FIGURE 1.

Molecular evolution of LVRN/APQ. Alignments of the human LVRN/APQ amino acid sequence with the sequences of other human M1 aminopeptidases (A, upper) and its orthologues (B, upper) are shown. Amino acid sequence alignments around the GXMEN and HEXXH(X)₁₈E motifs of M1 aminopeptidases are shown. Gaps are inserted into the sequence to obtain optimal alignments. Residues conserved among more than six enzymes are shaded. His³⁷⁹ residue of human LVRN/APQ is boxed in black. Evolutionary relationships of human M1 aminopeptidases (A, lower panel) and LVRN/APQ orthologues (B, lower panel) are shown. The bar shown below the phylogenetic tree represents the genetic distance. The sequence data used for analyses are as follows: A, LVRN/APQ (NM_173800) (18); APA (NM_001977) (46, 47); PSA, puromycin-sensitive aminopeptidase (NM_006310) (48); P-LAP/IRAP, placental leucine aminopeptidase/oxytocinase/insulin-regulated aminopeptidase (NM_005575) (3); A-LAP/ERAP1, adipocyte-derived leucine aminopeptidase/endoplasmic reticulum aminopeptidase-1 (NM_001040458) (49); L-RAP/ERAP2, leukocyte-derived arginine aminopeptidase/endoplasmic reticulum aminopeptidase-2 (NM_022350) (9); TRH-DE, thyrotropin-releasing hormone-degrading enzyme (NM_013381) (50); APN (NM_001150) (51); APB, aminopeptidase B (NM_020216) (52); LTA4H, leukotriene A₄ hydrolase (NM_000895) (53); and APO, aminopeptidase O (NM_032823) (54). B, human (Homo sapiens, NM_173800), monkeys (Pan troglodytes, XM_001149318, and Macaca mulatta, XM_001086413), cattle (Bos taurus, XM_001788658), horse (Equus caballus, XM_001918093), dog (Canis lupus familiaris, XM_538554), rat (Rattus norvegicus, XM_577617), and mouse (Mus musculus, XM_911283).