RNF138
Domain
The zinc finger domains (C2H2-type and C2HC-type zinc fingers) bind DNA and mediate recruitment to double-strand break sites. They show strong preference for DNA with 5'- or 3'-single-stranded overhangs, while they do not bind blunt-ended double-stranded DNA or poly(ADP-ribose) (PAR) polymers.
Function
E3 ubiquitin-protein ligase involved in DNA damage response by promoting DNA resection and homologous recombination (PubMed:26502055, PubMed:26502057). Recruited to sites of double-strand breaks following DNA damage and specifically promotes double-strand break repair via homologous recombination (PubMed:26502055, PubMed:26502057). Two different, non-exclusive, mechanisms have been proposed. According to a report, regulates the choice of double-strand break repair by favoring homologous recombination over non-homologous end joining (NHEJ): acts by mediating ubiquitination of XRCC5/Ku80, leading to remove the Ku complex from DNA breaks, thereby promoting homologous recombination (PubMed:26502055). According to another report, cooperates with UBE2Ds E2 ubiquitin ligases (UBE2D1, UBE2D2, UBE2D3 or UBE2D4) to promote homologous recombination by mediating ubiquitination of RBBP8/CtIP (PubMed:26502057). Together with NLK, involved in the ubiquitination and degradation of TCF/LEF (PubMed:16714285). Also exhibits auto-ubiquitination activity in combination with UBE2K (PubMed:16714285). May act as a negative regulator in the Wnt/beta-catenin-mediated signaling pathway (PubMed:16714285).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Auto-ubiquitinated.
Cellular localization
- Chromosome
- Recruited at DNA damage sites (PubMed:26502055). Localizes to sites of double-strand break: localization to double-strand break sites is mediated by the zinc fingers (PubMed:26502055, PubMed:26502057).
Alternative names
NARF, HSD-4, HSD4, RNF138, E3 ubiquitin-protein ligase RNF138, Nemo-like kinase-associated RING finger protein, RING finger protein 138, RING-type E3 ubiquitin transferase RNF138, NLK-associated RING finger protein, hNARF