E3 ubiquitin-protein ligase ARIH1 (Arih1)

Acts as an atypical E3 ubiquitin- protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: partners with CRL complexes and especially mediates addition of the first ubiquitin on CRLs targets. The first ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2.

E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes. Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear.