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ARIH2

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). 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 (By similarity). The initial ubiquitin is then elongated (By similarity). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated form of the ECS complex (PubMed:24076655). Mediates 'Lys-6', 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:16118314, PubMed:17646546, PubMed:19340006). May play a role in myelopoiesis (PubMed:19340006).

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

  • E3 ubiquitin-protein ligase ARIH2
  • ARI-2
  • Protein ariadne-2 homolog
  • RING-type E3 ubiquitin transferase ARIH2
  • Triad1 protein
  • TRIAD1
  • HT005
  • ARIH2
  • ARI2

Target type

Proteins

Molecular weight

57819Da