title: Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases.
abstract: In this study we report the cloning and characterization of a novel human aminopeptidase, which we designate leukocyte-derived arginine aminopeptidase (L-RAP). The sequence encodes a 960-amino acid protein with significant homology to placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase. The predicted L-RAP contains the HEXXH(X)18E zinc-binding motif, which is characteristic of the M1 family of zinc metallopeptidases. Phylogenetic analysis indicates that L-RAP forms a distinct subfamily with placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in the M1 family. Immunocytochemical analysis indicates that L-RAP is located in the lumenal side of the endoplasmic reticulum. Among various synthetic substrates tested, L-RAP revealed a preference for arginine, establishing that the enzyme is a novel arginine aminopeptidase with restricted substrate specificity. In addition to natural hormones such as angiotensin III and kallidin, L-RAP cleaved various N-terminal extended precursors to major histocompatibility complex class I-presented antigenic peptides. Like other proteins involved in antigen presentation, L-RAP is induced by interferon-gamma. These results indicate that L-RAP is a novel aminopeptidase that can trim the N-terminal extended precursors to antigenic peptides in the endoplasmic reticulum.
authors.affiliation: Laboratory of Cellular Biochemistry, RIKEN, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanioka
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Shinako
authors.initials: S
authors.lastname: Masuda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nomura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
mesh_terms: D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D003001:Cloning, Molecular; D010122:Cystinyl Aminopeptidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D007962:Leukocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D000626:Aminopeptidases; D010122:Cystinyl Aminopeptidase; C019721:aminopeptidase B