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Domain

Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate.

The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.

Function

E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:16118314, PubMed:17646546, PubMed:19340006, PubMed:24076655, PubMed:33268465, PubMed:34518685, PubMed:38418882). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-5-RING ubiquitin ligase complex (ECS complex, also named CRL5 complex) and initiating ubiquitination of ECS substrates: associates with ECS complex and specifically mediates addition of the first ubiquitin on ECS targets (PubMed:33268465, PubMed:34518685, PubMed:38418882). The initial ubiquitin is then elongated (PubMed:33268465). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the cullin-5 (CUL5) component of the ECS complex (PubMed:24076655). Together with the ECS(ASB9) complex, catalyzes ubiquitination of CKB (PubMed:33268465). Promotes ubiquitination of DCUN1D1 (PubMed:30587576). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006).

(Microbial infection) Following infection by HIV-1 virus, acts together with a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) hijacked by the HIV-1 Vif protein, to catalyze ubiquitination and degradation of APOBEC3F and APOBEC3G.

Pathway

Protein modification; protein ubiquitination.

Post-translational modifications

Ubiquitinated. Ubiquitination promotes proteasomal degradation.

Sequence similarities

Belongs to the RBR family. Ariadne subfamily.

Tissue specificity

Widely expressed with higher expression in granulocytes.

Cellular localization

  • Nucleus
  • Cytoplasm

Alternative names

ARI2, TRIAD1, HT005, ARIH2, E3 ubiquitin-protein ligase ARIH2, ARI-2, Protein ariadne-2 homolog, Triad1 protein

Target type

Proteins

Primary research area

Oncology

Molecular weight

57819Da

We found 5 products in 1 category

Primary Antibodies

Search our catalogue for 'ARIH2' (5)

Products

ab133744

Anti-ARIH2/TRIAD1 antibody [EPR7670]

Recombinant
RabMAb

ab133653

Anti-ARIH2/TRIAD1 antibody [EPR7671]

Recombinant
RabMAb