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NEDD4-like E3 ubiquitin-protein ligase WWP1; atrophin-1-interacting protein 5; AIP5; TGIF-interacting ubiquitin ligase 1; Tiul1; WW domain-containing protein 1 (WWP1)

Function: - E3 ubiquitin-protein ligase - accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester & directly transfers the ubiquitin to targeted substrates - ubiquitinates ERBB4 isoforms JM-A CYT-1 & JM-B CYT-1, KLF2, KLF5 & TP63 & promotes their proteasomal degradation - ubiquitinatescRNF11 without targeting it for degradation - ubiquitinates 7 promotes degradation of TGFBR1 - ubiquitination is enhanced by SMAD7 - ubiquitinates SMAD6 & SMAD7 - ubiquitinates & promotes degradation of SMAD2 in response to TGF-beta signaling (requires interaction with TGIF) - activated by NDFIP1- & NDFIP2-binding protein modification - auto-ubiquitinated & ubiquitinated by RNF11 - binds KLF2 AND HIVEP3 (putative) - binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA & adenovirus type 2 PIII - interacts with RNF11 (putative) - interacts with SPG20 - interacts with ERBB4 isoforms JM-B CYT-1 & JM-A CYT-1 - interacts with SMAD1, SMAD2, SMAD3, SMAD5, SMAD6, SMAD7, TGFBR1 & TGFBR2 - associates with the TGFBR1:TGFBR2 receptor complex in presence of SMAD7 - interacts with SKIL isoform 1 - interacts with TP63 isoform 1 & isoform 2 - interacts with STAMBP & RNF11 - interacts with NDFIP1 & NDFIP2 (probable) - interaction activates the E3 ubiquitin-protein ligase - interacts with TGIF Structure: - contains 1 C2 domain - contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain - contains 4 WW domains Compartment: - cytoplasm (putative) - cell membrane - nucleus Alternative splicing: - named isoforms=6 - additional isoforms seem to exist Expression: - expressed in heart, placenta, pancreas, kidney, liver, skeletal muscle, bone marrow, fetal brain - expressed at much lower levels in adult brain & lung - isoform 1 & isoform 5 predominate in most tissues tested - isoform 5 predominates in testis & bone

Related

E3 ubiquitin-protein ligase NEDD4; cell proliferation-inducing gene 53 protein; neural cell expressed developmentally down-regulated protein 4; NEDD-4 (NEDD4, KIAA0093, NEDD4-1, PIG53) WW domain-containing protein 1; kidney & brain protein; KIBRA; HBeAg-binding protein 3 (WWC1, KIAA0869)

General

phosphoprotein E3 ubiquitin ligase; ubiquitin-ligating enzyme E3; N end-recognizing protein

Properties

SIZE: entity length = 922 aa MW = 105 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: C2 domain {5-98} MOTIF: binding site FOR-BINDING-OF: phospholipid Ca+2-binding site WW domain (W/rsp5/WWP domain) {349-382} WW domain (W/rsp5/WWP domain) {381-414} WW domain (W/rsp5/WWP domain) {456-489} WW domain (W/rsp5/WWP domain) {496-529} HECT domain {588-922} MOTIF: Thr phosphorylation site {T822} cysteine residue {C890} cysteine residue {890}

Database Correlations

OMIM 602307 UniProt Q9H0M0 PFAM correlations Entrez Gene 11059 Kegg hsa:11059

References

  1. UniProt :accession Q9H0M0
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org//genes/WWP1ID42993ch8q21.html