB; 2VQV; X-ray; 3.30 A; A/B=648-1057.
DR PDB; 2VQW; X-ray; 3.00 A; G=648-1057.
DR PDB; 3UXG; X-ray; 1.85 A; B=343-359.
DR PDB; 3UZD; X-ray; 1.86 A; B=343-359.
DR PDB; 3V31; X-ray; 1.57 A; B=343-359.
DR PDB; 4CBT; X-ray; 3.03 A; A/B/C=648-1033.
DR PDB; 4CBY; X-ray; 2.72 A; A/B/C/D=648-1033.
DR PDB; 5A2S; X-ray; 2.65 A; A/B=648-1033.
DR PDB; 5ZOO; X-ray; 1.85 A; G=652-1053.
DR PDB; 5ZOP; X-ray; 2.70 A; G=652-1050.
DR PDB; 6FYZ; X-ray; 2.15 A; A/B/C=648-1033.
DR PDBsum; 2H8N; -.
DR PDBsum; 2O94; -.
DR PDBsum; 2VQJ; -.
DR PDBsum; 2VQM; -.
DR PDBsum; 2VQO; -.
DR PDBsum; 2VQQ; -.
DR PDBsum; 2VQV; -.
DR PDBsum; 2VQW; -.
DR PDBsum; 3UXG; -.
DR PDBsum; 3UZD; -.
DR PDBsum; 3V31; -.
DR PDBsum; 4CBT; -.
DR PDBsum; 4CBY; -.
DR PDBsum; 5A2S; -.
DR PDBsum; 5ZOO; -.
DR PDBsum; 5ZOP; -.
DR PDBsum; 6FYZ; -.
DR AlphaFoldDB; P56524; -.
DR SMR; P56524; -.
DR BioGRID; 115106; 401.
DR CORUM; P56524; -.
DR DIP; DIP-34565N; -.
DR ELM; P56524; -.
DR IntAct; P56524; 93.
DR MINT; P56524; -.
DR STRING; 9606.ENSP00000264606; -.
DR BindingDB; P56524; -.
DR ChEMBL; CHEMBL3524; -.
DR DrugBank; DB08613; 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB07879; N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide.
DR DrugBank; DB06603; Panobinostat.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P56524; -.
DR GuidetoPHARMACOLOGY; 2659; -.
DR GlyGen; P56524; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P56524; -.
DR MetOSite; P56524; -.
DR PhosphoSitePlus; P56524; -.
DR BioMuta; HDAC4; -.
DR DMDM; 259016348; -.
DR EPD; P56524; -.
DR jPOST; P56524; -.
DR MassIVE; P56524; -.
DR MaxQB; P56524; -.
DR PaxDb; P56524; -.
DR PeptideAtlas; P56524; -.
DR PRIDE; P56524; -.
DR ProteomicsDB; 24301; -.
DR ProteomicsDB; 56920; -. [P56524-1]
DR ProteomicsDB; 70417; -.
DR ABCD; P56524; 1 sequenced antibody.
DR Antibodypedia; 3835; 1253 antibodies from 51 providers.
DR DNASU; 9759; -.
DR Ensembl; ENST00000345617.7; ENSP00000264606.3; ENSG00000068024.18. [P56524-1]
DR GeneID; 9759; -.
DR KEGG; hsa:9759; -.
DR UCSC; uc002vyk.4; human. [P56524-1]
DR CTD; 9759; -.
DR DisGeNET; 9759; -.
DR GeneCards; HDAC4; -.
DR HGNC; HGNC:14063; HDAC4.
DR HPA; ENSG00000068024; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; HDAC4; -.
DR MIM; 605314; gene.
DR neXtProt; NX_P56524; -.
DR OpenTargets; ENSG00000068024; -.
DR Orphanet; 1001; 2q37 microdeletion syndrome.
DR PharmGKB; PA29229; -.
DR VEuPathDB; HostDB:ENSG00000068024; -.
DR eggNOG; KOG1343; Eukaryota.
DR GeneTree; ENSGT00940000157440; -.
DR HOGENOM; CLU_006530_2_0_1; -.
DR InParanoid; P56524; -.
DR OrthoDB; 1484694at2759; -.
DR PhylomeDB; P56524; -.
DR TreeFam; TF106174; -.
DR BRENDA; 3.5.1.98; 2681.
DR PathwayCommons; P56524; -.
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-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-HSA-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-HSA-8941284; RUNX2 regulates chondrocyte maturation.
DR Reactome; R-HSA-8951936; RUNX3 regulates p14-ARF.
DR SignaLink; P56524; -.
DR SIGNOR; P56524; -.
DR BioGRID-ORCS; 9759; 20 hits in 1091 CRISPR screens.
DR ChiTaRS; HDAC4; human.
DR EvolutionaryTrace; P56524; -.
DR GeneWiki; HDAC4; -.
DR GenomeRNAi; 9759; -.
DR Pharos; P56524; Tclin.
DR PRO; PR:P56524; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P56524; protein.
DR Bgee; ENSG00000068024; Expressed in sural nerve and 197 other tissues.
DR ExpressionAtlas; P56524; baseline and differential.
DR Genevisible; P56524; HS.
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; IDA:BHF-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017053; C:transcription repressor complex; IDA:BHF-UCL.
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:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030955; F:potassium ion binding; IDA:BHF-UCL.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:BHF-UCL.
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:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; TAS:BHF-UCL.
DR GO; GO:0006338; P:chromatin remodeling; IDA:BHF-UCL.
DR GO; GO:0016575; P:histone deacetylation; IDA:BHF-UCL.
DR GO; GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL.
DR GO; GO:0070933; P:histone H4 deacetylation; IDA:BHF-UCL.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS: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:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0043393; P:regulation of protein binding; IMP:BHF-UCL.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL.
DR GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
DR Gene3D; 3.40.800.20; -; 1.
DR IDEAL; IID00457; -.
DR InterPro; IPR033660; HDAC4/7.
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; IPR023696; Ureohydrolase_dom_sf.
DR PANTHER; PTHR45364; PTHR45364; 1.
DR PANTHER; PTHR45364:SF3; PTHR45364:SF3; 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; Alternative splicing; Autism spectrum disorder;
KW Chromatin regulator; Coiled coil; Cytoplasm; Hydrolase;
KW Intellectual disability; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..1084
FT /note="Histone deacetylase 4"
FT /id="PRO_0000114699"
FT REGION 118..313
FT /note="Interaction with MEF2A"
FT /evidence="ECO:0000269|PubMed:10487761"
FT REGION 133..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 509..531
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 548..585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 626..646
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 655..1084
FT /note="Histone deacetylase"
FT REGION 1061..1084
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 67..177
FT /evidence="ECO:0000255"
FT MOTIF 349..354
FT /note="PxLPxI/L motif; mediates interaction with ANKRA2 and
FT 14-3-3 proteins"
FT /evidence="ECO:0000269|PubMed:22649097"
FT MOTIF 1051..1084
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 240..279
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..531
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1068..1084
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 803
FT /evidence="ECO:0000250"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 669
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 675
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 751
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 210
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZM9"
FT MOD_RES 246
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000269|PubMed:10958686"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22649097,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 467
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000269|PubMed:10958686"
FT MOD_RES 565
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6NZM9"
FT MOD_RES 632
FT /note="Phosphoserine; by CaMK4"
FT /evidence="ECO:0000269|PubMed:10958686,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 559
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:12032081"
FT VAR_SEQ 1..117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057290"
FT VAR_SEQ 431
FT /note="T -> TDWYLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057291"
FT VARIANT 727
FT /note="P -> R (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036042"
FT VARIANT 754
FT /note="V -> I (in dbSNP:rs151043798)"
FT /evidence="ECO:0000269|PubMed:24169519"
FT /id="VAR_071965"
FT MUTAGEN 246
FT /note="S->A: Reduces phosphorylation and its subsequent
FT nuclear export."
FT /evidence="ECO:0000269|PubMed:10958686"
FT MUTAGEN 345
FT /note="L->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 346
FT /note="Y->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 347
FT /note="T->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 348
FT /note="S->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 349
FT /note="P->A: May affect interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097,
FT ECO:0000269|PubMed:25752541"
FT MUTAGEN 349
FT /note="P->G: Decreased interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 350
FT /note="S->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 351
FT /note="L->A,G: Loss of interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 352
FT /note="P->A: Loss of interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 353
FT /note="N->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 354
FT /note="I->A: May affect interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097,
FT ECO:0000269|PubMed:25752541"
FT MUTAGEN 354
FT /note="I->G: Loss of interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 355
FT /note="T->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 356
FT /note="L->A: No effect on interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:22649097"
FT MUTAGEN 467
FT /note="S->A: Reduces phosphorylation and its subsequent
FT nuclear export."
FT /evidence="ECO:0000269|PubMed:10958686,
FT ECO:0000269|PubMed:11470791"
FT MUTAGEN 559
FT /note="K->R: Abolishes sumoylation and reduces the histone
FT deacetylase activity."
FT /evidence="ECO:0000269|PubMed:12032081"
FT MUTAGEN 632
FT /note="S->A: Reduces phosphorylation and its subsequent
FT nuclear export."
FT /evidence="ECO:0000269|PubMed:10958686,
FT ECO:0000269|PubMed:11470791"
FT MUTAGEN 803
FT /note="H->L: Abolishes histone deacetylase activity."
FT /evidence="ECO:0000269|PubMed:10523670"
FT MUTAGEN 1056
FT /note="V->A: Reduces CaMK-dependent nuclear export."
FT /evidence="ECO:0000269|PubMed:11509672"
FT MUTAGEN 1062
FT /note="L->A: Reduces CaMK-dependent nuclear export."
FT /evidence="ECO:0000269|PubMed:11509672"
FT CONFLICT 373
FT /note="A -> T (in Ref. 1; AAD29046 and 2; BAA22957)"
FT /evidence="ECO:0000305"
FT HELIX 64..112
FT /evidence="ECO:0007829|PDB:2H8N"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:2H8N"
FT TURN 122..125
FT /evidence="ECO:0007829|PDB:2H8N"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:2H8N"
FT TURN 354..357
FT /evidence="ECO:0007829|PDB:3UXG"
FT STRAND 652..657
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 672..674
FT /evidence="ECO:0007829|PDB:5ZOO"
FT HELIX 681..691
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 694..697
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 698..701
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 708..711
FT /evidence="ECO:0007829|PDB:2VQM"
FT TURN 712..714
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 717..724
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 727..730
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 737..745
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 754..756
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 762..786
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 789..795
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 813..815
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 817..828
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 834..838
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 840..842
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 845..851
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 857..864
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 866..868
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 870..872
FT /evidence="ECO:0007829|PDB:6FYZ"
FT HELIX 883..885
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 889..894
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 898..900
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 904..913
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 915..922
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 925..931
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 936..938
FT /evidence="ECO:0007829|PDB:2VQM"
FT TURN 940..943
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 950..961
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 964..966
FT /evidence="ECO:0007829|PDB:2VQM"
FT STRAND 968..972
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 978..992
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 1002..1006
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 1011..1025
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 1029..1031
FT /evidence="ECO:0007829|PDB:2VQM"
FT HELIX 1042..1047
FT /evidence="ECO:0007829|PDB:2VQM"
SQ SEQUENCE 1084 AA; 119040 MW; BB7FD37652D12398 CRC64;
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPSAVPMD LRLDHQFSLP
VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL SRQHEAQLHE HIKQQQEMLA
MKHQQELLEH QRKLERHRQE QELEKQHREQ KLQQLKNKEK GKESAVASTE VKMKLQEFVL
NKKKALAHRN LNHCISSDPR YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP
LRKTASEPNL KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP
SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS LPNITLGLPA
TGPSAGTAGQ QDAERLTLPA LQQRLSLFPG THLTPYLSTS PLERDGGAAH SPLLQHMVLL
EQPPAQAPLV TGLGALPLHA QSLVGADRVS PSIHKLRQHR PLGRTQSAPL PQNAQALQHL
VIQQQHQQFL EKHKQQFQQQ QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY
LDRLPGQKEA HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ
RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP RFTTGLVYDT
LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC IRGRKATLEE LQTVHSEAHT
LLYGTNPLNR QKLDSKKLLG SLASVFVRLP CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE
LVFKVATGEL KNGFAVVRPP GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD
VHHGNGTQQA FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP
PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA RCFGYLTKQL
MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL PEKVLQQRPN ANAVRSMEKV
MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN EEAETVTAMA SLSVGVKPAE KRPDEEPMEE
EPPL
