| Primary Identifier | IPR041918 | Type | Domain |
| Short Name | UBA_HUWE1 |
| description | HUWE1 (also known as HECT, UBA and WWE domain-containing protein 1, or Mcl-1 ubiquitin ligase E3, amongst other names) may function as a ubiquitin-protein ligase involved in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase, and modulates base excision repair (BER) []. HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation []. Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involved in DNA damage-induced apoptosis []. Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation [].HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N terminus and a HECT domain at the C terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain is involved in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway []. |
