U box domain (IPR003613)

Short name: Ubox_domain

Domain relationships


Quality control of intracellular proteins is essential for cellular homeostasis. Molecular chaperones recognise and contribute to the refolding of misfolded or unfolded proteins, whereas the ubiquitin-proteasome system mediates the degradation of such abnormal proteins. Ubiquitin-protein ligases (E3s) determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. More recently, however, U-box proteins, which contain a domain (the U box) of about 70 amino acids that is conserved from yeast to humans, have been identified as a new type of E3 [PMID: 12944364].

Members of the U-box family of proteins constitute a class of ubiquitin-protein ligases (E3s) distinct from the HECT-type and RING finger-containing E3 families [PMID: 12944364]. Using yeast two-hybrid technology, all mammalian U-box proteins have been reported to interact with molecular chaperones or co-chaperones, including Hsp90, Hsp70, DnaJc7, EKN1, CRN, and VCP. This suggests that the function of U box-type E3s is to mediate the degradation of unfolded or misfolded proteins in conjunction with molecular chaperones as receptors that recognise such abnormal proteins [PMID: 15115282, PMID: 15189447].

Unlike the RING finger domain, IPR001841, that is stabilised by Zn2+ ions coordinated by the cysteines and a histidine, the U-box scaffold is probably stabilised by a system of salt-bridges and hydrogen bonds. The charged and polar residues that participate in this network of bonds are more strongly conserved in the U-box proteins than in classic RING fingers, which supports their role in maintaining the stability of the U box. Thus, the U box appears to have evolved from a RING finger domain by appropriation of a new set of residues required to stabilise its structure, concomitant with the loss of the original, metal-chelating residues [PMID: 10704423].

GO terms

Biological Process

GO:0016567 protein ubiquitination

Molecular Function

GO:0004842 ubiquitin-protein transferase activity

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.