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 27-MAR-2024, entry version 176. 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; 10090-ENSMUSP00000106443; -. DR PeptideAtlas; 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 AGR; MGI:1931221; -. DR CTD; 9734; -. DR MGI; MGI:1931221; Hdac9. DR eggNOG; KOG1343; Eukaryota. DR InParanoid; Q99N13; -. DR OrthoDB; 124800at2759; -. DR PhylomeDB; Q99N13; -. DR TreeFam; TF106174; -. DR BioGRID-ORCS; 79221; 1 hit in 50 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:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0031078; F:histone H3K14 deacetylase activity; IMP:ARUK-UCL. DR GO; GO:0032129; F:histone H3K9 deacetylase activity; IMP:ARUK-UCL. DR GO; GO:0034739; F:histone H4K16 deacetylase activity; 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:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IMP:ARUK-UCL. 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:0007399; P:nervous system development; TAS:UniProtKB. 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 Gene3D; 6.10.250.1550; -; 1. DR IDEAL; IID50025; -. DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N. DR PANTHER; PTHR45364:SF12; HISTONE DEACETYLASE 9; 1. DR PANTHER; PTHR45364; HISTONE DEACETYLASE 9-RELATED; 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 //