WWP1 Recombinant Rabbit mAb (S-4412-25)

WWP1, full name WW domain-containing E3 ubiquitin ligase 1, is a member of the NEDD4-like protein family composed of 922 amino acids with a molecular weight of approximately 110 kDa. Its protein structure, from the N-terminus to the C-terminus, consists of a C2 domain responsible for membrane localization, four tandem WW protein-interaction domains (responsible for recognizing PY motifs on substrate proteins), and a C-terminal HECT domain responsible for catalyzing ubiquitin transfer. Functionally, the E3 ligase activity of WWP1 is precisely regulated by a "multi-lock" mechanism: in its basal state, the WW domains bind to the HECT catalytic domain to form an autoinhibitory conformation, which is relieved upon phosphorylation or binding to activating proteins, thereby catalyzing the ubiquitination and degradation of various substrates. Its key substrates include SMAD proteins that regulate the TGF-β signaling pathway, tumor suppressors such as p63 and KLF5, and connexin 43 which affects cardiac function. Through the degradation of these critical proteins, WWP1 is broadly involved in embryonic development, immune regulation, viral infection, and tumorigenesis, while dysregulation or cancer-associated mutations of WWP1 are closely linked to various neurological disorders including Troyer syndrome, cardiac diseases, and multiple types of human cancers.