Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.31.1 (micrococcal nuclease)
 2,818 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The product of the RAD6 (UBC2) gene of Saccharomyces cerevisiae is a ubiquitin-conjugating enzyme (Rad6) which is implicated in DNA repair, induced mutagenesis, retrotransposition, sporulation and the degradation of proteins with destabilizing N-terminal amino acid residues. Deletion of the 23-residue acidic C-terminus of Rad6 impairs sporulation and N-end rule protein degradation in vivo but does not affect other functions such as DNA repair and induced mutagenesis. We have investigated the role of the C-terminus of Rad6 in in vitro interactions with various substrates and with a putative ubiquitin-protein ligase, E3-R. The removal of the Rad6 C-terminus had significant different effects on enzyme activity for individual substrates. Although the 23-residue truncated Rad6-149 protein had markedly impaired activity for histone H2B and micrococcal nuclease, the activity for cytochrome c was the same as that of the intact Rad6 protein. Similarly, truncation of Rad6 had no effect on its activity for several poor substrates, namely, beta-casein, beta-lactoglobulin and oxidized RNase. E3-R stimulated the activities of both Rad6 and Rad6-149 for the latter three substrates to similar degrees. E3-R appears to act by enhancing the low intrinsic affinity of Rad6 and Rad6-149 for these substrates. Thus Rad6 can act in three different modes in vitro depending on the substrate, namely unassisted C-terminus-dependent, unassisted C-terminus-independent and E3-R-assisted C-terminus-independent modes. We also examined the results of removing the C-terminal acidic region of Cdc34 (Ubc3), a ubiquitin-conjugating enzyme closely related to Rad6. Truncation of Cdc34 like that of Rad6 had no effect on activity for beta-casein, beta-lactoglobulin or oxidized RNase in the presence or absence of E3-R.
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PMID:Role of the C-terminus of Saccharomyces cerevisiae ubiquitin-conjugating enzyme (Rad6) in substrate and ubiquitin-protein-ligase (E3-R) interactions. 816 12