ARIH1

E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and

Full Name

Ariadne RBR E3 Ubiquitin Protein Ligase 1

Function

E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346, PubMed:23707686).
Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346).
The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346).
E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346).
Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349).
According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349).
According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119).
Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916).
In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear morphology (PubMed:29689197).

Biological Process

Positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: GO_Central
Protein polyubiquitination Source: GO_Central
Protein ubiquitination Source: UniProtKB
Ubiquitin-dependent protein catabolic process Source: GO_Central

Cellular Location

Nucleus; Cajal body; Cytoplasm. Mainly cytoplasmic (PubMed:11278816). Present in Lewy body (PubMed:21590270).

Involvement in disease

Defects in ARIH1 have been found in several individuals with thoracic aortic aneurysms and cerebrovascular disease.