ID ATX1_HUMAN Reviewed; 815 AA. AC P54253; Q17S02; Q9UJG2; Q9Y4J1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 17-JUN-2020, entry version 196. DE RecName: Full=Ataxin-1; DE AltName: Full=Spinocerebellar ataxia type 1 protein; GN Name=ATXN1; Synonyms=ATX1, SCA1; 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], INVOLVEMENT IN SCA1, AND TISSUE SPECIFICITY. RC TISSUE=Brain, and Cerebellum; RX PubMed=7951322; DOI=10.1038/ng0894-513; RA Banfi S., Servadio A., Chung M.-Y., Kwiatkowski T.J. Jr., McCall A.E., RA Duvick L.A., Shen Y., Roth E.J., Orr H.T., Zoghbi H.Y.; RT "Identification and characterization of the gene causing type 1 RT spinocerebellar ataxia."; RL Nat. Genet. 7:513-519(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 189-230, INVOLVEMENT IN SCA1, AND RP POLYMORPHISM. RX PubMed=8634720; DOI=10.1093/hmg/4.12.2411; RA Quan F., Janas J., Popovich B.W.; RT "A novel CAG repeat configuration in the SCA1 gene: implications for the RT molecular diagnostics of spinocerebellar ataxia type 1."; RL Hum. Mol. Genet. 4:2411-2413(1995). RN [5] RP INVOLVEMENT IN SCA1, AND SUBCELLULAR LOCATION. RX PubMed=7647801; DOI=10.1038/ng0595-94; RA Servadio A., Koshy B., Armstrong D., Antalffy B., Orr H.T., Zoghbi H.Y.; RT "Expression analysis of the ataxin-1 protein in tissues from normal and RT spinocerebellar ataxia type 1 individuals."; RL Nat. Genet. 10:94-98(1995). RN [6] RP SUBUNIT. RX PubMed=9097953; DOI=10.1093/hmg/6.4.513; RA Burright E.N., Davidson J.D., Duvick L.A., Koshy B., Zoghbi H.Y., Orr H.T.; RT "Identification of a self-association region within the SCA1 gene product, RT ataxin-1."; RL Hum. Mol. Genet. 6:513-518(1997). RN [7] RP INTERACTION WITH ANP32A. RX PubMed=9353121; DOI=10.1038/40159; RA Matilla A., Koshy B.T., Cummings C.J., Isobe T., Orr H.T., Zoghbi H.Y.; RT "The cerebellar leucine-rich acidic nuclear protein interacts with ataxin- RT 1."; RL Nature 389:974-978(1997). RN [8] RP RNA-BINDING DOMAIN. RX PubMed=11136710; DOI=10.1093/hmg/10.1.25; RA Yue S., Serra H.G., Zoghbi H.Y., Orr H.T.; RT "The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding RT activity that is inversely affected by the length of its polyglutamine RT tract."; RL Hum. Mol. Genet. 10:25-30(2001). RN [9] RP INTERACTION WITH UBQLN4. RX PubMed=11001934; DOI=10.1093/oxfordjournals.hmg.a018922; RA Davidson J.D., Riley B., Burright E.N., Duvick L.A., Zoghbi H.Y., Orr H.T.; RT "Identification and characterization of an ataxin-1-interacting protein: RT A1Up, a ubiquitin-like nuclear protein."; RL Hum. Mol. Genet. 9:2305-2312(2000). RN [10] RP INTERACTION WITH PQBP1. RX PubMed=12062018; DOI=10.1016/s0896-6273(02)00697-9; RA Okazawa H., Rich T., Chang A., Lin X., Waragai M., Kajikawa M., Enokido Y., RA Komuro A., Kato S., Shibata M., Hatanaka H., Mouradian M.M., Sudol M., RA Kanazawa I.; RT "Interaction between mutant ataxin-1 and PQBP-1 affects transcription and RT cell death."; RL Neuron 34:701-713(2002). RN [11] RP SUBCELLULAR LOCATION, AND INTERACTION WITH USP7. RX PubMed=12093161; DOI=10.1006/mcne.2002.1103; RA Hong S., Kim S.J., Ka S., Choi I., Kang S.; RT "USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 RT gene product."; RL Mol. Cell. Neurosci. 20:298-306(2002). RN [12] RP PHOSPHORYLATION AT SER-775, AND MUTAGENESIS OF SER-775. RX PubMed=12741986; DOI=10.1016/s0896-6273(03)00258-7; RA Emamian E.S., Kaytor M.D., Duvick L.A., Zu T., Tousey S.K., Zoghbi H.Y., RA Clark H.B., Orr H.T.; RT "Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in RT SCA1 transgenic mice."; RL Neuron 38:375-387(2003). RN [13] RP INTERACTION WITH ATXN1L. RX PubMed=16121196; DOI=10.1038/sj.emboj.7600785; RA Mizutani A., Wang L., Rajan H., Vig P.J.S., Alaynick W.A., Thaler J.P., RA Tsai C.-C.; RT "Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin- RT 1."; RL EMBO J. 24:3339-3351(2005). RN [14] RP SUMOYLATION AT LYS-16; LYS-194; LYS-609; LYS-696 AND LYS-745, AND RP MUTAGENESIS OF LYS-16; LYS-194; LYS-420; LYS-529; LYS-589; LYS-594; RP LYS-609; LYS-691; LYS-696; LYS-745 AND LYS-784. RX PubMed=15824120; DOI=10.1074/jbc.m501677200; RA Riley B.E., Zoghbi H.Y., Orr H.T.; RT "SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on RT a functional nuclear localization signal."; RL J. Biol. Chem. 280:21942-21948(2005). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [16] RP FUNCTION, AND INTERACTION WITH RBPJ. RX PubMed=21475249; DOI=10.1038/embor.2011.49; RA Tong X., Gui H., Jin F., Heck B.W., Lin P., Ma J., Fondell J.D., Tsai C.C.; RT "Ataxin-1 and Brother of ataxin-1 are components of the Notch signalling RT pathway."; RL EMBO Rep. 12:428-435(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP INDUCTION. RX PubMed=25768905; DOI=10.1016/j.cell.2015.02.012; RA Gennarino V.A., Singh R.K., White J.J., De Maio A., Han K., Kim J.Y., RA Jafar-Nejad P., di Ronza A., Kang H., Sayegh L.S., Cooper T.A., Orr H.T., RA Sillitoe R.V., Zoghbi H.Y.; RT "Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by RT increasing wild-type Ataxin1 levels."; RL Cell 160:1087-1098(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 563-693, AND SUBUNIT. RX PubMed=14583607; DOI=10.1074/jbc.m309817200; RA Chen Y.W., Allen M.D., Veprintsev D.B., Lowe J., Bycroft M.; RT "The structure of the AXH domain of spinocerebellar ataxin-1."; RL J. Biol. Chem. 279:3758-3765(2004). CC -!- FUNCTION: Chromatin-binding factor that repress Notch signaling in the CC absence of Notch intracellular domain by acting as a CBF1 corepressor. CC Binds to the HEY promoter and might assist, along with NCOR2, RBPJ- CC mediated repression. Binds RNA in vitro. May be involved in RNA CC metabolism (PubMed:21475249). In concert with CIC and ATXN1L, involved CC in brain development (By similarity). {ECO:0000250|UniProtKB:P54254, CC ECO:0000269|PubMed:21475249}. CC -!- SUBUNIT: Homooligomer (PubMed:9097953). Interacts with CIC (By CC similarity). Interacts with ANP32A, PQBP1, UBQLN4, ATXN1L and USP7 CC (PubMed:9353121, PubMed:11001934, PubMed:12062018, PubMed:12093161, CC PubMed:16121196). Directly interacts with RBPJ; this interaction is CC disrupted in the presence of Notch intracellular domain. Competes with CC ATXN1L for RBPJ-binding (PubMed:21475249). Found in a complex with CIC CC and ATXN1L (By similarity). {ECO:0000250|UniProtKB:P54254, CC ECO:0000269|PubMed:11001934, ECO:0000269|PubMed:12062018, CC ECO:0000269|PubMed:12093161, ECO:0000269|PubMed:14583607, CC ECO:0000269|PubMed:16121196, ECO:0000269|PubMed:21475249, CC ECO:0000269|PubMed:9097953, ECO:0000269|PubMed:9353121}. CC -!- INTERACTION: CC P54253; Q13444-2: ADAM15; NbExp=3; IntAct=EBI-930964, EBI-12137265; CC P54253; Q03989: ARID5A; NbExp=3; IntAct=EBI-930964, EBI-948603; CC P54253; P54253: ATXN1; NbExp=10; IntAct=EBI-930964, EBI-930964; CC P54253; Q99700: ATXN2; NbExp=4; IntAct=EBI-930964, EBI-697691; CC P54253; O14503: BHLHE40; NbExp=3; IntAct=EBI-930964, EBI-711810; CC P54253; Q6AI39: BICRAL; NbExp=3; IntAct=EBI-930964, EBI-1012434; CC P54253; Q5SWW7: C10orf55; NbExp=3; IntAct=EBI-930964, EBI-12809220; CC P54253; Q6P1W5: C1orf94; NbExp=9; IntAct=EBI-930964, EBI-946029; CC P54253; Q14012: CAMK1; NbExp=6; IntAct=EBI-930964, EBI-6380130; CC P54253; O75909: CCNK; NbExp=2; IntAct=EBI-930964, EBI-739806; CC P54253; P23528: CFL1; NbExp=5; IntAct=EBI-930964, EBI-352733; CC P54253; Q96RK0: CIC; NbExp=8; IntAct=EBI-930964, EBI-945857; CC P54253; P38432: COIL; NbExp=3; IntAct=EBI-930964, EBI-945751; CC P54253; Q8N684: CPSF7; NbExp=2; IntAct=EBI-930964, EBI-746909; CC P54253; P46108: CRK; NbExp=3; IntAct=EBI-930964, EBI-886; CC P54253; O43186: CRX; NbExp=3; IntAct=EBI-930964, EBI-748171; CC P54253; Q9NTM9: CUTC; NbExp=3; IntAct=EBI-930964, EBI-714918; CC P54253; Q13117-3: DAZ2; NbExp=3; IntAct=EBI-930964, EBI-13357576; CC P54253; Q15038: DAZAP2; NbExp=2; IntAct=EBI-930964, EBI-724310; CC P54253; Q8TE02: ELP5; NbExp=2; IntAct=EBI-930964, EBI-946189; CC P54253; Q32P44: EML3; NbExp=3; IntAct=EBI-930964, EBI-1046713; CC P54253; O95208-2: EPN2; NbExp=3; IntAct=EBI-930964, EBI-12135243; CC P54253; Q6NXG1: ESRP1; NbExp=6; IntAct=EBI-930964, EBI-10213520; CC P54253; O43909: EXTL3; NbExp=3; IntAct=EBI-930964, EBI-1754679; CC P54253; P0C7A2-2: FAM153B; NbExp=3; IntAct=EBI-930964, EBI-12940382; CC P54253; Q92567-2: FAM168A; NbExp=3; IntAct=EBI-930964, EBI-11978259; CC P54253; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-930964, EBI-12142257; CC P54253; Q96NZ1: FOXN4; NbExp=3; IntAct=EBI-930964, EBI-11749712; CC P54253; Q9UKD1: GMEB2; NbExp=5; IntAct=EBI-930964, EBI-948296; CC P54253; Q9UKJ3: GPATCH8; NbExp=4; IntAct=EBI-930964, EBI-948259; CC P54253; P15822: HIVEP1; NbExp=6; IntAct=EBI-930964, EBI-722264; CC P54253; Q9UBD0: HSFX1; NbExp=3; IntAct=EBI-930964, EBI-947253; CC P54253; Q96LI6: HSFY2; NbExp=3; IntAct=EBI-930964, EBI-3957665; CC P54253; P53990: IST1; NbExp=2; IntAct=EBI-930964, EBI-945994; CC P54253; P53990-3: IST1; NbExp=3; IntAct=EBI-930964, EBI-12188567; CC P54253; Q92993: KAT5; NbExp=3; IntAct=EBI-930964, EBI-399080; CC P54253; Q53G59: KLHL12; NbExp=2; IntAct=EBI-930964, EBI-740929; CC P54253; P60329: KRTAP12-4; NbExp=3; IntAct=EBI-930964, EBI-10176396; CC P54253; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-930964, EBI-10241252; CC P54253; Q14847-2: LASP1; NbExp=3; IntAct=EBI-930964, EBI-9088686; CC P54253; Q9H7H0: METTL17; NbExp=5; IntAct=EBI-930964, EBI-749353; CC P54253; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-930964, EBI-8487781; CC P54253; P23511-2: NFYA; NbExp=3; IntAct=EBI-930964, EBI-11061759; CC P54253; Q5HYW2: NHSL2; NbExp=3; IntAct=EBI-930964, EBI-2859639; CC P54253; O43809: NUDT21; NbExp=2; IntAct=EBI-930964, EBI-355720; CC P54253; Q495U3: PANX2; NbExp=3; IntAct=EBI-930964, EBI-17242559; CC P54253; Q13492-3: PICALM; NbExp=3; IntAct=EBI-930964, EBI-11031437; CC P54253; O15496: PLA2G10; NbExp=3; IntAct=EBI-930964, EBI-726466; CC P54253; Q9HAU0: PLEKHA5; NbExp=2; IntAct=EBI-930964, EBI-945934; CC P54253; Q494U1-3: PLEKHN1; NbExp=3; IntAct=EBI-930964, EBI-12014286; CC P54253; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-930964, EBI-1389308; CC P54253; P86479: PRR20C; NbExp=3; IntAct=EBI-930964, EBI-10172814; CC P54253; P86480: PRR20D; NbExp=3; IntAct=EBI-930964, EBI-12754095; CC P54253; P48634: PRRC2A; NbExp=4; IntAct=EBI-930964, EBI-347545; CC P54253; Q9NWB1: RBFOX1; NbExp=2; IntAct=EBI-930964, EBI-945906; CC P54253; O43251: RBFOX2; NbExp=10; IntAct=EBI-930964, EBI-746056; CC P54253; O43251-10: RBFOX2; NbExp=3; IntAct=EBI-930964, EBI-11963050; CC P54253; Q96I25: RBM17; NbExp=5; IntAct=EBI-930964, EBI-740272; CC P54253; Q06330: RBPJ; NbExp=7; IntAct=EBI-930964, EBI-632552; CC P54253; Q93062: RBPMS; NbExp=6; IntAct=EBI-930964, EBI-740322; CC P54253; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-930964, EBI-740343; CC P54253; Q15293: RCN1; NbExp=3; IntAct=EBI-930964, EBI-948278; CC P54253; Q04864: REL; NbExp=3; IntAct=EBI-930964, EBI-307352; CC P54253; Q04864-2: REL; NbExp=3; IntAct=EBI-930964, EBI-10829018; CC P54253; Q8N196: SIX5; NbExp=4; IntAct=EBI-930964, EBI-946167; CC P54253; Q9UPU3: SORCS3; NbExp=3; IntAct=EBI-930964, EBI-7484437; CC P54253; P41225: SOX3; NbExp=3; IntAct=EBI-930964, EBI-9078386; CC P54253; Q9NX95: SYBU; NbExp=3; IntAct=EBI-930964, EBI-948293; CC P54253; Q9NX95-5: SYBU; NbExp=3; IntAct=EBI-930964, EBI-12816095; CC P54253; Q92609: TBC1D5; NbExp=2; IntAct=EBI-930964, EBI-742381; CC P54253; Q96SF7: TBX15; NbExp=3; IntAct=EBI-930964, EBI-10191361; CC P54253; Q96A09: TENT5B; NbExp=5; IntAct=EBI-930964, EBI-752030; CC P54253; Q8N7U7-2: TPRX1; NbExp=3; IntAct=EBI-930964, EBI-14115717; CC P54253; Q12933: TRAF2; NbExp=8; IntAct=EBI-930964, EBI-355744; CC P54253; Q13049: TRIM32; NbExp=2; IntAct=EBI-930964, EBI-742790; CC P54253; Q86WV8: TSC1; NbExp=3; IntAct=EBI-930964, EBI-12806590; CC P54253; P26368: U2AF2; NbExp=5; IntAct=EBI-930964, EBI-742339; CC P54253; Q9NRR5: UBQLN4; NbExp=6; IntAct=EBI-930964, EBI-711226; CC P54253; Q70EL1: USP54; NbExp=3; IntAct=EBI-930964, EBI-946185; CC P54253; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-930964, EBI-11975223; CC P54253; Q96N03: VSTM2L; NbExp=3; IntAct=EBI-930964, EBI-948213; CC P54253; Q9H869: YY1AP1; NbExp=4; IntAct=EBI-930964, EBI-946122; CC P54253; A0A0C4DGF1: ZBTB32; NbExp=3; IntAct=EBI-930964, EBI-10188476; CC P54253; Q96K80: ZC3H10; NbExp=4; IntAct=EBI-930964, EBI-742550; CC P54253; Q9UKY1: ZHX1; NbExp=5; IntAct=EBI-930964, EBI-347767; CC P54253; Q96MN9: ZNF488; NbExp=6; IntAct=EBI-930964, EBI-948288; CC P54253-1; P38432: COIL; NbExp=6; IntAct=EBI-930975, EBI-945751; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:7647801}. Nucleus CC {ECO:0000269|PubMed:12093161, ECO:0000269|PubMed:7647801}. CC Note=Colocalizes with USP7 in the nucleus. CC {ECO:0000269|PubMed:12093161}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=1; CC Comment=At least 2 isoforms are produced.; CC Name=1; CC IsoId=P54253-1; Sequence=Displayed; CC -!- TISSUE SPECIFICITY: Widely expressed throughout the body. CC {ECO:0000269|PubMed:12062018}. CC -!- INDUCTION: ATXN1 protein levels are directly regulated by PUM1 protein: CC PUM1 acts by binding to the 3'-UTR of ATXN1 mRNA, affecting ATXN1 mRNA CC stability and leading to reduced ATXN1 protein levels. CC {ECO:0000269|PubMed:25768905}. CC -!- DOMAIN: The AXH domain is required for interaction with CIC. CC {ECO:0000250|UniProtKB:P54254}. CC -!- PTM: Ubiquitinated by UBE3A, leading to its degradation by the CC proteasome. The presence of expanded poly-Gln repeats in CC spinocerebellar ataxia 1 (SCA1) patients impairs ubiquitination and CC degradation, leading to accumulation of ATXN1 in neurons and subsequent CC toxicity. {ECO:0000250|UniProtKB:P54254}. CC -!- PTM: Phosphorylation at Ser-775 increases the pathogenicity of proteins CC with an expanded polyglutamine tract. {ECO:0000269|PubMed:12741986}. CC -!- PTM: Sumoylation is dependent on nuclear localization and CC phosphorylation at Ser-775. It is reduced in the presence of an CC expanded polyglutamine tract. {ECO:0000269|PubMed:12741986, CC ECO:0000269|PubMed:15824120}. CC -!- POLYMORPHISM: The poly-Gln region of ATXN1 is highly polymorphic (4 to CC 39 repeats) in the normal population and is expanded to about 40-83 CC repeats in spinocerebellar ataxia 1 (SCA1) patients. CC {ECO:0000269|PubMed:8634720}. CC -!- DISEASE: Spinocerebellar ataxia 1 (SCA1) [MIM:164400]: Spinocerebellar CC ataxia is a clinically and genetically heterogeneous group of CC cerebellar disorders. Patients show progressive incoordination of gait CC and often poor coordination of hands, speech and eye movements, due to CC cerebellum degeneration with variable involvement of the brainstem and CC spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias CC type I (ADCA I) which are characterized by cerebellar ataxia in CC combination with additional clinical features like optic atrophy, CC ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy CC and dementia. SCA1 is caused by expansion of a CAG repeat in the coding CC region of ATXN1. Longer expansions result in earlier onset and more CC severe clinical manifestations of the disease. CC {ECO:0000269|PubMed:7647801, ECO:0000269|PubMed:7951322, CC ECO:0000269|PubMed:8634720}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. The disease is caused by CC expansion of the polyglutamine tract to about 40-83 repeats, causing CC accumulation in neurons and exerting toxicity. CC {ECO:0000269|PubMed:7647801, ECO:0000269|PubMed:8634720}. CC -!- MISCELLANEOUS: Self-association seems to be necessary for formation of CC nuclear aggregates which are associated with pathogenesis. CC -!- SIMILARITY: Belongs to the ATXN1 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Ataxin-1 entry; CC URL="https://en.wikipedia.org/wiki/Ataxin_1"; 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; X79204; CAA55793.1; -; mRNA. DR EMBL; AL009031; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC117125; AAI17126.1; -; mRNA. DR EMBL; S82497; AAD14401.1; -; Genomic_DNA. DR CCDS; CCDS34342.1; -. [P54253-1] DR PIR; S46268; S46268. DR RefSeq; NP_000323.2; NM_000332.3. [P54253-1] DR RefSeq; NP_001121636.1; NM_001128164.1. [P54253-1] DR PDB; 1OA8; X-ray; 1.70 A; A/B/C/D=562-693. DR PDB; 2M41; NMR; -; B=566-688. DR PDB; 4APT; X-ray; 2.50 A; A/B/C/D=566-688. DR PDB; 4AQP; X-ray; 2.45 A; A/B/C/D=566-688. DR PDB; 4J2J; X-ray; 2.50 A; A/B/C=562-688. DR PDB; 4J2L; X-ray; 3.15 A; A/B=562-688. DR PDBsum; 1OA8; -. DR PDBsum; 2M41; -. DR PDBsum; 4APT; -. DR PDBsum; 4AQP; -. DR PDBsum; 4J2J; -. DR PDBsum; 4J2L; -. DR SMR; P54253; -. DR BioGRID; 112217; 266. DR CORUM; P54253; -. DR DIP; DIP-35353N; -. DR IntAct; P54253; 334. DR MINT; P54253; -. DR STRING; 9606.ENSP00000244769; -. DR BindingDB; P54253; -. DR MoonDB; P54253; Predicted. DR iPTMnet; P54253; -. DR PhosphoSitePlus; P54253; -. DR BioMuta; ATXN1; -. DR DMDM; 206729854; -. DR EPD; P54253; -. DR jPOST; P54253; -. DR MassIVE; P54253; -. DR MaxQB; P54253; -. DR PaxDb; P54253; -. DR PeptideAtlas; P54253; -. DR PRIDE; P54253; -. DR ProteomicsDB; 56658; -. [P54253-1] DR ABCD; P54253; 1 sequenced antibody. DR Antibodypedia; 1922; 795 antibodies. DR Ensembl; ENST00000244769; ENSP00000244769; ENSG00000124788. [P54253-1] DR Ensembl; ENST00000436367; ENSP00000416360; ENSG00000124788. [P54253-1] DR GeneID; 6310; -. DR KEGG; hsa:6310; -. DR UCSC; uc003nbt.4; human. [P54253-1] DR CTD; 6310; -. DR DisGeNET; 6310; -. DR EuPathDB; HostDB:ENSG00000124788.17; -. DR GeneCards; ATXN1; -. DR GeneReviews; ATXN1; -. DR HGNC; HGNC:10548; ATXN1. DR HPA; ENSG00000124788; Low tissue specificity. DR MalaCards; ATXN1; -. DR MIM; 164400; phenotype. DR MIM; 601556; gene. DR neXtProt; NX_P54253; -. DR OpenTargets; ENSG00000124788; -. DR Orphanet; 98755; Spinocerebellar ataxia type 1. DR PharmGKB; PA34958; -. DR eggNOG; KOG4053; Eukaryota. DR eggNOG; ENOG410XSNX; LUCA. DR GeneTree; ENSGT00390000005939; -. DR HOGENOM; CLU_019983_0_0_1; -. DR InParanoid; P54253; -. DR KO; K23616; -. DR OMA; ELPCTKL; -. DR PhylomeDB; P54253; -. DR TreeFam; TF350643; -. DR SIGNOR; P54253; -. DR BioGRID-ORCS; 6310; 13 hits in 789 CRISPR screens. DR ChiTaRS; ATXN1; human. DR EvolutionaryTrace; P54253; -. DR GeneWiki; Ataxin_1; -. DR GenomeRNAi; 6310; -. DR Pharos; P54253; Tbio. DR PRO; PR:P54253; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P54253; protein. DR Bgee; ENSG00000124788; Expressed in caudate nucleus and 243 other tissues. DR ExpressionAtlas; P54253; baseline and differential. DR Genevisible; P54253; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0042405; C:nuclear inclusion body; IDA:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0034046; F:poly(G) binding; IDA:UniProtKB. DR GO; GO:0008266; F:poly(U) RNA binding; IDA:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central. DR GO; GO:0007420; P:brain development; ISS:UniProtKB. DR GO; GO:0007612; P:learning; ISS:UniProtKB. DR GO; GO:0007613; P:memory; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0051168; P:nuclear export; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central. DR GO; GO:0006396; P:RNA processing; NAS:UniProtKB. DR GO; GO:0035176; P:social behavior; ISS:UniProtKB. DR InterPro; IPR003652; Ataxin_AXH_dom. DR InterPro; IPR036096; Ataxin_AXH_dom_sf. DR InterPro; IPR040172; ATXN1. DR InterPro; IPR020997; Capicua_tscrpt_rep_mod. DR PANTHER; PTHR13392:SF5; PTHR13392:SF5; 1. DR Pfam; PF12547; ATXN-1_C; 1. DR Pfam; PF08517; AXH; 1. DR SMART; SM00536; AXH; 1. DR SUPFAM; SSF102031; SSF102031; 1. DR PROSITE; PS51148; AXH; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; DNA-binding; KW Isopeptide bond; Neurodegeneration; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repressor; RNA-binding; Spinocerebellar ataxia; KW Transcription; Transcription regulation; Triplet repeat expansion; KW Ubl conjugation. FT CHAIN 1..815 FT /note="Ataxin-1" FT /id="PRO_0000064751" FT DOMAIN 562..693 FT /note="AXH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00496" FT REGION 494..604 FT /note="Self-association" FT /evidence="ECO:0000269|PubMed:9097953" FT REGION 538..815 FT /note="Interaction with USP7" FT /evidence="ECO:0000269|PubMed:12093161" FT REGION 540..766 FT /note="RNA-binding" FT /evidence="ECO:0000269|PubMed:11136710" FT MOTIF 794..797 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250|UniProtKB:P54254" FT COMPBIAS 197..225 FT /note="Poly-Gln" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54254" FT MOD_RES 88 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 238 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:18669648" FT MOD_RES 253 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P54254" FT MOD_RES 775 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12741986" FT CROSSLNK 16 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15824120" FT CROSSLNK 194 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15824120" FT CROSSLNK 609 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15824120" FT CROSSLNK 696 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15824120" FT CROSSLNK 745 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:15824120" FT VARIANT 209 FT /note="H -> Q (in dbSNP:rs11969612)" FT /id="VAR_046616" FT VARIANT 753 FT /note="P -> S (in dbSNP:rs16885)" FT /id="VAR_046617" FT MUTAGEN 16 FT /note="K->R: Sumoylation reduced to 40% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 194 FT /note="K->R: Sumoylation reduced to 46% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 420 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 529 FT /note="K->R: Sumoylation reduced to 57% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 589 FT /note="K->R: Sumoylation reduced to 53% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 594 FT /note="K->R: Sumoylation reduced to 68% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 609 FT /note="K->R: Sumoylation reduced to 43% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 691 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 696 FT /note="K->R: Sumoylation reduced to 42% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 745 FT /note="K->R: Sumoylation reduced to 44% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT MUTAGEN 775 FT /note="S->A: Reduces phosphorylation but does not affect FT nuclear localization." FT /evidence="ECO:0000269|PubMed:12741986" FT MUTAGEN 784 FT /note="K->R: Sumoylation reduced to 62% of wild-type." FT /evidence="ECO:0000269|PubMed:15824120" FT CONFLICT 211 FT /note="H -> HQ (in Ref. 1; CAA55793)" FT /evidence="ECO:0000305" FT STRAND 568..570 FT /evidence="ECO:0000244|PDB:2M41" FT HELIX 572..574 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 579..581 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 587..589 FT /evidence="ECO:0000244|PDB:1OA8" FT HELIX 590..592 FT /evidence="ECO:0000244|PDB:1OA8" FT HELIX 595..604 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 606..620 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 626..633 FT /evidence="ECO:0000244|PDB:1OA8" FT TURN 634..637 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 638..645 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 650..652 FT /evidence="ECO:0000244|PDB:1OA8" FT TURN 653..655 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 656..660 FT /evidence="ECO:0000244|PDB:1OA8" FT HELIX 662..669 FT /evidence="ECO:0000244|PDB:1OA8" FT STRAND 673..675 FT /evidence="ECO:0000244|PDB:4J2L" FT STRAND 681..687 FT /evidence="ECO:0000244|PDB:1OA8" SQ SEQUENCE 815 AA; 86923 MW; 657876F8FD19ECB2 CRC64; MKSNQERSNE CLPPKKREIP ATSRSSEEKA PTLPSDNHRV EGTAWLPGNP GGRGHGGGRH GPAGTSVELG LQQGIGLHKA LSTGLDYSPP SAPRSVPVAT TLPAAYATPQ PGTPVSPVQY AHLPHTFQFI GSSQYSGTYA SFIPSQLIPP TANPVTSAVA SAAGATTPSQ RSQLEAYSTL LANMGSLSQT PGHKAEQQQQ QQQQQQQQHQ HQQQQQQQQQ QQQQQHLSRA PGLITPGSPP PAQQNQYVHI SSSPQNTGRT ASPPAIPVHL HPHQTMIPHT LTLGPPSQVV MQYADSGSHF VPREATKKAE SSRLQQAIQA KEVLNGEMEK SRRYGAPSSA DLGLGKAGGK SVPHPYESRH VVVHPSPSDY SSRDPSGVRA SVMVLPNSNT PAADLEVQQA THREASPSTL NDKSGLHLGK PGHRSYALSP HTVIQTTHSA SEPLPVGLPA TAFYAGTQPP VIGYLSGQQQ AITYAGSLPQ HLVIPGTQPL LIPVGSTDME ASGAAPAIVT SSPQFAAVPH TFVTTALPKS ENFNPEALVT QAAYPAMVQA QIHLPVVQSV ASPAAAPPTL PPYFMKGSII QLANGELKKV EDLKTEDFIQ SAEISNDLKI DSSTVERIED SHSPGVAVIQ FAVGEHRAQV SVEVLVEYPF FVFGQGWSSC CPERTSQLFD LPCSKLSVGD VCISLTLKNL KNGSVKKGQP VDPASVLLKH SKADGLAGSR HRYAEQENGI NQGSAQMLSE NGELKFPEKM GLPAAPFLTK IEPSKPAATR KRRWSAPESR KLEKSEDEPP LTLPKPSLIP QEVKICIEGR SNVGK //