ATX2_HUMAN
ID ATX2_HUMAN Reviewed; 1313 AA.
AC Q99700; A6NLD4; Q24JQ7; Q6ZQZ7; Q99493;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Ataxin-2;
DE AltName: Full=Spinocerebellar ataxia type 2 protein;
DE AltName: Full=Trinucleotide repeat-containing gene 13 protein;
GN Name=ATXN2; Synonyms=ATX2, SCA2, TNRC13;
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] (ISOFORM 1), POLYMORPHISM, INVOLVEMENT IN SCA2,
RP TISSUE SPECIFICITY, AND VARIANT VAL-107.
RX PubMed=8896555; DOI=10.1038/ng1196-269;
RA Pulst S.-M., Nechiporuk A., Nechiporuk T., Gispert S., Chen X.-N.,
RA Lopes-Cendes I., Pearlman S., Starkman S., Orozco-Diaz G., Lunkes A.,
RA DeJong P., Rouleau G.A., Auburger G., Korenberg J.R., Figueroa C.,
RA Sahba S.;
RT "Moderate expansion of a normally biallelic trinucleotide repeat in
RT spinocerebellar ataxia type 2.";
RL Nat. Genet. 14:269-276(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), POLYMORPHISM, INVOLVEMENT IN SCA2,
RP AND TISSUE SPECIFICITY.
RX PubMed=8896556; DOI=10.1038/ng1196-277;
RA Sanpei K., Takano H., Igarashi S., Sato T., Oyake M., Sasaki H.,
RA Wakisaka A., Tashiro K., Ishida Y., Ikeuchi T., Koide R., Saito M.,
RA Sato A., Tanaka T., Hanyu S., Takiyama Y., Nishizawa M., Shimizu N.,
RA Nomura Y., Segawa M., Iwabuchi K., Eguchi I., Tanaka H., Takahashi H.,
RA Tsuji S.;
RT "Identification of the spinocerebellar ataxia type 2 gene using a direct
RT identification of repeat expansion and cloning technique, DIRECT.";
RL Nat. Genet. 14:277-284(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 81-1313 (ISOFORM 2), POLYMORPHISM,
RP INVOLVEMENT IN SCA2, TISSUE SPECIFICITY, AND VARIANT VAL-107.
RX PubMed=8896557; DOI=10.1038/ng1196-285;
RA Imbert G., Saudou F., Yvert G., Devys D., Trottier Y., Garnier J.-M.,
RA Weber C., Mandel J.-L., Cancel G., Abbas N., Duerr A., Didierjean O.,
RA Stevanin G., Agid Y., Brice A.;
RT "Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high
RT sensitivity to expanded CAG/glutamine repeats.";
RL Nat. Genet. 14:285-291(1996).
RN [7]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=9480749; DOI=10.1006/geno.1997.5131;
RA Sahba S., Nechiporuk A., Figueroa K.P., Nechiporuk T., Pulst S.-M.;
RT "Genomic structure of the human gene for spinocerebellar ataxia type 2
RT (SCA2) on chromosome 12q24.1.";
RL Genomics 47:359-364(1998).
RN [8]
RP INTERACTION WITH RBFOX1.
RX PubMed=10814712; DOI=10.1093/hmg/9.9.1303;
RA Shibata H., Huynh D.P., Pulst S.-M.;
RT "A novel protein with RNA-binding motifs interacts with ataxin-2.";
RL Hum. Mol. Genet. 9:1303-1313(2000).
RN [9]
RP INTERACTION WITH POLYRIBOSOMES.
RX PubMed=16835262; DOI=10.1093/hmg/ddl173;
RA Satterfield T.F., Pallanck L.J.;
RT "Ataxin-2 and its Drosophila homolog, ATX2, physically assemble with
RT polyribosomes.";
RL Hum. Mol. Genet. 15:2523-2532(2006).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH EGFR; SH3GL2 AND SH3GL3.
RX PubMed=18602463; DOI=10.1016/j.cellsig.2008.05.018;
RA Nonis D., Schmidt M.H., van de Loo S., Eich F., Dikic I., Nowock J.,
RA Auburger G.;
RT "Ataxin-2 associates with the endocytosis complex and affects EGF receptor
RT trafficking.";
RL Cell. Signal. 20:1725-1739(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-784, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-554; SER-684;
RP THR-741; SER-857; SER-861; SER-888 AND SER-889, AND IDENTIFICATION BY MASS
RP 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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-684, 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 [16]
RP INTERACTION WITH TARDBP, INVOLVEMENT IN ALS13, AND POLY-GLN REPEAT
RP EXPANSION.
RX PubMed=20740007; DOI=10.1038/nature09320;
RA Elden A.C., Kim H.J., Hart M.P., Chen-Plotkin A.S., Johnson B.S., Fang X.,
RA Armakola M., Geser F., Greene R., Lu M.M., Padmanabhan A., Clay-Falcone D.,
RA McCluskey L., Elman L., Juhr D., Gruber P.J., Rub U., Auburger G.,
RA Trojanowski J.Q., Lee V.M., Van Deerlin V.M., Bonini N.M., Gitler A.D.;
RT "Ataxin-2 intermediate-length polyglutamine expansions are associated with
RT increased risk for ALS.";
RL Nature 466:1069-1075(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-684 AND SER-784, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-784; SER-861 AND SER-865, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP INTERACTION WITH ATXN2L.
RX PubMed=23209657; DOI=10.1371/journal.pone.0050134;
RA Kaehler C., Isensee J., Nonhoff U., Terrey M., Hucho T., Lehrach H.,
RA Krobitsch S.;
RT "Ataxin-2-like is a regulator of stress granules and processing bodies.";
RL PLoS ONE 7:E50134-E50134(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-478; SER-508;
RP SER-624; SER-642; SER-684; SER-772; SER-784 AND SER-889, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-624 AND SER-728, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-640, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-893, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
CC -!- FUNCTION: Involved in EGFR trafficking, acting as negative regulator of
CC endocytic EGFR internalization at the plasma membrane.
CC {ECO:0000269|PubMed:18602463}.
CC -!- SUBUNIT: Monomer (By similarity). Can also form homodimers (By
CC similarity). Interacts with TARDBP; the interaction is RNA-dependent
CC (PubMed:20740007). Interacts with RBFOX1 (PubMed:10814712). Interacts
CC with polyribosomes (PubMed:16835262). Interacts with SH3GL2 and SH3GL3
CC (PubMed:18602463). Interacts with SH3KBP1 and CBL (By similarity).
CC Interacts with EGFR (PubMed:18602463). Interacts with ATXN2L
CC (PubMed:23209657). {ECO:0000250|UniProtKB:O70305,
CC ECO:0000269|PubMed:10814712, ECO:0000269|PubMed:16835262,
CC ECO:0000269|PubMed:18602463, ECO:0000269|PubMed:20740007,
CC ECO:0000269|PubMed:23209657}.
CC -!- INTERACTION:
CC Q99700; P54253: ATXN1; NbExp=4; IntAct=EBI-697691, EBI-930964;
CC Q99700; P26196: DDX6; NbExp=8; IntAct=EBI-697691, EBI-351257;
CC Q99700; Q13283: G3BP1; NbExp=4; IntAct=EBI-697691, EBI-1047359;
CC Q99700; P11940: PABPC1; NbExp=7; IntAct=EBI-697691, EBI-81531;
CC Q99700; Q99962: SH3GL2; NbExp=9; IntAct=EBI-697691, EBI-77938;
CC Q99700; Q99963: SH3GL3; NbExp=11; IntAct=EBI-697691, EBI-473910;
CC Q99700; Q13148: TARDBP; NbExp=3; IntAct=EBI-697691, EBI-372899;
CC Q99700-5; P54253: ATXN1; NbExp=6; IntAct=EBI-25891409, EBI-930964;
CC Q99700-5; P46379-2: BAG6; NbExp=3; IntAct=EBI-25891409, EBI-10988864;
CC Q99700-5; Q9BTH3: BIN1; NbExp=3; IntAct=EBI-25891409, EBI-25891390;
CC Q99700-5; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-25891409, EBI-2837444;
CC Q99700-5; P20963: CD247; NbExp=3; IntAct=EBI-25891409, EBI-1165705;
CC Q99700-5; P11940: PABPC1; NbExp=3; IntAct=EBI-25891409, EBI-81531;
CC Q99700-5; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-25891409, EBI-12123390;
CC Q99700-5; Q8IVP1: SH3GL3; NbExp=3; IntAct=EBI-25891409, EBI-6503765;
CC Q99700-5; Q9UJZ1: STOML2; NbExp=3; IntAct=EBI-25891409, EBI-1044428;
CC Q99700-5; P55854: SUMO3; NbExp=3; IntAct=EBI-25891409, EBI-474067;
CC Q99700-5; P40337-2: VHL; NbExp=3; IntAct=EBI-25891409, EBI-12157263;
CC Q99700-5; Q96E88; NbExp=3; IntAct=EBI-25891409, EBI-10976904;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q99700-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99700-2; Sequence=VSP_011575, VSP_011577;
CC Name=3;
CC IsoId=Q99700-3; Sequence=VSP_011574, VSP_011576, VSP_011578,
CC VSP_011579, VSP_011580, VSP_011581;
CC Name=4;
CC IsoId=Q99700-4; Sequence=VSP_011582;
CC Name=5;
CC IsoId=Q99700-5; Sequence=VSP_057285, VSP_057286, VSP_057287;
CC -!- TISSUE SPECIFICITY: Expressed in the brain, heart, liver, skeletal
CC muscle, pancreas and placenta. Isoform 1 is predominant in the brain
CC and spinal cord. Isoform 4 is more abundant in the cerebellum. In the
CC brain, broadly expressed in the amygdala, caudate nucleus, corpus
CC callosum, hippocampus, hypothalamus, substantia nigra, subthalamic
CC nucleus and thalamus. {ECO:0000269|PubMed:8896555,
CC ECO:0000269|PubMed:8896556, ECO:0000269|PubMed:8896557,
CC ECO:0000269|PubMed:9480749}.
CC -!- POLYMORPHISM: The poly-Gln region of ATXN2 is polymorphic: 17 to 29
CC repeats are found in the normal population. Higher numbers of repeats
CC result in different disease phenotypes depending on the length of the
CC expansion. {ECO:0000269|PubMed:20740007, ECO:0000269|PubMed:8896555,
CC ECO:0000269|PubMed:8896556, ECO:0000269|PubMed:8896557}.
CC -!- DISEASE: Spinocerebellar ataxia 2 (SCA2) [MIM:183090]: 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. SCA2 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. SCA2 is characterized by hyporeflexia, myoclonus and
CC action tremor and dopamine-responsive parkinsonism. In some patients,
CC SCA2 presents as pure familial parkinsonism without cerebellar signs.
CC {ECO:0000269|PubMed:8896555, ECO:0000269|PubMed:8896556,
CC ECO:0000269|PubMed:8896557}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. SCA2 is caused by
CC expansion of a CAG repeat resulting in about 36 to 52 repeats in some
CC patients. Longer expansions result in earlier the expansion, onset of
CC the disease.
CC -!- DISEASE: Amyotrophic lateral sclerosis 13 (ALS13) [MIM:183090]: A
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:20740007}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC An increased risk for developing amyotrophic lateral sclerosis seems to
CC be conferred by CAG repeat intermediate expansions greater than 23 but
CC below the threshold for developing spinocerebellar ataxia.
CC -!- SIMILARITY: Belongs to the ataxin-2 family. {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; U70323; AAB19200.1; -; mRNA.
DR EMBL; AK128613; BAC87528.1; -; mRNA.
DR EMBL; AC002395; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455720; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC114546; AAI14547.1; -; mRNA.
DR EMBL; Y08262; CAA69589.1; -; mRNA.
DR CCDS; CCDS81738.1; -. [Q99700-5]
DR RefSeq; NP_001297052.1; NM_001310123.1. [Q99700-5]
DR RefSeq; NP_002964.3; NM_002973.3.
DR PDB; 3KTR; X-ray; 1.70 A; B=912-928.
DR PDBsum; 3KTR; -.
DR AlphaFoldDB; Q99700; -.
DR SMR; Q99700; -.
DR BioGRID; 112218; 231.
DR DIP; DIP-33372N; -.
DR ELM; Q99700; -.
DR IntAct; Q99700; 75.
DR MINT; Q99700; -.
DR STRING; 9606.ENSP00000366843; -.
DR BindingDB; Q99700; -.
DR ChEMBL; CHEMBL1795085; -.
DR GlyGen; Q99700; 7 sites, 1 O-linked glycan (7 sites).
DR iPTMnet; Q99700; -.
DR MetOSite; Q99700; -.
DR PhosphoSitePlus; Q99700; -.
DR SwissPalm; Q99700; -.
DR BioMuta; ATXN2; -.
DR DMDM; 215273941; -.
DR EPD; Q99700; -.
DR jPOST; Q99700; -.
DR MassIVE; Q99700; -.
DR MaxQB; Q99700; -.
DR PaxDb; Q99700; -.
DR PeptideAtlas; Q99700; -.
DR PRIDE; Q99700; -.
DR ProteomicsDB; 61268; -.
DR ProteomicsDB; 78409; -. [Q99700-1]
DR ProteomicsDB; 78410; -. [Q99700-2]
DR ProteomicsDB; 78412; -. [Q99700-4]
DR Antibodypedia; 18563; 280 antibodies from 36 providers.
DR DNASU; 6311; -.
DR Ensembl; ENST00000535949.5; ENSP00000439338.1; ENSG00000204842.18. [Q99700-5]
DR Ensembl; ENST00000550104.5; ENSP00000446576.2; ENSG00000204842.18. [Q99700-1]
DR Ensembl; ENST00000616825.4; ENSP00000481448.1; ENSG00000204842.18. [Q99700-5]
DR GeneID; 6311; -.
DR KEGG; hsa:6311; -.
DR UCSC; uc001tsj.3; human. [Q99700-1]
DR CTD; 6311; -.
DR DisGeNET; 6311; -.
DR GeneCards; ATXN2; -.
DR GeneReviews; ATXN2; -.
DR HGNC; HGNC:10555; ATXN2.
DR HPA; ENSG00000204842; Low tissue specificity.
DR MalaCards; ATXN2; -.
DR MIM; 183090; phenotype.
DR MIM; 601517; gene.
DR neXtProt; NX_Q99700; -.
DR OpenTargets; ENSG00000204842; -.
DR Orphanet; 803; Amyotrophic lateral sclerosis.
DR Orphanet; 98756; Spinocerebellar ataxia type 2.
DR PharmGKB; PA34968; -.
DR VEuPathDB; HostDB:ENSG00000204842; -.
DR eggNOG; KOG2375; Eukaryota.
DR GeneTree; ENSGT00940000156812; -.
DR InParanoid; Q99700; -.
DR OMA; MMMHQNS; -.
DR OrthoDB; 282700at2759; -.
DR PhylomeDB; Q99700; -.
DR TreeFam; TF326591; -.
DR PathwayCommons; Q99700; -.
DR SignaLink; Q99700; -.
DR SIGNOR; Q99700; -.
DR BioGRID-ORCS; 6311; 15 hits in 1082 CRISPR screens.
DR ChiTaRS; ATXN2; human.
DR EvolutionaryTrace; Q99700; -.
DR GeneWiki; ATXN2; -.
DR GenomeRNAi; 6311; -.
DR Pharos; Q99700; Tbio.
DR PRO; PR:Q99700; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q99700; protein.
DR Bgee; ENSG00000204842; Expressed in buccal mucosa cell and 195 other tissues.
DR ExpressionAtlas; Q99700; baseline and differential.
DR Genevisible; Q99700; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0002091; P:negative regulation of receptor internalization; IMP:UniProtKB.
DR GO; GO:0033962; P:P-body assembly; IMP:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; NAS:UniProtKB.
DR GO; GO:0016070; P:RNA metabolic process; NAS:UniProtKB.
DR GO; GO:0050658; P:RNA transport; NAS:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; IMP:UniProtKB.
DR IDEAL; IID00580; -.
DR InterPro; IPR009818; Ataxin-2_C.
DR InterPro; IPR033093; ATXN2.
DR InterPro; IPR045117; ATXN2-like.
DR InterPro; IPR010920; LSM_dom_sf.
DR InterPro; IPR009604; LsmAD_domain.
DR InterPro; IPR025852; SM_dom_ATX.
DR PANTHER; PTHR12854; PTHR12854; 1.
DR PANTHER; PTHR12854:SF11; PTHR12854:SF11; 1.
DR Pfam; PF06741; LsmAD; 1.
DR Pfam; PF07145; PAM2; 1.
DR Pfam; PF14438; SM-ATX; 1.
DR SMART; SM01272; LsmAD; 1.
DR SUPFAM; SSF50182; SSF50182; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Amyotrophic lateral sclerosis;
KW Cytoplasm; Isopeptide bond; Methylation; Neurodegeneration; Parkinsonism;
KW Phosphoprotein; Reference proteome; Spinocerebellar ataxia;
KW Triplet repeat expansion; Ubl conjugation.
FT CHAIN 1..1313
FT /note="Ataxin-2"
FT /id="PRO_0000064756"
FT REGION 1..255
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 459..954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1137..1219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..69
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 161..192
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..232
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..488
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..545
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 577..602
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..681
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..707
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 731..781
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 784..803
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 804..818
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 819..841
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..891
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 892..909
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 910..932
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1150..1195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1203..1219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70305"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 640
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O70305"
FT MOD_RES 640
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 642
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 741
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 772
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 856
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70305"
FT MOD_RES 857
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 865
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 867
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70305"
FT MOD_RES 888
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 889
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 893
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..981
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011574"
FT VAR_SEQ 1..265
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057285"
FT VAR_SEQ 277..300
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057286"
FT VAR_SEQ 980..995
FT /note="PLYPIPMTPMPVNQAK -> YQICPNSGKTSIIRVP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8896557"
FT /id="VSP_011575"
FT VAR_SEQ 982..998
FT /note="YPIPMTPMPVNQAKTYR -> MYYAVEILFNRQSAFFS (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011576"
FT VAR_SEQ 996..1313
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8896557"
FT /id="VSP_011577"
FT VAR_SEQ 1106..1124
FT /note="ACPKLPYNKETSPSFYFAI -> V (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057287"
FT VAR_SEQ 1106..1123
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011578"
FT VAR_SEQ 1124
FT /note="I -> V (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011579"
FT VAR_SEQ 1244..1313
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_011582"
FT VAR_SEQ 1249..1257
FT /note="AHVQSGMVP -> VIPALANFL (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011580"
FT VAR_SEQ 1258..1313
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_011581"
FT VARIANT 107
FT /note="L -> V (in dbSNP:rs695871)"
FT /evidence="ECO:0000269|PubMed:8896555,
FT ECO:0000269|PubMed:8896557"
FT /id="VAR_047629"
FT VARIANT 248
FT /note="S -> N (in dbSNP:rs7969300)"
FT /id="VAR_047630"
FT CONFLICT 188
FT /note="Missing (in Ref. 1; AAB19200 and 6; CAA69589)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1313 AA; 140283 MW; 40A2883FF9D5D118 CRC64;
MRSAAAAPRS PAVATESRRF AAARWPGWRS LQRPARRSGR GGGGAAPGPY PSAAPPPPGP
GPPPSRQSSP PSASDCFGSN GNGGGAFRPG SRRLLGLGGP PRPFVVLLLP LASPGAPPAA
PTRASPLGAR ASPPRSGVSL ARPAPGCPRP ACEPVYGPLT MSLKPQQQQQ QQQQQQQQQQ
QQQQQQQQPP PAAANVRKPG GSGLLASPAA APSPSSSSVS SSSATAPSSV VAATSGGGRP
GLGRGRNSNK GLPQSTISFD GIYANMRMVH ILTSVVGSKC EVQVKNGGIY EGVFKTYSPK
CDLVLDAAHE KSTESSSGPK REEIMESILF KCSDFVVVQF KDMDSSYAKR DAFTDSAISA
KVNGEHKEKD LEPWDAGELT ANEELEALEN DVSNGWDPND MFRYNEENYG VVSTYDSSLS
SYTVPLERDN SEEFLKREAR ANQLAEEIES SAQYKARVAL ENDDRSEEEK YTAVQRNSSE
REGHSINTRE NKYIPPGQRN REVISWGSGR QNSPRMGQPG SGSMPSRSTS HTSDFNPNSG
SDQRVVNGGV PWPSPCPSPS SRPPSRYQSG PNSLPPRAAT PTRPPSRPPS RPSRPPSHPS
AHGSPAPVST MPKRMSSEGP PRMSPKAQRH PRNHRVSAGR GSISSGLEFV SHNPPSEAAT
PPVARTSPSG GTWSSVVSGV PRLSPKTHRP RSPRQNSIGN TPSGPVLASP QAGIIPTEAV
AMPIPAASPT PASPASNRAV TPSSEAKDSR LQDQRQNSPA GNKENIKPNE TSPSFSKAEN
KGISPVVSEH RKQIDDLKKF KNDFRLQPSS TSESMDQLLN KNREGEKSRD LIKDKIEPSA
KDSFIENSSS NCTSGSSKPN SPSISPSILS NTEHKRGPEV TSQGVQTSSP ACKQEKDDKE
EKKDAAEQVR KSTLNPNAKE FNPRSFSQPK PSTTPTSPRP QAQPSPSMVG HQQPTPVYTQ
PVCFAPNMMY PVPVSPGVQP LYPIPMTPMP VNQAKTYRAV PNMPQQRQDQ HHQSAMMHPA
SAAGPPIAAT PPAYSTQYVA YSPQQFPNQP LVQHVPHYQS QHPHVYSPVI QGNARMMAPP
THAQPGLVSS SATQYGAHEQ THAMYACPKL PYNKETSPSF YFAISTGSLA QQYAHPNATL
HPHTPHPQPS ATPTGQQQSQ HGGSHPAPSP VQHHQHQAAQ ALHLASPQQQ SAIYHAGLAP
TPPSMTPASN TQSPQNSFPA AQQTVFTIHP SHVQPAYTNP PHMAHVPQAH VQSGMVPSHP
TAHAPMMLMT TQPPGGPQAA LAQSALQPIP VSTTAHFPYM THPSVQAHHQ QQL
