WWP1_HUMAN
ID WWP1_HUMAN Reviewed; 922 AA.
AC Q9H0M0; O00307; Q5YLC1; Q96BP4;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=NEDD4-like E3 ubiquitin-protein ligase WWP1;
DE EC=2.3.2.26;
DE AltName: Full=Atrophin-1-interacting protein 5;
DE Short=AIP5;
DE AltName: Full=HECT-type E3 ubiquitin transferase WWP1;
DE AltName: Full=TGIF-interacting ubiquitin ligase 1;
DE Short=Tiul1;
DE AltName: Full=WW domain-containing protein 1;
GN Name=WWP1;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5 AND 6), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Mammary cancer;
RX PubMed=11779188; DOI=10.1006/bbrc.2001.6206;
RA Flasza M., Gorman P., Roylance R., Canfield A.E., Baron M.;
RT "Alternative splicing determines the domain structure of WWP1, a Nedd4
RT family protein.";
RL Biochem. Biophys. Res. Commun. 290:431-437(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, UBIQUITINATION OF SMAD2 AND TGFBR1,
RP AND INTERACTION WITH SMAD7 AND TGIF.
RX PubMed=15359284; DOI=10.1038/sj.emboj.7600398;
RA Seo S.R., Lallemand F., Ferrand N., Pessah M., L'Hoste S., Camonis J.,
RA Atfi A.;
RT "The novel E3 ubiquitin ligase Tiul1 associates with TGIF to target Smad2
RT for degradation.";
RL EMBO J. 23:3780-3792(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 191-870, AND INTERACTION WITH WBP1; WBP2;
RP SCNN1A; SCNN1B AND SCNN1G.
RC TISSUE=Bone marrow, and Brain;
RX PubMed=9169421; DOI=10.1074/jbc.272.23.14611;
RA Pirozzi G., McConnell S.J., Uveges A.J., Carter J.M., Sparks A.B.,
RA Kay B.K., Fowlkes D.M.;
RT "Identification of novel human WW domain-containing proteins by cloning of
RT ligand targets.";
RL J. Biol. Chem. 272:14611-14616(1997).
RN [7]
RP INTERACTION WITH DRPLA, AND TISSUE SPECIFICITY.
RX PubMed=9647693; DOI=10.1006/mcne.1998.0677;
RA Wood J.D., Yuan J., Margolis R.L., Colomer V., Duan K., Kushi J.,
RA Kaminsky Z., Kleiderlein J.J. Jr., Sharp A.H., Ross C.A.;
RT "Atrophin-1, the DRPLA gene product, interacts with two families of WW
RT domain-containing proteins.";
RL Mol. Cell. Neurosci. 11:149-160(1998).
RN [8]
RP INTERACTION WITH PIII.
RX PubMed=12450395; DOI=10.1021/bi020125b;
RA Galinier R., Gout E., Lortat-Jacob H., Wood J., Chroboczek J.;
RT "Adenovirus protein involved in virus internalization recruits ubiquitin-
RT protein ligases.";
RL Biochemistry 41:14299-14305(2002).
RN [9]
RP FUNCTION IN UBIQUITINATION OF TGFBR1; SMAD6 AND SMAD7, AND INTERACTION WITH
RP SMAD1; SMAD2; SMAD3; SMAD5; SMAD6; SMAD7; TGFBR1; TGFBR2 AND SKIL.
RX PubMed=15221015; DOI=10.1038/sj.onc.1207885;
RA Komuro A., Imamura T., Saitoh M., Yoshida Y., Yamori T., Miyazono K.,
RA Miyazawa K.;
RT "Negative regulation of transforming growth factor-beta (TGF-beta)
RT signaling by WW domain-containing protein 1 (WWP1).";
RL Oncogene 23:6914-6923(2004).
RN [10]
RP INTERACTION WITH HTLV-1 PROTEIN GAG (MICROBIAL INFECTION).
RX PubMed=17609263; DOI=10.1128/jvi.00642-07;
RA Heidecker G., Lloyd P.A., Soheilian F., Nagashima K., Derse D.;
RT "The role of WWP1-Gag interaction and Gag ubiquitination in assembly and
RT release of human T-cell leukemia virus type 1.";
RL J. Virol. 81:9769-9777(2007).
RN [11]
RP AUTOUBIQUITINATION.
RX PubMed=18724389; DOI=10.1038/onc.2008.288;
RA Chen C., Zhou Z., Liu R., Li Y., Azmi P.B., Seth A.K.;
RT "The WW domain containing E3 ubiquitin protein ligase 1 upregulates ErbB2
RT and EGFR through RING finger protein 11.";
RL Oncogene 27:6845-6855(2008).
RN [12]
RP INTERACTION WITH SPART.
RX PubMed=19580544; DOI=10.1042/bj20082398;
RA Edwards T.L., Clowes V.E., Tsang H.T., Connell J.W., Sanderson C.M.,
RA Luzio J.P., Reid E.;
RT "Endogenous spartin (SPG20) is recruited to endosomes and lipid droplets
RT and interacts with the ubiquitin E3 ligases AIP4 and AIP5.";
RL Biochem. J. 423:31-39(2009).
RN [13]
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 [14]
RP INTERACTION WITH ERBB4.
RX PubMed=19561640; DOI=10.1038/onc.2009.162;
RA Li Y., Zhou Z., Alimandi M., Chen C.;
RT "WW domain containing E3 ubiquitin protein ligase 1 targets the full-length
RT ErbB4 for ubiquitin-mediated degradation in breast cancer.";
RL Oncogene 28:2948-2958(2009).
RN [15]
RP INTERACTION WITH ARRDC1; ARRDC2 AND ARRDC3, AND DOMAIN.
RX PubMed=21191027; DOI=10.1128/jvi.02045-10;
RA Rauch S., Martin-Serrano J.;
RT "Multiple interactions between the ESCRT machinery and arrestin-related
RT proteins: implications for PPXY-dependent budding.";
RL J. Virol. 85:3546-3556(2011).
RN [16]
RP INTERACTION WITH EBOLA VIRUS PROTEIN VP40 (MICROBIAL INFECTION).
RX PubMed=28768865; DOI=10.1128/jvi.00812-17;
RA Han Z., Sagum C.A., Takizawa F., Ruthel G., Berry C.T., Kong J.,
RA Sunyer J.O., Freedman B.D., Bedford M.T., Sidhu S.S., Sudol M., Harty R.N.;
RT "Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate
RT Egress.";
RL J. Virol. 91:0-0(2017).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 546-917, MUTAGENESIS OF GLU-614;
RP HIS-621; ASP-675; GLU-798; MET-804; GLU-806; ARG-845; GLN-848 AND ARG-855,
RP AND FUNCTION.
RX PubMed=12535537; DOI=10.1016/s1097-2765(02)00774-8;
RA Verdecia M.A., Joazeiro C.A.P., Wells N.J., Ferrer J.-L., Bowman M.E.,
RA Hunter T., Noel J.P.;
RT "Conformational flexibility underlies ubiquitin ligation mediated by the
RT WWP1 HECT domain E3 ligase.";
RL Mol. Cell 11:249-259(2003).
CC -!- FUNCTION: E3 ubiquitin-protein ligase which accepts ubiquitin from an
CC E2 ubiquitin-conjugating enzyme in the form of a thioester and then
CC directly transfers the ubiquitin to targeted substrates. Ubiquitinates
CC ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and
CC promotes their proteasomal degradation. Ubiquitinates RNF11 without
CC targeting it for degradation. Ubiquitinates and promotes degradation of
CC TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6
CC and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response
CC to TGF-beta signaling, which requires interaction with TGIF.
CC {ECO:0000269|PubMed:12535537, ECO:0000269|PubMed:15221015,
CC ECO:0000269|PubMed:15359284}.
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;
CC -!- ACTIVITY REGULATION: Activated by NDFIP1- and NDFIP2-binding.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Binds KLF2 AND HIVEP3 (By similarity). Binds SCNN1A, SCNN1B,
CC SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with
CC RNF11 (By similarity). Interacts with SPART. Interacts with ERBB4
CC isoforms JM-B CYT-1 and JM-A CYT-1. Interacts with SMAD1, SMAD2, SMAD3,
CC SMAD5, SMAD6, SMAD7, TGFBR1 AND TGFBR2. Associates with the
CC TGFBR1:TGFBR2 receptor complex in presence of SMAD7. Interacts with
CC SKIL isoform 1. Interacts with TP63 isoform 1 and isoform 2. Interacts
CC with STAMBP and RNF11. Interacts with NDFIP1 and NDFIP2 (Probable);
CC this interaction activates the E3 ubiquitin-protein ligase. Interacts
CC with TGIF. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3
CC (PubMed:21191027). {ECO:0000250, ECO:0000269|PubMed:12450395,
CC ECO:0000269|PubMed:15221015, ECO:0000269|PubMed:15359284,
CC ECO:0000269|PubMed:19561640, ECO:0000269|PubMed:19580544,
CC ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:9169421,
CC ECO:0000269|PubMed:9647693}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 protein Gag.
CC {ECO:0000269|PubMed:17609263}.
CC -!- SUBUNIT: (Microbial infection) Interacts with ebola virus protein VP40.
CC {ECO:0000269|PubMed:28768865}.
CC -!- INTERACTION:
CC Q9H0M0; Q8N5I2: ARRDC1; NbExp=3; IntAct=EBI-742157, EBI-2339564;
CC Q9H0M0; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-742157, EBI-2875665;
CC Q9H0M0; P54252: ATXN3; NbExp=3; IntAct=EBI-742157, EBI-946046;
CC Q9H0M0; Q16630: CPSF6; NbExp=3; IntAct=EBI-742157, EBI-358410;
CC Q9H0M0; Q96D16: FBXL18; NbExp=3; IntAct=EBI-742157, EBI-744419;
CC Q9H0M0; P84022: SMAD3; NbExp=9; IntAct=EBI-742157, EBI-347161;
CC Q9H0M0; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-742157, EBI-3650647;
CC Q9H0M0; Q8WU02; NbExp=3; IntAct=EBI-742157, EBI-747182;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=A;
CC IsoId=Q9H0M0-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q9H0M0-2; Sequence=VSP_007601, VSP_007603;
CC Name=3; Synonyms=C;
CC IsoId=Q9H0M0-3; Sequence=VSP_007602;
CC Name=4; Synonyms=D;
CC IsoId=Q9H0M0-4; Sequence=Not described;
CC Name=5; Synonyms=E;
CC IsoId=Q9H0M0-5; Sequence=Not described;
CC Name=6; Synonyms=F;
CC IsoId=Q9H0M0-6; Sequence=VSP_007600;
CC -!- TISSUE SPECIFICITY: Detected in heart, placenta, pancreas, kidney,
CC liver, skeletal muscle, bone marrow, fetal brain, and at much lower
CC levels in adult brain and lung. Isoform 1 and isoform 5 predominate in
CC all tissues tested, except in testis and bone marrow, where isoform 5
CC is expressed at much higher levels than isoform 1.
CC {ECO:0000269|PubMed:11779188, ECO:0000269|PubMed:9647693}.
CC -!- DOMAIN: The WW domains mediate interaction with PPxY motif-containing
CC proteins. {ECO:0000269|PubMed:21191027}.
CC -!- PTM: Auto-ubiquitinated and ubiquitinated by RNF11.
CC {ECO:0000269|PubMed:15359284, ECO:0000269|PubMed:18724389,
CC ECO:0000269|PubMed:19343052}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/WWP1ID42993ch8q21.html";
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DR EMBL; AL136739; CAB66673.1; -; mRNA.
DR EMBL; AY043361; AAK94668.1; -; mRNA.
DR EMBL; AY345857; AAQ22764.1; -; mRNA.
DR EMBL; AC083845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103817; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015380; AAH15380.2; -; mRNA.
DR EMBL; BC036065; AAH36065.1; -; mRNA.
DR EMBL; U96113; AAC51324.1; -; mRNA.
DR CCDS; CCDS6242.1; -. [Q9H0M0-1]
DR RefSeq; NP_008944.1; NM_007013.3. [Q9H0M0-1]
DR RefSeq; XP_005250817.1; XM_005250760.3. [Q9H0M0-1]
DR PDB; 1ND7; X-ray; 2.10 A; A=546-917.
DR PDB; 2OP7; NMR; -; A=494-532.
DR PDB; 5HPS; X-ray; 2.05 A; A=537-917.
DR PDB; 5HPT; X-ray; 2.84 A; A/D/G=537-917.
DR PDB; 6J1X; X-ray; 2.30 A; B=379-922.
DR PDB; 6J1Y; X-ray; 2.55 A; A/B=410-922.
DR PDBsum; 1ND7; -.
DR PDBsum; 2OP7; -.
DR PDBsum; 5HPS; -.
DR PDBsum; 5HPT; -.
DR PDBsum; 6J1X; -.
DR PDBsum; 6J1Y; -.
DR AlphaFoldDB; Q9H0M0; -.
DR SMR; Q9H0M0; -.
DR BioGRID; 116243; 184.
DR CORUM; Q9H0M0; -.
DR IntAct; Q9H0M0; 60.
DR MINT; Q9H0M0; -.
DR STRING; 9606.ENSP00000427793; -.
DR MoonDB; Q9H0M0; Predicted.
DR iPTMnet; Q9H0M0; -.
DR PhosphoSitePlus; Q9H0M0; -.
DR BioMuta; WWP1; -.
DR DMDM; 32171908; -.
DR EPD; Q9H0M0; -.
DR jPOST; Q9H0M0; -.
DR MassIVE; Q9H0M0; -.
DR MaxQB; Q9H0M0; -.
DR PaxDb; Q9H0M0; -.
DR PeptideAtlas; Q9H0M0; -.
DR PRIDE; Q9H0M0; -.
DR ProteomicsDB; 80294; -. [Q9H0M0-1]
DR ProteomicsDB; 80295; -. [Q9H0M0-2]
DR ProteomicsDB; 80296; -. [Q9H0M0-3]
DR ProteomicsDB; 80297; -. [Q9H0M0-6]
DR ABCD; Q9H0M0; 3 sequenced antibodies.
DR Antibodypedia; 25465; 160 antibodies from 28 providers.
DR DNASU; 11059; -.
DR Ensembl; ENST00000265428.4; ENSP00000265428.4; ENSG00000123124.14. [Q9H0M0-1]
DR Ensembl; ENST00000517970.6; ENSP00000427793.1; ENSG00000123124.14. [Q9H0M0-1]
DR GeneID; 11059; -.
DR KEGG; hsa:11059; -.
DR MANE-Select; ENST00000517970.6; ENSP00000427793.1; NM_007013.4; NP_008944.1.
DR UCSC; uc003ydt.4; human. [Q9H0M0-1]
DR CTD; 11059; -.
DR DisGeNET; 11059; -.
DR GeneCards; WWP1; -.
DR HGNC; HGNC:17004; WWP1.
DR HPA; ENSG00000123124; Tissue enhanced (skeletal).
DR MIM; 602307; gene.
DR neXtProt; NX_Q9H0M0; -.
DR OpenTargets; ENSG00000123124; -.
DR PharmGKB; PA134960138; -.
DR VEuPathDB; HostDB:ENSG00000123124; -.
DR eggNOG; KOG0940; Eukaryota.
DR GeneTree; ENSGT00940000154635; -.
DR HOGENOM; CLU_002173_0_1_1; -.
DR InParanoid; Q9H0M0; -.
DR OMA; ANQGYHQ; -.
DR OrthoDB; 167687at2759; -.
DR PhylomeDB; Q9H0M0; -.
DR TreeFam; TF323658; -.
DR BRENDA; 2.3.2.26; 2681.
DR PathwayCommons; Q9H0M0; -.
DR Reactome; R-HSA-1253288; Downregulation of ERBB4 signaling.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q9H0M0; -.
DR SIGNOR; Q9H0M0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 11059; 14 hits in 1125 CRISPR screens.
DR ChiTaRS; WWP1; human.
DR EvolutionaryTrace; Q9H0M0; -.
DR GeneWiki; WWP1; -.
DR GenomeRNAi; 11059; -.
DR Pharos; Q9H0M0; Tbio.
DR PRO; PR:Q9H0M0; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9H0M0; protein.
DR Bgee; ENSG00000123124; Expressed in skeletal muscle tissue of rectus abdominis and 217 other tissues.
DR ExpressionAtlas; Q9H0M0; baseline and differential.
DR Genevisible; Q9H0M0; 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:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; NAS:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; TAS:UniProtKB.
DR CDD; cd00078; HECTc; 1.
DR CDD; cd00201; WW; 3.
DR Gene3D; 2.60.40.150; -; 1.
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 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; Alternative splicing; Cell membrane; Cytoplasm;
KW Host-virus interaction; Membrane; Nucleus; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway.
FT CHAIN 1..922
FT /note="NEDD4-like E3 ubiquitin-protein ligase WWP1"
FT /id="PRO_0000120336"
FT DOMAIN 1..116
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 349..382
FT /note="WW 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 381..414
FT /note="WW 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 456..489
FT /note="WW 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 496..529
FT /note="WW 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 588..922
FT /note="HECT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT REGION 210..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..354
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 890
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00104"
FT SITE 890
FT /note="Required for ubiquitin-thioester formation"
FT /evidence="ECO:0000250"
FT VAR_SEQ 23..240
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11779188"
FT /id="VSP_007600"
FT VAR_SEQ 112..242
FT /note="LERVKEQLKLSLENKNGIAQTGELTVVLDGLVIEQENITNCSSSPTIEIQEN
FT GDALHENGEPSARTTARLAVEGTNGIDNHVPTSTLVQNSCCSYVVNGDNTPSSPSQVAA
FT RPKNTPAPKPLASEPADDTV -> F (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11779188"
FT /id="VSP_007602"
FT VAR_SEQ 112..120
FT /note="LERVKEQLK -> CWLLKARME (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11779188"
FT /id="VSP_007601"
FT VAR_SEQ 121..922
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11779188"
FT /id="VSP_007603"
FT MUTAGEN 614
FT /note="E->A: Reduces ubiquitin transfer."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 621
FT /note="H->A: Strongly reduces ubiquitin transfer."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 675
FT /note="D->A: Reduces ubiquitin transfer."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 798
FT /note="E->A: Reduces ubiquitin transfer. Strongly reduces
FT ubiquitin transfer; when associated with A-845."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 804
FT /note="M->P: Strongly reduces ubiquitin transfer; when
FT associated with P-806."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 806
FT /note="E->P: Strongly reduces ubiquitin transfer; when
FT associated with P-804."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 845
FT /note="R->A: No effect."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 848
FT /note="Q->A: Abolishes ubiquitin transfer; when associated
FT with A-855."
FT /evidence="ECO:0000269|PubMed:12535537"
FT MUTAGEN 855
FT /note="R->A: Abolishes ubiquitin transfer; when associated
FT with A-848."
FT /evidence="ECO:0000269|PubMed:12535537"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:6J1X"
FT STRAND 397..401
FT /evidence="ECO:0007829|PDB:6J1X"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:6J1X"
FT STRAND 407..410
FT /evidence="ECO:0007829|PDB:6J1X"
FT HELIX 414..423
FT /evidence="ECO:0007829|PDB:6J1X"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:6J1Y"
FT HELIX 434..443
FT /evidence="ECO:0007829|PDB:6J1X"
FT HELIX 445..448
FT /evidence="ECO:0007829|PDB:6J1Y"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:6J1Y"
FT STRAND 462..466
FT /evidence="ECO:0007829|PDB:6J1Y"
FT STRAND 472..476
FT /evidence="ECO:0007829|PDB:6J1Y"
FT TURN 477..480
FT /evidence="ECO:0007829|PDB:6J1Y"
FT STRAND 481..485
FT /evidence="ECO:0007829|PDB:6J1Y"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:6J1Y"
FT STRAND 502..506
FT /evidence="ECO:0007829|PDB:6J1X"
FT TURN 509..511
FT /evidence="ECO:0007829|PDB:2OP7"
FT STRAND 512..516
FT /evidence="ECO:0007829|PDB:6J1X"
FT TURN 517..520
FT /evidence="ECO:0007829|PDB:6J1X"
FT STRAND 521..525
FT /evidence="ECO:0007829|PDB:6J1X"
FT TURN 527..529
FT /evidence="ECO:0007829|PDB:6J1X"
FT HELIX 547..559
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 564..571
FT /evidence="ECO:0007829|PDB:5HPS"
FT TURN 573..575
FT /evidence="ECO:0007829|PDB:1ND7"
FT HELIX 576..586
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 589..593
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 594..600
FT /evidence="ECO:0007829|PDB:5HPS"
FT TURN 601..603
FT /evidence="ECO:0007829|PDB:1ND7"
FT HELIX 611..623
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 626..628
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 629..636
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 641..643
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 645..649
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 653..669
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 680..686
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 693..699
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 701..712
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 715..718
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 723..730
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 733..740
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 743..745
FT /evidence="ECO:0007829|PDB:1ND7"
FT TURN 749..751
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 752..765
FT /evidence="ECO:0007829|PDB:5HPS"
FT TURN 766..769
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 770..783
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 786..791
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 794..802
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 809..814
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 817..820
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 826..837
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 840..851
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 860..863
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 867..870
FT /evidence="ECO:0007829|PDB:5HPT"
FT STRAND 874..876
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 881..883
FT /evidence="ECO:0007829|PDB:5HPT"
FT STRAND 886..888
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 889..891
FT /evidence="ECO:0007829|PDB:5HPS"
FT STRAND 893..895
FT /evidence="ECO:0007829|PDB:5HPS"
FT HELIX 902..914
FT /evidence="ECO:0007829|PDB:5HPS"
SQ SEQUENCE 922 AA; 105202 MW; 35B6E1C03A3147DA CRC64;
MATASPRSDT SNNHSGRLQL QVTVSSAKLK RKKNWFGTAI YTEVVVDGEI TKTAKSSSSS
NPKWDEQLTV NVTPQTTLEF QVWSHRTLKA DALLGKATID LKQALLIHNR KLERVKEQLK
LSLENKNGIA QTGELTVVLD GLVIEQENIT NCSSSPTIEI QENGDALHEN GEPSARTTAR
LAVEGTNGID NHVPTSTLVQ NSCCSYVVNG DNTPSSPSQV AARPKNTPAP KPLASEPADD
TVNGESSSFA PTDNASVTGT PVVSEENALS PNCTSTTVED PPVQEILTSS ENNECIPSTS
AELESEARSI LEPDTSNSRS SSAFEAAKSR QPDGCMDPVR QQSGNANTET LPSGWEQRKD
PHGRTYYVDH NTRTTTWERP QPLPPGWERR VDDRRRVYYV DHNTRTTTWQ RPTMESVRNF
EQWQSQRNQL QGAMQQFNQR YLYSASMLAA ENDPYGPLPP GWEKRVDSTD RVYFVNHNTK
TTQWEDPRTQ GLQNEEPLPE GWEIRYTREG VRYFVDHNTR TTTFKDPRNG KSSVTKGGPQ
IAYERGFRWK LAHFRYLCQS NALPSHVKIN VSRQTLFEDS FQQIMALKPY DLRRRLYVIF
RGEEGLDYGG LAREWFFLLS HEVLNPMYCL FEYAGKNNYC LQINPASTIN PDHLSYFCFI
GRFIAMALFH GKFIDTGFSL PFYKRMLSKK LTIKDLESID TEFYNSLIWI RDNNIEECGL
EMYFSVDMEI LGKVTSHDLK LGGSNILVTE ENKDEYIGLM TEWRFSRGVQ EQTKAFLDGF
NEVVPLQWLQ YFDEKELEVM LCGMQEVDLA DWQRNTVYRH YTRNSKQIIW FWQFVKETDN
EVRMRLLQFV TGTCRLPLGG FAELMGSNGP QKFCIEKVGK DTWLPRSHTC FNRLDLPPYK
SYEQLKEKLL FAIEETEGFG QE
