This entry represents a domain found in E3 ubiquitin-protein ligases HECW1 and HECW2 that lies upstream of the C2 domain. Its function is not clearly understood, but it might be to determine the substrate spectrum of the ligase [].
This is a region of 109 amino acids found in HECW1 proteins in Eukaryotes. Polymorphisms in the same region in the C.elegans homologue affects C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa [].
HECW1 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1), also known as NEDL1, is an HECT-type E3 ubiquitin protein ligase highly expressed in favorable neuroblastomas []. NEDL1 is thought to normally function in the quality control of cellular proteins by eliminating misfolded proteins. This is thought to be accomplished via a mechanism analogous to that of ER-associated degradation by forming tight complexes and aggregating misfolded proteins that have escaped ubiquitin-mediated degradation []. NEDL1 is thought to stimulate p53-mediated apoptosis [].NEDL1 shares large homology and structure with NEDL2, including a C2 domain at the N terminus, two WW domains in the middle of the protein, and a HECT domain at the C terminus []. NEDL2 regulates the stability of p73 []and functions as a regulator of the metaphase to anaphase transition [].This entry represents the C2 domain of NEDL1 and NEDL2.
