ARIH1
Description
The ARIH1 (ariadne RBR E3 ubiquitin protein ligase 1) is a protein-coding gene located on chromosome 15.
ARIH1 (Protein ariadne-1 homolog) is a human protein encoded by the ARIH1 gene. It interacts with EIF4E2 and UBE2L3.
ARIH1 acts as an E3 ubiquitin-protein ligase, catalyzing the ubiquitination of target proteins in collaboration with the ubiquitin-conjugating enzyme E2 UBE2L3. It functions as an atypical E3 ligase by associating with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates. ARIH1 specifically adds the first ubiquitin to CRL targets, which is then elongated by CDC34/UBE2R1 and UBE2R2. Its activity is activated upon binding to neddylated CRL complexes. ARIH1 plays a role in protein translation in response to DNA damage by ubiquitinating EIF4E2, although the consequences of EIF4E2 ubiquitination remain unclear. Some studies suggest that EIF4E2 ubiquitination promotes cap-binding and translation arrest, while others indicate it leads to EIF4E2 degradation. ARIH1 also acts as the ligase involved in ISGylation of EIF4E2. In vitro, ARIH1 regulates the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2, potentially influencing LINC complex formation, localization, and consequently, nuclear subcellular localization and morphology.
ARIH1 is also known as ARI, HARI, HHARI, UBCH7BP.
Associated Diseases
- cancer
- breast cancer
- acheiropody
- acromesomelic dysplasia 2C, Hunter-Thompson type
- acromesomelic dysplasia 2A
- Fuhrmann syndrome
- acrocapitofemoral dysplasia
- mesomelic dysplasia, Savarirayan type
- tibial hemimelia
- familial thoracic aortic aneurysm and aortic dissection
