Biol. Pharm. Bull. 27(6) 761—764 (2004)

The insulin-regulated aminopeptidase was identified as a major protein in intracellular vesicles that were derived from the low density microsomal fractions of adipocytes and muscles. The same vesicles also harbor the insulin-responsive glucose transporter GLUT4 and have been extensively characterized as GLUT4 vesicles. At the time of its discovery IRAP was named vp165 for vesicle protein of 165 kDa and gp160 for glycoprotein of 160 kDa. The purification and cloning of IRAP revealed that it is a type II membrane protein with an N-terminal 109 amino acid cytoplasmic tail, a single transmembrane segment, and a large 894 amino acid extracellular/intralumenal domain (Fig. 1). The theoretical Mr of IRAP is 117317. However, IRAP is heavily glycosylated and the molecular mass of the processed protein is larger, 165 kDa in most tissues and 140 kDa in the brain. The central portion of the extracellular/intralumenal domain of IRAP shares homology with the catalytic domains of aminopeptidases A and N and the thyrotropin-releasing hormone degrading enzyme. It contains the sites that are essential for catalytic function including the zinc-binding site (Fig. 1). These features define IRAP as a member of the family of zinc-dependent aminopeptidases. With the cloning of the human oxytocinase/placental leucine aminopeptidase (P-LAP) it became evident that IRAP and PLAP were homologues of the same protein. They are 87% identical at the amino acid level. Most recently IRAP was identified as a receptor for angiotensin IV. IRAP has a wide distribution and is found in all the major tissues. However, as shown by immunohistochemical analysis, the expression of IRAP is restricted to specific cell types in the various tissues (9, reviewed in 10). A remarkable characteristic of IRAP is its distinct intracellular localization and its redistribution to the cell surface in response to different stimuli (reviewed in 10).