LOCUS       NP_001365343            1089 aa            linear   PRI 20-FEB-2025
DEFINITION  histone deacetylase 4 isoform 1 [Homo sapiens].
ACCESSION   NP_001365343 XP_006712941
VERSION     NP_001365343.1
DBSOURCE    REFSEQ: accession NM_001378414.1
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 1089)
  AUTHORS   Liu,W. and Luo,G.
  TITLE     NEDD9 is transcriptionally regulated by HDAC4 and promotes breast
            cancer metastasis and macrophage M2 polarization via the
            FAK/NF-kappaB signaling pathway
  JOURNAL   Neoplasia 57, 101059 (2024)
   PUBMED   39326322
  REMARK    GeneRIF: NEDD9 is transcriptionally regulated by HDAC4 and promotes
            breast cancer metastasis and macrophage M2 polarization via the
            FAK/NF-kappaB signaling pathway.
REFERENCE   2  (residues 1 to 1089)
  AUTHORS   Khoroshkin,M., Buyan,A., Dodel,M., Navickas,A., Yu,J., Trejo,F.,
            Doty,A., Baratam,R., Zhou,S., Lee,S.B., Joshi,T., Garcia,K.,
            Choi,B., Miglani,S., Subramanyam,V., Modi,H., Carpenter,C.,
            Markett,D., Corces,M.R., Mardakheh,F.K., Kulakovskiy,I.V. and
            Goodarzi,H.
  TITLE     Systematic identification of post-transcriptional regulatory
            modules
  JOURNAL   Nat Commun 15 (1), 7872 (2024)
   PUBMED   39251607
  REMARK    Erratum:[Nat Commun. 2024 Oct 28;15(1):9277. doi:
            10.1038/s41467-024-52903-4.. PMID: 39468017]
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 1089)
  AUTHORS   Di Giorgio,E., Dalla,E., Tolotto,V., D'Este,F., Paluvai,H.,
            Ranzino,L. and Brancolini,C.
  TITLE     HDAC4 influences the DNA damage response and counteracts senescence
            by assembling with HDAC1/HDAC2 to control H2BK120 acetylation and
            homology-directed repair
  JOURNAL   Nucleic Acids Res 52 (14), 8218-8240 (2024)
   PUBMED   38874468
  REMARK    GeneRIF: HDAC4 influences the DNA damage response and counteracts
            senescence by assembling with HDAC1/HDAC2 to control H2BK120
            acetylation and homology-directed repair.
REFERENCE   4  (residues 1 to 1089)
  AUTHORS   Chen,Q. and Lao,J.
  TITLE     Interference with Histone Deacetylase 4 Regulates c-Jun N-terminal
            Kinase/Activating Protein-1 Signaling to Ameliorate Sepsis-induced
            Alveolar Epithelial Cell Injury
  JOURNAL   J Physiol Investig 67 (4), 174-186 (2024)
   PUBMED   39133038
  REMARK    GeneRIF: Interference with Histone Deacetylase 4 Regulates c-Jun
            N-terminal Kinase/Activating Protein-1 Signaling to Ameliorate
            Sepsis-induced Alveolar Epithelial Cell Injury.
REFERENCE   5  (residues 1 to 1089)
  AUTHORS   Dai,S., Guo,L., Dey,R., Guo,M., Zhang,X., Bates,D., Cayford,J.,
            Jiang,L., Wei,H., Chen,Z., Zhang,Y., Chen,L. and Chen,Y.
  TITLE     Structural insights into the HDAC4-MEF2A-DNA complex and its
            implication in long-range transcriptional regulation
  JOURNAL   Nucleic Acids Res 52 (5), 2711-2723 (2024)
   PUBMED   38281192
  REMARK    GeneRIF: Structural insights into the HDAC4-MEF2A-DNA complex and
            its implication in long-range transcriptional regulation.
REFERENCE   6  (residues 1 to 1089)
  AUTHORS   Pazin,M.J. and Kadonaga,J.T.
  TITLE     What's up and down with histone deacetylation and transcription?
  JOURNAL   Cell 89 (3), 325-328 (1997)
   PUBMED   9150131
  REMARK    Review article
REFERENCE   7  (residues 1 to 1089)
  AUTHORS   Wolffe,A.P.
  TITLE     Transcriptional control. Sinful repression
  JOURNAL   Nature 387 (6628), 16-17 (1997)
   PUBMED   9139815
REFERENCE   8  (residues 1 to 1089)
  AUTHORS   Ohara,O., Nagase,T., Ishikawa,K., Nakajima,D., Ohira,M., Seki,N.
            and Nomura,N.
  TITLE     Construction and characterization of human brain cDNA libraries
            suitable for analysis of cDNA clones encoding relatively large
            proteins
  JOURNAL   DNA Res 4 (1), 53-59 (1997)
   PUBMED   9179496
REFERENCE   9  (residues 1 to 1089)
  AUTHORS   Wilson,L.C., Leverton,K., Oude Luttikhuis,M.E., Oley,C.A.,
            Flint,J., Wolstenholme,J., Duckett,D.P., Barrow,M.A., Leonard,J.V.,
            Read,A.P. et al.
  TITLE     Brachydactyly and mental retardation: an Albright hereditary
            osteodystrophy-like syndrome localized to 2q37
  JOURNAL   Am J Hum Genet 56 (2), 400-407 (1995)
   PUBMED   7847374
REFERENCE   10 (residues 1 to 1089)
  AUTHORS   Doherty,E.S. and Lacbawan,F.L.
  TITLE     2q37 Microdeletion Syndrome - RETIRED CHAPTER, FOR HISTORICAL
            REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301337
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC062017.6 and AC017028.11.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Feb 12, 2020 this sequence version replaced XP_006712941.1.
            
            Summary: Histones play a critical role in transcriptional
            regulation, cell cycle progression, and developmental events.
            Histone acetylation/deacetylation alters chromosome structure and
            affects transcription factor access to DNA. The protein encoded by
            this gene belongs to class II of the histone deacetylase/acuc/apha
            family. It possesses histone deacetylase activity and represses
            transcription when tethered to a promoter. This protein does not
            bind DNA directly, but through transcription factors MEF2C and
            MEF2D. It seems to interact in a multiprotein complex with RbAp48
            and HDAC3. [provided by RefSeq, Jul 2008].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR11853566.16775.1,
                                           SRR14038194.3429702.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000543185.6/ ENSP00000440481.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1089
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2q37.3"
     Protein         1..1089
                     /product="histone deacetylase 4 isoform 1"
                     /EC_number="3.5.1.98"
                     /note="histone deacetylase A"
                     /calculated_mol_wt=119574
     Region          <91..152
                     /region_name="ClassIIa_HDAC4_Gln-rich-N"
                     /note="Glutamine-rich N-terminal helical domain of HDAC4,
                     a Class IIa histone deacetylase; cd10162"
                     /db_xref="CDD:197398"
     Site            order(93,97,108..109,112,119,123..124)
                     /site_type="other"
                     /note="dimer interface A, B [polypeptide binding]"
                     /db_xref="CDD:197398"
     Region          118..313
                     /region_name="Interaction with MEF2A.
                     /evidence=ECO:0000269|PubMed:10487761"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Region          133..166
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Region          206..226
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            210
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6NZM9; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Region          240..315
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            246
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CaMK4 and SIK1.
                     /evidence=ECO:0000269|PubMed:10958686; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Region          349..354
                     /region_name="PxLPxI/L motif, mediates interaction with
                     ANKRA2 and 14-3-3 proteins.
                     /evidence=ECO:0000269|PubMed:22649097"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            350
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:22649097,
                     ECO:0007744|PubMed:19690332; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Site            472
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CaMK4 and SIK1.
                     /evidence=ECO:0000269|PubMed:10958686; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Region          514..536
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Region          553..590
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            570
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q6NZM9; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Region          631..651
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            637
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CaMK4.
                     /evidence=ECO:0000269|PubMed:10958686,
                     ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163,
                     ECO:0007744|PubMed:24275569; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Site            638
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:18669648; propagated from
                     UniProtKB/Swiss-Prot (P56524.3)"
     Region          654..1062
                     /region_name="HDAC4"
                     /note="Histone deacetylase 4; cd10006"
                     /db_xref="CDD:212530"
     Region          660..1089
                     /region_name="Histone deacetylase"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Site            order(807..808,816..817,845,847,939,979)
                     /site_type="active"
                     /db_xref="CDD:212530"
     Region          1056..1089
                     /region_name="Nuclear export signal.
                     /evidence=ECO:0000250"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     Region          1066..1089
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P56524.3)"
     CDS             1..1089
                     /gene="HDAC4"
                     /gene_synonym="AHO3; BDMR; HA6116; HD4; HDAC-4; HDAC-A;
                     HDACA; NEDCHF; NEDCHID"
                     /coded_by="NM_001378414.1:263..3532"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS92981.1"
                     /db_xref="GeneID:9759"
                     /db_xref="HGNC:HGNC:14063"
                     /db_xref="MIM:605314"
ORIGIN      
        1 mssqshpdgl sgrdqpvell nparvnhmps tvdvatalpl qvapsavpmd lrldhqfslp
       61 vaepalreqq lqqellalkq kqqiqrqili aefqrqheql srqheaqlhe hikqqqemla
      121 mkhqqelleh qrklerhrqe qelekqhreq klqqlknkek gkesavaste vkmklqefvl
      181 nkkkalahrn lnhcissdpr ywygktqhss ldqssppqsg vstsynhpvl gmydakddfp
      241 lrktasepnl klrsrlkqkv aerrsspllr rkdgpvvtal kkrpldvtds acssapgsgp
      301 sspnnssgsv saengiapav psipaetsla hrlvaregsa aplplytsps lpnitlglpa
      361 tgpsagtagq qdaerltlpa lqqrlslfpg thltpylsts plerdggaah spllqhmvll
      421 eqppaqaplv tdwylsglga lplhaqslvg adrvspsihk lrqhrplgrt qsaplpqnaq
      481 alqhlviqqq hqqflekhkq qfqqqqlqmn kiipkpsepa rqpeshpeet eeelrehqal
      541 ldepyldrlp gqkeahaqag vqvkqepies deeeaeppre vepgqrqpse qellfrqqal
      601 lleqqrihql rnyqasmeaa gipvsfgghr plsraqsspa satfpvsvqe pptkprfttg
      661 lvydtlmlkh qctcgssssh pehagriqsi wsrlqetglr gkcecirgrk atleelqtvh
      721 seahtllygt nplnrqklds kkllgslasv fvrlpcggvg vdsdtiwnev hsagaarlav
      781 gcvvelvfkv atgelkngfa vvrppghhae estpmgfcyf nsvavaakll qqrlsvskil
      841 ivdwdvhhgn gtqqafysdp svlymslhry ddgnffpgsg apdevgtgpg vgfnvnmaft
      901 ggldppmgda eylaafrtvv mpiasefapd vvlvssgfda veghptplgg ynlsarcfgy
      961 ltkqlmglag grivlalegg hdltaicdas eacvsallgn eldplpekvl qqrpnanavr
     1021 smekvmeihs kywrclqrtt stagrsliea qtceneeaet vtamaslsvg vkpaekrpde
     1081 epmeeeppl
//
