RNF166 Recombinant Rabbit mAb (S-3509-12)

RNF166 (RING Finger Protein 166) is a RING-type E3 ubiquitin ligase (~26.1 kDa, 237 amino acids) containing an N-terminal catalytic RING domain and C-terminal ubiquitin-interacting motifs (UIMs) that functions as a "reader-writer" enzyme capable of recognizing MARUbylation (mono-ADP-ribosylated ubiquitin) and catalyzing atypical K11-, K29-, and K33-linked polyubiquitination chains on diverse substrates. Originally identified as a key regulator of antibacterial autophagy (xenophagy), RNF166 recruits autophagy adaptors p62/SQSTM1 and NDP52 to intracellular pathogens such as Salmonella and Listeria by specifically ubiquitinating p62 at lysines 91 and 189 with K29/K33 linkages, thereby promoting LC3 recruitment and bacterial clearance without altering general autophagic flux. Beyond host defense, RNF166 plays multifaceted roles in immune signaling by enhancing TRAF3/6 ubiquitination to positively regulate RNA virus-induced interferon-β production, in neurodegeneration by acting as a pro-apoptotic factor that ubiquitinates and degrades XIAP (X-linked inhibitor of apoptosis protein) to activate caspase-dependent cell death in Parkinson's disease models, and in metabolic disease by regulating podocyte mitochondrial function and apoptosis via CYLD signaling in diabetic nephropathy. Additionally, recent studies reveal that RNF166, together with its paralog RNF114, stabilizes tankyrase enzymes through K11-linked diubiquitylation, counteracting RNF146-mediated K48-linked degradation and modulating Wnt/β-catenin cancer signaling pathways.