RNF167 is an E3 ubiquitin ligase that interacts with TSSC5 (SLC22A18; 602631) and, together with UBCH6 (UBE2E1; 602916), facilitates TSSC5 polyubiquitylation (Yamada and Gorbsky, 2006).

Using bacterial 2-hybrid screening with CDC34 (116948) as bait, Yamada and Gorbsky (2006) isolated RNF167, which they called RING105. The predicted 350-amino acid protein contains an N-terminal transmembrane (TM) domain, followed by a protease-associated domain, a second TM domain, a RING finger domain, and a putative PEST sequence. Fluorescence microscopy and immunoblot analyses demonstrated that the 45-kD RING105 protein was expressed on cytoplasmic membranes and was most abundant in liver and kidney.

Yamada and Gorbsky (2006) found that ectopic expression of RING105 in HeLa and embryonic kidney cells resulted in protein degradation in the absence of a proteasome inhibitor. Immunoprecipitation analysis with UBCH5A (UBE2D1; 602961) and UBCH6 showed that RING105 had autoubiquitylation activity. Bacterial 2-hybrid screening with RING105 as bait revealed an interaction with TSSC5, which, like RING105, localized to cytoplasmic membranes. Immunoprecipitation and immunoblot analyses with truncated forms of TSSC5 demonstrated that TSSC5 was polyubiquitylated on its sixth hydrophilic loop in an accelerated manner in the presence of RING105 and UBCH6. FACS analysis showed that RING105 delayed cell-cycle transition in a RING finger domain-dependent manner. Yamada and Gorbsky (2006) proposed that UBCH6 and RING105 may define a ubiquitin-proteasome pathway that targets TSSC5.

Stumpf (2024) mapped the RNF167 gene to chromosome 17p13.2 based on an alignment of the RNF167 sequence (GenBank AK025329) with the genomic sequence (GRCh38).