GenomeNet

Database: UniProt/SWISS-PROT
Entry: HDAC4_HUMAN
LinkDB: HDAC4_HUMAN
Original site: 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   28-MAR-2018, entry version 189.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   to 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
RT   suitable for analysis of cDNA clones encoding relatively large
RT   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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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.,
RA   Kouzarides T.;
RT   "HDAC4 deacetylase associates with and represses the MEF2
RT   transcription factor.";
RL   EMBO J. 18:5099-5107(1999).
RN   [8]
RP   FUNCTION, INTERACTION WITH MEF2C AND MEF2D, AND MUTAGENESIS OF
RP   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.,
RA   Heng H.H., 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
RP   SER-246; 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
RT   phosphorylation-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
RT   class II 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
RT   and 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.,
RA   Freemont P., Taylor-Papadimitriou J.;
RT   "Breast cancer associated transcriptional repressor PLU-1/JARID1B
RT   interacts 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
RT   preferentially transmits signals to histone deacetylase 4 in cardiac
RT   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
RP   BY 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
RT   behavioral 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-
RT   regulation of 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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation 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.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome 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.,
RA   Mundlos S., 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
RP   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   [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
RT   breast 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
RT   all affected individuals.";
RL   Am. J. Med. Genet. A 164A:1826-1829(2014).
RN   [26]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, AND IDENTIFICATION
RP   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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [27]
RP   INTERACTION WITH CUL7 AND ANKRA2, AND MUTAGENESIS OF PRO-349 AND
RP   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.,
RA   Weist R., 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.,
RA   Seok S.H., Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.;
RT   "ARD1-mediated Hsp70 acetylation balances stress-induced protein
RT   refolding and degradation.";
RL   Nat. Commun. 7:12882-12882(2016).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 343-359 IN COMPLEX WITH
RP   ANKRA2, PHOSPHORYLATION AT SER-350, MOTIF, AND MUTAGENESIS OF LEU-345;
RP   TYR-346; THR-347; SER-348; PRO-349; SER-350; LEU-351; PRO-352;
RP   ASN-353; ILE-354; 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
RT   repeat tumbler lock.";
RL   Sci. Signal. 5:RA39-RA39(2012).
RN   [30]
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.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
RN   [31]
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.,
RA   Huet F., Thauvin-Robinet C., Jaeger A.S., Le Gras S., Jost B.,
RA   Gerard B., Peoc'h K., 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
RT   cognition.";
RL   Eur. J. Hum. Genet. 22:776-783(2014).
CC   -!- FUNCTION: Responsible for the deacetylation of lysine residues on
CC       the N-terminal part of the core histones (H2A, H2B, H3 and H4).
CC       Histone deacetylation gives a tag for epigenetic repression and
CC       plays an important role in transcriptional regulation, cell cycle
CC       progression and developmental events. Histone deacetylases act via
CC       the formation of large multiprotein complexes. Involved in muscle
CC       maturation via its interaction with the myocyte enhancer factors
CC       such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated
CC       epigenetic regulation of ESR1 expression in breast cancer.
CC       Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their
CC       preferential binding to co-chaperone STUB1 (PubMed:27708256).
CC       {ECO:0000269|PubMed:10523670, ECO:0000269|PubMed:24413532,
CC       ECO:0000269|PubMed:27708256}.
CC   -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of
CC       a histone to yield a deacetylated histone.
CC   -!- SUBUNIT: Homodimer. Homodimerization via its N-terminal domain
CC       (PubMed:12032081). Interacts with MEF2A (PubMed:10487761).
CC       Interacts with MEF2C and MEF2D (PubMed:10523670). Interacts with
CC       AHRR (By similarity). Interacts with NR2C1 (PubMed:11463856).
CC       Interacts with HDAC7 (By similarity). Interacts with a 14-3-3
CC       chaperone protein in a phosphorylation dependent manner
CC       (PubMed:10958686). Interacts with BTBD14B (By similarity).
CC       Interacts with KDM5B (PubMed:17373667). Interacts with MYOCD (By
CC       similarity). Interacts with MORC2 (PubMed:20110259). Interacts
CC       (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts
CC       with CUL7 (as part of the 3M complex); negatively regulated by
CC       ANKRA2 (PubMed:25752541). Interacts with EP300 in the presence of
CC       TFAP2C (PubMed:24413532). Interacts with HSPA1A and HSPA1B leading
CC       to their deacetylation at 'Lys-77' (PubMed:27708256).
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   -!- INTERACTION:
CC       Self; NbExp=4; IntAct=EBI-308629, EBI-308629;
CC       Q9H9E1:ANKRA2; NbExp=3; IntAct=EBI-308629, EBI-10215533;
CC       P10275:AR; NbExp=4; IntAct=EBI-308629, EBI-608057;
CC       P15336:ATF2; NbExp=2; IntAct=EBI-308629, EBI-1170906;
CC       P41182:BCL6; NbExp=3; IntAct=EBI-308629, EBI-765407;
CC       Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-308629, EBI-714781;
CC       Q96JN2-2:CCDC136; NbExp=3; IntAct=EBI-308629, EBI-10171416;
CC       Q01850:CDR2; NbExp=3; IntAct=EBI-308629, EBI-1181367;
CC       O54946-2:Dnajb6 (xeno); NbExp=2; IntAct=EBI-308629, EBI-13941040;
CC       Q8AZK7:EBNA-LP (xeno); NbExp=5; IntAct=EBI-308629, EBI-1185167;
CC       O95967:EFEMP2; NbExp=3; IntAct=EBI-308629, EBI-743414;
CC       Q08379:GOLGA2; NbExp=3; IntAct=EBI-308629, EBI-618309;
CC       P08393:ICP0 (xeno); NbExp=3; IntAct=EBI-308629, EBI-6148881;
CC       Q15323:KRT31; NbExp=3; IntAct=EBI-308629, EBI-948001;
CC       O76015:KRT38; NbExp=3; IntAct=EBI-308629, EBI-1047263;
CC       Q6A162:KRT40; NbExp=3; IntAct=EBI-308629, EBI-10171697;
CC       O95751:LDOC1; NbExp=3; IntAct=EBI-308629, EBI-740738;
CC       A9UHW6:MIF4GD; NbExp=4; IntAct=EBI-308629, EBI-373498;
CC       Q5JR59:MTUS2; NbExp=3; IntAct=EBI-308629, EBI-742948;
CC       Q8ND90:PNMA1; NbExp=3; IntAct=EBI-308629, EBI-302345;
CC       Q6NUQ1:RINT1; NbExp=3; IntAct=EBI-308629, EBI-726876;
CC       Q13761:RUNX3; NbExp=9; IntAct=EBI-308629, EBI-925990;
CC       P31947:SFN; NbExp=4; IntAct=EBI-308629, EBI-476295;
CC       P63279:UBE2I; NbExp=3; IntAct=EBI-308629, EBI-80168;
CC       P31946:YWHAB; NbExp=3; IntAct=EBI-308629, EBI-359815;
CC       P62258:YWHAE; NbExp=4; IntAct=EBI-308629, EBI-356498;
CC       P61981:YWHAG; NbExp=9; IntAct=EBI-308629, EBI-359832;
CC       Q04917:YWHAH; NbExp=4; IntAct=EBI-308629, EBI-306940;
CC       P63104:YWHAZ; NbExp=5; IntAct=EBI-308629, EBI-347088;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between
CC       the nucleus and the cytoplasm. Upon muscle cells differentiation,
CC       it accumulates in the nuclei of myotubes, suggesting a positive
CC       role of nuclear HDAC4 in muscle differentiation. The export to
CC       cytoplasm depends on the interaction with a 14-3-3 chaperone
CC       protein and is due to its phosphorylation at Ser-246, Ser-467 and
CC       Ser-632 by CaMK4 and SIK1. The nuclear localization probably
CC       depends on sumoylation.
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         Note=No experimental confirmation available.;
CC   -!- TISSUE SPECIFICITY: Ubiquitous.
CC   -!- DOMAIN: The nuclear export sequence mediates the shuttling between
CC       the nucleus and the cytoplasm.
CC   -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin
CC       repeats of 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
CC       high-affinity docking site for 14-3-3.
CC       {ECO:0000269|PubMed:10958686, ECO:0000269|PubMed:22649097}.
CC   -!- PTM: Sumoylation on Lys-559 is promoted by the E3 SUMO-protein
CC       ligase RANBP2, and prevented by phosphorylation by CaMK4.
CC       {ECO:0000269|PubMed:12032081}.
CC   -!- DISEASE: Brachydactyly-mental retardation syndrome (BDMR)
CC       [MIM:600430]: A syndrome resembling the physical anomalies found
CC       in Albright hereditary osteodystrophy. Common features are mild
CC       facial dysmorphism, congenital heart defects, distinct
CC       brachydactyly type E, mental retardation, developmental delay,
CC       seizures, autism spectrum disorder, and stocky build. Soft tissue
CC       ossification is absent, and there are no abnormalities in
CC       parathyroid hormone or calcium metabolism.
CC       {ECO:0000269|PubMed:20691407, ECO:0000269|PubMed:23188045,
CC       ECO:0000269|PubMed:24715439}. Note=The gene represented in this
CC       entry is involved in disease pathogenesis. HDAC4 point mutations
CC       and chromosomal microdeletions encompassing this gene have been
CC       found in BDMR patients (PubMed:20691407, PubMed:24715439,
CC       PubMed:23188045). However, HDAC4 haploinsufficiency is not fully
CC       penetrant and multiple genes may contribute to manifestation of
CC       the 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};
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   UniGene; Hs.20516; -.
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   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   ProteinModelPortal; P56524; -.
DR   SMR; P56524; -.
DR   BioGrid; 115106; 195.
DR   CORUM; P56524; -.
DR   DIP; DIP-34565N; -.
DR   ELM; P56524; -.
DR   IntAct; P56524; 136.
DR   MINT; P56524; -.
DR   STRING; 9606.ENSP00000264606; -.
DR   BindingDB; P56524; -.
DR   ChEMBL; CHEMBL3524; -.
DR   DrugBank; DB05015; Belinostat.
DR   DrugBank; DB06603; Panobinostat.
DR   DrugBank; DB06176; Romidepsin.
DR   GuidetoPHARMACOLOGY; 2659; -.
DR   iPTMnet; P56524; -.
DR   PhosphoSitePlus; P56524; -.
DR   BioMuta; HDAC4; -.
DR   DMDM; 259016348; -.
DR   EPD; P56524; -.
DR   MaxQB; P56524; -.
DR   PaxDb; P56524; -.
DR   PeptideAtlas; P56524; -.
DR   PRIDE; P56524; -.
DR   Ensembl; ENST00000345617; ENSP00000264606; ENSG00000068024. [P56524-1]
DR   Ensembl; ENST00000543185; ENSP00000440481; ENSG00000068024. [P56524-2]
DR   GeneID; 9759; -.
DR   KEGG; hsa:9759; -.
DR   UCSC; uc002vyk.4; human. [P56524-1]
DR   CTD; 9759; -.
DR   DisGeNET; 9759; -.
DR   EuPathDB; HostDB:ENSG00000068024.16; -.
DR   GeneCards; HDAC4; -.
DR   GeneReviews; HDAC4; -.
DR   HGNC; HGNC:14063; HDAC4.
DR   HPA; CAB004431; -.
DR   HPA; HPA048723; -.
DR   MalaCards; HDAC4; -.
DR   MIM; 600430; phenotype.
DR   MIM; 605314; gene.
DR   neXtProt; NX_P56524; -.
DR   OpenTargets; ENSG00000068024; -.
DR   Orphanet; 1001; 2q37 microdeletion syndrome.
DR   PharmGKB; PA29229; -.
DR   eggNOG; KOG1343; Eukaryota.
DR   eggNOG; COG0123; LUCA.
DR   GeneTree; ENSGT00530000062809; -.
DR   HOGENOM; HOG000232065; -.
DR   HOVERGEN; HBG057100; -.
DR   InParanoid; P56524; -.
DR   KO; K11406; -.
DR   OMA; KCECIRG; -.
DR   OrthoDB; EOG091G0EQO; -.
DR   PhylomeDB; P56524; -.
DR   TreeFam; TF106174; -.
DR   BRENDA; 3.5.1.98; 2681.
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-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   SIGNOR; P56524; -.
DR   ChiTaRS; HDAC4; human.
DR   EvolutionaryTrace; P56524; -.
DR   GeneWiki; HDAC4; -.
DR   GenomeRNAi; 9759; -.
DR   PRO; PR:P56524; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000068024; -.
DR   CleanEx; HS_HDAC4; -.
DR   ExpressionAtlas; P56524; baseline and differential.
DR   Genevisible; P56524; HS.
DR   GO; GO:0031672; C:A band; IEA:Ensembl.
DR   GO; GO:0042641; C:actomyosin; IEA:Ensembl.
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:0031594; C:neuromuscular junction; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0043234; C:protein complex; IEA:Ensembl.
DR   GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL.
DR   GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR   GO; GO:0033613; F:activating transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0001047; F:core promoter binding; IDA:UniProtKB.
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:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC.
DR   GO; GO:0030955; F:potassium ion binding; IDA:BHF-UCL.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR   GO; GO:0033558; F:protein deacetylase activity; IDA:BHF-UCL.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR   GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
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:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR   GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
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:0008285; P:negative regulation of cell proliferation; IEA:Ensembl.
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:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR   GO; GO:1902894; P:negative regulation of pri-miRNA transcription by RNA polymerase II; IEA:Ensembl.
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:0002076; P:osteoblast development; IEA:Ensembl.
DR   GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0051091; P:positive regulation of DNA binding transcription factor activity; IMP:BHF-UCL.
DR   GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
DR   GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IEA:Ensembl.
DR   GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
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:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IEA:Ensembl.
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:0048742; P:regulation of skeletal muscle fiber development; IEA:Ensembl.
DR   GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR   GO; GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
DR   GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.800.20; -; 1.
DR   InterPro; IPR033660; HDAC4.
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; PTHR10625; PTHR10625; 1.
DR   PANTHER; PTHR10625:SF100; PTHR10625:SF100; 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; Complete proteome; Cytoplasm;
KW   Hydrolase; Isopeptide bond; Mental retardation; Metal-binding;
KW   Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repressor;
KW   Transcription; Transcription regulation; Ubl conjugation; Zinc.
FT   CHAIN         1   1084       Histone deacetylase 4.
FT                                /FTId=PRO_0000114699.
FT   REGION      118    313       Interaction with MEF2A.
FT                                {ECO:0000269|PubMed:10487761}.
FT   REGION      655   1084       Histone deacetylase.
FT   COILED       67    177       {ECO:0000255}.
FT   MOTIF       349    354       PxLPxI/L motif; mediates interaction with
FT                                ANKRA2 and 14-3-3 proteins.
FT                                {ECO:0000269|PubMed:22649097}.
FT   MOTIF      1051   1084       Nuclear export signal. {ECO:0000250}.
FT   ACT_SITE    803    803       {ECO:0000250}.
FT   METAL       667    667       Zinc. {ECO:0000250}.
FT   METAL       669    669       Zinc. {ECO:0000250}.
FT   METAL       675    675       Zinc. {ECO:0000250}.
FT   METAL       751    751       Zinc. {ECO:0000250}.
FT   MOD_RES     210    210       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q6NZM9}.
FT   MOD_RES     246    246       Phosphoserine; by CaMK4 and SIK1.
FT                                {ECO:0000269|PubMed:10958686}.
FT   MOD_RES     350    350       Phosphoserine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000269|PubMed:22649097}.
FT   MOD_RES     467    467       Phosphoserine; by CaMK4 and SIK1.
FT                                {ECO:0000269|PubMed:10958686}.
FT   MOD_RES     565    565       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q6NZM9}.
FT   MOD_RES     632    632       Phosphoserine; by CaMK4.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569,
FT                                ECO:0000269|PubMed:10958686}.
FT   MOD_RES     633    633       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   CROSSLNK    559    559       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000269|PubMed:12032081}.
FT   VAR_SEQ       1    117       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_057290.
FT   VAR_SEQ     431    431       T -> TDWYLS (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_057291.
FT   VARIANT     727    727       P -> R (in a breast cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_036042.
FT   VARIANT     754    754       V -> I (in dbSNP:rs151043798).
FT                                {ECO:0000269|PubMed:24169519}.
FT                                /FTId=VAR_071965.
FT   MUTAGEN     246    246       S->A: Reduces phosphorylation and its
FT                                subsequent nuclear export.
FT                                {ECO:0000269|PubMed:10958686}.
FT   MUTAGEN     345    345       L->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     346    346       Y->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     347    347       T->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     348    348       S->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     349    349       P->A: May affect interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097,
FT                                ECO:0000269|PubMed:25752541}.
FT   MUTAGEN     349    349       P->G: Decreased interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     350    350       S->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     351    351       L->A,G: Loss of interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     352    352       P->A: Loss of interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     353    353       N->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     354    354       I->A: May affect interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097,
FT                                ECO:0000269|PubMed:25752541}.
FT   MUTAGEN     354    354       I->G: Loss of interaction with ANKRA2.
FT                                {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     355    355       T->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     356    356       L->A: No effect on interaction with
FT                                ANKRA2. {ECO:0000269|PubMed:22649097}.
FT   MUTAGEN     467    467       S->A: Reduces phosphorylation and its
FT                                subsequent nuclear export.
FT                                {ECO:0000269|PubMed:10958686,
FT                                ECO:0000269|PubMed:11470791}.
FT   MUTAGEN     559    559       K->R: Abolishes sumoylation and reduces
FT                                the histone deacetylase activity.
FT                                {ECO:0000269|PubMed:12032081}.
FT   MUTAGEN     632    632       S->A: Reduces phosphorylation and its
FT                                subsequent nuclear export.
FT                                {ECO:0000269|PubMed:10958686,
FT                                ECO:0000269|PubMed:11470791}.
FT   MUTAGEN     803    803       H->L: Abolishes histone deacetylase
FT                                activity. {ECO:0000269|PubMed:10523670}.
FT   MUTAGEN    1056   1056       V->A: Reduces CaMK-dependent nuclear
FT                                export. {ECO:0000269|PubMed:11509672}.
FT   MUTAGEN    1062   1062       L->A: Reduces CaMK-dependent nuclear
FT                                export. {ECO:0000269|PubMed:11509672}.
FT   CONFLICT    373    373       A -> T (in Ref. 1; AAD29046 and 2;
FT                                BAA22957). {ECO:0000305}.
FT   HELIX        64    112       {ECO:0000244|PDB:2H8N}.
FT   HELIX       115    121       {ECO:0000244|PDB:2H8N}.
FT   TURN        122    125       {ECO:0000244|PDB:2H8N}.
FT   HELIX       126    128       {ECO:0000244|PDB:2H8N}.
FT   TURN        354    357       {ECO:0000244|PDB:3UXG}.
FT   STRAND      652    657       {ECO:0000244|PDB:2VQM}.
FT   HELIX       660    662       {ECO:0000244|PDB:2VQM}.
FT   STRAND      673    675       {ECO:0000244|PDB:2VQJ}.
FT   HELIX       681    691       {ECO:0000244|PDB:2VQM}.
FT   HELIX       694    697       {ECO:0000244|PDB:2VQM}.
FT   STRAND      698    701       {ECO:0000244|PDB:2VQM}.
FT   HELIX       708    711       {ECO:0000244|PDB:2VQM}.
FT   TURN        712    714       {ECO:0000244|PDB:2VQM}.
FT   HELIX       717    724       {ECO:0000244|PDB:2VQM}.
FT   HELIX       727    730       {ECO:0000244|PDB:2VQM}.
FT   HELIX       737    745       {ECO:0000244|PDB:2VQM}.
FT   STRAND      746    748       {ECO:0000244|PDB:2VQM}.
FT   STRAND      754    756       {ECO:0000244|PDB:2VQM}.
FT   HELIX       762    786       {ECO:0000244|PDB:2VQM}.
FT   STRAND      789    795       {ECO:0000244|PDB:2VQM}.
FT   STRAND      813    815       {ECO:0000244|PDB:2VQM}.
FT   HELIX       817    828       {ECO:0000244|PDB:2VQM}.
FT   STRAND      834    838       {ECO:0000244|PDB:2VQM}.
FT   STRAND      840    842       {ECO:0000244|PDB:2VQM}.
FT   HELIX       845    851       {ECO:0000244|PDB:2VQM}.
FT   STRAND      857    864       {ECO:0000244|PDB:2VQM}.
FT   HELIX       866    868       {ECO:0000244|PDB:2VQM}.
FT   STRAND      870    872       {ECO:0000244|PDB:4CBT}.
FT   HELIX       883    885       {ECO:0000244|PDB:2VQM}.
FT   STRAND      889    894       {ECO:0000244|PDB:2VQM}.
FT   STRAND      898    900       {ECO:0000244|PDB:2VQM}.
FT   HELIX       904    913       {ECO:0000244|PDB:2VQM}.
FT   HELIX       915    922       {ECO:0000244|PDB:2VQM}.
FT   STRAND      925    931       {ECO:0000244|PDB:2VQM}.
FT   STRAND      936    938       {ECO:0000244|PDB:2VQM}.
FT   TURN        940    943       {ECO:0000244|PDB:2VQM}.
FT   HELIX       950    961       {ECO:0000244|PDB:2VQM}.
FT   HELIX       964    966       {ECO:0000244|PDB:2VQM}.
FT   STRAND      968    972       {ECO:0000244|PDB:2VQM}.
FT   HELIX       978    992       {ECO:0000244|PDB:2VQM}.
FT   HELIX      1002   1006       {ECO:0000244|PDB:2VQM}.
FT   HELIX      1011   1025       {ECO:0000244|PDB:2VQM}.
FT   HELIX      1029   1031       {ECO:0000244|PDB:2VQM}.
FT   HELIX      1042   1047       {ECO:0000244|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
//
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