ID HDAC9_HUMAN Reviewed; 1011 AA. AC Q9UKV0; A7E2F3; B7Z4I4; B7Z917; B7Z928; B7Z940; C9JS87; E7EX34; F8W9E0; AC O94845; O95028; Q2M2R6; Q86SL1; Q86US3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 18-OCT-2001, sequence version 2. DT 27-MAR-2024, entry version 212. DE RecName: Full=Histone deacetylase 9; DE Short=HD9; DE EC=3.5.1.98 {ECO:0000269|PubMed:11535832}; DE AltName: Full=Histone deacetylase 7B; DE Short=HD7; DE Short=HD7b; DE AltName: Full=Histone deacetylase-related protein; DE AltName: Full=MEF2-interacting transcription repressor MITR; GN Name=HDAC9; Synonyms=HDAC7, HDAC7B, HDRP, KIAA0744, MITR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4), TISSUE SPECIFICITY, RP INTERACTION WITH MEF2, FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY RP REGULATION. RC TISSUE=Brain; RX PubMed=11535832; DOI=10.1073/pnas.191375098; RA Zhou X., Marks P.A., Rifkind R.A., Richon V.M.; RT "Cloning and characterization of a histone deacetylase, HDAC9."; RL Proc. Natl. Acad. Sci. U.S.A. 98:10572-10577(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), TISSUE SPECIFICITY, AND CHROMOSOMAL RP TRANSLOCATION WITH TGFB2. RC TISSUE=Lens; RX PubMed=12706107; DOI=10.1016/s0888-7543(03)00046-6; RA David D., Cardoso J., Marques B., Marques R., Silva E.D., Santos H., RA Boavida M.G.; RT "Molecular characterization of a familial translocation implicates RT disruption of HDAC9 and possible position effect on TGFbeta2 in the RT pathogenesis of Peters' anomaly."; RL Genomics 81:489-503(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), TISSUE SPECIFICITY, ALTERNATIVE RP SPLICING (ISOFORMS 3; 6 AND 7), INTERACTION WITH ETV6; NCOR1 AND BCL6, RP FUNCTION, SUBCELLULAR LOCATION, AND SUMOYLATION. RC TISSUE=Brain; RX PubMed=12590135; DOI=10.1074/jbc.m212935200; RA Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., RA Zelent A.; RT "The histone deacetylase 9 gene encodes multiple protein isoforms."; RL J. Biol. Chem. 278:16059-16072(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 8; 9; 10 AND 11). RC TISSUE=Brain, and Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 2-1011 (ISOFORM 6). 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 [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-650 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=10523670; DOI=10.1128/mcb.19.11.7816; RA Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H., RA 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 [10] RP IDENTIFICATION (ISOFORM 3), INTERACTION WITH HDAC1, AND FUNCTION. RX PubMed=10487760; DOI=10.1093/emboj/18.18.5085; RA Sparrow D.B., Miska E.A., Langley E., Reynaud-Deonauth S., Kotecha S., RA Towers N., Spohr G., Kouzarides T., Mohun T.J.; RT "MEF-2 function is modified by a novel co-repressor, MITR."; RL EMBO J. 18:5085-5098(1999). RN [11] RP IDENTIFICATION (ISOFORM 3), TISSUE SPECIFICITY, INTERACTION WITH HDAC1 AND RP HDAC3, AND FUNCTION. RX PubMed=10655483; DOI=10.1073/pnas.97.3.1056; RA Zhou X., Richon V.M., Rifkind R.A., Marks P.A.; RT "Identification of a transcriptional repressor related to the noncatalytic RT domain of histone deacetylases 4 and 5."; RL Proc. Natl. Acad. Sci. U.S.A. 97:1056-1061(2000). RN [12] RP INTERACTION WITH MEF2. RX PubMed=10487761; DOI=10.1093/emboj/18.18.5099; RA Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T.; RT "HDAC4 deacetylase associates with and represses the MEF2 transcription RT factor."; RL EMBO J. 18:5099-5107(1999). RN [13] RP SUMOYLATION. 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 FUNCTION. 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 [15] RP INTERACTION WITH FOXP3. RX PubMed=17360565; DOI=10.1073/pnas.0700298104; RA Li B., Samanta A., Song X., Iacono K.T., Bembas K., Tao R., Basu S., RA Riley J.L., Hancock W.W., Shen Y., Saouaf S.J., Greene M.I.; RT "FOXP3 interactions with histone acetyltransferase and class II histone RT deacetylases are required for repression."; RL Proc. Natl. Acad. Sci. U.S.A. 104:4571-4576(2007). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY RP 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 [17] RP PHOSPHORYLATION. RX PubMed=20188095; DOI=10.1016/j.febslet.2010.02.057; RA Harrison B.C., Huynh K., Lundgaard G.L., Helmke S.M., Perryman M.B., RA McKinsey T.A.; RT "Protein kinase C-related kinase targets nuclear localization signals in a RT subset of class IIa histone deacetylases."; RL FEBS Lett. 584:1103-1110(2010). RN [18] RP VARIANT THR-921. RX PubMed=21248752; DOI=10.1038/nature09639; RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M., RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.; RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene RT PBRM1 in renal carcinoma."; RL Nature 469:539-542(2011). RN [19] RP INVOLVEMENT IN ARCND4. RX PubMed=34750192; DOI=10.1136/jmedgenet-2021-107825; RA Romanelli Tavares V.L., Guimaraes-Ramos S.L., Zhou Y., Masotti C., RA Ezquina S., Moreira D.P., Buermans H., Freitas R.S., Den Dunnen J.T., RA Twigg S.R.F., Passos-Bueno M.R.; RT "New locus underlying auriculocondylar syndrome (ARCND): 430 kb duplication RT involving TWIST1 regulatory elements."; RL J. Med. Genet. 59:895-905(2022). CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the CC N-terminal part of the core histones (H2A, H2B, H3 and H4). 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 {ECO:0000269|PubMed:11535832}. CC -!- FUNCTION: Isoform 3 lacks active site residues and therefore is CC catalytically inactive. Represses MEF2-dependent transcription by CC recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and CC to be involved in heart development. Protects neurons from apoptosis, CC both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN CC transcription via HDAC1 recruitment to JUN promoter. 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 Evidence={ECO:0000269|PubMed:11535832}; CC -!- ACTIVITY REGULATION: Inhibited by Trichostatin A (TSA) and CC suberoylanilide hydroxamic acid. {ECO:0000269|PubMed:11535832}. CC -!- SUBUNIT: Homodimer. Interacts with CTBP1. The phosphorylated form CC interacts with 14-3-3 (By similarity). Interacts with HDAC1 and HDAC3, CC and probably with HDAC4 and HDAC5. Interacts with MEF2, MAPK10, ETV6, CC NCOR1 and BCL6. Interacts with FOXP3 in the absence of T-cell CC stimulation. {ECO:0000250|UniProtKB:Q99N13, CC ECO:0000269|PubMed:10487760, ECO:0000269|PubMed:10487761, CC ECO:0000269|PubMed:10655483, ECO:0000269|PubMed:11535832, CC ECO:0000269|PubMed:12590135, ECO:0000269|PubMed:17360565}. CC -!- INTERACTION: CC Q9UKV0; P41182: BCL6; NbExp=2; IntAct=EBI-765444, EBI-765407; CC Q9UKV0; Q06413: MEF2C; NbExp=3; IntAct=EBI-765444, EBI-2684075; CC Q9UKV0-3; P41212: ETV6; NbExp=3; IntAct=EBI-765476, EBI-1372759; CC Q9UKV0-3; Q60974: Ncor1; Xeno; NbExp=2; IntAct=EBI-765476, EBI-349004; CC Q9UKV0-7; Q60974: Ncor1; Xeno; NbExp=3; IntAct=EBI-1372717, EBI-349004; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q9UKV0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UKV0-2; Sequence=VSP_002082; CC Name=3; Synonyms=HDRP, MITR; CC IsoId=Q9UKV0-3; Sequence=VSP_002083, VSP_002084; CC Name=4; Synonyms=HDAC9a; CC IsoId=Q9UKV0-4; Sequence=VSP_002085, VSP_002086; CC Name=5; Synonyms=HDAC9b, HDAC9fl; CC IsoId=Q9UKV0-5; Sequence=VSP_023768; CC Name=6; CC IsoId=Q9UKV0-6; Sequence=VSP_023766, VSP_023767, VSP_023768; CC Name=7; CC IsoId=Q9UKV0-7; Sequence=VSP_023766, VSP_023768; CC Name=8; CC IsoId=Q9UKV0-8; Sequence=VSP_043428, VSP_023767, VSP_002083, CC VSP_002084; CC Name=9; CC IsoId=Q9UKV0-9; Sequence=VSP_023767, VSP_002083, VSP_002084; CC Name=10; CC IsoId=Q9UKV0-10; Sequence=VSP_046827, VSP_023766, VSP_002083, CC VSP_002084; CC Name=11; CC IsoId=Q9UKV0-11; Sequence=VSP_046827, VSP_046828, VSP_023767, CC VSP_002083, VSP_002084; CC -!- TISSUE SPECIFICITY: Broadly expressed, with highest levels in brain, CC heart, muscle and testis. Isoform 3 is present in human bladder CC carcinoma cells (at protein level). {ECO:0000269|PubMed:10655483, CC ECO:0000269|PubMed:11535832, ECO:0000269|PubMed:12590135, CC ECO:0000269|PubMed:12706107}. 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; which impairs nuclear accumulation CC (By similarity). Isoform 7 is phosphorylated on Tyr-1010. CC Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear CC import. {ECO:0000250, ECO:0000269|PubMed:20188095}. CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:12032081, CC ECO:0000269|PubMed:12590135}. CC -!- DISEASE: Auriculocondylar syndrome 4 (ARCND4) [MIM:620457]: An CC autosomal dominant form of auriculocondylar syndrome, a craniofacial CC malformation syndrome characterized by variable mandibular anomalies, CC including mild to severe micrognathia, temporomandibular joint CC ankylosis, cleft palate, and a characteristic ear malformation that CC consists of separation of the lobule from the external ear, giving the CC appearance of a question mark (question-mark ear). Other frequently CC described features include prominent cheeks, cupped and posteriorly CC rotated ears, preauricular tags, and microstomia. Glossoptosis, CC masticatory abnormalities, orthodontic problems, and malocclusion occur CC in a majority of affected subjects. {ECO:0000269|PubMed:34750192}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving HDAC9 is found in a CC family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 CC resulting in lack of HDAC9 protein. {ECO:0000269|PubMed:12706107}. CC -!- MISCELLANEOUS: [Isoform 3]: Major form in most tissues. Inactive due to CC lack of active site residues. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: Excluded from the nucleus. Does not CC interact with ETV6. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA34464.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAI11736.1; Type=Frameshift; Evidence={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; AY032737; AAK66821.1; -; mRNA. DR EMBL; AY032738; AAK66822.1; -; mRNA. DR EMBL; AJ459808; CAD30851.1; -; mRNA. DR EMBL; AY197371; AAO27363.1; -; mRNA. DR EMBL; AB018287; BAA34464.2; ALT_INIT; mRNA. DR EMBL; AK297404; BAH12570.1; -; mRNA. DR EMBL; AK304298; BAH14153.1; -; mRNA. DR EMBL; AK304343; BAH14164.1; -; mRNA. DR EMBL; AK304410; BAH14176.1; -; mRNA. DR EMBL; AC002088; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC002124; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC002410; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC002433; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004744; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004994; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005249; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC010082; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC074193; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091697; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471073; EAW93702.1; -; Genomic_DNA. DR EMBL; CH471073; EAW93703.1; -; Genomic_DNA. DR EMBL; BC111735; AAI11736.1; ALT_FRAME; mRNA. DR EMBL; BC150328; AAI50329.1; -; mRNA. DR EMBL; BC152405; AAI52406.1; -; mRNA. DR EMBL; AF124924; AAF04254.1; -; mRNA. DR CCDS; CCDS47553.1; -. [Q9UKV0-7] DR CCDS; CCDS47554.1; -. [Q9UKV0-5] DR CCDS; CCDS47555.1; -. [Q9UKV0-1] DR CCDS; CCDS47557.1; -. [Q9UKV0-3] DR CCDS; CCDS56465.1; -. [Q9UKV0-8] DR CCDS; CCDS56466.1; -. [Q9UKV0-9] DR CCDS; CCDS56467.1; -. [Q9UKV0-10] DR CCDS; CCDS56468.1; -. [Q9UKV0-11] DR CCDS; CCDS83163.1; -. [Q9UKV0-6] DR RefSeq; NP_001191073.1; NM_001204144.2. [Q9UKV0-8] DR RefSeq; NP_001191074.1; NM_001204145.2. [Q9UKV0-9] DR RefSeq; NP_001191075.1; NM_001204146.2. DR RefSeq; NP_001191076.1; NM_001204147.2. [Q9UKV0-11] DR RefSeq; NP_001191077.1; NM_001204148.2. [Q9UKV0-10] DR RefSeq; NP_001308797.1; NM_001321868.1. DR RefSeq; NP_001308798.1; NM_001321869.1. DR RefSeq; NP_001308799.1; NM_001321870.1. DR RefSeq; NP_001308800.1; NM_001321871.1. DR RefSeq; NP_001308801.1; NM_001321872.1. DR RefSeq; NP_001308802.1; NM_001321873.1. DR RefSeq; NP_001308803.1; NM_001321874.1. DR RefSeq; NP_001308804.1; NM_001321875.1. DR RefSeq; NP_001308805.1; NM_001321876.1. DR RefSeq; NP_001308806.1; NM_001321877.1. [Q9UKV0-6] DR RefSeq; NP_001308807.1; NM_001321878.1. DR RefSeq; NP_001308808.1; NM_001321879.1. DR RefSeq; NP_001308813.1; NM_001321884.1. DR RefSeq; NP_001308814.1; NM_001321885.1. DR RefSeq; NP_001308815.1; NM_001321886.1. DR RefSeq; NP_001308816.1; NM_001321887.1. DR RefSeq; NP_001308817.1; NM_001321888.1. DR RefSeq; NP_001308818.1; NM_001321889.1. DR RefSeq; NP_001308819.1; NM_001321890.1. DR RefSeq; NP_001308820.1; NM_001321891.1. [Q9UKV0-9] DR RefSeq; NP_001308822.1; NM_001321893.1. [Q9UKV0-9] DR RefSeq; NP_001308823.1; NM_001321894.1. DR RefSeq; NP_001308824.1; NM_001321895.1. DR RefSeq; NP_001308825.1; NM_001321896.1. [Q9UKV0-10] DR RefSeq; NP_001308826.1; NM_001321897.1. [Q9UKV0-6] DR RefSeq; NP_001308827.1; NM_001321898.1. DR RefSeq; NP_001308828.1; NM_001321899.1. DR RefSeq; NP_001308829.1; NM_001321900.1. [Q9UKV0-3] DR RefSeq; NP_001308830.1; NM_001321901.1. DR RefSeq; NP_001308831.1; NM_001321902.1. DR RefSeq; NP_055522.1; NM_014707.3. [Q9UKV0-3] DR RefSeq; NP_478056.1; NM_058176.2. [Q9UKV0-1] DR RefSeq; NP_848510.1; NM_178423.2. [Q9UKV0-5] DR RefSeq; NP_848512.1; NM_178425.3. [Q9UKV0-7] DR RefSeq; XP_011513940.1; XM_011515638.2. DR RefSeq; XP_011513941.1; XM_011515639.2. DR RefSeq; XP_016868315.1; XM_017012826.1. DR RefSeq; XP_016868317.1; XM_017012828.1. DR AlphaFoldDB; Q9UKV0; -. DR SMR; Q9UKV0; -. DR BioGRID; 115083; 75. DR DIP; DIP-39904N; -. DR ELM; Q9UKV0; -. DR IntAct; Q9UKV0; 34. DR MINT; Q9UKV0; -. DR STRING; 9606.ENSP00000408617; -. DR BindingDB; Q9UKV0; -. DR ChEMBL; CHEMBL4145; -. DR DrugBank; DB12565; Abexinostat. DR DrugBank; DB05015; Belinostat. DR DrugBank; DB01262; Decitabine. DR DrugBank; DB11841; Entinostat. DR DrugBank; DB12645; Givinostat. DR DrugBank; DB06603; Panobinostat. DR DrugBank; DB06819; Phenylbutyric acid. DR DrugBank; DB03766; Propanoic acid. DR DrugBank; DB12847; Pyroxamide. DR DrugBank; DB06176; Romidepsin. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB02546; Vorinostat. DR DrugCentral; Q9UKV0; -. DR GuidetoPHARMACOLOGY; 2620; -. DR GlyGen; Q9UKV0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UKV0; -. DR PhosphoSitePlus; Q9UKV0; -. DR BioMuta; HDAC9; -. DR DMDM; 19865267; -. DR jPOST; Q9UKV0; -. DR MassIVE; Q9UKV0; -. DR MaxQB; Q9UKV0; -. DR PaxDb; 9606-ENSP00000408617; -. DR PeptideAtlas; Q9UKV0; -. DR ProteomicsDB; 11455; -. DR ProteomicsDB; 18971; -. DR ProteomicsDB; 30309; -. DR ProteomicsDB; 84881; -. [Q9UKV0-1] DR ProteomicsDB; 84882; -. [Q9UKV0-2] DR ProteomicsDB; 84883; -. [Q9UKV0-3] DR ProteomicsDB; 84884; -. [Q9UKV0-4] DR ProteomicsDB; 84885; -. [Q9UKV0-5] DR ProteomicsDB; 84886; -. [Q9UKV0-6] DR ProteomicsDB; 84887; -. [Q9UKV0-7] DR ProteomicsDB; 84888; -. [Q9UKV0-8] DR Antibodypedia; 6494; 729 antibodies from 39 providers. DR DNASU; 9734; -. DR Ensembl; ENST00000401921.5; ENSP00000383912.1; ENSG00000048052.25. [Q9UKV0-6] DR Ensembl; ENST00000405010.7; ENSP00000384382.3; ENSG00000048052.25. [Q9UKV0-3] DR Ensembl; ENST00000406451.8; ENSP00000384657.3; ENSG00000048052.25. [Q9UKV0-5] DR Ensembl; ENST00000417496.6; ENSP00000401669.2; ENSG00000048052.25. [Q9UKV0-8] DR Ensembl; ENST00000428307.6; ENSP00000395655.2; ENSG00000048052.25. [Q9UKV0-9] DR Ensembl; ENST00000432645.6; ENSP00000410337.2; ENSG00000048052.25. [Q9UKV0-1] DR Ensembl; ENST00000441542.7; ENSP00000408617.2; ENSG00000048052.25. [Q9UKV0-7] DR Ensembl; ENST00000456174.6; ENSP00000388568.2; ENSG00000048052.25. [Q9UKV0-10] DR Ensembl; ENST00000524023.1; ENSP00000430036.1; ENSG00000048052.25. [Q9UKV0-11] DR Ensembl; ENST00000686413.1; ENSP00000509161.1; ENSG00000048052.25. [Q9UKV0-7] DR GeneID; 9734; -. DR KEGG; hsa:9734; -. DR MANE-Select; ENST00000686413.1; ENSP00000509161.1; NM_178425.4; NP_848512.1. [Q9UKV0-7] DR UCSC; uc003sud.2; human. [Q9UKV0-1] DR AGR; HGNC:14065; -. DR CTD; 9734; -. DR DisGeNET; 9734; -. DR GeneCards; HDAC9; -. DR HGNC; HGNC:14065; HDAC9. DR HPA; ENSG00000048052; Low tissue specificity. DR MalaCards; HDAC9; -. DR MIM; 606543; gene. DR MIM; 620457; phenotype. DR neXtProt; NX_Q9UKV0; -. DR OpenTargets; ENSG00000048052; -. DR PharmGKB; PA38377; -. DR VEuPathDB; HostDB:ENSG00000048052; -. DR eggNOG; KOG1343; Eukaryota. DR GeneTree; ENSGT00940000160307; -. DR HOGENOM; CLU_006530_2_0_1; -. DR InParanoid; Q9UKV0; -. DR OMA; EYLEAFX; -. DR OrthoDB; 124800at2759; -. DR PhylomeDB; Q9UKV0; -. DR TreeFam; TF106174; -. DR BRENDA; 3.5.1.98; 2681. DR PathwayCommons; Q9UKV0; -. 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-350054; Notch-HLH transcription pathway. DR SignaLink; Q9UKV0; -. DR SIGNOR; Q9UKV0; -. DR BioGRID-ORCS; 9734; 23 hits in 1183 CRISPR screens. DR ChiTaRS; HDAC9; human. DR GeneWiki; HDAC9; -. DR GenomeRNAi; 9734; -. DR Pharos; Q9UKV0; Tclin. DR PRO; PR:Q9UKV0; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9UKV0; Protein. DR Bgee; ENSG00000048052; Expressed in oocyte and 203 other cell types or tissues. DR ExpressionAtlas; Q9UKV0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB. DR GO; GO:0035097; C:histone methyltransferase complex; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0140297; F:DNA-binding transcription factor binding; IDA:BHF-UCL. DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL. DR GO; GO:0042826; F:histone deacetylase binding; IDA:BHF-UCL. DR GO; GO:0031078; F:histone H3K14 deacetylase activity; ISS:ARUK-UCL. DR GO; GO:0032129; F:histone H3K9 deacetylase activity; ISS:ARUK-UCL. DR GO; GO:0034739; F:histone H4K16 deacetylase activity; IDA:ARUK-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB. DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:BHF-UCL. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IDA:BHF-UCL. DR GO; GO:0003714; F:transcription corepressor activity; ISS: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:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL. DR GO; GO:0042632; P:cholesterol homeostasis; IDA:ARUK-UCL. DR GO; GO:0007507; P:heart development; ISS:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; TAS:UniProtKB. DR GO; GO:0001818; P:negative regulation of cytokine production; IDA:ARUK-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl. DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL. DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL. DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; ISS:UniProtKB. DR GO; GO:0051153; P:regulation of striated muscle cell differentiation; ISS:UniProtKB. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR CDD; cd10163; ClassIIa_HDAC9_Gln-rich-N; 1. DR CDD; cd10009; HDAC9; 1. DR Gene3D; 6.10.250.1550; -; 1. DR Gene3D; 3.40.800.20; Histone deacetylase domain; 1. DR InterPro; IPR046949; HDAC4/5/7/9. 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; IPR023696; Ureohydrolase_dom_sf. DR PANTHER; PTHR45364:SF12; HISTONE DEACETYLASE 9; 1. DR PANTHER; PTHR45364; HISTONE DEACETYLASE 9-RELATED; 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; Arginase/deacetylase; 1. DR Genevisible; Q9UKV0; HS. PE 1: Evidence at protein level; KW Alternative splicing; Chromatin regulator; Chromosomal rearrangement; KW Hydrolase; Metal-binding; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc. FT CHAIN 1..1011 FT /note="Histone deacetylase 9" FT /id="PRO_0000114710" FT REGION 23..27 FT /note="Interaction with CTBP1" FT /evidence="ECO:0000250" FT REGION 110..139 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 136..154 FT /note="Interaction with MEF2" FT /evidence="ECO:0000250" FT REGION 175..343 FT /note="Interaction with MAPK10" FT /evidence="ECO:0000250" FT REGION 183..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 218..261 FT /note="Interaction with ETV6" FT /evidence="ECO:0000269|PubMed:12590135" FT REGION 262..304 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 494..536 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 631..978 FT /note="Histone deacetylase" FT COMPBIAS 183..202 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 210..249 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 497..514 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 516..536 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 783 FT /evidence="ECO:0000250" FT BINDING 646 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 648 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 654 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 731 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT MOD_RES 22 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 220 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99N13" FT MOD_RES 240 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99N13" FT MOD_RES 451 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99N13" FT MOD_RES 554 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q99N13" FT VAR_SEQ 1..31 FT /note="Missing (in isoform 10 and isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046827" FT VAR_SEQ 1 FT /note="M -> MMSSPAQPDLMWNLVPWVLFCGCCRIFPDGVAGREQLLAQQRM (in FT isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043428" FT VAR_SEQ 88 FT /note="K -> KLQQ (in isoform 6, isoform 7 and isoform 10)" FT /evidence="ECO:0000303|PubMed:12590135, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334" FT /id="VSP_023766" FT VAR_SEQ 177..178 FT /note="Missing (in isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046828" FT VAR_SEQ 218..261 FT /note="Missing (in isoform 6, isoform 8, isoform 9 and FT isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_023767" FT VAR_SEQ 487..574 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10523670" FT /id="VSP_002082" FT VAR_SEQ 575..590 FT /note="PFLEPTHTRALSVRQA -> VIGKDLAPGFVIKVII (in isoform 3, FT isoform 8, isoform 9, isoform 10 and isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9872452" FT /id="VSP_002083" FT VAR_SEQ 591..1011 FT /note="Missing (in isoform 3, isoform 8, isoform 9, isoform FT 10 and isoform 11)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9872452" FT /id="VSP_002084" FT VAR_SEQ 861..879 FT /note="GTGLGEGYNINIAWTGGLD -> RFISLEPHFYLYLSGNCIA (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:11535832" FT /id="VSP_002085" FT VAR_SEQ 880..1011 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11535832" FT /id="VSP_002086" FT VAR_SEQ 1006..1011 FT /note="MSLKFS -> KYWKSVRMVAVPRGCALAGAQLQEETETVSALASLTVDVEQP FT FAQEDSRTAGEPMEEEPAL (in isoform 5, isoform 6 and isoform FT 7)" FT /evidence="ECO:0000303|PubMed:12590135, FT ECO:0000303|PubMed:12706107, ECO:0000303|PubMed:15489334" FT /id="VSP_023768" FT VARIANT 921 FT /note="P -> T (found in a renal cell carcinoma sample; FT somatic mutation; dbSNP:rs1333490692)" FT /evidence="ECO:0000269|PubMed:21248752" FT /id="VAR_064719" FT CONFLICT 16 FT /note="V -> A (in Ref. 5; BAH12570)" FT /evidence="ECO:0000305" FT CONFLICT 99 FT /note="L -> I (in Ref. 9; AAF04254)" FT /evidence="ECO:0000305" FT CONFLICT 153 FT /note="S -> I (in Ref. 5; BAH14164)" FT /evidence="ECO:0000305" FT CONFLICT 315 FT /note="S -> F (in Ref. 5; BAH14176)" FT /evidence="ECO:0000305" FT CONFLICT 332 FT /note="L -> M (in Ref. 5; BAH14164)" FT /evidence="ECO:0000305" FT CONFLICT 416 FT /note="V -> F (in Ref. 5; BAH14164)" FT /evidence="ECO:0000305" FT CONFLICT 437 FT /note="T -> P (in Ref. 9; AAF04254)" FT /evidence="ECO:0000305" FT CONFLICT 644..647 FT /note="HQCV -> KPNS (in Ref. 9; AAF04254)" FT /evidence="ECO:0000305" FT CONFLICT 746 FT /note="H -> R (in Ref. 3; AAO27363)" FT /evidence="ECO:0000305" SQ SEQUENCE 1011 AA; 111297 MW; 43ED2785E73CD924 CRC64; MHSMISSVDV KSEVPVGLEP ISPLDLRTDL RMMMPVVDPV VREKQLQQEL LLIQQQQQIQ KQLLIAEFQK QHENLTRQHQ AQLQEHIKEL LAIKQQQELL EKEQKLEQQR QEQEVERHRR EQQLPPLRGK DRGRERAVAS TEVKQKLQEF LLSKSATKDT PTNGKNHSVS RHPKLWYTAA HHTSLDQSSP PLSGTSPSYK YTLPGAQDAK DDFPLRKTAS EPNLKVRSRL KQKVAERRSS PLLRRKDGNV VTSFKKRMFE VTESSVSSSS PGSGPSSPNN GPTGSVTENE TSVLPPTPHA EQMVSQQRIL IHEDSMNLLS LYTSPSLPNI TLGLPAVPSQ LNASNSLKEK QKCETQTLRQ GVPLPGQYGG SIPASSSHPH VTLEGKPPNS SHQALLQHLL LKEQMRQQKL LVAGGVPLHP QSPLATKERI SPGIRGTHKL PRHRPLNRTQ SAPLPQSTLA QLVIQQQHQQ FLEKQKQYQQ QIHMNKLLSK SIEQLKQPGS HLEEAEEELQ GDQAMQEDRA PSSGNSTRSD SSACVDDTLG QVGAVKVKEE PVDSDEDAQI QEMESGEQAA FMQQPFLEPT HTRALSVRQA PLAAVGMDGL EKHRLVSRTH SSPAASVLPH PAMDRPLQPG SATGIAYDPL MLKHQCVCGN STTHPEHAGR IQSIWSRLQE TGLLNKCERI QGRKASLEEI QLVHSEHHSL LYGTNPLDGQ KLDPRILLGD DSQKFFSSLP CGGLGVDSDT IWNELHSSGA ARMAVGCVIE LASKVASGEL KNGFAVVRPP GHHAEESTAM GFCFFNSVAI TAKYLRDQLN ISKILIVDLD VHHGNGTQQA FYADPSILYI SLHRYDEGNF FPGSGAPNEV GTGLGEGYNI NIAWTGGLDP PMGDVEYLEA FRTIVKPVAK EFDPDMVLVS AGFDALEGHT PPLGGYKVTA KCFGHLTKQL MTLADGRVVL ALEGGHDLTA ICDASEACVN ALLGNELEPL AEDILHQSPN MNAVISLQKI IEIQSMSLKF S //