InterPro domain: IPR023318

This superfamily represents an alpha orthogonal bundle domain found in ubiquitin-activating enzyme and ubiquitin-like NEDD8-activating enzyme.

Ubiquitin-activating enzyme (E1 enzyme) activates ubiquitin by first adenylating with ATP its C-terminal glycine residue and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thiolester and free AMP. Later the ubiquitin moiety is transferred to a cysteine residue on one of the many forms of ubiquitin-conjugating enzymes (E2) [ 1 ]. This domain carries the last of five conserved cysteines that is part of the active site of the enzyme, responsible for ubiquitin thiolester complex formation, the active site being represented by the sequence motif PICTLKNFP [ 2 ]. Not all proteins in this entry contain a functional active site.

1. Molecular cloning, sequence, and tissue distribution of the human ubiquitin-activating enzyme E1. Proc. Natl. Acad. Sci. U.S.A. 88, 258-62
2. Molecular cloning of cDNA encoding a ubiquitin-activating enzyme (E1) from goldfish (Carassius auratus) and expression analysis of the cloned gene. Biochim. Biophys. Acta 1492, 259-63