Apg7p is distantly related to Uba1p and its relatives. (A) Schematic representation of the similarity domains among UBA1, UBA2, UBA3, and APG7. The putative active site cysteines are located within similarity box III (UBA domain), as indicated. The essential ATP-binding domains are located within similarity box I. UBA1 contains another ATP-binding motif within similarity box Ib, which is nonessential for function. The similarity boxes correspond to those of Johnson et al. (1997) and Liakopoulos et al. (1998), except box Ib. (B) The phylogenetic tree of E1 enzymes. The homologous regions of E1-like enzymes containing the ATP-binding domain and active site cysteine were multi-aligned and analyzed by a CLUSTAL W multiple alignment program (Thompson et al., 1994). Shown are ScAPG7 (residues 321 to 520 of S. cerevisiae Apg7p; PID: g731742), PpAPG7 (residues 322 to 521 of P. pastoris Gsa7p), HsAPG7/GSA7 (residues 235 to 434 of Homo sapiens APG′7/GSA7), SpAPG7/GSA7 (residues 332 to 531 of Schizosaccharomyces pombe Apg7p/Gsa7p; PID g2894280), HsUBA1 (residues 465 to 664 of H. sapiens UBA1; PID: g340072), MmUBA1 (residues 465 to 664 of Mus musculus UBA1; PID: g220629), ScUBA1 (residues 431 to 630 of S. cerevisiae Uba1p; PID: g4715), AtUBA1 (residues 489 to 688 of A. thaliana UBA1; PID: g1750376), TaUBA1 (residues 459 to 658 of Triticum aestivum UBA1; PID g136632), ScUBA2 (residues 18 to 219 of S. cerevisiae Uba2p; PID: g1717852), SpUBA2 (residues 22 to 221 of S. pombe Uba2p; PID: g2956755), HsUBA3 (residues 45 to 244 of H. sapiens UBA3; PID: g3342564), and ScUBA3 (residues 1 to 200 of S. cerevisiae Uba3p; PID: g2980755) (Hatfield et al., 1990; Handley et al., 1991; McGrath et al., 1991; Imai et al., 1992; Dohmen et al., 1995; Hatfield et al., 1997; Liakopoulos et al., 1998; Mizushima et al., 1998a; Osaka et al., 1998, Yuan et al., 1999).