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   27-MAR-2024, entry version 209.
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="https://atlasgeneticsoncology.org/gene/42993/WWP1";
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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   PDB; 8EI4; X-ray; 2.43 A; A=546-917.
DR   PDBsum; 1ND7; -.
DR   PDBsum; 2OP7; -.
DR   PDBsum; 5HPS; -.
DR   PDBsum; 5HPT; -.
DR   PDBsum; 6J1X; -.
DR   PDBsum; 6J1Y; -.
DR   PDBsum; 8EI4; -.
DR   AlphaFoldDB; Q9H0M0; -.
DR   SMR; Q9H0M0; -.
DR   BioGRID; 116243; 261.
DR   CORUM; Q9H0M0; -.
DR   IntAct; Q9H0M0; 61.
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; 9606-ENSP00000427793; -.
DR   PeptideAtlas; Q9H0M0; -.
DR   ProteomicsDB; 80294; -. [Q9H0M0-1]
DR   ProteomicsDB; 80295; -. [Q9H0M0-2]
DR   ProteomicsDB; 80296; -. [Q9H0M0-3]
DR   ProteomicsDB; 80297; -. [Q9H0M0-6]
DR   Pumba; Q9H0M0; -.
DR   ABCD; Q9H0M0; 3 sequenced antibodies.
DR   Antibodypedia; 25465; 190 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   AGR; HGNC:17004; -.
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; YNGRCEY; -.
DR   OrthoDB; 5480520at2759; -.
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; 15 hits in 1212 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 219 other cell types or tissues.
DR   ExpressionAtlas; Q9H0M0; baseline and differential.
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:monoatomic ion transmembrane transport; TAS:Reactome.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; 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; cd04021; C2_E3_ubiquitin_ligase; 1.
DR   CDD; cd00078; HECTc; 1.
DR   CDD; cd00201; WW; 3.
DR   Gene3D; 2.20.70.10; -; 3.
DR   Gene3D; 2.60.40.150; C2 domain; 1.
DR   Gene3D; 3.30.2160.10; Hect, E3 ligase catalytic domain; 1.
DR   Gene3D; 3.30.2410.10; Hect, E3 ligase catalytic domain; 1.
DR   Gene3D; 3.90.1750.10; Hect, E3 ligase catalytic domains; 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   PANTHER; PTHR11254; HECT DOMAIN UBIQUITIN-PROTEIN LIGASE; 1.
DR   PANTHER; PTHR11254:SF299; NEDD4-LIKE E3 UBIQUITIN-PROTEIN LIGASE WWP1; 1.
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; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF56204; Hect, E3 ligase catalytic domain; 1.
DR   SUPFAM; SSF51045; WW domain; 4.
DR   PROSITE; PS50004; C2; 1.
DR   PROSITE; PS50237; HECT; 1.
DR   PROSITE; PS01159; WW_DOMAIN_1; 4.
DR   PROSITE; PS50020; WW_DOMAIN_2; 4.
DR   Genevisible; Q9H0M0; HS.
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
//