Ube2j1 and Ube2j2 are homologs of the yeast ubiquitin-conjugating enzyme UBC6, which catalyzes the covalent attachment of ubiquitin to other proteins. These proteins constitute a distinct family of ubiquitin-conjugating enzymes sharing a conserved non-canonical active site sequence and a C-terminal transmembrane domain. By analogy with yeast UBC6, Ube2j1 and Ube2j2 are localized to the endoplasmic reticulum and seem to function in the selective degradation of misfolded membrane proteins and in general mediation of the stress response.