IDENTIFICATION OF A FAMILY OF CLOSELY-RELATED HUMAN UBIQUITIN-CONJUGATING ENZYMES

Two very closely related human E2 ubiquitin conjugating enzymes, UbcH5 B and UbcH5C, have been iden tified. These enzymes are products of dis tinct genes and are 88-89% identical in amino acid sequence to the rec ently described human E2, UbcH5 (now designated UbcH5A), UbcH5A-C are homologous to a family of five ubiquitin conjugating enzymes from Arab idopsis thaliana, AtUBC8-12. They are also closely related to Saccharo myces cerevisiae ScUBC4 and ScUBC5, which are involved in the stress r esponse, and play a central role in the targeting of short-lived regul atory proteins for degradation, mRNAs encoding UbcH5A-C were co-expres sed in all cell lines and tissues evaluated, with UbcH5C transcripts g enerally expressed at the highest levels, Analysis of Southern blots s uggests that there are likely to be other related members of this fami ly, Both UbcH5B and UbcH5C form thiol ester adducts with ubiquitin, an d have activities similar to UbcH5A and AtUBC8 in the conjugation of u biquitin to target proteins in the presence of the human ubiquitin pro tein ligase E6-AP. These results establish the existence of a highly c onserved, and widely expressed, family of human ubiquitin conjugating enzymes.