HDAC9_MOUSE
ID HDAC9_MOUSE Reviewed; 588 AA.
AC Q99N13; Q4QQN7; Q8R4Y6; Q9EPT2;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Histone deacetylase 9;
DE Short=HD9;
DE EC=3.5.1.98;
DE AltName: Full=Histone deacetylase 7B;
DE Short=HD7b;
DE AltName: Full=Histone deacetylase-related protein;
DE AltName: Full=MEF2-interacting transcription repressor MITR;
GN Name=Hdac9; Synonyms=Hdac7b, Hdrp, Mitr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), HOMODIMERIZATION, INTERACTION WITH
RP CTBP1; HDAC1; HDAC3; HDAC4 AND HDAC5, AND MUTAGENESIS OF 25-ASP-LEU-26.
RC STRAIN=NIH Swiss; TISSUE=Embryonic heart;
RX PubMed=11022042; DOI=10.1074/jbc.m007364200;
RA Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.;
RT "Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting
RT transcription repressor (MITR) contributes to transcriptional repression of
RT the MEF2 transcription factor.";
RL J. Biol. Chem. 276:35-39(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=Swiss Webster / NIH;
RA Zhou X., Richon V.M., Rifkind R.A., Marks P.A.;
RT "Cloning of the mouse HDRP cDNA.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 [4]
RP FUNCTION, PHOSPHORYLATION AT SER-220 AND SER-450, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=11390982; DOI=10.1073/pnas.131198498;
RA Zhang C.L., McKinsey T.A., Olson E.N.;
RT "The transcriptional corepressor MITR is a signal-responsive inhibitor of
RT myogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:7354-7359(2001).
RN [5]
RP PHOSPHORYLATION AT SER-220 AND SER-450, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12202037; DOI=10.1016/s0092-8674(02)00861-9;
RA Zhang C.L., McKinsey T.A., Chang S., Antos C.L., Hill J.A., Olson E.N.;
RT "Class II histone deacetylases act as signal-responsive repressors of
RT cardiac hypertrophy.";
RL Cell 110:479-488(2002).
RN [6]
RP PHOSPHORYLATION AT SER-240, AND SUBCELLULAR LOCATION.
RX PubMed=15546868; DOI=10.1074/jbc.m411894200;
RA Deng X., Ewton D.Z., Mercer S.E., Friedman E.;
RT "Mirk/dyrk1B decreases the nuclear accumulation of class II histone
RT deacetylases during skeletal muscle differentiation.";
RL J. Biol. Chem. 280:4894-4905(2005).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DOWN-REGULATION BY
RP DENERVATION, INTERACTION WITH HDAC1 AND HDAC3, AND SUBCELLULAR LOCATION.
RX PubMed=15711539; DOI=10.1038/nn1408;
RA Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., Schaeffer L.;
RT "Histone deacetylase 9 couples neuronal activity to muscle chromatin
RT acetylation and gene expression.";
RL Nat. Neurosci. 8:313-321(2005).
RN [8]
RP DOWN-REGULATION BY NEURONAL APOPTOSIS, FUNCTION, AND INTERACTION WITH HDAC1
RP AND MAPK10.
RX PubMed=16611996; DOI=10.1128/mcb.26.9.3550-3564.2006;
RA Morrison B.E., Majdzadeh N., Zhang X., Lyles A., Bassel-Duby R.,
RA Olson E.N., D'Mello S.R.;
RT "Neuroprotection by histone deacetylase-related protein.";
RL Mol. Cell. Biol. 26:3550-3564(2006).
RN [9]
RP INDUCTION BY MEF2, AND DEVELOPMENTAL STAGE.
RX PubMed=17101791; DOI=10.1128/mcb.01415-06;
RA Haberland M., Arnold M.A., McAnally J., Phan D., Kim Y., Olson E.N.;
RT "Regulation of HDAC9 gene expression by MEF2 establishes a negative-
RT feedback loop in the transcriptional circuitry of muscle differentiation.";
RL Mol. Cell. Biol. 27:518-525(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-552, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 139-158 IN COMPLEX WITH MEF2 AND
RP DNA.
RX PubMed=15567413; DOI=10.1016/j.jmb.2004.10.033;
RA Han A., He J., Wu Y., Liu J.O., Chen L.;
RT "Mechanism of recruitment of class II histone deacetylases by myocyte
RT enhancer factor-2.";
RL J. Mol. Biol. 345:91-102(2005).
CC -!- FUNCTION: Devoided of intrinsic deacetylase activity, promotes the
CC deacetylation of lysine residues on the N-terminal part of the core
CC histones (H2A, H2B, H3 and H4) by recruiting HDAC1 and HDAC3. 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. Represses MEF2-dependent transcription,
CC inhibits skeletal myogenesis and may be involved in heart development.
CC Protects neurons from apoptosis, both by inhibiting JUN phosphorylation
CC by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to
CC JUN promoter. {ECO:0000269|PubMed:11390982,
CC ECO:0000269|PubMed:12202037, ECO:0000269|PubMed:15711539,
CC ECO:0000269|PubMed:16611996}.
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. Interacts with ETV6 (By similarity). Interacts with
CC MEF2, HDAC1, HDAC3, HDAC4, HDAC5, CTBP1 and MAPK10. The phosphorylated
CC form interacts with 14-3-3. Interacts with FOXP3 in the absence of T-
CC cell stimulation (By similarity). {ECO:0000250|UniProtKB:Q9UKV0,
CC ECO:0000269|PubMed:11022042, ECO:0000269|PubMed:15567413,
CC ECO:0000269|PubMed:15711539, ECO:0000269|PubMed:16611996}.
CC -!- INTERACTION:
CC Q99N13; Q9Z2V5: Hdac6; NbExp=2; IntAct=EBI-645361, EBI-1009256;
CC Q99N13; P60335: Pcbp1; NbExp=6; IntAct=EBI-645361, EBI-309059;
CC Q99N13; Q3TKT4: Smarca4; NbExp=3; IntAct=EBI-645361, EBI-1210244;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11390982,
CC ECO:0000269|PubMed:15546868, ECO:0000269|PubMed:15711539}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q99N13-1; Sequence=Displayed;
CC Name=2; Synonyms=Hdrpa;
CC IsoId=Q99N13-2; Sequence=VSP_023769;
CC Name=3;
CC IsoId=Q99N13-3; Sequence=VSP_029173;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in heart, brain and
CC spleen. Expressed in skeletal muscle. {ECO:0000269|PubMed:11390982,
CC ECO:0000269|PubMed:15711539}.
CC -!- DEVELOPMENTAL STAGE: At 10.5 dpc, expressed in heart, skeletal muscle
CC and neural lineages. At 11.5d pc, expressed in heart, dorsal root
CC ganglia and neural tube. At 12.5 dpc, expressed in heart, skeletal
CC muscle, dorsal root ganglia, neural tube and retina. Strongly up-
CC regulated in muscle between 14 and 19 dpc as a result of motor
CC innervation. {ECO:0000269|PubMed:11390982, ECO:0000269|PubMed:15711539,
CC ECO:0000269|PubMed:17101791}.
CC -!- INDUCTION: By MEF2 during muscle differentiation. Down-regulated by
CC muscle denervation. Down-regulated by trichostatin A or sodium
CC butyrate, and during neuronal apoptosis (at protein level).
CC {ECO:0000269|PubMed:17101791}.
CC -!- PTM: Sumoylated. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-
CC binding, impairs interaction with MEF2, and antagonizes antimyogenic
CC activity. Phosphorylated on Ser-240 by DYRK1B; which impairs nuclear
CC accumulation. Phosphorylated by the PKC kinases PKN1 and PKN2,
CC impairing nuclear import. {ECO:0000269|PubMed:11390982,
CC ECO:0000269|PubMed:12202037, ECO:0000269|PubMed:15546868}.
CC -!- DISRUPTION PHENOTYPE: Mice do not present any abnormality at early age
CC but develop cardiac hypertrophy by eight months of age.
CC {ECO:0000269|PubMed:12202037}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {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; AF324492; AAG48332.1; -; mRNA.
DR EMBL; AF235053; AAK15027.1; -; mRNA.
DR EMBL; AF279371; AAL86358.1; -; mRNA.
DR EMBL; BC098187; AAH98187.1; -; mRNA.
DR CCDS; CCDS36432.1; -. [Q99N13-1]
DR RefSeq; NP_077038.2; NM_024124.3.
DR PDB; 1TQE; X-ray; 2.70 A; X/Y=139-158.
DR PDBsum; 1TQE; -.
DR AlphaFoldDB; Q99N13; -.
DR SMR; Q99N13; -.
DR BioGRID; 219748; 9.
DR DIP; DIP-41905N; -.
DR ELM; Q99N13; -.
DR IntAct; Q99N13; 9.
DR STRING; 10090.ENSMUSP00000106443; -.
DR BindingDB; Q99N13; -.
DR ChEMBL; CHEMBL3832944; -.
DR iPTMnet; Q99N13; -.
DR PhosphoSitePlus; Q99N13; -.
DR MaxQB; Q99N13; -.
DR PaxDb; Q99N13; -.
DR PeptideAtlas; Q99N13; -.
DR PRIDE; Q99N13; -.
DR ProteomicsDB; 271500; -. [Q99N13-1]
DR ProteomicsDB; 271501; -. [Q99N13-2]
DR ProteomicsDB; 271502; -. [Q99N13-3]
DR DNASU; 79221; -.
DR GeneID; 79221; -.
DR KEGG; mmu:79221; -.
DR UCSC; uc007nja.1; mouse. [Q99N13-3]
DR UCSC; uc007njb.1; mouse. [Q99N13-2]
DR UCSC; uc007njc.2; mouse. [Q99N13-1]
DR CTD; 9734; -.
DR MGI; MGI:1931221; Hdac9.
DR eggNOG; KOG1343; Eukaryota.
DR InParanoid; Q99N13; -.
DR OrthoDB; 1484694at2759; -.
DR PhylomeDB; Q99N13; -.
DR TreeFam; TF106174; -.
DR BioGRID-ORCS; 79221; 1 hit in 44 CRISPR screens.
DR ChiTaRS; Hdac9; mouse.
DR EvolutionaryTrace; Q99N13; -.
DR PRO; PR:Q99N13; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q99N13; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0004407; F:histone deacetylase activity; TAS:UniProtKB.
DR GO; GO:0034739; F:histone deacetylase activity (H4-K16 specific); ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0033558; F:protein lysine deacetylase activity; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:MGI.
DR GO; GO:0042113; P:B cell activation; TAS:UniProtKB.
DR GO; GO:0030183; P:B cell differentiation; TAS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:MGI.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IGI:MGI.
DR GO; GO:0006281; P:DNA repair; IGI:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0016575; P:histone deacetylation; ISO:MGI.
DR GO; GO:0070932; P:histone H3 deacetylation; ISO:MGI.
DR GO; GO:0070933; P:histone H4 deacetylation; ISO:MGI.
DR GO; GO:1990678; P:histone H4-K16 deacetylation; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI.
DR GO; GO:0051005; P:negative regulation of lipoprotein lipase activity; ISO:MGI.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; TAS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:MGI.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IGI:MGI.
DR GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; IGI:MGI.
DR IDEAL; IID50025; -.
DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N.
DR InterPro; IPR017320; Histone_deAcase_II_euk.
DR PANTHER; PTHR45364; PTHR45364; 1.
DR Pfam; PF12203; HDAC4_Gln; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator; Hydrolase;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..588
FT /note="Histone deacetylase 9"
FT /id="PRO_0000114711"
FT REGION 23..27
FT /note="Interaction with CTBP1"
FT /evidence="ECO:0000269|PubMed:11022042"
FT REGION 110..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 136..154
FT /note="Interaction with MEF2"
FT REGION 175..343
FT /note="Interaction with MAPK10"
FT /evidence="ECO:0000269|PubMed:16611996"
FT REGION 183..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..261
FT /note="Interaction with ETV6"
FT /evidence="ECO:0000250"
FT REGION 264..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 110..142
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 146..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 183..203
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..242
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 264..292
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..523
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UKV0"
FT MOD_RES 220
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11390982,
FT ECO:0000269|PubMed:12202037"
FT MOD_RES 240
FT /note="Phosphoserine; by DYRK1B"
FT /evidence="ECO:0000269|PubMed:15546868"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11390982,
FT ECO:0000269|PubMed:12202037"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 177..178
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11022042"
FT /id="VSP_029173"
FT VAR_SEQ 219..262
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_023769"
FT MUTAGEN 25..26
FT /note="DL->AS: Abolishes binding to CTBP1 and impairs
FT function in transcription repression."
FT /evidence="ECO:0000269|PubMed:11022042"
FT CONFLICT 120
FT /note="R -> K (in Ref. 2; AAK15027/AAL86358)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="R -> K (in Ref. 2; AAK15027/AAL86358)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="N -> T (in Ref. 3; AAH98187)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="N -> T (in Ref. 1; AAG48332)"
FT /evidence="ECO:0000305"
FT HELIX 143..153
FT /evidence="ECO:0007829|PDB:1TQE"
SQ SEQUENCE 588 AA; 65687 MW; 4ED7FA9F02BD4621 CRC64;
MHSMISSVDV KSEVPMGLEP ISPLDLRTDL RMMMPVVDPV VREKQLQQEL LLIQQQQQIQ
KQLLIAEFQK QHENLTRQHQ AQLQEHIKEL LAIKQQQELL EKEQKLEQQR QEQEVERHRR
EQQLPPLRGK DRGRERAVAS TEVKQKLQEF LLSKSATKDT PTNGKNHSVG RHPKLWYTAA
HHTSLDQSSP PLSGTSPSYK YTLPGAQDSK DDFPLRKTAS EPNLKVRSRL KQKVAERRSS
PLLRRKDGNL VTSFKKRVFE VAESSVSSSS PGSGPSSPNN GPAGNVTENE ASALPPTPHP
EQLVPQQRIL IHEDSMNLLS LYTSPSLPNI TLGLPAVPSP LNASNSLKDK QKCETQMLRQ
GVPLPSQYGS SIAASSSHVH VAMEGKPNSS HQALLQHLLL KEQMRQQKLL VAGGVPLHPQ
SPLATKERIS PGIRGTHKLP RHRPLNRTQS APLPQSTLAQ LVIQQQHQQF LEKQKQYQQQ
IHMNKLLSKS IEQLKQPGSH LEEAEEELQG DQSMEDRAAS KDNSARSDSS ACVEDTLGQV
GAVKVKEEPV DSDEDAQIQE MECGEQAAFM QQVIGKDLAP GFVIKVII
