U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 A (UBE4A) and similar proteins
This subfamily includes yeast ubiquitin fusion degradation protein 2 (UFD2p) and its mammalian homolog, UBE4A. Yeast UFD2p, also known as ubiquitin conjugation factor E4 or UB fusion protein 2, is a polyubiquitin chain conjugation factor (E4) in the ubiquitin fusion degradation (UFD) pathway which catalyzes elongation of the ubiquitin chain through Lys48 linkage. It binds to substrates conjugated with one to three ubiquitin molecules and catalyzes the addition of further ubiquitin moieties in the presence of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3), yielding multiubiquitylated substrates that are targets for the 26S proteasome. UFD2p is implicated in cell survival under stress conditions and is essential for homoeostasis of unsaturated fatty acids. It interacts with UBL-UBA proteins Rad23 and Dsk2, which are involved in the endoplasmic reticulum-associated degradation, ubiquitin fusion degradation, and OLE-1 gene induction pathways. UBE4A is a U-box-type ubiquitin-protein ligase that is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. It may have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation. Members of this family contain an N-terminal ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.
Jiyao W et al.(2023). "The conserved domain database in 2023.",