NED4L_HUMAN
ID NED4L_HUMAN Reviewed; 975 AA.
AC Q96PU5; O43165; Q3LSM7; Q7Z5F1; Q7Z5F2; Q7Z5N3; Q8N5A7; Q8WUU9; Q9BW58;
AC Q9H2W4; Q9NT88;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=E3 ubiquitin-protein ligase NEDD4-like;
DE EC=2.3.2.26 {ECO:0000269|PubMed:28820317};
DE EC=2.3.2.36 {ECO:0000269|PubMed:33608556};
DE AltName: Full=HECT-type E3 ubiquitin transferase NED4L;
DE AltName: Full=NEDD4.2;
DE AltName: Full=Nedd4-2;
GN Name=NEDD4L {ECO:0000303|PubMed:11840194};
GN Synonyms=KIAA0439 {ECO:0000303|PubMed:11244092}, NEDL3;
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 4), AND ALTERNATIVE SPLICING.
RX PubMed=11840194; DOI=10.1038/sj.ejhg.5200747;
RA Chen H., Ross C.A., Wang N., Huo Y., MacKinnon D.F., Potash J.B.,
RA Simpson S.G., McMahon F.J., DePaulo J.R. Jr., McInnis M.G.;
RT "NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is
RT a homologue of the mouse Nedd4-2 gene.";
RL Eur. J. Hum. Genet. 9:922-930(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH SCNN1A; SCNN1B
RP AND SCNN1G.
RC TISSUE=Kidney;
RX PubMed=14556380; DOI=10.1016/s1631-0691(03)00154-9;
RA Malbert-Colas L., Nicolas G., Galand C., Lecomte M.-C., Dhermy D.;
RT "Identification of new partners of the epithelial sodium channel alpha
RT subunit.";
RL C. R. Biol. 326:615-624(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 6 AND 7), TISSUE SPECIFICITY, AND
RP INDUCTION.
RC TISSUE=Prostate;
RX PubMed=14615060; DOI=10.1016/j.mce.2003.08.009;
RA Qi H., Grenier J., Fournier A., Labrie C.;
RT "Androgens differentially regulate the expression of NEDD4L transcripts in
RT LNCaP human prostate cancer cells.";
RL Mol. Cell. Endocrinol. 210:51-62(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
RA Okamoto Y., Miyazaki K., Sakamoto M., Kato C., Nakagawara A.;
RT "Homo sapiens NEDD4-like ubiquitin ligase 3.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8).
RA Qi H., Labrie C.;
RT "NEDD4L transcripts expressed in human prostate cells.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 101-975 (ISOFORM 5).
RC TISSUE=Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8).
RC TISSUE=Brain;
RX PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VIII. 78
RT new cDNA clones from brain which code for large proteins in vitro.";
RL DNA Res. 4:307-313(1997).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 52-975 (ISOFORM 3).
RC TISSUE=Testis;
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 [11]
RP PROTEIN SEQUENCE OF 448-462, INTERACTION WITH YWHAB; YWHAG; YWHAE; YWHAQ
RP AND YWHAH, PHOSPHORYLATION AT SER-448, MUTAGENESIS OF SER-448, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=15677482; DOI=10.1074/jbc.m412884200;
RA Ichimura T., Yamamura H., Sasamoto K., Tominaga Y., Taoka M., Kakiuchi K.,
RA Shinkawa T., Takahashi N., Shimada S., Isobe T.;
RT "14-3-3 proteins modulate the expression of epithelial Na+ channels by
RT phosphorylation-dependent interaction with Nedd4-2 ubiquitin ligase.";
RL J. Biol. Chem. 280:13187-13194(2005).
RN [12]
RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
RX PubMed=11046148; DOI=10.1128/mcb.20.22.8526-8535.2000;
RA Winberg G., Matskova L., Chen F., Plant P., Rotin D., Gish G., Ingham R.,
RA Ernberg I., Pawson T.;
RT "Latent membrane protein 2A of Epstein-Barr virus binds WW domain E3
RT protein-ubiquitin ligases that ubiquitinate B-cell tyrosine kinases.";
RL Mol. Cell. Biol. 20:8526-8535(2000).
RN [13]
RP INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.
RX PubMed=11244092; DOI=10.1074/jbc.c000906200;
RA Harvey K.F., Dinudom A., Cook D.I., Kumar S.;
RT "The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial
RT sodium channel.";
RL J. Biol. Chem. 276:8597-8601(2001).
RN [14]
RP INTERACTION WITH SGK1 AND SCNN1A, AND PHOSPHORYLATION.
RX PubMed=11696533; DOI=10.1074/jbc.c100623200;
RA Snyder P.M., Olson D.R., Thomas B.C.;
RT "Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated
RT inhibition of the epithelial Na+ channel.";
RL J. Biol. Chem. 277:5-8(2002).
RN [15]
RP ACTIVITY REGULATION, AND INTERACTION WITH NDFIP1.
RX PubMed=11748237; DOI=10.1074/jbc.m110443200;
RA Harvey K.F., Shearwin-Whyatt L.M., Fotia A., Parton R.G., Kumar S.;
RT "N4WBP5, a potential target for ubiquitination by the Nedd4 family of
RT proteins, is a novel Golgi-associated protein.";
RL J. Biol. Chem. 277:9307-9317(2002).
RN [16]
RP FUNCTION.
RX PubMed=12911626; DOI=10.1046/j.1471-4159.2003.01937.x;
RA Boehmer C., Henke G., Schniepp R., Palmada M., Rothstein J.D., Broeer S.,
RA Lang F.;
RT "Regulation of the glutamate transporter EAAT1 by the ubiquitin ligase
RT Nedd4-2 and the serum and glucocorticoid-inducible kinase isoforms SGK1/3
RT and protein kinase B.";
RL J. Neurochem. 86:1181-1188(2003).
RN [17]
RP FUNCTION, MUTAGENESIS OF CYS-942, AND INTERACTION WITH SCN5A.
RX PubMed=15217910; DOI=10.1161/01.res.0000136816.05109.89;
RA van Bemmelen M.X., Rougier J.-S., Gavillet B., Apotheloz F., Daidie D.,
RA Tateyama M., Rivolta I., Thomas M.A., Kass R.S., Staub O., Abriel H.;
RT "Cardiac voltage-gated sodium channel Nav1.5 is regulated by Nedd4-2
RT mediated ubiquitination.";
RL Circ. Res. 95:284-291(2004).
RN [18]
RP FUNCTION, INTERACTION WITH CLCN5, AND INDUCTION.
RX PubMed=15489223; DOI=10.1074/jbc.m411491200;
RA Hryciw D.H., Ekberg J., Lee A., Lensink I.L., Kumar S., Guggino W.B.,
RA Cook D.I., Pollock C.A., Poronnik P.;
RT "Nedd4-2 functionally interacts with ClC-5: involvement in constitutive
RT albumin endocytosis in proximal tubule cells.";
RL J. Biol. Chem. 279:54996-55007(2004).
RN [19]
RP PHOSPHORYLATION AT SER-342; THR-367 AND SER-448.
RX PubMed=15328345; DOI=10.1074/jbc.m407858200;
RA Snyder P.M., Olson D.R., Kabra R., Zhou R., Steines J.C.;
RT "cAMP and serum and glucocorticoid-inducible kinase (SGK) regulate the
RT epithelial Na(+) channel through convergent phosphorylation of Nedd4-2.";
RL J. Biol. Chem. 279:45753-45758(2004).
RN [20]
RP FUNCTION.
RX PubMed=15040001; DOI=10.1002/jcp.10430;
RA Henke G., Maier G., Wallisch S., Boehmer C., Lang F.;
RT "Regulation of the voltage gated K+ channel Kv1.3 by the ubiquitin ligase
RT Nedd4-2 and the serum and glucocorticoid inducible kinase SGK1.";
RL J. Cell. Physiol. 199:194-199(2004).
RN [21]
RP INTERACTION WITH SCN2A; SCN3A AND SCN5A.
RX PubMed=15548568; DOI=10.1152/ajpcell.00460.2004;
RA Rougier J.-S., van Bemmelen M.X., Bruce M.C., Jespersen T., Gavillet B.,
RA Apotheloz F., Cordonier S., Staub O., Rotin D., Abriel H.;
RT "Molecular determinants of voltage-gated sodium channel regulation by the
RT Nedd4/Nedd4-like proteins.";
RL Am. J. Physiol. 288:C692-C701(2005).
RN [22]
RP FUNCTION, INTERACTION WITH SMAD2; SMAD3; SMAD6 AND SMAD7, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15496141; DOI=10.1042/bj20040738;
RA Kuratomi G., Komuro A., Goto K., Shinozaki M., Miyazawa K., Miyazono K.,
RA Imamura T.;
RT "NEDD4-2 (neural precursor cell expressed, developmentally down-regulated
RT 4-2) negatively regulates TGF-beta (transforming growth factor-beta)
RT signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta
RT type I receptor.";
RL Biochem. J. 386:461-470(2005).
RN [23]
RP FUNCTION.
RX PubMed=15576372; DOI=10.1074/jbc.m411053200;
RA Zhou R., Snyder P.M.;
RT "Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase
RT (SGK) ubiquitination and degradation.";
RL J. Biol. Chem. 280:4518-4523(2005).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-479, 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 [25]
RP SUBCELLULAR LOCATION.
RX PubMed=18819914; DOI=10.1074/jbc.m804120200;
RA Putz U., Howitt J., Lackovic J., Foot N., Kumar S., Silke J., Tan S.S.;
RT "Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal
RT secretion of Nedd4 family proteins.";
RL J. Biol. Chem. 283:32621-32627(2008).
RN [26]
RP IDENTIFICATION BY 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-318; SER-342; SER-446;
RP SER-449; SER-464; SER-479 AND SER-487, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [28]
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 [29]
RP INTERACTION WITH NPC2, AND TISSUE SPECIFICITY.
RX PubMed=19664597; DOI=10.1016/j.bbrc.2009.07.158;
RA Araki N., Ishigami T., Ushio H., Minegishi S., Umemura M., Miyagi Y.,
RA Aoki I., Morinaga H., Tamura K., Toya Y., Uchino K., Umemura S.;
RT "Identification of NPC2 protein as interaction molecule with C2 domain of
RT human Nedd4L.";
RL Biochem. Biophys. Res. Commun. 388:290-296(2009).
RN [30]
RP ACTIVATION BY NDFIP1 AND NDFIP2, AND AUTOUBIQUITINATION.
RX PubMed=19343052; DOI=10.1038/embor.2009.30;
RA Mund T., Pelham H.R.;
RT "Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP
RT proteins.";
RL EMBO Rep. 10:501-507(2009).
RN [31]
RP FUNCTION AS A UBIQUITIN-PROTEIN LIGASE FOR TNK2, AND INTERACTION WITH TNK2.
RX PubMed=19144635; DOI=10.1074/jbc.m806877200;
RA Chan W., Tian R., Lee Y.-F., Sit S.T., Lim L., Manser E.;
RT "Down-regulation of active ACK1 is mediated by association with the E3
RT ubiquitin ligase Nedd4-2.";
RL J. Biol. Chem. 284:8185-8194(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-446, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP PHOSPHORYLATION AT SER-342 AND SER-449, AND INTERACTION WITH WNK1.
RX PubMed=20525693; DOI=10.1074/jbc.m110.103432;
RA Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S.,
RA Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.;
RT "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium
RT channel are regulated by multiple with no lysine (WNK) family members.";
RL J. Biol. Chem. 285:25161-25167(2010).
RN [34]
RP INTERACTION WITH TNK2.
RX PubMed=20086093; DOI=10.1128/mcb.00013-10;
RA Lin Q., Wang J., Childress C., Sudol M., Carey D.J., Yang W.;
RT "HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal
RT growth factor (EGF)-induced degradation of EGF receptor and ACK.";
RL Mol. Cell. Biol. 30:1541-1554(2010).
RN [35]
RP PHOSPHORYLATION BY SGK1, AND INTERACTION WITH SGK1.
RX PubMed=20730100; DOI=10.1371/journal.pone.0012163;
RA Wiemuth D., Lott J.S., Ly K., Ke Y., Teesdale-Spittle P., Snyder P.M.,
RA McDonald F.J.;
RT "Interaction of serum- and glucocorticoid regulated kinase 1 (SGK1) with
RT the WW-domains of Nedd4-2 is required for epithelial sodium channel
RT regulation.";
RL PLoS ONE 5:E12163-E12163(2010).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-479 AND SER-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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 [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-479; SER-483 AND SER-487, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [39]
RP INTERACTION WITH KCNQ1.
RX PubMed=22024150; DOI=10.1016/j.hrthm.2011.10.026;
RA Krzystanek K., Rasmussen H.B., Grunnet M., Staub O., Olesen S.P.,
RA Abriel H., Jespersen T.;
RT "Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation
RT of KCNQ1 potassium channels.";
RL Heart Rhythm 9:440-448(2012).
RN [40]
RP INTERACTION WITH ARRDC4.
RX PubMed=23236378; DOI=10.1371/journal.pone.0050557;
RA Shea F.F., Rowell J.L., Li Y., Chang T.H., Alvarez C.E.;
RT "Mammalian alpha arrestins link activated seven transmembrane receptors to
RT Nedd4 family e3 ubiquitin ligases and interact with beta arrestins.";
RL PLoS ONE 7:E50557-E50557(2012).
RN [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [42]
RP INTERACTION WITH PRRG4.
RX PubMed=23873930; DOI=10.1074/jbc.m113.484683;
RA Yazicioglu M.N., Monaldini L., Chu K., Khazi F.R., Murphy S.L., Huang H.,
RA Margaritis P., High K.A.;
RT "Cellular localization and characterization of cytosolic binding partners
RT for Gla domain-containing proteins PRRG4 and PRRG2.";
RL J. Biol. Chem. 288:25908-25914(2013).
RN [43]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23999003; DOI=10.1016/j.jdermsci.2013.07.010;
RA Yoo J.C., Lim T.Y., Park J.S., Hah Y.S., Park N., Hong S.G., Park J.Y.,
RA Yoon T.J.;
RT "SYT14L, especially its C2 domain, is involved in regulating melanocyte
RT differentiation.";
RL J. Dermatol. Sci. 72:246-251(2013).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-312; THR-318; SER-448;
RP SER-475; SER-479 AND SER-483, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [45]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [46]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH NDFIP1 AND NDFIP2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26363003; DOI=10.1042/bj20141282;
RA Kang Y., Guo J., Yang T., Li W., Zhang S.;
RT "Regulation of the human ether-a-go-go-related gene (hERG) potassium
RT channel by Nedd4 family interacting proteins (Ndfips).";
RL Biochem. J. 472:71-82(2015).
RN [47]
RP FUNCTION IN UBIQUITINATION OF BRAT1.
RX PubMed=25631046; DOI=10.1074/jbc.m114.613687;
RA Low L.H., Chow Y.L., Li Y., Goh C.P., Putz U., Silke J., Ouchi T.,
RA Howitt J., Tan S.S.;
RT "Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination
RT and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during
RT the DNA damage response.";
RL J. Biol. Chem. 290:7141-7150(2015).
RN [48]
RP INTERACTION WITH LDLRAD3.
RX PubMed=26854353; DOI=10.1021/acs.biochem.5b01218;
RA Noyes N.C., Hampton B., Migliorini M., Strickland D.K.;
RT "Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by
RT LRAD3.";
RL Biochemistry 55:1204-1213(2016).
RN [49]
RP FUNCTION, INTERACTION WITH USP36, DEUBIQUITINATION BY USP36, AND
RP MUTAGENESIS OF CYS-942.
RX PubMed=27445338; DOI=10.1074/jbc.m116.722637;
RA Anta B., Martin-Rodriguez C., Gomis-Perez C., Calvo L., Lopez-Benito S.,
RA Calderon-Garcia A.A., Vicente-Garcia C., Villarroel A., Arevalo J.C.;
RT "Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell-
RT expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the
RT Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3
RT (Kv7.2/3).";
RL J. Biol. Chem. 291:19132-19145(2016).
RN [50]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN PVNH7, VARIANTS PVNH7
RP CYS-679; HIS-694; LYS-893 AND GLN-897, AND CHARACTERIZATION OF VARIANTS
RP PVNH7 HIS-694; LYS-893 AND GLN-897.
RX PubMed=27694961; DOI=10.1038/ng.3676;
RG Deciphering Developmental Disorders study;
RA Broix L., Jagline H., Ivanova L.E., Schmucker S., Drouot N.,
RA Clayton-Smith J., Pagnamenta A.T., Metcalfe K.A., Isidor B., Louvier U.W.,
RA Poduri A., Taylor J.C., Tilly P., Poirier K., Saillour Y., Lebrun N.,
RA Stemmelen T., Rudolf G., Muraca G., Saintpierre B., Elmorjani A., Moise M.,
RA Weirauch N.B., Guerrini R., Boland A., Olaso R., Masson C., Tripathy R.,
RA Keays D., Beldjord C., Nguyen L., Godin J., Kini U., Nischke P.,
RA Deleuze J.F., Bahi-Buisson N., Sumara I., Hinckelmann M.V., Chelly J.;
RT "Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway
RT deregulation and cause periventricular nodular heterotopia.";
RL Nat. Genet. 48:1349-1358(2016).
RN [51]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28820317; DOI=10.1080/15384101.2017.1361063;
RA Nazio F., Carinci M., Cecconi F.;
RT "ULK1 ubiquitylation is regulated by phosphorylation on its carboxy
RT terminus.";
RL Cell Cycle 16:1744-1747(2017).
RN [52]
RP FUNCTION.
RX PubMed=31959741; DOI=10.1038/s41419-020-2242-5;
RA Lee D.E., Yoo J.E., Kim J., Kim S., Kim S., Lee H., Cheong H.;
RT "NEDD4L downregulates autophagy and cell growth by modulating ULK1 and a
RT glutamine transporter.";
RL Cell Death Dis. 11:38-38(2020).
RN [53]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33608556; DOI=10.1038/s41467-021-21456-1;
RA Gao P., Ma X., Yuan M., Yi Y., Liu G., Wen M., Jiang W., Ji R., Zhu L.,
RA Tang Z., Yu Q., Xu J., Yang R., Xia S., Yang M., Pan J., Yuan H., An H.;
RT "E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-
RT linked cysteine ubiquitination of TRAF3.";
RL Nat. Commun. 12:1194-1194(2021).
RN [54]
RP VARIANTS LEU-355 AND ARG-497.
RX PubMed=15140763; DOI=10.1152/ajprenal.00353.2003;
RA Fouladkou F., Alikhani-Koopaei R., Vogt B., Flores S.Y., Malbert-Colas L.,
RA Lecomte M.-C., Loffing J., Frey F.J., Frey B.M., Staub O.;
RT "A naturally occurring human Nedd4-2 variant displays impaired ENaC
RT regulation in Xenopus laevis oocytes.";
RL Am. J. Physiol. 287:F550-F561(2004).
RN [55] {ECO:0007744|PDB:3JVZ, ECO:0007744|PDB:3JW0}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 596-975, INTERACTION WITH UBE2D2,
RP AND FUNCTION.
RX PubMed=20064473; DOI=10.1016/j.molcel.2009.11.010;
RA Kamadurai H.B., Kamadurai H.B., Souphron J., Scott D.C., Duda D.M.,
RA Miller D.J., Stringer D., Piper R.C., Schulman B.A.;
RT "Insights into ubiquitin transfer cascades from a structure of a UbcH5B
RT approximately ubiquitin-HECT(NEDD4L) complex.";
RL Mol. Cell 36:1095-1102(2009).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates the
CC polyubiquitination of lysine and cysteine residues on target proteins
CC and is thereby implicated in the regulation of various signaling
CC pathways including autophagy, innate immunity or DNA repair
CC (PubMed:31959741, PubMed:33608556, PubMed:20064473). Inhibits TGF-beta
CC signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-
CC dependent degradation (PubMed:15496141). Downregulates autophagy and
CC cell growth by ubiquitinating and reducing cellular ULK1 or ASCT2
CC levels (PubMed:28820317, PubMed:31959741). Promotes ubiquitination and
CC internalization of various plasma membrane channels such as ENaC,
CC SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8,
CC KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5
CC (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and
CC degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this
CC ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).
CC Plays a role in dendrite formation by melanocytes (PubMed:23999003).
CC Involved in the regulation of TOR signaling (PubMed:27694961).
CC Ubiquitinates and regulates protein levels of NTRK1 once this one is
CC activated by NGF (PubMed:27445338). Plays a role in antiviral innate
CC immunity by catalyzing 'Lys-29'-linked cysteine ubiquitination of
CC TRAF3, resulting in enhanced 'Lys-48' and 'Lys-63'-linked
CC ubiquitination of TRAF3 (PubMed:33608556).
CC {ECO:0000250|UniProtKB:Q8CFI0, ECO:0000269|PubMed:12911626,
CC ECO:0000269|PubMed:15040001, ECO:0000269|PubMed:15217910,
CC ECO:0000269|PubMed:15489223, ECO:0000269|PubMed:15496141,
CC ECO:0000269|PubMed:15576372, ECO:0000269|PubMed:19144635,
CC ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:25631046,
CC ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:27445338,
CC ECO:0000269|PubMed:27694961, ECO:0000269|PubMed:33608556}.
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:28820317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-S-ubiquitinyl-L-cysteine.; EC=2.3.2.36;
CC Evidence={ECO:0000269|PubMed:33608556};
CC -!- ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding.
CC {ECO:0000269|PubMed:11748237, ECO:0000269|PubMed:26363003}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with UBE2E3 (By similarity). Interacts with NDFIP1;
CC this interaction activates the E3 ubiquitin-protein ligase
CC (PubMed:11748237, PubMed:26363003). Interacts with NDFIP2; this
CC interaction activates the E3 ubiquitin-protein ligase
CC (PubMed:26363003). Interacts (via WW domains) with SCNN1A
CC (PubMed:11696533, PubMed:11244092, PubMed:14556380). Interacts (via WW
CC domains) with SCNN1B (PubMed:11244092, PubMed:14556380). Interacts (via
CC WW domains) with SCNN1G (PubMed:11244092, PubMed:14556380). Interacts
CC (via WW domains) with SCN1A (By similarity). Interacts (via WW domains)
CC with SCN2A (PubMed:15548568). Interacts (via WW domains) with SCN3A
CC (PubMed:15548568). Interacts (via WW domains) with SCN5A
CC (PubMed:15217910, PubMed:15548568). Interacts (via WW domains) with
CC SCN8A (By similarity). Interacts (via WW domains) with SCN9A (By
CC similarity). Interacts (via WW domains) with SCN10A (By similarity).
CC Interacts (via WW domains) with CLCN5 (PubMed:15489223). Interacts with
CC SMAD2 (PubMed:15496141). Interacts with SMAD3 (PubMed:15496141).
CC Interacts with SMAD6 (PubMed:15496141). Interacts with SMAD7
CC (PubMed:15496141). The phosphorylated form interacts with 14-3-3
CC proteins (PubMed:15677482). Interacts with TNK2 (PubMed:19144635,
CC PubMed:20086093). Interacts with WNK1 (PubMed:20525693). Interacts with
CC SGK1 (PubMed:11696533, PubMed:20730100). Interacts (via C2 domain) with
CC NPC2 (PubMed:19664597). Interacts with ARRDC4 (PubMed:23236378).
CC Interacts with KCNQ1; promotes internalization of KCNQ1
CC (PubMed:22024150). Interacts (via domains WW1, 3 and 4) with USP36; the
CC interaction inhibits ubiquitination of, at least, NTRK1, KCNQ2 and
CC KCNQ3 by NEDD4L (PubMed:27445338). Interacts with PRRG4 (via
CC cytoplasmic domain) (PubMed:23873930). Interacts with LDLRAD3; the
CC interaction is direct (PubMed:26854353). Interacts with UBE2D2
CC (PubMed:20064473). {ECO:0000250|UniProtKB:Q8CFI0,
CC ECO:0000269|PubMed:11244092, ECO:0000269|PubMed:11696533,
CC ECO:0000269|PubMed:11748237, ECO:0000269|PubMed:14556380,
CC ECO:0000269|PubMed:15217910, ECO:0000269|PubMed:15489223,
CC ECO:0000269|PubMed:15496141, ECO:0000269|PubMed:15548568,
CC ECO:0000269|PubMed:15677482, ECO:0000269|PubMed:19144635,
CC ECO:0000269|PubMed:19664597, ECO:0000269|PubMed:20064473,
CC ECO:0000269|PubMed:20086093, ECO:0000269|PubMed:20525693,
CC ECO:0000269|PubMed:20730100, ECO:0000269|PubMed:22024150,
CC ECO:0000269|PubMed:23236378, ECO:0000269|PubMed:23873930,
CC ECO:0000269|PubMed:26363003, ECO:0000269|PubMed:26854353,
CC ECO:0000269|PubMed:27445338}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
CC {ECO:0000269|PubMed:11046148}.
CC -!- INTERACTION:
CC Q96PU5; Q15038: DAZAP2; NbExp=3; IntAct=EBI-717962, EBI-724310;
CC Q96PU5; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-717962, EBI-720768;
CC Q96PU5; O14669: PRRG2; NbExp=2; IntAct=EBI-717962, EBI-9824765;
CC Q96PU5; Q9BZD6: PRRG4; NbExp=2; IntAct=EBI-717962, EBI-3918643;
CC Q96PU5; P49281: SLC11A2; NbExp=2; IntAct=EBI-717962, EBI-4319335;
CC Q96PU5-2; Q96B67: ARRDC3; NbExp=5; IntAct=EBI-6955201, EBI-2875665;
CC Q96PU5-2; Q15038: DAZAP2; NbExp=3; IntAct=EBI-6955201, EBI-724310;
CC Q96PU5-5; O15105: SMAD7; NbExp=3; IntAct=EBI-7196393, EBI-3861591;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15496141,
CC ECO:0000269|PubMed:18819914, ECO:0000269|PubMed:27694961}. Golgi
CC apparatus {ECO:0000269|PubMed:26363003}. Endosome, multivesicular body
CC {ECO:0000269|PubMed:26363003}. Note=May be recruited to exosomes by
CC NDFIP1.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=Nedd4-2c;
CC IsoId=Q96PU5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PU5-2; Sequence=VSP_015448;
CC Name=3; Synonyms=NEDD4Le;
CC IsoId=Q96PU5-3; Sequence=VSP_015447;
CC Name=4; Synonyms=NEDD4La, NEDD4Lb, NEDD4Lf;
CC IsoId=Q96PU5-4; Sequence=VSP_015444;
CC Name=5; Synonyms=NEDD4Ld;
CC IsoId=Q96PU5-5; Sequence=VSP_043848;
CC Name=6; Synonyms=NEDD4Lh;
CC IsoId=Q96PU5-6; Sequence=VSP_015446, VSP_043848;
CC Name=7; Synonyms=NEDD4Lg;
CC IsoId=Q96PU5-7; Sequence=VSP_015446;
CC Name=8;
CC IsoId=Q96PU5-9; Sequence=VSP_015444, VSP_043848;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC prostate, pancreas, and kidney (PubMed:14615060, PubMed:15496141,
CC PubMed:19664597). Expressed in melanocytes (PubMed:23999003).
CC {ECO:0000269|PubMed:14615060, ECO:0000269|PubMed:15496141,
CC ECO:0000269|PubMed:19664597, ECO:0000269|PubMed:23999003}.
CC -!- INDUCTION: By androgens in prostate, and by albumin in kidney.
CC {ECO:0000269|PubMed:14615060, ECO:0000269|PubMed:15489223}.
CC -!- PTM: Phosphorylated by SGK1 or PKA; which impairs interaction with
CC SCNN. Interaction with YWHAH inhibits dephosphorylation.
CC {ECO:0000269|PubMed:11696533, ECO:0000269|PubMed:15328345,
CC ECO:0000269|PubMed:15677482, ECO:0000269|PubMed:20525693,
CC ECO:0000269|PubMed:20730100}.
CC -!- PTM: Auto-ubiquitinated (PubMed:19343052). Deubiquitinated by USP36, no
CC effect on NEDD4L protein levels. Both proteins interact and regulate
CC each other's ubiquitination levels (PubMed:27445338).
CC {ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:27445338}.
CC -!- DISEASE: Periventricular nodular heterotopia 7 (PVNH7) [MIM:617201]: A
CC form of periventricular nodular heterotopia, a disorder resulting from
CC a defect in the pattern of neuronal migration in which ectopic
CC collections of neurons lie along the lateral ventricles of the brain or
CC just beneath, contiguously or in isolated patches. PVNH7 is an
CC autosomal dominant disease characterized by delayed psychomotor
CC development, intellectual disability, and seizures in some patients.
CC Additional features include cleft palate and toe syndactyly.
CC {ECO:0000269|PubMed:27694961}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA23711.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA23711.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AF210730; AAG43524.1; -; mRNA.
DR EMBL; AF385931; AAM46208.1; -; mRNA.
DR EMBL; AY312514; AAP75706.1; -; mRNA.
DR EMBL; AY112983; AAM76728.1; -; mRNA.
DR EMBL; AY112984; AAM76729.1; -; mRNA.
DR EMBL; AY112985; AAM76730.1; -; mRNA.
DR EMBL; AB071179; BAB69424.1; -; mRNA.
DR EMBL; DQ181796; ABA10330.1; -; mRNA.
DR EMBL; AC015988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090236; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107896; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW63065.1; -; Genomic_DNA.
DR EMBL; BC000621; AAH00621.2; -; mRNA.
DR EMBL; BC019345; AAH19345.1; -; mRNA.
DR EMBL; BC032597; AAH32597.1; -; mRNA.
DR EMBL; AB007899; BAA23711.1; ALT_INIT; mRNA.
DR EMBL; AL137469; CAB70754.1; -; mRNA.
DR CCDS; CCDS45872.1; -. [Q96PU5-1]
DR CCDS; CCDS45873.1; -. [Q96PU5-5]
DR CCDS; CCDS45874.1; -. [Q96PU5-7]
DR CCDS; CCDS45875.1; -. [Q96PU5-4]
DR CCDS; CCDS45876.1; -. [Q96PU5-9]
DR CCDS; CCDS58632.1; -. [Q96PU5-2]
DR CCDS; CCDS59323.1; -. [Q96PU5-6]
DR PIR; T46412; T46412.
DR RefSeq; NP_001138436.1; NM_001144964.1. [Q96PU5-4]
DR RefSeq; NP_001138437.1; NM_001144965.1. [Q96PU5-4]
DR RefSeq; NP_001138438.1; NM_001144966.2. [Q96PU5-4]
DR RefSeq; NP_001138439.1; NM_001144967.2. [Q96PU5-1]
DR RefSeq; NP_001138440.1; NM_001144968.1. [Q96PU5-7]
DR RefSeq; NP_001138441.1; NM_001144969.1. [Q96PU5-6]
DR RefSeq; NP_001138442.1; NM_001144970.2. [Q96PU5-9]
DR RefSeq; NP_001138443.1; NM_001144971.1. [Q96PU5-9]
DR RefSeq; NP_001230889.1; NM_001243960.1. [Q96PU5-2]
DR RefSeq; NP_056092.2; NM_015277.5. [Q96PU5-5]
DR RefSeq; XP_016881168.1; XM_017025679.1. [Q96PU5-4]
DR PDB; 2LAJ; NMR; -; A=496-535.
DR PDB; 2LB2; NMR; -; A=386-420.
DR PDB; 2LTY; NMR; -; A=385-417.
DR PDB; 2MPT; NMR; -; A=496-539, B=945-957.
DR PDB; 2NSQ; X-ray; 1.85 A; A=1-154.
DR PDB; 2ONI; X-ray; 2.20 A; A=594-967.
DR PDB; 3JVZ; X-ray; 3.30 A; C/D=596-975.
DR PDB; 3JW0; X-ray; 3.10 A; C/D=596-975.
DR PDB; 5HPK; X-ray; 2.43 A; A=594-975.
DR PDB; 6ZBT; X-ray; 1.80 A; E/F/G/H=338-347.
DR PDB; 6ZC9; X-ray; 1.90 A; E/F/G/H=444-453.
DR PDB; 7LP1; X-ray; 1.35 A; A=494-532.
DR PDB; 7LP3; X-ray; 1.61 A; A/C=193-226.
DR PDB; 7LP4; NMR; -; A=493-539.
DR PDB; 7LP5; NMR; -; A=493-539.
DR PDB; 7NMZ; X-ray; 2.30 A; C=335-455.
DR PDBsum; 2LAJ; -.
DR PDBsum; 2LB2; -.
DR PDBsum; 2LTY; -.
DR PDBsum; 2MPT; -.
DR PDBsum; 2NSQ; -.
DR PDBsum; 2ONI; -.
DR PDBsum; 3JVZ; -.
DR PDBsum; 3JW0; -.
DR PDBsum; 5HPK; -.
DR PDBsum; 6ZBT; -.
DR PDBsum; 6ZC9; -.
DR PDBsum; 7LP1; -.
DR PDBsum; 7LP3; -.
DR PDBsum; 7LP4; -.
DR PDBsum; 7LP5; -.
DR PDBsum; 7NMZ; -.
DR AlphaFoldDB; Q96PU5; -.
DR BMRB; Q96PU5; -.
DR SMR; Q96PU5; -.
DR BioGRID; 116915; 301.
DR CORUM; Q96PU5; -.
DR DIP; DIP-41935N; -.
DR IntAct; Q96PU5; 52.
DR MINT; Q96PU5; -.
DR STRING; 9606.ENSP00000383199; -.
DR GlyGen; Q96PU5; 2 sites, 2 O-linked glycans (2 sites).
DR iPTMnet; Q96PU5; -.
DR PhosphoSitePlus; Q96PU5; -.
DR BioMuta; NEDD4L; -.
DR DMDM; 73921204; -.
DR EPD; Q96PU5; -.
DR jPOST; Q96PU5; -.
DR MassIVE; Q96PU5; -.
DR MaxQB; Q96PU5; -.
DR PaxDb; Q96PU5; -.
DR PeptideAtlas; Q96PU5; -.
DR PRIDE; Q96PU5; -.
DR ProteomicsDB; 77752; -. [Q96PU5-1]
DR ProteomicsDB; 77753; -. [Q96PU5-2]
DR ProteomicsDB; 77754; -. [Q96PU5-3]
DR ProteomicsDB; 77755; -. [Q96PU5-4]
DR ProteomicsDB; 77756; -. [Q96PU5-5]
DR ProteomicsDB; 77757; -. [Q96PU5-6]
DR ProteomicsDB; 77758; -. [Q96PU5-7]
DR ProteomicsDB; 77760; -. [Q96PU5-9]
DR Antibodypedia; 5421; 272 antibodies from 33 providers.
DR DNASU; 23327; -.
DR Ensembl; ENST00000256830.13; ENSP00000256830.8; ENSG00000049759.20. [Q96PU5-3]
DR Ensembl; ENST00000356462.10; ENSP00000348847.5; ENSG00000049759.20. [Q96PU5-2]
DR Ensembl; ENST00000357895.9; ENSP00000350569.4; ENSG00000049759.20. [Q96PU5-7]
DR Ensembl; ENST00000382850.8; ENSP00000372301.3; ENSG00000049759.20. [Q96PU5-5]
DR Ensembl; ENST00000400345.8; ENSP00000383199.2; ENSG00000049759.20. [Q96PU5-1]
DR Ensembl; ENST00000431212.6; ENSP00000389406.1; ENSG00000049759.20. [Q96PU5-4]
DR Ensembl; ENST00000435432.6; ENSP00000393395.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000456173.6; ENSP00000405440.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000456986.5; ENSP00000411947.1; ENSG00000049759.20. [Q96PU5-4]
DR Ensembl; ENST00000586263.5; ENSP00000468546.1; ENSG00000049759.20. [Q96PU5-6]
DR Ensembl; ENST00000674517.1; ENSP00000501665.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000675502.1; ENSP00000502428.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000675801.1; ENSP00000502688.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000675865.1; ENSP00000502003.1; ENSG00000049759.20. [Q96PU5-9]
DR Ensembl; ENST00000676226.1; ENSP00000502325.1; ENSG00000049759.20. [Q96PU5-9]
DR GeneID; 23327; -.
DR KEGG; hsa:23327; -.
DR MANE-Select; ENST00000400345.8; ENSP00000383199.2; NM_001144967.3; NP_001138439.1.
DR UCSC; uc002lgx.4; human. [Q96PU5-1]
DR CTD; 23327; -.
DR DisGeNET; 23327; -.
DR GeneCards; NEDD4L; -.
DR HGNC; HGNC:7728; NEDD4L.
DR HPA; ENSG00000049759; Low tissue specificity.
DR MalaCards; NEDD4L; -.
DR MIM; 606384; gene.
DR MIM; 617201; phenotype.
DR neXtProt; NX_Q96PU5; -.
DR OpenTargets; ENSG00000049759; -.
DR Orphanet; 98892; Periventricular nodular heterotopia.
DR PharmGKB; PA31534; -.
DR VEuPathDB; HostDB:ENSG00000049759; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000156873; -.
DR InParanoid; Q96PU5; -.
DR OMA; PAHIAMQ; -.
DR OrthoDB; 271539at2759; -.
DR PhylomeDB; Q96PU5; -.
DR TreeFam; TF323658; -.
DR BioCyc; MetaCyc:ENSG00000049759-MON; -.
DR BRENDA; 2.3.2.26; 2681.
DR BRENDA; 2.3.2.B8; 2681.
DR PathwayCommons; Q96PU5; -.
DR Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q96PU5; -.
DR SIGNOR; Q96PU5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 23327; 13 hits in 1118 CRISPR screens.
DR ChiTaRS; NEDD4L; human.
DR EvolutionaryTrace; Q96PU5; -.
DR GeneWiki; NEDD4L; -.
DR GenomeRNAi; 23327; -.
DR Pharos; Q96PU5; Tbio.
DR PRO; PR:Q96PU5; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q96PU5; protein.
DR Bgee; ENSG00000049759; Expressed in ventricular zone and 191 other tissues.
DR ExpressionAtlas; Q96PU5; baseline and differential.
DR Genevisible; Q96PU5; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0019870; F:potassium channel inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:BHF-UCL.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:Reactome.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:1901017; P:negative regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:2000009; P:negative regulation of protein localization to cell surface; IDA:BHF-UCL.
DR GO; GO:1902306; P:negative regulation of sodium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:2000650; P:negative regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:2001288; P:positive regulation of caveolin-mediated endocytosis; ISS:BHF-UCL.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:BHF-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0003254; P:regulation of membrane depolarization; IDA:BHF-UCL.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
DR GO; GO:1901016; P:regulation of potassium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISS:BHF-UCL.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 4.
DR DisProt; DP02292; -.
DR Gene3D; 2.60.40.150; -; 1.
DR IDEAL; IID00114; -.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR024928; E3_ub_ligase_SMURF1.
DR InterPro; IPR000569; HECT_dom.
DR InterPro; IPR035983; Hect_E3_ubiquitin_ligase.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00632; HECT; 1.
DR Pfam; PF00397; WW; 4.
DR PIRSF; PIRSF001569; E3_ub_ligase_SMURF1; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 1.
DR SMART; SM00119; HECTc; 1.
DR SMART; SM00456; WW; 4.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51045; SSF51045; 4.
DR SUPFAM; SSF56204; SSF56204; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50237; HECT; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 4.
DR PROSITE; PS50020; WW_DOMAIN_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Differentiation; Direct protein sequencing; Disease variant; Endosome;
KW Golgi apparatus; Host-virus interaction; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..975
FT /note="E3 ubiquitin-protein ligase NEDD4-like"
FT /id="PRO_0000120323"
FT DOMAIN 4..126
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 193..226
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 385..418
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 497..530
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 548..581
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 640..974
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 178..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 244..261
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 424..455
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 942
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 318
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 342
FT /note="Phosphoserine; by WNK1 and WNK4"
FT /evidence="ECO:0000269|PubMed:15328345,
FT ECO:0000269|PubMed:20525693, ECO:0007744|PubMed:18669648"
FT MOD_RES 367
FT /note="Phosphothreonine; by SGK1"
FT /evidence="ECO:0000305|PubMed:15328345"
FT MOD_RES 446
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 448
FT /note="Phosphoserine; by PKA and SGK1"
FT /evidence="ECO:0000269|PubMed:15328345,
FT ECO:0000269|PubMed:15677482, ECO:0007744|PubMed:23186163"
FT MOD_RES 449
FT /note="Phosphoserine; by WNK1 and WNK4"
FT /evidence="ECO:0000269|PubMed:20525693,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 475
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..121
FT /note="Missing (in isoform 4 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11840194,
FT ECO:0000303|PubMed:14615060, ECO:0000303|PubMed:9455477,
FT ECO:0000303|Ref.5"
FT /id="VSP_015444"
FT VAR_SEQ 1..16
FT /note="MATGLGEPVYGLSEDE -> MRRLAFEQ (in isoform 6 and
FT isoform 7)"
FT /evidence="ECO:0000303|PubMed:14615060"
FT /id="VSP_015446"
FT VAR_SEQ 356..459
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_015447"
FT VAR_SEQ 356..419
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015448"
FT VAR_SEQ 356..375
FT /note="Missing (in isoform 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14615060,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:9455477,
FT ECO:0000303|Ref.4, ECO:0000303|Ref.5"
FT /id="VSP_043848"
FT VARIANT 355
FT /note="P -> L (impaired ability to inhibit SCNN;
FT dbSNP:rs767136811)"
FT /evidence="ECO:0000269|PubMed:15140763"
FT /id="VAR_023415"
FT VARIANT 497
FT /note="S -> R"
FT /evidence="ECO:0000269|PubMed:15140763"
FT /id="VAR_023416"
FT VARIANT 679
FT /note="Y -> C (in PVNH7; dbSNP:rs879255599)"
FT /evidence="ECO:0000269|PubMed:27694961"
FT /id="VAR_077880"
FT VARIANT 694
FT /note="Q -> H (in PVNH7; increased degradation; changed
FT function in regulation of TOR signaling;
FT dbSNP:rs879255598)"
FT /evidence="ECO:0000269|PubMed:27694961"
FT /id="VAR_077881"
FT VARIANT 893
FT /note="E -> K (in PVNH7; increased degradation; changed
FT function in regulation of TOR signaling;
FT dbSNP:rs879255597)"
FT /evidence="ECO:0000269|PubMed:27694961"
FT /id="VAR_077882"
FT VARIANT 897
FT /note="R -> Q (in PVNH7; increased degradation; changed
FT function in regulation of TOR signaling;
FT dbSNP:rs879255596)"
FT /evidence="ECO:0000269|PubMed:27694961"
FT /id="VAR_077883"
FT MUTAGEN 448
FT /note="S->A: Abolishes interaction with 1433F."
FT /evidence="ECO:0000269|PubMed:15677482"
FT MUTAGEN 942
FT /note="C->S: Abolishes activity. No effect on USP36 protein
FT levels."
FT /evidence="ECO:0000269|PubMed:15217910,
FT ECO:0000269|PubMed:27445338"
FT CONFLICT 52
FT /note="A -> P (in Ref. 3; AAM76729/AAM76730)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="E -> K (in Ref. 2; AAP75706)"
FT /evidence="ECO:0000305"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:2NSQ"
FT TURN 16..18
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 20..31
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:2NSQ"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 73..82
FT /evidence="ECO:0007829|PDB:2NSQ"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 87..95
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 103..111
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 145..152
FT /evidence="ECO:0007829|PDB:2NSQ"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:7LP3"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:7LP3"
FT TURN 214..217
FT /evidence="ECO:0007829|PDB:7LP3"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:7LP3"
FT STRAND 391..396
FT /evidence="ECO:0007829|PDB:2LB2"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:2LB2"
FT STRAND 400..405
FT /evidence="ECO:0007829|PDB:2LB2"
FT TURN 406..409
FT /evidence="ECO:0007829|PDB:2LB2"
FT STRAND 410..414
FT /evidence="ECO:0007829|PDB:2LB2"
FT HELIX 417..419
FT /evidence="ECO:0007829|PDB:2LB2"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:7LP1"
FT TURN 509..511
FT /evidence="ECO:0007829|PDB:2LAJ"
FT STRAND 513..517
FT /evidence="ECO:0007829|PDB:7LP1"
FT TURN 518..521
FT /evidence="ECO:0007829|PDB:7LP1"
FT STRAND 522..526
FT /evidence="ECO:0007829|PDB:7LP1"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:7LP1"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:7LP4"
FT HELIX 594..607
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 616..622
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 624..626
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 627..637
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 641..645
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 646..652
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 653..655
FT /evidence="ECO:0007829|PDB:3JVZ"
FT HELIX 660..675
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 678..680
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 681..687
FT /evidence="ECO:0007829|PDB:2ONI"
FT TURN 688..690
FT /evidence="ECO:0007829|PDB:3JW0"
FT STRAND 693..695
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 699..702
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 706..723
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 728..731
FT /evidence="ECO:0007829|PDB:3JW0"
FT HELIX 733..739
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 746..749
FT /evidence="ECO:0007829|PDB:2ONI"
FT TURN 750..752
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 754..765
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 769..771
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 774..781
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 784..791
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 794..796
FT /evidence="ECO:0007829|PDB:2ONI"
FT TURN 801..803
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 804..816
FT /evidence="ECO:0007829|PDB:2ONI"
FT TURN 817..819
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 821..834
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 837..840
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 845..853
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 860..865
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 868..870
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 878..889
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 892..903
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 913..915
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 919..922
FT /evidence="ECO:0007829|PDB:5HPK"
FT STRAND 926..929
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 933..935
FT /evidence="ECO:0007829|PDB:3JW0"
FT STRAND 938..940
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 941..943
FT /evidence="ECO:0007829|PDB:2ONI"
FT STRAND 945..948
FT /evidence="ECO:0007829|PDB:2ONI"
FT HELIX 954..965
FT /evidence="ECO:0007829|PDB:2ONI"
SQ SEQUENCE 975 AA; 111932 MW; 2C958625B4A1AB3F CRC64;
MATGLGEPVY GLSEDEGESR ILRVKVVSGI DLAKKDIFGA SDPYVKLSLY VADENRELAL
VQTKTIKKTL NPKWNEEFYF RVNPSNHRLL FEVFDENRLT RDDFLGQVDV PLSHLPTEDP
TMERPYTFKD FLLRPRSHKS RVKGFLRLKM AYMPKNGGQD EENSDQRDDM EHGWEVVDSN
DSASQHQEEL PPPPLPPGWE EKVDNLGRTY YVNHNNRTTQ WHRPSLMDVS SESDNNIRQI
NQEAAHRRFR SRRHISEDLE PEPSEGGDVP EPWETISEEV NIAGDSLGLA LPPPPASPGS
RTSPQELSEE LSRRLQITPD SNGEQFSSLI QREPSSRLRS CSVTDAVAEQ GHLPPPSAPA
GRARSSTVTG GEEPTPSVAY VHTTPGLPSG WEERKDAKGR TYYVNHNNRT TTWTRPIMQL
AEDGASGSAT NSNNHLIEPQ IRRPRSLSSP TVTLSAPLEG AKDSPVRRAV KDTLSNPQSP
QPSPYNSPKP QHKVTQSFLP PGWEMRIAPN GRPFFIDHNT KTTTWEDPRL KFPVHMRSKT
SLNPNDLGPL PPGWEERIHL DGRTFYIDHN SKITQWEDPR LQNPAITGPA VPYSREFKQK
YDYFRKKLKK PADIPNRFEM KLHRNNIFEE SYRRIMSVKR PDVLKARLWI EFESEKGLDY
GGVAREWFFL LSKEMFNPYY GLFEYSATDN YTLQINPNSG LCNEDHLSYF TFIGRVAGLA
VFHGKLLDGF FIRPFYKMML GKQITLNDME SVDSEYYNSL KWILENDPTE LDLMFCIDEE
NFGQTYQVDL KPNGSEIMVT NENKREYIDL VIQWRFVNRV QKQMNAFLEG FTELLPIDLI
KIFDENELEL LMCGLGDVDV NDWRQHSIYK NGYCPNHPVI QWFWKAVLLM DAEKRIRLLQ
FVTGTSRVPM NGFAELYGSN GPQLFTIEQW GSPEKLPRAH TCFNRLDLPP YETFEDLREK
LLMAVENAQG FEGVD
