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

More general terms

• phosphoprotein
• E3 ubiquitin ligase

Additional terms

• 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)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11059
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:11059
• OMIM: https://mirror.omim.org/entry/602307
• UniProt: http://www.uniprot.org/uniprot/Q9H0M0.html