High impact information on UBC5

• UBC4 and UBC5 are individually dispensable class I E2 enzymes involved in the degradation of short-lived and abnormal proteins [1].
• UBC1, UBC4 and UBC5 are functionally overlapping and constitute an enzyme family essential for cell growth and viability [2].
• Such a high degree of similarity between the human E2(Mr = 17,000) and the yeast DNA repair enzyme is suggestive of important common structural constraints or roles in addition to ubiquitin carrier activity, since in yeast this function itself is not necessarily dependent on high conservation of primary structure [3].
• We find that cells at high temperature or cells deficient in the ubiquitin-conjugating enzymes Ubc4 and Ubc5 are hypersensitive to AZC-induced proliferation arrest [4].
• Of particular importance is a phenylalanine residue at position 62 of UbcH5 that is conserved among the members of the UBC4/UBC5 subfamily but is not present in any of the other known E2s, whereas the N-terminal 60 amino acids do not contribute significantly to the specificity of these interactions [5].

Biological context of UBC5

• Partial amino acid sequence analysis of E(2)15kDa revealed a substantial identity (approximately 80% in two peptide regions) with yeast E2s encoded by UBC4/UBC5 genes [6].
• Surprisingly, the structure of this E2 was markedly more similar to the Saccharomyces cerevisiae DNA repair gene RAD6, than to the S. cerevisiae UBC4/UBC5 genes which are required for the degradation of short-lived proteins and support much of the ubiquitination of yeast proteins [7].
• Loss of UBC4 and UBC5 activity impairs cell growth, leads to inviability at elevated temperatures or in the presence of an amino acid analog, and induces the stress response [8].
• C. elegans ubc-2 is constitutively expressed at all life cycle stages and, unlike yeast UBC4 and UBC5, is not induced by heat shock [9].
• Ubc4 and Ubc5 are functionally redundant E2 enzymes that represent ideal candidates for ubiquitinating damaged nascent proteins because they lack significant substrate specificity, are required for the degradation of bulk, damaged proteins, and contribute to cellular stress-tolerance mechanisms [10].

Anatomical context of UBC5

• A rabbit reticulocyte ubiquitin carrier protein that supports ubiquitin-dependent proteolysis (E214k) is homologous to the yeast DNA repair gene RAD6 [11].

Associations of UBC5 with chemical compounds

• The conservation of this phenylalanine residue throughout evolution underlines the importance of the ability to interact with hect domain proteins for the cellular function of UBC4/UBC5 subfamily members [5].

Other interactions of UBC5

• The products of yeast UBC4 and UBC5 genes along with that of UBC1 gene constitute a subfamily of functionally overlapping E2s that mediate the selective degradation of short-lived and abnormal proteins in vivo [6].
• This suggested that mammalian homologues of UBC4/UBC5 remained to be identified [7].

Analytical, diagnostic and therapeutic context of UBC5

• We have isolated a 20-kDa ubiquitin carrier protein [E2(20 kDa)] from wheat by using ubiquitin covalent affinity chromatography and anion-exchange HPLC that catalyzes multiubiquitin chain formation in vitro [12].

References