Aminopeptidase-N is a membrane-bound metalloprotease catalyzing the removal of N-terminal amino acids from peptides. Look et al. (1989) determined the complete primary structure of GP150, known as CD13. The large extracellular carboxyterminal domain contained a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. This enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS.
NCBI Summary:
Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Its function in proximal tubular epithelial cells and other cell types is less clear. The large extracellular carboxyterminal domain contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with known enzymes of this class showed that CD13 and aminopeptidase N are identical. The latter enzyme was thought to be involved in the metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the CNS. Human aminopeptidase N is a receptor for one strain of human coronavirus that is an important cause of upper respiratory tract infections. Defects in this gene appear to be a cause of various types of leukemia or lymphoma.
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Pasqualini R et al reported that aminopeptidase N is a receptor for tumor-homing
peptides and a target for inhibiting angiogenesis. Phage that display a surface
peptide with the NGR sequence motif home selectively to tumor vasculature in vivo.
A drug coupled to an NGR peptide has more potent antitumor effects than the free
drug. The receptor for the NGR peptides in tumor vasculature is aminopeptidase N
(APN; also called CD13). NGR phage specifically bound to immunocaptured APN
and to cells engineered to express APN on their surface. Antibodies against APN
inhibited in vivo tumor homing by the NGR phage. Immunohistochemical staining
showed that APN expression is up-regulated in endothelial cells within mouse and
human tumors. In another tissue that undergoes angiogenesis, corpus luteum, blood
vessels also expressed APN, but APN was not detected in blood vessels of various
other normal tissues stained under the same conditions. APN antagonists specifically
inhibited angiogenesis in chorioallantoic membranes and in the retina and
suppressed tumor growth. Thus, APN is involved in angiogenesis and can serve as a
target for delivering drugs into tumors and for inhibiting angiogenesis.
Cellular localization
Plasma membrane
Comment
Ovarian function
Ovulation, Steroid metabolism, Luteinization
Comment
Tachibana et al. (1996) showed that an aminopeptidase inhibitor, bestatin, enhances progesterone and oestradiol secretion by porcine granulosa cells stimulated with FSH in vitro. They indicated that the inhibition of membrane-bound aminopeptidase(s) on the cell surfaces affects the steroidogenesis of granulosa cells, and that these aminopeptidase(s) are important regulators of granulosa cell differentiation. Nakamura et al. (1996) injected an inhibitor of cell-surface aminopeptidases, bestatin, i.p. four times during 2 days into 20 day old female ICR mice, in which follicular growth and ovulation were stimulated by PMSG and hCG. The mean +/- SD number of ovulated oocytes in bestatin-treated mice was significantly higher than that in control mice (47.00 +/- 18.13 (n = 26) versus 35.90 +/- 10.14 (n = 28)). In addition, the administration of bestatin via the ovarian bursa prior to PMSG administration significantly increased the number of ovulated oocytes per oviduct from the treated compared with the contralateral ovary. Nakamura et al. (1998) indicated that stress inhibited the ovarian response to gonadotropins and that bestatin restored the response suppressed by stress.
Expression regulated by
Comment
Ovarian localization
Theca, Luteal cells
Comment
Fujiwara et al. (1992) reported that aminopeptidase-N was detected by immunofluorescence staining on theca interna cells in secondary follicles and on luteinized thecal cells in preovulatory follicles and corpora lutea. However, aminopeptidase-N was not detected on granulosa cells. Peptidase activity was also detected by histochemical staining on theca interna cells and luteinized thecal cells. Luteinized granulosa cells showed peptidase activity, despite the lack of aminopeptidase-N.