ubiquitin-like (Ubl) domain found in FAS-associated factor 1 (FAF1) and similar proteins
FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem Ubl domains, which show high structural similarity with UBX domain. FAF1 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to Ubl domains.
Feature 1: key conserved lysine K27, 1 residue position
Conserved feature residue pattern:[KR]
Evidence:
Comment:K27 (Ub numbering) is a lysine conserved in the Ubl_ubiquitin_like family; it is one of 7 lysines involved in chain linkage in ubiquitin (K6, K11, K27, K29, K33, K48, or K63, Ub numbering); may have other functions, for example for NEDD8 it is involved in the mechanism of protein neddylation
Jiyao W et al.(2023). "The conserved domain database in 2023.",