The U-box is a protein domain with about 70 amino acids. Although the U-box domain is similar with the RING domain, the zinc-binding sites in the RING domain are replaced by conserved charged and polar residues to maintain structure and activity (1). Previously, the U-box protein was considered as a ubiquitin chain assembly factor to catalyze the formation of a ubiquitin chain on ubiquitinated substrates, while recent studies showed that it could mediate polyubiquitylation in the absence of a HECT type or RING-finger type E3. Although the understanding of the detailed mechanisms and functions of the U-box proteins are still limited, it is proposed that they are involved in various biological processes such as the cellular stress response to the intracellular accumulation of abnormal proteins (2).

1. http://www.ebi.ac.uk/interpro/entry/IPR003613

2. Hatakeyama, S. and K. I. Nakayama (2003) U-box proteins as a new family of ubiquitin ligases. Biochem. Biophys. Res. Commun., 302(4): 635-45. PMID: 12646216