Ubiquitin regulatory domain X (UBX) found in UBX domain protein 6 (UBXN6) and similar proteins
UBXN6, also termed UBX domain-containing protein 1 (UBXD1), and UBXDC2, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like 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. UBXN6 acts 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. Unlike other p97 cofactors that binds the N-domain of p97 through their UBX domain, UBXN6 binds p97 in two regions, at the p97 C terminus via a PUB domain and at the p97 N-domain with a short linear interaction motif termed VIM. Its UBX domain is not functional for the binding of p97. The UBXN6-p97 complex regulates the endolysosomal sorting of ubiquitylated plasma membrane protein caveolin-1 (CAV1), as well as the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53. In addition, UBXN6 is a regulatory component of endoplasmic reticulum-associated degradation (ERAD) that may modulate the adaptor binding to p97.
Feature 1: key conserved lysine K6, 1 residue position
Conserved feature residue pattern:[KR]
Evidence:
Comment:K6/R (Ub numbering) is one of 7 lysines involved in chain linkage in ubiquitin (K6, K11, K27, K29, K33, K48, or K63, Ub numbering), the other 6 lysines are not conserved in this subfamily; may have other functions
Jiyao W et al.(2023). "The conserved domain database in 2023.",