Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins
UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, 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. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 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 overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.
Feature 1:putative UBX-p97 interaction site [polypeptide binding site]
Evidence:
Comment:based on the structural evidence of the Rattus norvegicus UBX domain of p47/UBXN2C (1S3S) bound with p97, contacts at 4A
Comment:Hexameric p97 N terminal domains are complexed with UBX domain of p47 through a loop that is highly conserved in UBX domains but is absent in ubiquitin.
Jiyao W et al.(2023). "The conserved domain database in 2023.",