WWP1
Domain
The WW domains mediate interaction with PPxY motif-containing proteins.
Function
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF. Activates the Hippo signaling pathway in response to cell contact inhibition and recruitment to the Crumbs complex at the cell membrane (PubMed:34404733). Monoubiquitinates AMOTL2 which facilitates its interaction with and activation of LATS2 (PubMed:34404733). LATS2 then phosphorylates YAP1, excluding it from the nucleus and therefore ultimately represses YAP1-driven transcription of target genes (PubMed:34404733).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Auto-ubiquitinated and ubiquitinated by RNF11.
Tissue Specificity
Detected in heart, placenta, pancreas, kidney, liver, skeletal muscle, bone marrow, fetal brain, and at much lower levels in adult brain and lung. Isoform 1 and isoform 5 predominate in all tissues tested, except in testis and bone marrow, where isoform 5 is expressed at much higher levels than isoform 1.
Cellular localization
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Nucleus
- Cell junction
- Translocates to the plasma membrane in response to increased cell-cell contact inhibition and subsequent interaction with the Crumbs complex.
Alternative names
NEDD4-like E3 ubiquitin-protein ligase WWP1, Atrophin-1-interacting protein 5, HECT-type E3 ubiquitin transferase WWP1, TGIF-interacting ubiquitin ligase 1, WW domain-containing protein 1, AIP5, Tiul1, WWP1