HUWE1_HUMAN
ID HUWE1_HUMAN Reviewed; 4374 AA.
AC Q7Z6Z7; O15029; Q4G2Z2; Q5H961; Q6P4D0; Q8NG67; Q9BUI0; Q9HCJ4; Q9NSL6;
AC Q9P0A9;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=E3 ubiquitin-protein ligase HUWE1;
DE EC=2.3.2.26 {ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:30217973};
DE AltName: Full=ARF-binding protein 1;
DE Short=ARF-BP1;
DE AltName: Full=HECT, UBA and WWE domain-containing protein 1;
DE AltName: Full=HECT-type E3 ubiquitin transferase HUWE1;
DE AltName: Full=Homologous to E6AP carboxyl terminus homologous protein 9;
DE Short=HectH9;
DE AltName: Full=Large structure of UREB1;
DE Short=LASU1;
DE AltName: Full=Mcl-1 ubiquitin ligase E3;
DE Short=Mule;
DE AltName: Full=Upstream regulatory element-binding protein 1;
DE Short=URE-B1;
DE Short=URE-binding protein 1;
GN Name=HUWE1; Synonyms=KIAA0312, KIAA1578, UREB1; ORFNames=HSPC272;
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), FUNCTION, INTERACTION WITH CDKN2A,
RP AND MUTAGENESIS OF CYS-4341.
RX PubMed=15989956; DOI=10.1016/j.cell.2005.03.037;
RA Chen D., Kon N., Li M., Zhang W., Qin J., Gu W.;
RT "ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor.";
RL Cell 121:1071-1083(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PATHWAY, CATALYTIC
RP ACTIVITY, AND MUTAGENESIS OF CYS-4341.
RX PubMed=15989957; DOI=10.1016/j.cell.2005.06.009;
RA Zhong Q., Gao W., Du F., Wang X.;
RT "Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the
RT polyubiquitination of Mcl-1 and regulates apoptosis.";
RL Cell 121:1085-1095(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=15767685; DOI=10.1128/mcb.25.7.2819-2831.2005;
RA Liu Z., Oughtred R., Wing S.S.;
RT "Characterization of E3Histone, a novel testis ubiquitin protein ligase
RT which ubiquitinates histones.";
RL Mol. Cell. Biol. 25:2819-2831(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 959-4374 (ISOFORM 3).
RC TISSUE=Brain;
RA Miyazaki K., Okamoto Y., Sakamoto M., Kato C., Ozaki T., Watanabe K.,
RA Nakagawara A.;
RT "Homo sapiens LASU1 (large structure of UREB1) mRNA, complete cds.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1166-4374 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [7]
RP SEQUENCE REVISION TO 2310.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (SEP-2011) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1246-2418.
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2451-4374.
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3953-4374.
RC TISSUE=Ovary, and Placenta;
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4029-4374.
RA Kim J.W., Lee Y., Hong Y.M., Hong M., Choe I.S.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4067-4374.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4320-4374.
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF TYR-4268 AND CYS-4341.
RX PubMed=15567145; DOI=10.1016/j.bbrc.2004.11.004;
RA Yoon S.Y., Lee Y., Kim J.H., Chung A.-S., Joo J.H., Kim C.-N., Kim N.-S.,
RA Choe I.S., Kim J.W.;
RT "Over-expression of human UREB1 in colorectal cancer: HECT domain of human
RT UREB1 inhibits the activity of tumor suppressor p53 protein.";
RL Biochem. Biophys. Res. Commun. 326:7-17(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2362, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1395; SER-1907; SER-2362;
RP SER-2887 AND SER-2918, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [17]
RP FUNCTION, AND INTERACTION WITH CDC6.
RX PubMed=17567951; DOI=10.1091/mbc.e07-02-0173;
RA Hall J.R., Kow E., Nevis K.R., Lu C.K., Luce K.S., Zhong Q., Cook J.G.;
RT "Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA
RT damage.";
RL Mol. Biol. Cell 18:3340-3350(2007).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1084, 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 [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2362, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP FUNCTION, INTERACTION WITH MYCN, AND MUTAGENESIS OF CYS-4341.
RX PubMed=18488021; DOI=10.1038/ncb1727;
RA Zhao X., Heng J.I.-T., Guardavaccaro D., Jiang R., Pagano M., Guillemot F.,
RA Iavarone A., Lasorella A.;
RT "The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and
RT proliferation by destabilizing the N-Myc oncoprotein.";
RL Nat. Cell Biol. 10:643-653(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1368; SER-1907; SER-2362;
RP SER-2365; SER-2887; SER-3662; SER-3919; THR-3924 AND THR-3927, AND
RP IDENTIFICATION BY 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 [24]
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 [25]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH POLB.
RX PubMed=19713937; DOI=10.1038/emboj.2009.243;
RA Parsons J.L., Tait P.S., Finch D., Dianova I.I., Edelmann M.J.,
RA Khoronenkova S.V., Kessler B.M., Sharma R.A., McKenna W.G., Dianov G.L.;
RT "Ubiquitin ligase ARF-BP1/Mule modulates base excision repair.";
RL EMBO J. 28:3207-3215(2009).
RN [26]
RP FUNCTION, AND INTERACTION WITH PA2G4.
RX PubMed=19037095; DOI=10.1091/mbc.e08-09-0983;
RA Liu Z., Oh S.M., Okada M., Liu X., Cheng D., Peng J., Brat D.J., Sun S.Y.,
RA Zhou W., Gu W., Ye K.;
RT "Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor.";
RL Mol. Biol. Cell 20:757-768(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1370; SER-1395; SER-1907;
RP SER-2362; SER-2391; SER-2595; SER-2619; THR-2751; SER-2887; SER-3116;
RP SER-3752; SER-3757; SER-3808; SER-3816; SER-3919 AND THR-3924, AND
RP IDENTIFICATION BY 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 [29]
RP FUNCTION, AND INTERACTION WITH NR1D1.
RX PubMed=20534529; DOI=10.1073/pnas.1000438107;
RA Yin L., Joshi S., Wu N., Tong X., Lazar M.A.;
RT "E3 ligases Arf-bp1 and Pam mediate lithium-stimulated degradation of the
RT circadian heme receptor Rev-erb alpha.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11614-11619(2010).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1084; SER-1368; SER-1395;
RP THR-1722; SER-1907; SER-2362; SER-2365; SER-2595; SER-3127; SER-3662;
RP SER-3757; SER-3760 AND SER-3919, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [31]
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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1084; SER-1907; SER-2362 AND
RP SER-2365, AND 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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1368; SER-1382; SER-1395;
RP THR-1722; SER-1907; SER-2266; SER-2362; SER-2365; SER-2527; SER-2532;
RP SER-2535; THR-2554; SER-2595; SER-2887; SER-2888; THR-2889; SER-3116;
RP SER-3117; SER-3122; SER-3127; SER-3135; SER-3555; SER-3662; SER-3752;
RP SER-3757; SER-3760; SER-3808; SER-3816; SER-3827 AND THR-3830, AND
RP IDENTIFICATION 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 [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-740; SER-1368; SER-1395;
RP THR-2035; SER-2584; SER-2826; SER-2833; SER-2835; SER-2861; SER-3757;
RP SER-3759; SER-3816; SER-3827; SER-3906; SER-3919; THR-3924 AND THR-3927,
RP AND 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 [35]
RP FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY.
RX PubMed=26214738; DOI=10.1038/nature14601;
RA Senyilmaz D., Virtue S., Xu X., Tan C.Y., Griffin J.L., Miller A.K.,
RA Vidal-Puig A., Teleman A.A.;
RT "Regulation of mitochondrial morphology and function by stearoylation of
RT TFR1.";
RL Nature 525:124-128(2015).
RN [36]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH AMBRA1.
RX PubMed=30217973; DOI=10.1038/s41467-018-05722-3;
RA Di Rita A., Peschiaroli A., D'Acunzo P., Strobbe D., Hu Z., Gruber J.,
RA Nygaard M., Lambrughi M., Melino G., Papaleo E., Dengjel J., El Alaoui S.,
RA Campanella M., Doetsch V., Rogov V.V., Strappazzon F., Cecconi F.;
RT "HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating
RT AMBRA1 activation via IKKalpha.";
RL Nat. Commun. 9:3755-3755(2018).
RN [37]
RP STRUCTURE BY NMR OF 1317-1356.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-074, a human UBA domain.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 4005-4374.
RG Structural genomics consortium (SGC);
RT "Hect domain of human huwe1/mule.";
RL Submitted (MAY-2009) to the PDB data bank.
RN [39]
RP VARIANTS MRXST HIS-2981; TRP-4013 AND CYS-4187, AND INVOLVEMENT IN MRXST.
RX PubMed=18252223; DOI=10.1016/j.ajhg.2007.11.002;
RA Froyen G., Corbett M., Vandewalle J., Jarvela I., Lawrence O., Meldrum C.,
RA Bauters M., Govaerts K., Vandeleur L., Van Esch H., Chelly J.,
RA Sanlaville D., van Bokhoven H., Ropers H.-H., Laumonnier F., Ranieri E.,
RA Schwartz C.E., Abidi F., Tarpey P.S., Futreal P.A., Whibley A.,
RA Raymond F.L., Stratton M.R., Fryns J.-P., Scott R., Peippo M., Sipponen M.,
RA Partington M., Mowat D., Field M., Hackett A., Marynen P., Turner G.,
RA Gecz J.;
RT "Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10
RT and the E3 ubiquitin ligase HUWE1 are associated with mental retardation.";
RL Am. J. Hum. Genet. 82:432-443(2008).
RN [40]
RP VARIANT ASP-950.
RX PubMed=23092983; DOI=10.1038/tp.2012.102;
RA Nava C., Lamari F., Heron D., Mignot C., Rastetter A., Keren B., Cohen D.,
RA Faudet A., Bouteiller D., Gilleron M., Jacquette A., Whalen S., Afenjar A.,
RA Perisse D., Laurent C., Dupuits C., Gautier C., Gerard M., Huguet G.,
RA Caillet S., Leheup B., Leboyer M., Gillberg C., Delorme R., Bourgeron T.,
RA Brice A., Depienne C.;
RT "Analysis of the chromosome X exome in patients with autism spectrum
RT disorders identified novel candidate genes, including TMLHE.";
RL Transl. Psychiatry 2:E179-E179(2012).
RN [41]
RP VARIANTS MRXST GLN-110 AND TRP-110.
RX PubMed=25985138; DOI=10.1038/ng.3304;
RA Taylor J.C., Martin H.C., Lise S., Broxholme J., Cazier J.B., Rimmer A.,
RA Kanapin A., Lunter G., Fiddy S., Allan C., Aricescu A.R., Attar M.,
RA Babbs C., Becq J., Beeson D., Bento C., Bignell P., Blair E., Buckle V.J.,
RA Bull K., Cais O., Cario H., Chapel H., Copley R.R., Cornall R., Craft J.,
RA Dahan K., Davenport E.E., Dendrou C., Devuyst O., Fenwick A.L., Flint J.,
RA Fugger L., Gilbert R.D., Goriely A., Green A., Greger I.H., Grocock R.,
RA Gruszczyk A.V., Hastings R., Hatton E., Higgs D., Hill A., Holmes C.,
RA Howard M., Hughes L., Humburg P., Johnson D., Karpe F., Kingsbury Z.,
RA Kini U., Knight J.C., Krohn J., Lamble S., Langman C., Lonie L., Luck J.,
RA McCarthy D., McGowan S.J., McMullin M.F., Miller K.A., Murray L.,
RA Nemeth A.H., Nesbit M.A., Nutt D., Ormondroyd E., Oturai A.B.,
RA Pagnamenta A., Patel S.Y., Percy M., Petousi N., Piazza P., Piret S.E.,
RA Polanco-Echeverry G., Popitsch N., Powrie F., Pugh C., Quek L.,
RA Robbins P.A., Robson K., Russo A., Sahgal N., van Schouwenburg P.A.,
RA Schuh A., Silverman E., Simmons A., Soerensen P.S., Sweeney E., Taylor J.,
RA Thakker R.V., Tomlinson I., Trebes A., Twigg S.R., Uhlig H.H., Vyas P.,
RA Vyse T., Wall S.A., Watkins H., Whyte M.P., Witty L., Wright B., Yau C.,
RA Buck D., Humphray S., Ratcliffe P.J., Bell J.I., Wilkie A.O., Bentley D.,
RA Donnelly P., McVean G.;
RT "Factors influencing success of clinical genome sequencing across a broad
RT spectrum of disorders.";
RL Nat. Genet. 47:717-726(2015).
RN [42]
RP VARIANTS MRXST GLN-4063 AND ARG-4310, AND CHARACTERIZATION OF VARIANTS
RP MRXST GLN-4063 AND ARG-4310.
RX PubMed=27130160; DOI=10.1136/bmjopen-2015-009537;
RA Friez M.J., Brooks S.S., Stevenson R.E., Field M., Basehore M.J.,
RA Ades L.C., Sebold C., McGee S., Saxon S., Skinner C., Craig M.E.,
RA Murray L., Simensen R.J., Yap Y.Y., Shaw M.A., Gardner A., Corbett M.,
RA Kumar R., Bosshard M., van Loon B., Tarpey P.S., Abidi F., Gecz J.,
RA Schwartz C.E.;
RT "HUWE1 mutations in Juberg-Marsidi and Brooks syndromes: the results of an
RT X-chromosome exome sequencing study.";
RL BMJ Open 6:E009537-E009537(2016).
RN [43]
RP VARIANT MRXST TRP-110.
RX PubMed=27884935; DOI=10.1136/jmedgenet-2016-104215;
RA Miller K.A., Twigg S.R., McGowan S.J., Phipps J.M., Fenwick A.L.,
RA Johnson D., Wall S.A., Noons P., Rees K.E., Tidey E.A., Craft J.,
RA Taylor J., Taylor J.C., Goos J.A., Swagemakers S.M., Mathijssen I.M.,
RA van der Spek P.J., Lord H., Lester T., Abid N., Cilliers D., Hurst J.A.,
RA Morton J.E., Sweeney E., Weber A., Wilson L.C., Wilkie A.O.;
RT "Diagnostic value of exome and whole genome sequencing in
RT craniosynostosis.";
RL J. Med. Genet. 54:260-268(2017).
RN [44]
RP VARIANTS MRXST GLN-110; PHE-115; ARG-660; GLN-669; VAL-1328; MET-2089;
RP CYS-3070; SER-3194; CYS-4023; PHE-4069; LYS-4075; CYS-4106; VAL-4157;
RP ASP-4244 AND ASN-4295.
RX PubMed=29180823; DOI=10.1038/s41431-017-0038-6;
RA Moortgat S., Berland S., Aukrust I., Maystadt I., Baker L., Benoit V.,
RA Caro-Llopis A., Cooper N.S., Debray F.G., Faivre L., Gardeitchik T.,
RA Haukanes B.I., Houge G., Kivuva E., Martinez F., Mehta S.G., Nassogne M.C.,
RA Powell-Hamilton N., Pfundt R., Rosello M., Prescott T., Vasudevan P.,
RA van Loon B., Verellen-Dumoulin C., Verloes A., Lippe C.V., Wakeling E.,
RA Wilkie A.O.M., Wilson L., Yuen A., Study D., Low K.J., Newbury-Ecob R.A.;
RT "HUWE1 variants cause dominant X-linked intellectual disability: a clinical
RT study of 21 patients.";
RL Eur. J. Hum. Genet. 26:64-74(2018).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which mediates ubiquitination and
CC subsequent proteasomal degradation of target proteins (PubMed:15989957,
CC PubMed:19713937, PubMed:15567145, PubMed:15767685, PubMed:18488021,
CC PubMed:17567951, PubMed:19037095, PubMed:20534529, PubMed:30217973).
CC Regulates apoptosis by catalyzing the polyubiquitination and
CC degradation of MCL1 (PubMed:15989957). Mediates monoubiquitination of
CC DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby
CC playing a role in base-excision repair (PubMed:19713937). Also
CC ubiquitinates the p53/TP53 tumor suppressor and core histones including
CC H1, H2A, H2B, H3 and H4 (PubMed:15567145, PubMed:15767685,
CC PubMed:15989956). Ubiquitinates MFN2 to negatively regulate
CC mitochondrial fusion in response to decreased stearoylation of TFRC
CC (PubMed:26214738). Ubiquitination of MFN2 also takes place following
CC induction of mitophagy; AMBRA1 acts as a cofactor for HUWE1-mediated
CC ubiquitination (PubMed:30217973). Regulates neural differentiation and
CC proliferation by catalyzing the polyubiquitination and degradation of
CC MYCN (PubMed:18488021). May regulate abundance of CDC6 after DNA damage
CC by polyubiquitinating and targeting CDC6 to degradation
CC (PubMed:17567951). Mediates polyubiquitination of isoform 2 of PA2G4
CC (PubMed:19037095). Acts in concert with MYCBP2 to regulate the
CC circadian clock gene expression by promoting the lithium-induced
CC ubiquination and degradation of NR1D1 (PubMed:20534529). Binds to an
CC upstream initiator-like sequence in the preprodynorphin gene (By
CC similarity). {ECO:0000250|UniProtKB:P51593,
CC ECO:0000269|PubMed:15567145, ECO:0000269|PubMed:15767685,
CC ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957,
CC ECO:0000269|PubMed:17567951, ECO:0000269|PubMed:18488021,
CC ECO:0000269|PubMed:19037095, ECO:0000269|PubMed:19713937,
CC ECO:0000269|PubMed:20534529, ECO:0000269|PubMed:26214738,
CC ECO:0000269|PubMed:30217973}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.26; Evidence={ECO:0000269|PubMed:15989957,
CC ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:26214738,
CC ECO:0000269|PubMed:30217973};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:15989957, ECO:0000269|PubMed:19713937,
CC ECO:0000269|PubMed:26214738, ECO:0000269|PubMed:30217973}.
CC -!- SUBUNIT: Interacts with isoform p14ARF of CDKN2A which strongly
CC inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and
CC CDC6. Interacts with isoform 2 of PA2G4. Interacts with NR1D1
CC (PubMed:20534529). Interacts with AMBRA1 (PubMed:30217973).
CC {ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:17567951,
CC ECO:0000269|PubMed:18488021, ECO:0000269|PubMed:19037095,
CC ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:20534529,
CC ECO:0000269|PubMed:30217973}.
CC -!- INTERACTION:
CC Q7Z6Z7; Q8N726: CDKN2A; NbExp=5; IntAct=EBI-625934, EBI-625922;
CC Q7Z6Z7; P04792: HSPB1; NbExp=3; IntAct=EBI-625934, EBI-352682;
CC Q7Z6Z7; Q07820: MCL1; NbExp=6; IntAct=EBI-625934, EBI-1003422;
CC Q7Z6Z7; P20393: NR1D1; NbExp=3; IntAct=EBI-625934, EBI-2811738;
CC Q7Z6Z7; P04637: TP53; NbExp=3; IntAct=EBI-625934, EBI-366083;
CC Q7Z6Z7; Q13107: USP4; NbExp=4; IntAct=EBI-625934, EBI-723290;
CC Q7Z6Z7-2; P27797: CALR; NbExp=3; IntAct=EBI-10975491, EBI-1049597;
CC Q7Z6Z7-2; P12830: CDH1; NbExp=3; IntAct=EBI-10975491, EBI-727477;
CC Q7Z6Z7-2; P36957: DLST; NbExp=3; IntAct=EBI-10975491, EBI-351007;
CC Q7Z6Z7-2; Q8TDX7: NEK7; NbExp=3; IntAct=EBI-10975491, EBI-1055945;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19713937}. Nucleus
CC {ECO:0000269|PubMed:19713937}. Mitochondrion
CC {ECO:0000269|PubMed:30217973}. Note=Mainly expressed in the cytoplasm
CC of most tissues, except in the nucleus of spermatogonia, primary
CC spermatocytes and neuronal cells (By similarity). Recruited to
CC mitochondria following interaction with AMBRA1 (PubMed:30217973).
CC {ECO:0000250|UniProtKB:Q7TMY8, ECO:0000269|PubMed:30217973}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=LASU1, Large structure of UREB1;
CC IsoId=Q7Z6Z7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z6Z7-2; Sequence=VSP_011146;
CC Name=3;
CC IsoId=Q7Z6Z7-3; Sequence=VSP_015272;
CC -!- TISSUE SPECIFICITY: Weakly expressed in heart, brain and placenta but
CC not in other tissues. Expressed in a number of cell lines,
CC predominantly in those from colorectal carcinomas.
CC {ECO:0000269|PubMed:15567145}.
CC -!- DOMAIN: The HECT domain mediates inhibition of the transcriptional
CC activity of p53.
CC -!- PTM: Phosphorylated on tyrosine; phosphorylation is probably required
CC for its ability to inhibit TP53 transactivation.
CC {ECO:0000250|UniProtKB:Q7TMY8}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic,
CC Turner type (MRXST) [MIM:309590]: An X-linked neurodevelopmental
CC disorder with highly variable clinical manifestations. Common features
CC consist of moderate to profound intellectual disability, delayed or
CC absent speech, short stature with small hands and feet, and non-
CC specific but recurrent dysmorphic facial features such as macrocephaly,
CC microcephaly, a broad nasal tip, deep set eyes, epicanthic folds, short
CC palpebral fissures and a short philtrum. Patients may manifest other
CC features, such as hypotonia, seizures and delayed bone age.
CC {ECO:0000269|PubMed:18252223, ECO:0000269|PubMed:25985138,
CC ECO:0000269|PubMed:27130160, ECO:0000269|PubMed:27884935,
CC ECO:0000269|PubMed:29180823}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the UPL family. TOM1/PTR1 subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC62492.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF28950.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF28950.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB13404.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA, contains the C-terminal part of ATP5ME.; Evidence={ECO:0000305};
CC Sequence=BAC06833.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY772009; AAV90838.1; -; mRNA.
DR EMBL; DQ097177; AAY98258.1; -; mRNA.
DR EMBL; AY929612; AAX24125.1; -; mRNA.
DR EMBL; AL592046; CAI39580.1; -; Genomic_DNA.
DR EMBL; Z94044; CAI39580.1; JOINED; Genomic_DNA.
DR EMBL; Z97054; CAI39580.1; JOINED; Genomic_DNA.
DR EMBL; Z94044; CAI42354.1; -; Genomic_DNA.
DR EMBL; AL592046; CAI42354.1; JOINED; Genomic_DNA.
DR EMBL; Z97054; CAI42354.1; JOINED; Genomic_DNA.
DR EMBL; Z97054; CAI42654.1; -; Genomic_DNA.
DR EMBL; AL592046; CAI42654.1; JOINED; Genomic_DNA.
DR EMBL; Z94044; CAI42654.1; JOINED; Genomic_DNA.
DR EMBL; AB071605; BAC06833.1; ALT_FRAME; mRNA.
DR EMBL; AB002310; BAA20771.3; -; mRNA.
DR EMBL; AB046798; BAB13404.1; ALT_SEQ; mRNA.
DR EMBL; AF161390; AAF28950.1; ALT_SEQ; mRNA.
DR EMBL; BC002602; AAH02602.2; -; mRNA.
DR EMBL; BC063505; AAH63505.1; -; mRNA.
DR EMBL; AF057569; AAC62492.1; ALT_INIT; mRNA.
DR EMBL; CR456813; CAG33094.1; -; mRNA.
DR EMBL; AL162050; CAB82393.1; -; mRNA.
DR CCDS; CCDS35301.1; -. [Q7Z6Z7-1]
DR PIR; T47165; T47165.
DR RefSeq; NP_113584.3; NM_031407.6. [Q7Z6Z7-1]
DR RefSeq; XP_005262022.1; XM_005261965.3. [Q7Z6Z7-1]
DR PDB; 2EKK; NMR; -; A=1317-1356.
DR PDB; 2MUL; NMR; -; A=2951-3003.
DR PDB; 3G1N; X-ray; 2.60 A; A/B=4005-4374.
DR PDB; 3H1D; X-ray; 1.89 A; A=3993-4374.
DR PDB; 5C6H; X-ray; 2.05 A; B/D/F/H/J/L/N/P/R/T/V/X=1969-1994.
DR PDB; 5LP8; X-ray; 2.70 A; A/B=3951-4374.
DR PDB; 6FYH; X-ray; 2.91 A; A=4255-4374.
DR PDB; 6MIW; X-ray; 2.00 A; A=1611-1700.
DR PDB; 6PFL; X-ray; 2.10 A; A/B=1611-1700.
DR PDB; 7AZX; X-ray; 2.25 A; C=3870-3897.
DR PDB; 7JQ9; EM; 3.10 A; A=1-4374.
DR PDB; 7MOP; EM; 3.30 A; A=1-4374.
DR PDB; 7MWD; EM; 3.70 A; A=1-4374.
DR PDB; 7MWE; EM; 3.40 A; A=1-4374.
DR PDB; 7MWF; EM; 3.30 A; A=1-4374.
DR PDBsum; 2EKK; -.
DR PDBsum; 2MUL; -.
DR PDBsum; 3G1N; -.
DR PDBsum; 3H1D; -.
DR PDBsum; 5C6H; -.
DR PDBsum; 5LP8; -.
DR PDBsum; 6FYH; -.
DR PDBsum; 6MIW; -.
DR PDBsum; 6PFL; -.
DR PDBsum; 7AZX; -.
DR PDBsum; 7JQ9; -.
DR PDBsum; 7MOP; -.
DR PDBsum; 7MWD; -.
DR PDBsum; 7MWE; -.
DR PDBsum; 7MWF; -.
DR BMRB; Q7Z6Z7; -.
DR SMR; Q7Z6Z7; -.
DR BioGRID; 115385; 611.
DR CORUM; Q7Z6Z7; -.
DR DIP; DIP-34362N; -.
DR ELM; Q7Z6Z7; -.
DR IntAct; Q7Z6Z7; 126.
DR MINT; Q7Z6Z7; -.
DR STRING; 9606.ENSP00000340648; -.
DR ChEMBL; CHEMBL4295881; -.
DR CarbonylDB; Q7Z6Z7; -.
DR GlyGen; Q7Z6Z7; 7 sites, 1 O-linked glycan (7 sites).
DR iPTMnet; Q7Z6Z7; -.
DR MetOSite; Q7Z6Z7; -.
DR PhosphoSitePlus; Q7Z6Z7; -.
DR SwissPalm; Q7Z6Z7; -.
DR BioMuta; HUWE1; -.
DR DMDM; 73915353; -.
DR CPTAC; CPTAC-217; -.
DR CPTAC; CPTAC-218; -.
DR EPD; Q7Z6Z7; -.
DR jPOST; Q7Z6Z7; -.
DR MassIVE; Q7Z6Z7; -.
DR MaxQB; Q7Z6Z7; -.
DR PaxDb; Q7Z6Z7; -.
DR PeptideAtlas; Q7Z6Z7; -.
DR PRIDE; Q7Z6Z7; -.
DR ProteomicsDB; 69472; -. [Q7Z6Z7-1]
DR ProteomicsDB; 69473; -. [Q7Z6Z7-2]
DR ProteomicsDB; 69474; -. [Q7Z6Z7-3]
DR ABCD; Q7Z6Z7; 2 sequenced antibodies.
DR Antibodypedia; 448; 174 antibodies from 35 providers.
DR DNASU; 10075; -.
DR Ensembl; ENST00000262854.11; ENSP00000262854.6; ENSG00000086758.16. [Q7Z6Z7-1]
DR Ensembl; ENST00000342160.7; ENSP00000340648.3; ENSG00000086758.16. [Q7Z6Z7-1]
DR Ensembl; ENST00000612484.4; ENSP00000479451.1; ENSG00000086758.16. [Q7Z6Z7-3]
DR GeneID; 10075; -.
DR KEGG; hsa:10075; -.
DR MANE-Select; ENST00000262854.11; ENSP00000262854.6; NM_031407.7; NP_113584.3.
DR UCSC; uc033eew.2; human. [Q7Z6Z7-1]
DR CTD; 10075; -.
DR DisGeNET; 10075; -.
DR GeneCards; HUWE1; -.
DR HGNC; HGNC:30892; HUWE1.
DR HPA; ENSG00000086758; Low tissue specificity.
DR MalaCards; HUWE1; -.
DR MIM; 300697; gene.
DR MIM; 309590; phenotype.
DR neXtProt; NX_Q7Z6Z7; -.
DR OpenTargets; ENSG00000086758; -.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA128394567; -.
DR VEuPathDB; HostDB:ENSG00000086758; -.
DR eggNOG; KOG0939; Eukaryota.
DR GeneTree; ENSGT00940000156319; -.
DR HOGENOM; CLU_000058_0_0_1; -.
DR InParanoid; Q7Z6Z7; -.
DR OMA; ADEMKYG; -.
DR OrthoDB; 25515at2759; -.
DR PhylomeDB; Q7Z6Z7; -.
DR TreeFam; TF323417; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q7Z6Z7; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q7Z6Z7; -.
DR SIGNOR; Q7Z6Z7; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 10075; 249 hits in 753 CRISPR screens.
DR ChiTaRS; HUWE1; human.
DR EvolutionaryTrace; Q7Z6Z7; -.
DR GeneWiki; HUWE1; -.
DR GenomeRNAi; 10075; -.
DR Pharos; Q7Z6Z7; Tbio.
DR PRO; PR:Q7Z6Z7; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q7Z6Z7; protein.
DR Bgee; ENSG00000086758; Expressed in skin of leg and 204 other tissues.
DR ExpressionAtlas; Q7Z6Z7; baseline and differential.
DR Genevisible; Q7Z6Z7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; IBA:GO_Central.
DR GO; GO:0016574; P:histone ubiquitination; IDA:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; IBA:GO_Central.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; IMP:UniProtKB.
DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; IDA:CACAO.
DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd14288; UBA_HUWE1; 1.
DR Gene3D; 3.30.720.50; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR010309; E3_Ub_ligase_DUF908.
DR InterPro; IPR010314; E3_Ub_ligase_DUF913.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR025527; HUWE1/Rev1_UBM.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR041918; UBA_HUWE1.
DR InterPro; IPR004170; WWE-dom.
DR InterPro; IPR037197; WWE_dom_sf.
DR Pfam; PF06012; DUF908; 1.
DR Pfam; PF06025; DUF913; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF14377; UBM; 3.
DR Pfam; PF02825; WWE; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF117839; SSF117839; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS50918; WWE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Biological rhythms;
KW Chromosomal rearrangement; Cytoplasm; Differentiation; Disease variant;
KW DNA damage; DNA repair; DNA-binding; Intellectual disability; Methylation;
KW Mitochondrion; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..4374
FT /note="E3 ubiquitin-protein ligase HUWE1"
FT /id="PRO_0000120340"
FT DOMAIN 1316..1355
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 1370..1389
FT /note="UIM"
FT /evidence="ECO:0000305"
FT DOMAIN 1603..1680
FT /note="WWE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00248"
FT DOMAIN 4038..4374
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 706..759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 978..1001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1014..1037
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1291..1320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1396..1415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1689..1735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2018..2065
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2262..2342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2356..2480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2694..2970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3036..3059
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3245..3267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3404..3424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3471..3512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3537..3568
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3737..3758
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3781..3848
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3894..3931
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 737..756
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1291..1310
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1699..1721
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2018..2035
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2036..2060
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2262..2295
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2384..2402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2406..2471
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2694..2718
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2719..2776
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2815..2887
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2905..2934
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3041..3059
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3245..3260
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3471..3502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3783..3799
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3813..3830
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3894..3911
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 4341
FT /note="Glycyl thioester intermediate"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TMY8"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TMY8"
FT MOD_RES 740
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1084
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1382
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 1722
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1907
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2035
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2266
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2267
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q7TMY8"
FT MOD_RES 2362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2365
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2532
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2554
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2584
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2595
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 2619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2751
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2826
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2833
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2835
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2861
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2887
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2888
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2889
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2918
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 3116
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3135
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3149
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q7TMY8"
FT MOD_RES 3555
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 3752
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3757
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 3759
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 3760
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 3816
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 3827
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 3830
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3906
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 3919
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 3924
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:24275569"
FT MOD_RES 3927
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 4271
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P51593"
FT VAR_SEQ 982..990
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_015272"
FT VAR_SEQ 3016..3031
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9205841"
FT /id="VSP_011146"
FT VARIANT 110
FT /note="R -> Q (in MRXST; dbSNP:rs1557036768)"
FT /evidence="ECO:0000269|PubMed:25985138,
FT ECO:0000269|PubMed:29180823"
FT /id="VAR_082247"
FT VARIANT 110
FT /note="R -> W (in MRXST; dbSNP:rs1057520538)"
FT /evidence="ECO:0000269|PubMed:25985138,
FT ECO:0000269|PubMed:27884935"
FT /id="VAR_082248"
FT VARIANT 115
FT /note="S -> F (in MRXST; dbSNP:rs1557036757)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082249"
FT VARIANT 483
FT /note="N -> S (in dbSNP:rs41307640)"
FT /id="VAR_061986"
FT VARIANT 660
FT /note="G -> R (in MRXST; dbSNP:rs1557006903)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082250"
FT VARIANT 669
FT /note="H -> Q (in MRXST; dbSNP:rs1557006873)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082251"
FT VARIANT 950
FT /note="V -> D (found in patients with autism spectrum
FT disorders; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:23092983"
FT /id="VAR_076253"
FT VARIANT 1328
FT /note="M -> V (in MRXST; dbSNP:rs1556978515)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082252"
FT VARIANT 2089
FT /note="I -> M (in MRXST; dbSNP:rs1556955128)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082253"
FT VARIANT 2981
FT /note="R -> H (in MRXST; dbSNP:rs121918526)"
FT /evidence="ECO:0000269|PubMed:18252223"
FT /id="VAR_045670"
FT VARIANT 3070
FT /note="R -> C (in MRXST; dbSNP:rs886041876)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082254"
FT VARIANT 3194
FT /note="F -> S (in MRXST)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082255"
FT VARIANT 4013
FT /note="R -> W (in MRXST; dbSNP:rs121918525)"
FT /evidence="ECO:0000269|PubMed:18252223"
FT /id="VAR_045671"
FT VARIANT 4023
FT /note="R -> C (in MRXST; dbSNP:rs1556914274)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082256"
FT VARIANT 4063
FT /note="R -> Q (in MRXST; increased protein levels in
FT patient cells)"
FT /evidence="ECO:0000269|PubMed:27130160"
FT /id="VAR_082257"
FT VARIANT 4069
FT /note="I -> F (in MRXST; dbSNP:rs1556913268)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082258"
FT VARIANT 4075
FT /note="N -> K (in MRXST; dbSNP:rs1556913258)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082259"
FT VARIANT 4106
FT /note="Y -> C (in MRXST; dbSNP:rs1556913180)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082260"
FT VARIANT 4157
FT /note="L -> V (in MRXST; dbSNP:rs1556912828)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082261"
FT VARIANT 4187
FT /note="R -> C (in MRXST; dbSNP:rs121918527)"
FT /evidence="ECO:0000269|PubMed:18252223"
FT /id="VAR_045672"
FT VARIANT 4244
FT /note="E -> D (in MRXST; dbSNP:rs1556910184)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082262"
FT VARIANT 4295
FT /note="K -> N (in MRXST)"
FT /evidence="ECO:0000269|PubMed:29180823"
FT /id="VAR_082263"
FT VARIANT 4310
FT /note="G -> R (in MRXST; decreased protein levels in
FT patient cells; dbSNP:rs1556909287)"
FT /evidence="ECO:0000269|PubMed:27130160"
FT /id="VAR_082264"
FT MUTAGEN 4268
FT /note="Y->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15567145"
FT MUTAGEN 4341
FT /note="C->A,D: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15567145,
FT ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:15989957,
FT ECO:0000269|PubMed:18488021"
FT CONFLICT 1111
FT /note="K -> N (in Ref. 5; BAC06833)"
FT /evidence="ECO:0000305"
FT CONFLICT 1124
FT /note="P -> L (in Ref. 1; AAV90838 and 5; BAC06833)"
FT /evidence="ECO:0000305"
FT CONFLICT 1190
FT /note="D -> H (in Ref. 5; BAC06833)"
FT /evidence="ECO:0000305"
FT CONFLICT 1962
FT /note="Missing (in Ref. 6; BAA20771)"
FT /evidence="ECO:0000305"
FT CONFLICT 2525
FT /note="H -> Y (in Ref. 5; BAC06833 and 9; AAF28950)"
FT /evidence="ECO:0000305"
FT CONFLICT 4022
FT /note="R -> L (in Ref. 10; AAH02602)"
FT /evidence="ECO:0000305"
FT HELIX 18..26
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 32..38
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 55..68
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 90..103
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 116..122
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 128..144
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 147..149
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 153..155
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 179..183
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 193..196
FT /evidence="ECO:0007829|PDB:7MOP"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 254..266
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 270..289
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 304..314
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 321..335
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 343..350
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 351..353
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 354..357
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 358..371
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 380..394
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 397..405
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 408..418
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 423..440
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 445..449
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 452..470
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 502..519
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 525..527
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 531..533
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 536..544
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 545..549
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 552..568
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 573..578
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 581..589
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 598..611
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 612..614
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 616..623
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 626..630
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 631..635
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 637..639
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 640..643
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 647..649
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 654..669
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 671..673
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 674..693
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 766..782
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 786..788
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 789..795
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 799..804
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 805..807
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 813..817
FT /evidence="ECO:0007829|PDB:7MOP"
FT HELIX 819..835
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 839..852
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 856..858
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 863..865
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 869..875
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 883..885
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 887..889
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 891..910
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 915..925
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 928..955
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 958..961
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 968..974
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1043..1075
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1098..1114
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1125..1142
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1151..1159
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1160..1162
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1163..1175
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 1176..1179
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1182..1185
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1195..1210
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1212..1215
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1238..1254
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1257..1259
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1263..1266
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1267..1287
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1319..1329
FT /evidence="ECO:0007829|PDB:2EKK"
FT HELIX 1332..1341
FT /evidence="ECO:0007829|PDB:2EKK"
FT HELIX 1345..1353
FT /evidence="ECO:0007829|PDB:2EKK"
FT HELIX 1417..1426
FT /evidence="ECO:0007829|PDB:7MOP"
FT HELIX 1433..1453
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1455..1457
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1458..1471
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1474..1497
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1511..1519
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1521..1539
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1541..1550
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1553..1574
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1583..1607
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1612..1614
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1616..1621
FT /evidence="ECO:0007829|PDB:6MIW"
FT TURN 1622..1625
FT /evidence="ECO:0007829|PDB:6MIW"
FT STRAND 1626..1629
FT /evidence="ECO:0007829|PDB:6MIW"
FT HELIX 1632..1643
FT /evidence="ECO:0007829|PDB:6MIW"
FT STRAND 1647..1653
FT /evidence="ECO:0007829|PDB:6MIW"
FT STRAND 1656..1661
FT /evidence="ECO:0007829|PDB:6MIW"
FT TURN 1662..1665
FT /evidence="ECO:0007829|PDB:6MIW"
FT STRAND 1666..1669
FT /evidence="ECO:0007829|PDB:6MIW"
FT TURN 1670..1672
FT /evidence="ECO:0007829|PDB:6MIW"
FT STRAND 1675..1681
FT /evidence="ECO:0007829|PDB:6MIW"
FT HELIX 1752..1767
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1772..1785
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1789..1797
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1800..1806
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1809..1811
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1816..1828
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1831..1847
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1863..1865
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1867..1873
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1875..1880
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1882..1892
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1893..1895
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1901..1903
FT /evidence="ECO:0007829|PDB:7MOP"
FT TURN 1905..1907
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1908..1916
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1917..1920
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 1924..1927
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1940..1953
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 1976..1991
FT /evidence="ECO:0007829|PDB:5C6H"
FT STRAND 2064..2066
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2068..2081
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2083..2091
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2108..2114
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2128..2141
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2147..2165
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2170..2187
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2211..2218
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2221..2226
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2228..2231
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2239..2258
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 2517..2519
FT /evidence="ECO:0007829|PDB:7MOP"
FT HELIX 2647..2658
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2662..2695
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 2958..2960
FT /evidence="ECO:0007829|PDB:2MUL"
FT HELIX 2970..2975
FT /evidence="ECO:0007829|PDB:2MUL"
FT HELIX 2978..2988
FT /evidence="ECO:0007829|PDB:2MUL"
FT HELIX 3183..3190
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3191..3193
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 3198..3200
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3202..3212
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3216..3233
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 3289..3293
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 3296..3303
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 3322..3324
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 3326..3328
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3329..3345
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3388..3397
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3431..3437
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3441..3445
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3447..3460
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3576..3587
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3595..3609
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3613..3649
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3708..3710
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3711..3714
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3719..3734
FT /evidence="ECO:0007829|PDB:7JQ9"
FT HELIX 3854..3868
FT /evidence="ECO:0007829|PDB:7JQ9"
FT TURN 3869..3871
FT /evidence="ECO:0007829|PDB:7JQ9"
FT STRAND 3876..3879
FT /evidence="ECO:0007829|PDB:7AZX"
FT STRAND 3885..3889
FT /evidence="ECO:0007829|PDB:7AZX"
FT HELIX 3952..3972
FT /evidence="ECO:0007829|PDB:5LP8"
FT TURN 3977..3979
FT /evidence="ECO:0007829|PDB:5LP8"
FT HELIX 3983..3991
FT /evidence="ECO:0007829|PDB:5LP8"
FT HELIX 3994..4008
FT /evidence="ECO:0007829|PDB:3H1D"
FT TURN 4009..4011
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4016..4021
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4023..4025
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4026..4034
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4041..4043
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4044..4050
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4061..4072
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4076..4078
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4080..4083
FT /evidence="ECO:0007829|PDB:3H1D"
FT TURN 4085..4087
FT /evidence="ECO:0007829|PDB:3G1N"
FT STRAND 4088..4093
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4095..4099
FT /evidence="ECO:0007829|PDB:3G1N"
FT HELIX 4103..4120
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4130..4137
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4143..4145
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4146..4149
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4151..4162
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4165..4167
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4168..4170
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4172..4175
FT /evidence="ECO:0007829|PDB:3H1D"
FT TURN 4176..4178
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4181..4183
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4186..4189
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4193..4197
FT /evidence="ECO:0007829|PDB:3H1D"
FT TURN 4200..4202
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4203..4215
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4217..4219
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4220..4233
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4236..4239
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4244..4252
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4259..4264
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4266..4271
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4276..4287
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4290..4301
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4302..4304
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4311..4313
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4317..4320
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4323..4328
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4337..4339
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4340..4342
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4344..4348
FT /evidence="ECO:0007829|PDB:3H1D"
FT HELIX 4353..4365
FT /evidence="ECO:0007829|PDB:3H1D"
FT STRAND 4370..4372
FT /evidence="ECO:0007829|PDB:5LP8"
SQ SEQUENCE 4374 AA; 481891 MW; FA9D3A7712F6393B CRC64;
MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR
FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT
TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA
ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM
ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI
LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP
VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG
DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ
RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL
KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV
LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG
SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH
AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI
LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV
LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH
AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL
PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS MDASTQGLLE GIGLDGDTLA
PMETDEPTAS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR
QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP
MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD
AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF TCIKNLWNRK
PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEDTGQEEGG SRREPQVNQQ
QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA
MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT
DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL
PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL
LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF
DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML
TLLRVPRLNK NSKNSNGQEL EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET
KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS
TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG
SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN
AVQLVKTTPL KPSPLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG VMTQEVGQLL
QDMGDDVYQQ YRSLTRQSSD FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR
DGKKDKEGDR ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE
LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL
GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG
LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ
GASQDSSSNQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ
EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR
EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD
DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV
RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL
LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT
LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE
ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS TDAATSESKE
TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL LMPVEPEELG PTRPSGEAET
TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTSAAGSS
EQPRAGSSTP GDAPPAVAEV QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS
RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS
TNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA SSDTPMDPVT
FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ EARQRQLMHE RLFGHSSTSA
LSAILRSPAF TSRLSGNRGV QYTRLAVQRG GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL
LDHEALSCLL VLLFVDEPKL NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI
ETPKLTTSEE KGKKSSKSCG SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI
FQIQRSGGRK HTEKHASGGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH FTQQRTKETN
CESDRERGNK ACSPCSSQSS SSGICTDFWD LLVKLDNMNV SRKGKNSVKS VPVSAGGEGE
TSPYSLEASP LGQLMNMLSH PVIRRSSLLT EKLLRLLSLI SIALPENKVS EAQANSGSGA
SSTTTATSTT STTTTTAAST TPTPPTAPTP VTSAPALVAA TAISTIVVAA STTVTTPTTA
TTTVSISPTT KGSKSPAKVS DGGSSSTDFK MVSSGLTENQ LQLSVEVLTS HSCSEEGLED
AANVLLQLSR GDSGTRDTVL KLLLNGARHL GYTLCKQIGT LLAELREYNL EQQRRAQCET
LSPDGLPEEQ PQTTKLKGKM QSRFDMAENV VIVASQKRPL GGRELQLPSM SMLTSKTSTQ
KFFLRVLQVI IQLRDDTRRA NKKAKQTGRL GSSGLGSASS IQAAVRQLEA EADAIIQMVR
EGQRARRQQQ AATSESSQSE ASVRREESPM DVDQPSPSAQ DTQSIASDGT PQGEKEKEER
PPELPLLSEQ LSLDELWDML GECLKELEES HDQHAVLVLQ PAVEAFFLVH ATERESKPPV
RDTRESQLAH IKDEPPPLSP APLTPATPSS LDPFFSREPS SMHISSSLPP DTQKFLRFAE
THRTVLNQIL RQSTTHLADG PFAVLVDYIR VLDFDVKRKY FRQELERLDE GLRKEDMAVH
VRRDHVFEDS YRELHRKSPE EMKNRLYIVF EGEEGQDAGG LLREWYMIIS REMFNPMYAL
FRTSPGDRVT YTINPSSHCN PNHLSYFKFV GRIVAKAVYD NRLLECYFTR SFYKHILGKS
VRYTDMESED YHFYQGLVYL LENDVSTLGY DLTFSTEVQE FGVCEVRDLK PNGANILVTE
ENKKEYVHLV CQMRMTGAIR KQLAAFLEGF YEIIPKRLIS IFTEQELELL ISGLPTIDID
DLKSNTEYHK YQSNSIQIQW FWRALRSFDQ ADRAKFLQFV TGTSKVPLQG FAALEGMNGI
QKFQIHRDDR STDRLPSAHT CFNQLDLPAY ESFEKLRHML LLAIQECSEG FGLA
