Alternative titles; symbols
HGNC Approved Gene Symbol: ANPEP
Cytogenetic location: 15q26.1 Genomic coordinates (GRCh38): 15:89,784,895-89,814,852 (from NCBI)
Alanyl aminopeptidase, or aminopeptidase N (EC 3.4.11.2), is located in the small intestinal and renal microvillar membrane, as well as in other plasma membranes. In small intestine, it plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases (Kruse et al., 1988). Aminopeptidase N is also a potent angiogenic regulator (Petrovic et al., 2007).
A surface antigen glycoprotein of about 150 kD, GP150, is recognized by monoclonal antibodies MY7 and MCS2. Look et al. (1986) isolated the complete GP150 gene, or ANPEP, from a human placenta genomic library.
Look et al. (1989) determined the complete primary structure of GP150, or CD13. The predicted 967-amino acid integral membrane protein has a 24-amino acid hydrophobic segment near its N terminus. Sequence analysis indicated that the hydrophobic segment is not cleaved, but rather serves as both a signal for membrane insertion and as a stable membrane-spanning segment. The remainder of the molecule consists of a large extracellular C-terminal domain that contains a pentapeptide consensus sequence characteristic of members of the zinc-binding metalloproteinase superfamily. Sequence comparisons with enzymes of this class showed that CD13 is identical to aminopeptidase N, an enzyme thought to be involved in metabolism of regulatory peptides by diverse cell types, including small intestinal and renal tubular epithelial cells, macrophages, granulocytes, and synaptic membranes from the central nervous system.
Delmas et al. (1992) showed that aminopeptidase N acts as a receptor for the transmissible gastroenteritis virus (TGEV), a major pathogen causing fatal diarrhea in newborn pigs.
Yeager et al. (1992) showed that human aminopeptidase N is a receptor for one strain of human coronavirus that is an important cause of upper respiratory tract infections.
Wisner et al. (2006) showed that opiorphin, an analgesic pentapeptide originating from PROL1 (608936), was a physiologic inhibitor of neutral ecto-endopeptidase (MME; 120520) and ecto-aminopeptidase N.
Using fluorescence microscopy and a matrigel invasion assay, Petrovic et al. (2007) showed that CD13 was required for endothelial cell invasion in response to bradykinin. Inhibition of CD13 abrogated internalization of bradykinin receptor B2 (BDKRB2; 113503) and reduced endothelial cell motility. Membrane disruption experiments indicated that CD13 was necessary for membrane integrity and membrane protein organization.
By study of somatic cell hybrid DNA and by in situ hybridization, Look et al. (1986) assigned the GP150 gene to chromosome 15q25-q26. This chromosomal location coincides with that of the oncogene FES (190030), which is also expressed in myeloid cells. Like FES, GP150 is distal to the breakpoint in t(15;17)(q22;q21.1) of acute promyelocytic leukemia.
By analysis of mouse-human somatic cell hybrids, Watt and Willard (1990) assigned the ANPEP gene, which they called PEPN, to chromosome 15q11-qter. With a genomic DNA probe, they detected a frequent DraIII polymorphism useful as a marker for human chromosome 15.
By probing DNA from rodent-human cell hybrids with cDNA, Kruse et al. (1988) demonstrated that the ANPEP gene is located on chromosome 15q13-qter. Kruse et al. (1988) stated that ANPEP is identical to peptidase E in the A-B-C-D-E-S system of nomenclature; however, PEPE has been mapped to chromosome 17q23-qter (see 170200) and, thus, must be a different gene.
Rangel et al. (2007) used targeted disruption to generate Anpep-null mice and observed no developmental, fertility, behavioral, or physiologic abnormalities. However, in oxygen-induced retinopathy experiments, Anpep-null mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Rangel et al. (2007) concluded that Anpep-null mice can undergo physiologic angiogenesis but exhibit a severely impaired angiogenic response under pathologic conditions.
Delmas, B., Gelfi, J., L'Haridon, R., Vogel, L. K., Sjostrom, H., Noren, O., Laude, H. Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV. Nature 357: 417-420, 1992. [PubMed: 1350661] [Full Text: https://doi.org/10.1038/357417a0]
Kruse, T. A., Bolund, L., Grzeschik, K.-H., Ropers, H. H., Olsen, J., Sjostrom, H., Noren, O. Assignment of the human aminopeptidase N (peptidase E) gene to chromosome 15q13-qter. FEBS Lett. 239: 305-308, 1988. [PubMed: 2903074] [Full Text: https://doi.org/10.1016/0014-5793(88)80940-2]
Look, A. T., Ashmun, R. A., Shapiro, L. H., Peiper, S. C. Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J. Clin. Invest. 83: 1299-1307, 1989. [PubMed: 2564851] [Full Text: https://doi.org/10.1172/JCI114015]
Look, A. T., Peiper, S. C., Rebentisch, M. B., Ashmun, R. A., Roussel, M. F., Lemons, R. S., Le Beau, M. M., Rubin, C. M., Sherr, C. J. Molecular cloning, expression, and chromosomal localization of the gene encoding a human myeloid membrane antigen (gp150). J. Clin. Invest. 78: 914-921, 1986. [PubMed: 2428842] [Full Text: https://doi.org/10.1172/JCI112680]
Petrovic, N., Schacke, W., Gahagan, J. R., O'Conor, C. A., Winnicka, B., Conway, R. E., Mina-Osorio, P., Shapiro, L. H. CD13/APN regulates endothelial invasion and filopodia formation. Blood 110: 142-150, 2007. [PubMed: 17363739] [Full Text: https://doi.org/10.1182/blood-2006-02-002931]
Rangel, R., Sun, Y., Guzman-Rojas, L., Ozawa, M. G., Sun, J., Giordano, R. J., Van Pelt, C. S., Tinkey, P. T., Behringer, R. R., Sidman, R. L., Arap, W., Pasqualini, R. Impaired angiogenesis in aminopeptidase N-null mice. Proc. Nat. Acad. Sci. 104: 4588-4593, 2007. [PubMed: 17360568] [Full Text: https://doi.org/10.1073/pnas.0611653104]
Watt, V. M., Willard, H. F. The human aminopeptidase N gene: isolation, chromosome localization, and DNA polymorphism analysis. Hum. Genet. 85: 651-654, 1990. [PubMed: 1977688] [Full Text: https://doi.org/10.1007/BF00193592]
Wisner, A., Dufour, E., Messaoudi, M., Nejdi, A., Marcel, A., Ungeheuer, M.-N., Rougeot, C. Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways. Proc. Nat. Acad. Sci. 103: 17979-17984, 2006. [PubMed: 17101991] [Full Text: https://doi.org/10.1073/pnas.0605865103]
Yeager, C. L., Ashmun, R. A., Williams, R. K., Cardellichio, C. B., Shapiro, L. H., Look, A. T., Holmes, K. V. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature 357: 420-422, 1992. [PubMed: 1350662] [Full Text: https://doi.org/10.1038/357420a0]