ATX3_HUMAN
ID ATX3_HUMAN Reviewed; 361 AA.
AC P54252; A7LFZ5; D6RDL9; E9PB63; O15284; O15285; O15286; Q8N189; Q96TC3;
AC Q96TC4; Q9H3N0;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2017, sequence version 5.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Ataxin-3;
DE EC=3.4.19.12;
DE AltName: Full=Machado-Joseph disease protein 1;
DE AltName: Full=Spinocerebellar ataxia type 3 protein;
GN Name=ATXN3; Synonyms=ATX3, MJD, MJD1, SCA3;
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), VARIANTS MET-212 AND GLY-306 DELINS
RP GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-ARG, VARIANT
RP 349-TYR--LEU-364 DEL (ISOFORM 1), AND INVOLVEMENT IN SCA3.
RC TISSUE=Brain;
RX PubMed=7874163; DOI=10.1038/ng1194-221;
RA Kawaguchi Y., Okamoto T., Taniwaki M., Aizawa M., Inoue M., Katayama S.,
RA Kawakami H., Nakamura S., Nishimura M., Akiguchi I., Kimura J.,
RA Narumiya S., Kakizuka A.;
RT "CAG expansions in a novel gene for Machado-Joseph disease at chromosome
RT 14q32.1.";
RL Nat. Genet. 8:221-228(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS MET-212 AND GLY-306
RP DELINS GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-ARG, AND VARIANT
RP 349-TYR--LEU-364 DEL (ISOFORM 1).
RX PubMed=9274833; DOI=10.1016/s0168-0102(97)00056-4;
RA Goto J., Watanabe M., Ichikawa Y., Yee S.-B., Ihara N., Endo K.,
RA Igarashi S., Takiyama Y., Gaspar C., Maciel P., Tsuji S., Rouleau G.A.,
RA Kanazawa I.;
RT "Machado-Joseph disease gene products carrying different carboxyl
RT termini.";
RL Neurosci. Res. 28:373-377(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANT
RP 349-TYR--LEU-364 DEL (ISOFORM 1).
RX PubMed=11450850; DOI=10.1007/s100380170060;
RA Ichikawa Y., Goto J., Hattori M., Toyoda A., Ishii K., Jeong S.-Y.,
RA Hashida H., Masuda N., Ogata K., Kasai F., Hirai M., Maciel P.,
RA Rouleau G.A., Sakaki Y., Kanazawa I.;
RT "The genomic structure and expression of MJD, the Machado-Joseph disease
RT gene.";
RL J. Hum. Genet. 46:413-422(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-212.
RG NIEHS SNPs program;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLY-306
RP DELINS GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-GLN-ARG.
RC TISSUE=Mammary gland;
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 [8]
RP SUBCELLULAR LOCATION.
RX PubMed=9580663; DOI=10.1093/hmg/7.6.991;
RA Tait D., Riccio M., Sittler A., Scherzinger E., Santi S., Ognibene A.,
RA Maraldi N.M., Lehrach H., Wanker E.E.;
RT "Ataxin-3 is transported into the nucleus and associates with the nuclear
RT matrix.";
RL Hum. Mol. Genet. 7:991-997(1998).
RN [9]
RP FUNCTION.
RX PubMed=12297501; DOI=10.1074/jbc.m205259200;
RA Li F., Macfarlan T., Pittman R.N., Chakravarti D.;
RT "Ataxin-3 is a histone-binding protein with two independent transcriptional
RT corepressor activities.";
RL J. Biol. Chem. 277:45004-45012(2002).
RN [10]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=17696782; DOI=10.1515/bc.2007.107;
RA Tzvetkov N., Breuer P.;
RT "Josephin domain-containing proteins from a variety of species are active
RT de-ubiquitination enzymes.";
RL Biol. Chem. 388:973-978(2007).
RN [11]
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 [12]
RP FUNCTION, AND MUTAGENESIS OF CYS-14.
RX PubMed=23625928; DOI=10.1074/jbc.m113.463406;
RA Seki T., Gong L., Williams A.J., Sakai N., Todi S.V., Paulson H.L.;
RT "JosD1, a membrane-targeted deubiquitinating enzyme, is activated by
RT ubiquitination and regulates membrane dynamics, cell motility, and
RT endocytosis.";
RL J. Biol. Chem. 288:17145-17155(2013).
RN [13]
RP UBIQUITINATION AT MET-1 AND LYS-200.
RX PubMed=23696636; DOI=10.1074/jbc.c113.477596;
RA Scaglione K.M., Basrur V., Ashraf N.S., Konen J.R., Elenitoba-Johnson K.S.,
RA Todi S.V., Paulson H.L.;
RT "The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus
RT of substrates.";
RL J. Biol. Chem. 288:18784-18788(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265, AND IDENTIFICATION BY
RP 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 [15]
RP INTERACTION WITH BECN1, FUNCTION, AND DOMAIN.
RX PubMed=28445460; DOI=10.1038/nature22078;
RA Ashkenazi A., Bento C.F., Ricketts T., Vicinanza M., Siddiqi F., Pavel M.,
RA Squitieri F., Hardenberg M.C., Imarisio S., Menzies F.M., Rubinsztein D.C.;
RT "Polyglutamine tracts regulate beclin 1-dependent autophagy.";
RL Nature 545:108-111(2017).
RN [16]
RP SUBCELLULAR LOCATION, INTERACTION WITH CASP7; PRKN; UBR2; VCP; RAD23A AND
RP RAD23B, INTERACTION WITH TUBULIN, AND CHARACTERIZATION OF VARIANT
RP 349-TYR--LEU-364 DEL (ISOFORM 1).
RX PubMed=30455355; DOI=10.1074/jbc.ra118.005801;
RA Weishaeupl D., Schneider J., Peixoto Pinheiro B., Ruess C., Dold S.M.,
RA von Zweydorf F., Gloeckner C.J., Schmidt J., Riess O., Schmidt T.;
RT "Physiological and pathophysiological characteristics of ataxin-3
RT isoforms.";
RL J. Biol. Chem. 294:644-661(2019).
RN [17]
RP 3D-STRUCTURE MODELING.
RX PubMed=12486728; DOI=10.1002/prot.10280;
RA Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U., Lengauer T.;
RT "Structural modeling of ataxin-3 reveals distant homology to adaptins.";
RL Proteins 50:355-370(2003).
RN [18]
RP STRUCTURE BY NMR OF 1-182, AND INTERACTION WITH RAD23A AND RAD23B.
RX PubMed=16020535; DOI=10.1073/pnas.0501732102;
RA Nicastro G., Menon R.P., Masino L., Knowles P.P., McDonald N.Q.,
RA Pastore A.;
RT "The solution structure of the Josephin domain of ataxin-3: structural
RT determinants for molecular recognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10493-10498(2005).
RN [19]
RP STRUCTURE BY NMR OF 1-185, FUNCTION, AND MUTAGENESIS OF CYS-14; SER-236;
RP SER-256 AND SER-335.
RX PubMed=16118278; DOI=10.1073/pnas.0506344102;
RA Mao Y., Senic-Matuglia F., Di Fiore P.P., Polo S., Hodsdon M.E.,
RA De Camilli P.;
RT "Deubiquitinating function of ataxin-3: insights from the solution
RT structure of the Josephin domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:12700-12705(2005).
CC -!- FUNCTION: Deubiquitinating enzyme involved in protein homeostasis
CC maintenance, transcription, cytoskeleton regulation, myogenesis and
CC degradation of misfolded chaperone substrates (PubMed:12297501,
CC PubMed:17696782, PubMed:23625928, PubMed:28445460, PubMed:16118278).
CC Binds long polyubiquitin chains and trims them, while it has weak or no
CC activity against chains of 4 or less ubiquitins (PubMed:17696782).
CC Involved in degradation of misfolded chaperone substrates via its
CC interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP,
CC and restricts the length of ubiquitin chain attached to STUB1/CHIP
CC substrates and preventing further chain extension (By similarity).
CC Interacts with key regulators of transcription and represses
CC transcription: acts as a histone-binding protein that regulates
CC transcription (PubMed:12297501). Regulates autophagy via the
CC deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of
CC BECN1 (PubMed:28445460). {ECO:0000250|UniProtKB:Q9CVD2,
CC ECO:0000269|PubMed:12297501, ECO:0000269|PubMed:16118278,
CC ECO:0000269|PubMed:17696782, ECO:0000269|PubMed:23625928,
CC ECO:0000269|PubMed:28445460}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:17696782};
CC -!- SUBUNIT: Interacts with STUB1/CHIP (when monoubiquitinated) (By
CC similarity). Interacts with DNA repair proteins RAD23A and RAD23B
CC (PubMed:16020535, PubMed:30455355). Interacts with BECN1 (via its poly-
CC Gln domain) (PubMed:28445460). Interacts with PRKN, UBR2, VCP and
CC tubulin. Short isoform 1 interacts with CASP7 (PubMed:30455355).
CC {ECO:0000250|UniProtKB:Q9CVD2, ECO:0000269|PubMed:16020535,
CC ECO:0000269|PubMed:28445460, ECO:0000269|PubMed:30455355}.
CC -!- INTERACTION:
CC P54252; Q9H7C9: AAMDC; NbExp=3; IntAct=EBI-946046, EBI-10308705;
CC P54252; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-946046, EBI-22011868;
CC P54252; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-946046, EBI-10173507;
CC P54252; O43488: AKR7A2; NbExp=3; IntAct=EBI-946046, EBI-748855;
CC P54252; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-946046, EBI-2875816;
CC P54252; Q14CB8: ARHGAP19; NbExp=4; IntAct=EBI-946046, EBI-954525;
CC P54252; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-946046, EBI-14199987;
CC P54252; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-946046, EBI-9089489;
CC P54252; P06276: BCHE; NbExp=3; IntAct=EBI-946046, EBI-7936069;
CC P54252; Q96G97-4: BSCL2; NbExp=3; IntAct=EBI-946046, EBI-10178113;
CC P54252; Q6UWD8: C16orf54; NbExp=3; IntAct=EBI-946046, EBI-18041102;
CC P54252; Q8N865: C7orf31; NbExp=3; IntAct=EBI-946046, EBI-10174456;
CC P54252; P29466-3: CASP1; NbExp=9; IntAct=EBI-946046, EBI-12248206;
CC P54252; P42574: CASP3; NbExp=9; IntAct=EBI-946046, EBI-524064;
CC P54252; Q96LX7-5: CCDC17; NbExp=3; IntAct=EBI-946046, EBI-12165781;
CC P54252; P40227: CCT6A; NbExp=3; IntAct=EBI-946046, EBI-356687;
CC P54252; Q5VV42: CDKAL1; NbExp=3; IntAct=EBI-946046, EBI-10194801;
CC P54252; Q16740: CLPP; NbExp=3; IntAct=EBI-946046, EBI-1056029;
CC P54252; Q02930-3: CREB5; NbExp=3; IntAct=EBI-946046, EBI-10192698;
CC P54252; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-946046, EBI-2872414;
CC P54252; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-946046, EBI-3508943;
CC P54252; Q9P1A6-3: DLGAP2; NbExp=3; IntAct=EBI-946046, EBI-12019838;
CC P54252; P50570-2: DNM2; NbExp=3; IntAct=EBI-946046, EBI-10968534;
CC P54252; Q3B7T1: EDRF1; NbExp=3; IntAct=EBI-946046, EBI-2870947;
CC P54252; Q01844: EWSR1; NbExp=4; IntAct=EBI-946046, EBI-739737;
CC P54252; Q01844-3: EWSR1; NbExp=9; IntAct=EBI-946046, EBI-25973273;
CC P54252; Q01844-4: EWSR1; NbExp=3; IntAct=EBI-946046, EBI-25896785;
CC P54252; O15287: FANCG; NbExp=3; IntAct=EBI-946046, EBI-81610;
CC P54252; P23142-4: FBLN1; NbExp=3; IntAct=EBI-946046, EBI-11956479;
CC P54252; Q9UHY8: FEZ2; NbExp=6; IntAct=EBI-946046, EBI-396453;
CC P54252; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-946046, EBI-6425864;
CC P54252; P06241-3: FYN; NbExp=3; IntAct=EBI-946046, EBI-10691738;
CC P54252; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-946046, EBI-11110431;
CC P54252; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-946046, EBI-739467;
CC P54252; O75409: H2AP; NbExp=3; IntAct=EBI-946046, EBI-6447217;
CC P54252; P68431: H3C12; NbExp=3; IntAct=EBI-946046, EBI-79722;
CC P54252; Q969S8: HDAC10; NbExp=3; IntAct=EBI-946046, EBI-301762;
CC P54252; O75330-3: HMMR; NbExp=3; IntAct=EBI-946046, EBI-12098658;
CC P54252; P22692: IGFBP4; NbExp=3; IntAct=EBI-946046, EBI-2831948;
CC P54252; Q16891: IMMT; NbExp=4; IntAct=EBI-946046, EBI-473801;
CC P54252; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-946046, EBI-714379;
CC P54252; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-946046, EBI-1108377;
CC P54252; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-946046, EBI-10258746;
CC P54252; Q9UDY8-2: MALT1; NbExp=3; IntAct=EBI-946046, EBI-12056869;
CC P54252; Q9H8H3: METTL7A; NbExp=3; IntAct=EBI-946046, EBI-1390168;
CC P54252; O94851: MICAL2; NbExp=3; IntAct=EBI-946046, EBI-2804835;
CC P54252; A4FUJ8: MKL1; NbExp=3; IntAct=EBI-946046, EBI-21250407;
CC P54252; Q13064: MKRN3; NbExp=3; IntAct=EBI-946046, EBI-2340269;
CC P54252; Q9Y483-4: MTF2; NbExp=3; IntAct=EBI-946046, EBI-10698053;
CC P54252; Q8WY64: MYLIP; NbExp=3; IntAct=EBI-946046, EBI-6952711;
CC P54252; Q15466: NR0B2; NbExp=3; IntAct=EBI-946046, EBI-3910729;
CC P54252; Q8NFH3: NUP43; NbExp=3; IntAct=EBI-946046, EBI-1059321;
CC P54252; Q96DC9: OTUB2; NbExp=9; IntAct=EBI-946046, EBI-746259;
CC P54252; Q96DC9-2: OTUB2; NbExp=9; IntAct=EBI-946046, EBI-25973449;
CC P54252; Q9BWI9: OTUB2; NbExp=6; IntAct=EBI-946046, EBI-10300896;
CC P54252; Q8N3R9: PALS1; NbExp=3; IntAct=EBI-946046, EBI-2513978;
CC P54252; Q9NVD7: PARVA; NbExp=9; IntAct=EBI-946046, EBI-747655;
CC P54252; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-946046, EBI-11022007;
CC P54252; O15530-4: PDPK1; NbExp=3; IntAct=EBI-946046, EBI-9087775;
CC P54252; Q9BSU1: PHAF1; NbExp=4; IntAct=EBI-946046, EBI-946080;
CC P54252; O75925: PIAS1; NbExp=9; IntAct=EBI-946046, EBI-629434;
CC P54252; P42336: PIK3CA; NbExp=3; IntAct=EBI-946046, EBI-2116585;
CC P54252; Q03405-2: PLAUR; NbExp=3; IntAct=EBI-946046, EBI-11028203;
CC P54252; Q8NBT0: POC1A; NbExp=3; IntAct=EBI-946046, EBI-2557132;
CC P54252; P17612: PRKACA; NbExp=3; IntAct=EBI-946046, EBI-476586;
CC P54252; P51665: PSMD7; NbExp=9; IntAct=EBI-946046, EBI-357659;
CC P54252; P54725: RAD23A; NbExp=9; IntAct=EBI-946046, EBI-746453;
CC P54252; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-946046, EBI-438710;
CC P54252; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-946046, EBI-740343;
CC P54252; Q6ZNA4-2: RNF111; NbExp=6; IntAct=EBI-946046, EBI-21535400;
CC P54252; Q96EP0: RNF31; NbExp=3; IntAct=EBI-946046, EBI-948111;
CC P54252; Q8N5Z7: RPL6; NbExp=6; IntAct=EBI-946046, EBI-25973375;
CC P54252; Q8TBK5: RPL6; NbExp=9; IntAct=EBI-946046, EBI-1642329;
CC P54252; Q66K80: RUSC1-AS1; NbExp=3; IntAct=EBI-946046, EBI-10248967;
CC P54252; P16581: SELE; NbExp=3; IntAct=EBI-946046, EBI-8007671;
CC P54252; P50454: SERPINH1; NbExp=3; IntAct=EBI-946046, EBI-350723;
CC P54252; Q8IVP1: SH3GL3; NbExp=3; IntAct=EBI-946046, EBI-6503765;
CC P54252; Q9NQ40: SLC52A3; NbExp=3; IntAct=EBI-946046, EBI-25845274;
CC P54252; O95416: SOX14; NbExp=3; IntAct=EBI-946046, EBI-9087806;
CC P54252; Q99932-2: SPAG8; NbExp=6; IntAct=EBI-946046, EBI-11959123;
CC P54252; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-946046, EBI-2510414;
CC P54252; Q9NRP7: STK36; NbExp=3; IntAct=EBI-946046, EBI-863797;
CC P54252; Q8TDW5-2: SYTL5; NbExp=3; IntAct=EBI-946046, EBI-12243980;
CC P54252; Q9Y458: TBX22; NbExp=3; IntAct=EBI-946046, EBI-6427217;
CC P54252; O95551: TDP2; NbExp=3; IntAct=EBI-946046, EBI-2819865;
CC P54252; Q9Y4R8: TELO2; NbExp=3; IntAct=EBI-946046, EBI-1043674;
CC P54252; Q15554-4: TERF2; NbExp=3; IntAct=EBI-946046, EBI-25840535;
CC P54252; Q8IYF3-3: TEX11; NbExp=6; IntAct=EBI-946046, EBI-11523345;
CC P54252; Q8NA77: TEX19; NbExp=3; IntAct=EBI-946046, EBI-13323487;
CC P54252; P37173: TGFBR2; NbExp=3; IntAct=EBI-946046, EBI-296151;
CC P54252; Q9BXR5: TLR10; NbExp=3; IntAct=EBI-946046, EBI-16825459;
CC P54252; Q9UMX0: UBQLN1; NbExp=6; IntAct=EBI-946046, EBI-741480;
CC P54252; P13051-2: UNG; NbExp=3; IntAct=EBI-946046, EBI-25834258;
CC P54252; Q92995: USP13; NbExp=3; IntAct=EBI-946046, EBI-714351;
CC P54252; P55072: VCP; NbExp=4; IntAct=EBI-946046, EBI-355164;
CC P54252; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-946046, EBI-2850578;
CC P54252; Q15007-2: WTAP; NbExp=3; IntAct=EBI-946046, EBI-25840023;
CC P54252; Q9H0M0: WWP1; NbExp=3; IntAct=EBI-946046, EBI-742157;
CC P54252; Q9H4I2-2: ZHX3; NbExp=3; IntAct=EBI-946046, EBI-10693326;
CC P54252; Q96NC0: ZMAT2; NbExp=3; IntAct=EBI-946046, EBI-2682299;
CC P54252; Q8N895: ZNF366; NbExp=3; IntAct=EBI-946046, EBI-2813661;
CC P54252-1; P54252-1: ATXN3; NbExp=6; IntAct=EBI-946068, EBI-946068;
CC P54252-1; Q14457: BECN1; NbExp=10; IntAct=EBI-946068, EBI-949378;
CC P54252-1; P54257: HAP1; NbExp=6; IntAct=EBI-946068, EBI-712814;
CC P54252-1; P0CG48: UBC; NbExp=2; IntAct=EBI-946068, EBI-3390054;
CC P54252-1; P55072: VCP; NbExp=16; IntAct=EBI-946068, EBI-355164;
CC P54252-2; O60260: PRKN; NbExp=5; IntAct=EBI-9684323, EBI-716346;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000269|PubMed:9580663}.
CC Nucleus {ECO:0000269|PubMed:30455355}. Note=Predominantly nuclear, but
CC not exclusively, inner nuclear matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=2;
CC IsoId=P54252-2; Sequence=Displayed;
CC Name=1; Synonyms=MJD1a;
CC IsoId=P54252-1; Sequence=VSP_002784;
CC Name=3;
CC IsoId=P54252-3; Sequence=VSP_002783;
CC Name=4;
CC IsoId=P54252-4; Sequence=VSP_047086;
CC Name=5;
CC IsoId=P54252-5; Sequence=VSP_047085;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: The UIM domains bind ubiquitin and interact with various E3
CC ubiquitin-protein ligase, such as STUB1/CHIP. They are essential to
CC limit the length of ubiquitin chains (By similarity).
CC {ECO:0000250|UniProtKB:Q9CVD2}.
CC -!- DOMAIN: The poly-Gln domain is involved in the interaction with BECN1
CC and subsequent starvation-induced autophagy (PubMed:28445460).
CC {ECO:0000269|PubMed:28445460}.
CC -!- PTM: Monoubiquitinated N-terminally by UBE2W, possibly leading to
CC activate the deubiquitinating enzyme activity (PubMed:23696636).
CC {ECO:0000269|PubMed:23696636}.
CC -!- POLYMORPHISM: The poly-Gln region of ATXN3 is highly polymorphic (14 to
CC 41 repeats) in the normal population and is expanded to about 55-82
CC repeats in spinocerebellar ataxia 3 (SCA3) patients (PubMed:7874163,
CC PubMed:9274833). {ECO:0000269|PubMed:7874163,
CC ECO:0000269|PubMed:9274833}.
CC -!- DISEASE: Spinocerebellar ataxia 3 (SCA3) [MIM:109150]: 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. SCA3 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. The molecular defect in SCA3 is the a CAG repeat
CC expansion in ATX3 coding region. Longer expansions result in earlier
CC onset and more severe clinical manifestations of the disease.
CC {ECO:0000269|PubMed:7874163}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/atxn3/";
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DR EMBL; S75313; AAB33571.1; -; mRNA.
DR EMBL; U64820; AAB63352.1; -; mRNA.
DR EMBL; U64821; AAB63353.1; -; mRNA.
DR EMBL; U64822; AAB63354.1; -; mRNA.
DR EMBL; AB050194; BAB18798.1; -; mRNA.
DR EMBL; AB038653; BAB55645.1; -; Genomic_DNA.
DR EMBL; AB038653; BAB55646.1; -; Genomic_DNA.
DR EMBL; EU009923; ABS29269.1; -; Genomic_DNA.
DR EMBL; AL049872; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121773; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW81472.1; -; Genomic_DNA.
DR EMBL; BC033711; AAH33711.1; -; mRNA.
DR CCDS; CCDS32143.1; -. [P54252-3]
DR CCDS; CCDS45154.1; -. [P54252-4]
DR CCDS; CCDS53908.1; -. [P54252-5]
DR CCDS; CCDS9900.1; -. [P54252-2]
DR PIR; S50830; S50830.
DR RefSeq; NP_001121168.1; NM_001127696.1. [P54252-4]
DR RefSeq; NP_001158252.1; NM_001164780.1. [P54252-5]
DR RefSeq; NP_004984.2; NM_004993.5. [P54252-2]
DR RefSeq; NP_109376.1; NM_030660.4. [P54252-3]
DR PDB; 1YZB; NMR; -; A=1-182.
DR PDB; 2AGA; NMR; -; A=1-185.
DR PDB; 2DOS; NMR; -; A=1-171.
DR PDB; 2JRI; NMR; -; A=1-182.
DR PDB; 2KLZ; NMR; -; A=222-263.
DR PDB; 4WTH; X-ray; 2.25 A; A/B=278-324.
DR PDB; 4YS9; X-ray; 2.00 A; B=278-324.
DR PDBsum; 1YZB; -.
DR PDBsum; 2AGA; -.
DR PDBsum; 2DOS; -.
DR PDBsum; 2JRI; -.
DR PDBsum; 2KLZ; -.
DR PDBsum; 4WTH; -.
DR PDBsum; 4YS9; -.
DR AlphaFoldDB; P54252; -.
DR BMRB; P54252; -.
DR SASBDB; P54252; -.
DR SMR; P54252; -.
DR BioGRID; 110433; 445.
DR ELM; P54252; -.
DR IntAct; P54252; 133.
DR MINT; P54252; -.
DR STRING; 9606.ENSP00000478320; -.
DR BindingDB; P54252; -.
DR ChEMBL; CHEMBL4523240; -.
DR MEROPS; C86.001; -.
DR iPTMnet; P54252; -.
DR MetOSite; P54252; -.
DR PhosphoSitePlus; P54252; -.
DR BioMuta; ATXN3; -.
DR DMDM; 290457685; -.
DR EPD; P54252; -.
DR jPOST; P54252; -.
DR MassIVE; P54252; -.
DR MaxQB; P54252; -.
DR PaxDb; P54252; -.
DR PeptideAtlas; P54252; -.
DR PRIDE; P54252; -.
DR ProteomicsDB; 14137; -.
DR ProteomicsDB; 19154; -.
DR ProteomicsDB; 56655; -. [P54252-1]
DR ProteomicsDB; 56656; -. [P54252-2]
DR ProteomicsDB; 56657; -. [P54252-3]
DR Antibodypedia; 13668; 334 antibodies from 32 providers.
DR DNASU; 4287; -.
DR Ensembl; ENST00000340660.10; ENSP00000339110.6; ENSG00000066427.25. [P54252-3]
DR Ensembl; ENST00000502250.5; ENSP00000425322.1; ENSG00000066427.25. [P54252-5]
DR Ensembl; ENST00000503767.5; ENSP00000426697.1; ENSG00000066427.25. [P54252-4]
DR Ensembl; ENST00000532032.5; ENSP00000437157.1; ENSG00000066427.25. [P54252-1]
DR Ensembl; ENST00000644486.2; ENSP00000496695.1; ENSG00000066427.25. [P54252-2]
DR GeneID; 4287; -.
DR KEGG; hsa:4287; -.
DR MANE-Select; ENST00000644486.2; ENSP00000496695.1; NM_004993.6; NP_004984.2.
DR UCSC; uc001yac.5; human. [P54252-2]
DR CTD; 4287; -.
DR DisGeNET; 4287; -.
DR GeneCards; ATXN3; -.
DR GeneReviews; ATXN3; -.
DR HGNC; HGNC:7106; ATXN3.
DR HPA; ENSG00000066427; Low tissue specificity.
DR MalaCards; ATXN3; -.
DR MIM; 109150; phenotype.
DR MIM; 607047; gene.
DR neXtProt; NX_P54252; -.
DR OpenTargets; ENSG00000066427; -.
DR Orphanet; 276238; Machado-Joseph disease type 1.
DR Orphanet; 276241; Machado-Joseph disease type 2.
DR Orphanet; 276244; Machado-Joseph disease type 3.
DR PharmGKB; PA134971833; -.
DR VEuPathDB; HostDB:ENSG00000066427; -.
DR eggNOG; KOG2935; Eukaryota.
DR GeneTree; ENSGT00390000001830; -.
DR InParanoid; P54252; -.
DR OMA; QQIQRPK; -.
DR OrthoDB; 1482722at2759; -.
DR PhylomeDB; P54252; -.
DR TreeFam; TF314228; -.
DR PathwayCommons; P54252; -.
DR Reactome; R-HSA-5689877; Josephin domain DUBs.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR SignaLink; P54252; -.
DR SIGNOR; P54252; -.
DR BioGRID-ORCS; 4287; 8 hits in 1119 CRISPR screens.
DR ChiTaRS; ATXN3; human.
DR EvolutionaryTrace; P54252; -.
DR GeneWiki; Ataxin_3; -.
DR GenomeRNAi; 4287; -.
DR Pharos; P54252; Tbio.
DR PRO; PR:P54252; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P54252; protein.
DR Bgee; ENSG00000066427; Expressed in calcaneal tendon and 186 other tissues.
DR ExpressionAtlas; P54252; baseline and differential.
DR Genevisible; P54252; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031966; C:mitochondrial membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0042405; C:nuclear inclusion body; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0051117; F:ATPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISS:ParkinsonsUK-UCL.
DR GO; GO:0071218; P:cellular response to misfolded protein; ISS:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IMP:MGI.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:MGI.
DR GO; GO:0035520; P:monoubiquitinated protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0006289; P:nucleotide-excision repair; TAS:ProtInc.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:1904379; P:protein localization to cytosolic proteasome complex involved in ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; ISS:UniProtKB.
DR GO; GO:0010810; P:regulation of cell-substrate adhesion; IMP:MGI.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:ParkinsonsUK-UCL.
DR DisProt; DP00576; -.
DR InterPro; IPR033865; Ataxin-3.
DR InterPro; IPR006155; Josephin.
DR InterPro; IPR003903; UIM_dom.
DR PANTHER; PTHR14159; PTHR14159; 1.
DR Pfam; PF02099; Josephin; 1.
DR Pfam; PF02809; UIM; 3.
DR SMART; SM01246; Josephin; 1.
DR SMART; SM00726; UIM; 3.
DR PROSITE; PS50957; JOSEPHIN; 1.
DR PROSITE; PS50330; UIM; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Hydrolase; Isopeptide bond;
KW Neurodegeneration; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Repeat; Spinocerebellar ataxia; Thiol protease; Transcription;
KW Transcription regulation; Triplet repeat expansion; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..361
FT /note="Ataxin-3"
FT /id="PRO_0000053831"
FT DOMAIN 1..180
FT /note="Josephin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00331"
FT DOMAIN 224..243
FT /note="UIM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 244..263
FT /note="UIM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT DOMAIN 331..349
FT /note="UIM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213"
FT REGION 258..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..319
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 14
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23625928"
FT ACT_SITE 119
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:16020535,
FT ECO:0000305|PubMed:16118278"
FT ACT_SITE 134
FT /evidence="ECO:0000305|PubMed:16020535,
FT ECO:0000305|PubMed:16118278"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CVD2"
FT CROSSLNK 1
FT /note="Peptide (Met-Gly) (interchain with G-Cter in
FT ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23696636"
FT CROSSLNK 200
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:23696636"
FT VAR_SEQ 1..179
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_047085"
FT VAR_SEQ 10..64
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002783"
FT VAR_SEQ 63..77
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_047086"
FT VAR_SEQ 332..361
FT /note="DAMSEEDMLQAAVTMSLETVRNDLKTEGKK -> KACSPFIMFATFTLYLTY
FT ELHVIFALHYSSFPL (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:7874163,
FT ECO:0000303|PubMed:9274833"
FT /id="VSP_002784"
FT VARIANT 212
FT /note="V -> M (in dbSNP:rs1048755)"
FT /evidence="ECO:0000269|PubMed:7874163,
FT ECO:0000269|PubMed:9274833, ECO:0000269|Ref.4"
FT /id="VAR_013688"
FT VARIANT 306
FT /note="G -> QQQQQQQQQQQQR"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7874163, ECO:0000269|PubMed:9274833"
FT /id="VAR_013689"
FT MUTAGEN 14
FT /note="C->A: Loss of deubiquitination activity."
FT /evidence="ECO:0000269|PubMed:16118278,
FT ECO:0000269|PubMed:23625928"
FT MUTAGEN 236
FT /note="S->A: Inhibits substrate trapping."
FT /evidence="ECO:0000269|PubMed:16118278"
FT MUTAGEN 256
FT /note="S->A: Inhibits substrate trapping."
FT /evidence="ECO:0000269|PubMed:16118278"
FT MUTAGEN 335
FT /note="S->A: No effect on ubiquitination."
FT /evidence="ECO:0000269|PubMed:16118278"
FT CONFLICT 252
FT /note="A -> T (in Ref. 2; AAB63352/AAB63353/AAB63354)"
FT /evidence="ECO:0000305"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:2AGA"
FT HELIX 14..22
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:2JRI"
FT HELIX 30..49
FT /evidence="ECO:0007829|PDB:1YZB"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:2AGA"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:1YZB"
FT HELIX 78..85
FT /evidence="ECO:0007829|PDB:1YZB"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:1YZB"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:1YZB"
FT HELIX 106..108
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 109..116
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:1YZB"
FT HELIX 145..158
FT /evidence="ECO:0007829|PDB:1YZB"
FT STRAND 161..167
FT /evidence="ECO:0007829|PDB:1YZB"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:1YZB"
FT HELIX 178..180
FT /evidence="ECO:0007829|PDB:2JRI"
FT HELIX 222..240
FT /evidence="ECO:0007829|PDB:2KLZ"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:2KLZ"
FT HELIX 246..257
FT /evidence="ECO:0007829|PDB:2KLZ"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:4YS9"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:4YS9"
FT VARIANT P54252-1:349..364
FT /note="Missing (in short isoform 1, due to a stop-gain
FT single nucleotide variant, has reduced half-life due to
FT increased proteasomal degradation, has reduced solubility
FT and increased tendency to form aggregates, increased
FT localization to the nucleus)"
FT /evidence="ECO:0000269|PubMed:11450850,
FT ECO:0000269|PubMed:30455355, ECO:0000269|PubMed:7874163,
FT ECO:0000269|PubMed:9274833"
FT /id="VAR_082841"
SQ SEQUENCE 361 AA; 41250 MW; 90C3EF73BB26CAFD CRC64;
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERMRMAE GGVTSEDYRT
FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLRIDPINER SFICNYKEHW
FTVRKLGKQW FNLNSLLTGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM
IRVQQMHRPK LIGEELAQLK EQRVHKTDLE RVLEANDGSG MLDEDEEDLQ RALALSRQEI
DMEDEEADLR RAIQLSMQGS SRNISQDMTQ TSGTNLTSEE LRKRREAYFE KQQQKQQQQQ
QQQQQGDLSG QSSHPCERPA TSSGALGSDL GDAMSEEDML QAAVTMSLET VRNDLKTEGK
K
