Produced in E. coli.

A number of E2s in Saccharomyces cerevisiae and their homologues have been identified. One such family of E2s is the UBC4/5, characterised as essential for the degradation of short-lived, regulatory and abnormal proteins. Protein levels of S. cerevisiae UbC4/5 are up-regulated in response to stress, and their loss results in severe effects on cellular functions. A human gene product that is 79% identical to S. cerevisiae UBC4/5 in amino-acid sequence was identified as UbcH5a. In addition, two other human members of this highly conserved E2 class were also cloned and designated as UbcH5b and UbcH5c, having 88% and 89% identity to UbcH5a, respectively. Members of the UbcH5a/b/c are the most active class of E2s in cell extracts. The importance of this enzyme class is underscored by the critical role of UBC4/5 in S. cerevisiae. UbcH5a stimulates the conjugation of ubiquitin to the tumour-repressor p53 in the presence of E6-AP and E6. Moreover, UbcH5 family is implicated in c-fos recognition, the modulation of which is controlled by the ubiquitin-proteasome pathway. UbcH5b and UbcH5c are associated with the signal-induced conjugation and subsequent degradation of IkBalpha in the presence of the SCF complexes. UbcH5c also catalyses the ubiquitination leading to the processing of p105 precursor to form p50, a subunit of the heterodimeric transcription factor NF-kB. The range and diversity of substrates and E3s with which this class of E2 enzymes interact, suggest their complex roles in cellular functions require to be studied further.