Alanine aminopeptidase explained

Membrane alanyl aminopeptidase also known as alanyl aminopeptidase (AAP) or aminopeptidase N (AP-N) is an enzyme that in humans is encoded by the ANPEP gene.

Function

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. Defects in this gene appear to be a cause of various types of leukemia or lymphoma.^[1]

AAP is also used by some viruses as a receptor to which these viruses bind to and then enter cells. It is a receptor for human coronavirus 229E, feline coronavirus serotype II (FCoV-II), TGEV, PEDV,^[2] canine coronavirus genotype II (CCoV-II)^[3] as well as several Deltacoronaviruses.^[4]

Further reading

• Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT, Holmes KV . Human aminopeptidase N is a receptor for human coronavirus 229E . Nature . 357 . 6377 . 420–422 . June 1992 . 1350662 . 7095410 . 10.1038/357420a0 . free . 1992Natur.357..420Y .
• Shapiro LH, Ashmun RA, Roberts WM, Look AT . Separate promoters control transcription of the human aminopeptidase N gene in myeloid and intestinal epithelial cells . The Journal of Biological Chemistry . 266 . 18 . 11999–12007 . June 1991 . 1675638 . 10.1016/S0021-9258(18)99056-3 . free .
• O'Connell PJ, Gerkis V, d'Apice AJ . Variable O-glycosylation of CD13 (aminopeptidase N) . The Journal of Biological Chemistry . 266 . 7 . 4593–4597 . March 1991 . 1705556 . 10.1016/S0021-9258(20)64364-2 . free .
• Watt VM, Willard HF . The human aminopeptidase N gene: isolation, chromosome localization, and DNA polymorphism analysis . Human Genetics . 85 . 6 . 651–654 . October 1990 . 1977688 . 10.1007/BF00193592 . 19678944 .
• Look AT, Peiper SC, Rebentisch MB, Ashmun RA, Roussel MF, Lemons RS, Le Beau MM, Rubin CM, Sherr CJ . Molecular cloning, expression, and chromosomal localization of the gene encoding a human myeloid membrane antigen (gp150) . The Journal of Clinical Investigation . 78 . 4 . 914–921 . October 1986 . 2428842 . 423717 . 10.1172/JCI112680 .
• Look AT, Ashmun RA, Shapiro LH, Peiper SC . Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N . The Journal of Clinical Investigation . 83 . 4 . 1299–1307 . April 1989 . 2564851 . 303821 . 10.1172/JCI114015 .
• Olsen J, Cowell GM, Kønigshøfer E, Danielsen EM, Møller J, Laustsen L, Hansen OC, Welinder KG, Engberg J, Hunziker W . Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA . FEBS Letters . 238 . 2 . 307–314 . October 1988 . 2901990 . 10.1016/0014-5793(88)80502-7 . free .
• Kruse TA, Bolund L, Grzeschik KH, Ropers HH, Olsen J, Sjöström H, Norén O . Assignment of the human aminopeptidase N (peptidase E) gene to chromosome 15q13-qter . FEBS Letters . 239 . 2 . 305–308 . November 1988 . 2903074 . 10.1016/0014-5793(88)80940-2 . free .
• Tokioka-Terao M, Hiwada K, Kokubu T . Purification and characterization of aminopeptidase N from human plasma . Enzyme . 32 . 2 . 65–75 . 1985 . 6149934 . 10.1159/000469453 . 2024-08-20 .
• Watanabe Y, Iwaki-Egawa S, Mizukoshi H, Fujimoto Y . Identification of an alanine aminopeptidase in human maternal serum as a membrane-bound aminopeptidase N . Biological Chemistry Hoppe-Seyler . 376 . 7 . 397–400 . July 1995 . 7576235 . 10.1515/bchm3.1995.376.7.397 .
• Favaloro EJ, Browning T, Facey D . CD13 (GP150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated . Experimental Hematology . 21 . 13 . 1695–1701 . December 1993 . 7902291 .
• Núñez L, Amigo L, Rigotti A, Puglielli L, Mingrone G, Greco AV, Nervi F . Cholesterol crystallization-promoting activity of aminopeptidase-N isolated from the vesicular carrier of biliary lipids . FEBS Letters . 329 . 1–2 . 84–88 . August 1993 . 8102610 . 10.1016/0014-5793(93)80199-5 . 23782523 .
• Söderberg C, Giugni TD, Zaia JA, Larsson S, Wahlberg JM, Möller E . CD13 (human aminopeptidase N) mediates human cytomegalovirus infection . Journal of Virology . 67 . 11 . 6576–6585 . November 1993 . 8105105 . 238095 . 10.1128/JVI.67.11.6576-6585.1993 .
• Kolb AF, Maile J, Heister A, Siddell SG . Characterization of functional domains in the human coronavirus HCV 229E receptor . The Journal of General Virology . 77 . 10 . 2515–2521 . October 1996 . 8887485 . 10.1099/0022-1317-77-10-2515 . free .
• Norén K, Hansen GH, Clausen H, Norén O, Sjöström H, Vogel LK . Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity . Experimental Cell Research . 231 . 1 . 112–118 . February 1997 . 9056417 . 10.1006/excr.1996.3455 .
• Kolb AF, Hegyi A, Siddell SG . Identification of residues critical for the human coronavirus 229E receptor function of human aminopeptidase N . The Journal of General Virology . 78 . 11 . 2795–2802 . November 1997 . 9367365 . 10.1099/0022-1317-78-11-2795 . free .
• Hegyi A, Kolb AF . Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N . The Journal of General Virology . 79 . 6 . 1387–1391 . June 1998 . 9634079 . 10.1099/0022-1317-79-6-1387 . free .
• Dong X, An B, Salvucci Kierstead L, Storkus WJ, Amoscato AA, Salter RD . Modification of the amino terminus of a class II epitope confers resistance to degradation by CD13 on dendritic cells and enhances presentation to T cells . Journal of Immunology . 164 . 1 . 129–135 . January 2000 . 10605003 . 10.4049/jimmunol.164.1.129 . free .
• Pasqualini R, Koivunen E, Kain R, Lahdenranta J, Sakamoto M, Stryhn A, Ashmun RA, Shapiro LH, Arap W, Ruoslahti E . Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis . Cancer Research . 60 . 3 . 722–727 . February 2000 . 10676659 . 4469333 .
• Renold A, Cescato R, Beuret N, Vogel LK, Wahlberg JM, Brown JL, Fiedler K, Spiess M . Basolateral sorting signals differ in their ability to redirect apical proteins to the basolateral cell surface . The Journal of Biological Chemistry . 275 . 13 . 9290–9295 . March 2000 . 10734069 . 10.1074/jbc.275.13.9290 . free .

External links

• The MEROPS online database for peptidases and their inhibitors: M01.001

Notes and References

1. Web site: Entrez Gene: ANPEP alanyl (membrane) aminopeptidase (aminopeptidase N, aminopeptidase M, microsomal aminopeptidase, CD13, p150).
2. Jaimes JA, Millet JK, Stout AE, André NM, Whittaker GR . A Tale of Two Viruses: The Distinct Spike Glycoproteins of Feline Coronaviruses . Viruses . 12 . 1 . 83 . January 2020 . 31936749 . 7019228 . 10.3390/v12010083 . free .
3. Licitra BN, Whittaker GR, Dubovi EJ, Duhamel GE . Genotypic characterization of canine coronaviruses associated with fatal canine neonatal enteritis in the United States . Journal of Clinical Microbiology . 52 . 12 . 4230–4238 . December 2014 . 25253797 . 4313292 . 10.1128/JCM.02158-14 .
4. Liang QZ, Wang B, Ji CM, Hu F, Qin P, Feng Y, Tang YD, Huang YW . Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17 . Journal of Virology . 97 . 2 . e0194722 . February 2023 . 36656013 . 9973037 . 10.1128/jvi.01947-22 .