ID   HDA4_CAEEL              Reviewed;         869 AA.
AC   O17323; H1ZUW2; Q400M0;
DT   16-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 3.
DT   27-MAR-2024, entry version 147.
DE   RecName: Full=Histone deacetylase 4;
DE            EC=3.5.1.98;
DE   AltName: Full=CeHDA-7;
DE   AltName: Full=Histone deacetylase 7;
GN   Name=hda-4; Synonyms=hda-7; ORFNames=C10E2.3;
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), TISSUE SPECIFICITY, AND INTERACTION
RP   WITH MEF-2 (ISOFORM B).
RC   STRAIN=Bristol N2;
RX   PubMed=12054517; DOI=10.1016/s0006-291x(02)00374-1;
RA   Choi K.Y., Ji Y.J., Jee C., Kim do H., Ahnn J.;
RT   "Characterization of CeHDA-7, a class II histone deacetylase interacting
RT   with MEF-2 in Caenorhabditis elegans.";
RL   Biochem. Biophys. Res. Commun. 293:1295-1300(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC   STRAIN=Bristol N2;
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [3] {ECO:0000305}
RP   FUNCTION, PHOSPHORYLATION AT SER-251, AND MUTAGENESIS OF 80-GLN--THR-869
RP   AND SER-251.
RX   PubMed=17170704; DOI=10.1038/sj.emboj.7601479;
RA   van der Linden A.M., Nolan K.M., Sengupta P.;
RT   "KIN-29 SIK regulates chemoreceptor gene expression via an MEF2
RT   transcription factor and a class II HDAC.";
RL   EMBO J. 26:358-370(2007).
RN   [4] {ECO:0000305}
RP   FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-416 AND SER-515.
RX   PubMed=18832350; DOI=10.1534/genetics.108.094771;
RA   van der Linden A.M., Wiener S., You Y.J., Kim K., Avery L., Sengupta P.;
RT   "The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A
RT   to regulate chemoreceptor gene expression and sensory behaviors in
RT   Caenorhabditis elegans.";
RL   Genetics 180:1475-1491(2008).
CC   -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC       N-terminal part of the core histones (H2A, H2B, H3 and H4) (By
CC       similarity). Histone deacetylation gives a tag for epigenetic
CC       repression and plays an important role in transcriptional regulation,
CC       cell cycle progression and developmental events (By similarity).
CC       Histone deacetylases act via the formation of large multiprotein
CC       complexes (By similarity). Involved in transduction of sensory signals,
CC       together with egl-4, kin-29 and mef-2; binding to transcription factor
CC       mef-2 enables negative modulation of chemoreceptor gene expression in
CC       chemosensory neurons (PubMed:17170704, PubMed:18832350). May be
CC       involved in muscle development (By similarity).
CC       {ECO:0000250|UniProtKB:P56524, ECO:0000269|PubMed:17170704,
CC       ECO:0000269|PubMed:18832350}.
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: [Isoform b]: Interacts with mef-2.
CC       {ECO:0000269|PubMed:12054517}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=a;
CC         IsoId=O17323-1; Sequence=Displayed;
CC       Name=b;
CC         IsoId=O17323-2; Sequence=VSP_044209;
CC   -!- TISSUE SPECIFICITY: Expressed in body-wall muscle cells, hypodermal
CC       seam cells and neuronal cells including sensory amphid neuronal
CC       processes, the nerve ring, ventral nerve cords and motor neuronal
CC       commissures. {ECO:0000269|PubMed:12054517}.
CC   -!- PTM: Phosphorylated by serine/threonine-protein kinase kin-29 at Ser-
CC       251; the phosphorylation inhibits repression of transcription by mef-2
CC       (PubMed:17170704). May be phosphorylated by either cyclic-AMP dependent
CC       or cyclic-GMP dependent protein kinases (PubMed:18832350).
CC       {ECO:0000269|PubMed:17170704, ECO:0000269|PubMed:18832350}.
CC   -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC       subfamily. {ECO:0000305}.
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DR   EMBL; FO080490; CCD64116.1; -; Genomic_DNA.
DR   EMBL; FO080492; CCD64116.1; JOINED; Genomic_DNA.
DR   EMBL; FO080490; CCF23337.1; -; Genomic_DNA.
DR   EMBL; FO080492; CCF23337.1; JOINED; Genomic_DNA.
DR   PIR; T32425; T32425.
DR   RefSeq; NP_001257278.1; NM_001270349.1. [O17323-1]
DR   RefSeq; NP_001257279.1; NM_001270350.1. [O17323-2]
DR   AlphaFoldDB; O17323; -.
DR   SMR; O17323; -.
DR   BioGRID; 46606; 3.
DR   IntAct; O17323; 1.
DR   MINT; O17323; -.
DR   STRING; 6239.C10E2.3a.1; -.
DR   EPD; O17323; -.
DR   PaxDb; 6239-C10E2-3a; -.
DR   PeptideAtlas; O17323; -.
DR   EnsemblMetazoa; C10E2.3a.1; C10E2.3a.1; WBGene00001837. [O17323-1]
DR   EnsemblMetazoa; C10E2.3b.1; C10E2.3b.1; WBGene00001837. [O17323-2]
DR   GeneID; 181723; -.
DR   KEGG; cel:CELE_C10E2.3; -.
DR   UCSC; C10E2.3; c. elegans.
DR   AGR; WB:WBGene00001837; -.
DR   WormBase; C10E2.3a; CE42060; WBGene00001837; hda-4. [O17323-1]
DR   WormBase; C10E2.3b; CE37192; WBGene00001837; hda-4. [O17323-2]
DR   eggNOG; KOG1343; Eukaryota.
DR   GeneTree; ENSGT00940000169192; -.
DR   InParanoid; O17323; -.
DR   OMA; QKVIAIH; -.
DR   OrthoDB; 124800at2759; -.
DR   Reactome; R-CEL-3108214; SUMOylation of DNA damage response and repair proteins.
DR   Reactome; R-CEL-4551638; SUMOylation of chromatin organization proteins.
DR   Reactome; R-CEL-8951936; RUNX3 regulates p14-ARF.
DR   PRO; PR:O17323; -.
DR   Proteomes; UP000001940; Chromosome X.
DR   Bgee; WBGene00001837; Expressed in pharyngeal muscle cell (C elegans) and 3 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISS:WormBase.
DR   GO; GO:0000118; C:histone deacetylase complex; ISS:WormBase.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0005516; F:calmodulin binding; ISS:WormBase.
DR   GO; GO:0004407; F:histone deacetylase activity; ISS:WormBase.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR   GO; GO:0003714; F:transcription corepressor activity; ISS:WormBase.
DR   GO; GO:0006325; P:chromatin organization; ISS:WormBase.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:WormBase.
DR   GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IMP:UniProtKB.
DR   GO; GO:0045664; P:regulation of neuron differentiation; IMP:WormBase.
DR   GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR   CDD; cd11681; HDAC_classIIa; 1.
DR   Gene3D; 3.40.800.20; Histone deacetylase domain; 1.
DR   InterPro; IPR000286; His_deacetylse.
DR   InterPro; IPR023801; His_deacetylse_dom.
DR   InterPro; IPR037138; His_deacetylse_dom_sf.
DR   InterPro; IPR023696; Ureohydrolase_dom_sf.
DR   PANTHER; PTHR10625:SF15; HISTONE DEACETYLASE; 1.
DR   PANTHER; PTHR10625; HISTONE DEACETYLASE HDAC1-RELATED; 1.
DR   Pfam; PF00850; Hist_deacetyl; 1.
DR   PRINTS; PR01270; HDASUPER.
DR   SUPFAM; SSF52768; Arginase/deacetylase; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromatin regulator; Hydrolase; Nucleus;
KW   Phosphoprotein; Reference proteome; Repressor; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..869
FT                   /note="Histone deacetylase 4"
FT                   /id="PRO_0000114742"
FT   REGION          1..25
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          128..167
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          180..218
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          460..802
FT                   /note="Histone deacetylase"
FT   COMPBIAS        128..146
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        153..167
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        608
FT                   /evidence="ECO:0000250"
FT   MOD_RES         251
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:17170704"
FT   VAR_SEQ         1..53
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000303|PubMed:12054517"
FT                   /id="VSP_044209"
FT   MUTAGEN         80..869
FT                   /note="Missing: In oy59; Suppresses reduced chemoreceptor
FT                   gene expression phenotype in a Ser/Thr kinase kin-29 mutant
FT                   background."
FT                   /evidence="ECO:0000269|PubMed:17170704"
FT   MUTAGEN         251
FT                   /note="S->A: Abolishes phosphorylation; causes significant
FT                   down-regulation of chemoreceptor str-1 expression."
FT                   /evidence="ECO:0000269|PubMed:17170704"
FT   MUTAGEN         416
FT                   /note="S->A: Localizes to cytoplasm; does not affect
FT                   chemoreceptor str-1 expression; when associated with
FT                   A-515."
FT                   /evidence="ECO:0000269|PubMed:18832350"
FT   MUTAGEN         515
FT                   /note="S->A: Localizes to cytoplasm; does not affect
FT                   chemoreceptor str-1 expression; when associated with
FT                   A-416."
FT                   /evidence="ECO:0000269|PubMed:18832350"
SQ   SEQUENCE   869 AA;  94411 MW;  0F186275170F82C3 CRC64;
     MEEASSSTGS AGGAGPSVPN LPSTSEAAIG QTNLEPESIA LLQSQLQEYR QKQMDLIGHF
     QRAQQELSVQ HMHNLYAALQ QQQQLQNLQT ERSAVNPLLI SQQHSTEDQN SGPAAPLSLA
     NSLTNLLSSS NGNLSVPQTP TKEHHPTAPT SNRKCDLPRS NSTTISQLTK DRLKNMIANR
     SKGESNSQSN LMSNSVTANG NGHDNGRKLK NSNSQVNVSS PHFEPYRLPT SLANAHNLQQ
     ASEFQLRKVN SEPNLKMRIR AKLLSKGSSP VQHVQQNNSQ FNFTHPQLKR SDSETSQNVP
     LDFMQSSSQT NLPHLMLPSP SLPNLAAAGA FHGLNLPVGQ DLNAFMAVAN LSPFLSLPSL
     LNKKLELGGL TDEGDRNGLI GSSSTSSLAS NVSMGSHQYQ SLLKQQIRDL VLRRKSLVRE
     DPEGEGLAEL YNGLLPQAKL QQLQALAAES GFLAKQEPTC TTGLGYDQAM VRHECCCGNN
     ASHVENGGRI QSIWSKLIEH GHVQKCEKVT AKKASLEQLQ LVHSQTYTTF FAVSPTACLK
     IDANSLPLKR FLQLPCGGIG VDSDTYFNDA STQTAARLAA GTLIELSSQV AEGRLKNGFA
     CIRPPGHHAE HEQAMGFCFF NNVAVAVKVL QTKYPAQCAK IAIIDWDVHH GNGTQLSFEN
     DPNVLYMSLH RHDKGNFFPG TGSVTEVGKN DAKGLTVNVP FSGDVMRDPE YLAAWRTVIE
     PVMASFCPDF IIVSAGFDAC HGHPNALGGY EVTPEMFGYM TKSLLNYASG KVVLALEGGY
     DLKSISEAAQ QCVQALIGES DDAGRLSSVA LESLPNPSAV ETLQKVIAIH KSYWPALHGQ
     EAAINTTEMQ WRNLKLQVQM QQQQQQQQT
//