Aminopeptidase N

Details

Name
Aminopeptidase N
Synonyms
  • 3.4.11.2
  • Alanyl aminopeptidase
  • Aminopeptidase M
  • AP-M
  • AP-N
  • APN
  • CD13
  • gp150
  • Microsomal aminopeptidase
  • Myeloid plasma membrane glycoprotein CD13
  • PEPN
Gene Name
ANPEP
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010756|Aminopeptidase N
MAKGFYISKSLGILGILLGVAAVCTIIALSVVYSQEKNKNANSSPVASTTPSASATTNPA
SATTLDQSKAWNRYRLPNTLKPDSYRVTLRPYLTPNDRGLYVFKGSSTVRFTCKEATDVI
IIHSKKLNYTLSQGHRVVLRGVGGSQPPDIDKTELVEPTEYLVVHLKGSLVKDSQYEMDS
EFEGELADDLAGFYRSEYMEGNVRKVVATTQMQAADARKSFPCFDEPAMKAEFNITLIHP
KDLTALSNMLPKGPSTPLPEDPNWNVTEFHTTPKMSTYLLAFIVSEFDYVEKQASNGVLI
RIWARPSAIAAGHGDYALNVTGPILNFFAGHYDTPYPLPKSDQIGLPDFNAGAMENWGLV
TYRENSLLFDPLSSSSSNKERVVTVIAHELAHQWFGNLVTIEWWNDLWLNEGFASYVEYL
GADYAEPTWNLKDLMVLNDVYRVMAVDALASSHPLSTPASEINTPAQISELFDAISYSKG
ASVLRMLSSFLSEDVFKQGLASYLHTFAYQNTIYLNLWDHLQEAVNNRSIQLPTTVRDIM
NRWTLQMGFPVITVDTSTGTLSQEHFLLDPDSNVTRPSEFNYVWIVPITSIRDGRQQQDY
WLIDVRAQNDLFSTSGNEWVLLNLNVTGYYRVNYDEENWRKIQTQLQRDHSAIPVINRAQ
IINDAFNLASAHKVPVTLALNNTLFLIEERQYMPWEAALSSLSYFKLMFDRSEVYGPMKN
YLKKQVTPLFIHFRNNTNNWREIPENLMDQYSEVNAISTACSNGVPECEEMVSGLFKQWM
ENPNNNPIHPNLRSTVYCNAIAQGGEEEWDFAWEQFRNATLVNEADKLRAALACSKELWI
LNRYLSYTLNPDLIRKQDATSTIISITNNVIGQGLVWDFVQSNWKKLFNDYGGGSFSFSN
LIQAVTRRFSTEYELQQLEQFKKDNEETGFGSGTRALEQALEKTKANIKWVKENKEVVLQ
WFTENSK
Number of residues
967
Molecular Weight
109538.68
Theoretical pI
5.14
GO Classification
Functions
aminopeptidase activity / metalloaminopeptidase activity / metallopeptidase activity / peptide binding / receptor activity / virus receptor activity / zinc ion binding
Processes
angiogenesis / angiotensin maturation / cell differentiation / cellular protein metabolic process / peptide catabolic process / proteolysis
Components
cytosol / endoplasmic reticulum-Golgi intermediate compartment / external side of plasma membrane / extracellular exosome / extracellular space / integral component of plasma membrane / lysosomal membrane
General Function
Zinc ion binding
Specific Function
Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. May play a critical role in the pathogenesis of cholesterol gallstone disease. May be involved in the metabolism of regulatory peptides of diverse cell types, responsible for the processing of peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. Found to cleave antigen peptides bound to major histocompatibility complex class II molecules of presenting cells and to degrade neurotransmitters at synaptic junctions. Is also implicated as a regulator of IL-8 bioavailability in the endometrium, and therefore may contribute to the regulation of angiogenesis. Is used as a marker for acute myeloid leukemia and plays a role in tumor invasion. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein. Mediates as well human cytomegalovirus (HCMV) infection.(Microbial infection) Acts as a receptor for human coronavirus 229E/HCoV-229E.
Pfam Domain Function
Transmembrane Regions
9-32
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010757|Aminopeptidase N (ANPEP)
ATGGCCAAGGGCTTCTATATTTCCAAGTCCCTGGGCATCCTGGGGATCCTCCTGGGCGTG
GCAGCCGTGTGCACAATCATCGCACTGTCAGTGGTGTACTCCCAGGAGAAGAACAAGAAC
GCCAACAGCTCCCCCGTGGCCTCCACCACCCCGTCCGCCTCAGCCACCACCAACCCCGCC
TCGGCCACCACCTTGGACCAAAGTAAAGCGTGGAATCGTTACCGCCTCCCCAACACGCTG
AAACCCGATTCCTACCGGGTGACGCTGAGACCGTACCTCACCCCCAATGACAGGGGCCTG
TACGTTTTTAAGGGCTCCAGCACCGTCCGTTTCACCTGCAAGGAGGCCACTGACGTCATC
ATCATCCACAGCAAGAAGCTCAACTACACCCTCAGCCAGGGGCACAGGGTGGTCCTGCGT
GGTGTGGGAGGCTCCCAGCCCCCCGACATTGACAAGACTGAGCTGGTGGAGCCCACCGAG
TACCTGGTGGTGCACCTCAAGGGCTCCCTGGTGAAGGACAGCCAGTATGAGATGGACAGC
GAGTTCGAGGGGGAGTTGGCAGATGACCTGGCGGGCTTCTACCGCAGCGAGTACATGGAG
GGCAATGTCAGAAAGGTGGTGGCCACTACACAGATGCAGGCTGCAGATGCCCGGAAGTCC
TTCCCATGCTTCGATGAGCCGGCCATGAAGGCCGAGTTCAACATCACGCTTATCCACCCC
AAGGACCTGACAGCCCTGTCCAACATGCTTCCCAAAGGTCCCAGCACCCCACTTCCAGAA
GACCCCAACTGGAATGTCACTGAGTTCCACACCACGCCCAAGATGTCCACGTACTTGCTG
GCCTTCATTGTCAGTGAGTTCGACTACGTGGAGAAGCAGGCATCCAATGGTGTCTTGATC
CGGATCTGGGCCCGGCCCAGTGCCATTGCGGCGGGCCACGGCGATTATGCCCTGAACGTG
ACGGGCCCCATCCTTAACTTCTTTGCTGGTCATTATGACACACCCTACCCACTCCCAAAA
TCAGACCAGATTGGCCTGCCAGACTTCAACGCCGGCGCCATGGAGAACTGGGGACTGGTG
ACCTACCGGGAGAACTCCCTGCTGTTCGACCCCCTGTCCTCCTCCAGCAGCAACAAGGAG
CGGGTGGTCACTGTGATTGCTCATGAGCTGGCCCACCAGTGGTTCGGGAACCTGGTGACC
ATAGAGTGGTGGAATGACCTGTGGCTGAACGAGGGCTTCGCCTCCTACGTGGAGTACCTG
GGTGCTGACTATGCGGAGCCCACCTGGAACTTGAAAGACCTCATGGTGCTGAATGATGTG
TACCGCGTGATGGCAGTGGATGCACTGGCCTCCTCCCACCCGCTGTCCACACCCGCCTCG
GAGATCAACACGCCGGCCCAGATCAGTGAGCTGTTTGACGCCATCTCCTACAGCAAGGGC
GCCTCAGTCCTCAGGATGCTCTCCAGCTTCCTGTCCGAGGACGTATTCAAGCAGGGCCTG
GCGTCCTACCTCCACACCTTTGCCTACCAGAACACCATCTACCTGAACCTGTGGGACCAC
CTGCAGGAGGCTGTGAACAACCGGTCCATCCAACTCCCCACCACCGTGCGGGACATCATG
AACCGCTGGACCCTGCAGATGGGCTTCCCGGTCATCACGGTGGATACCAGCACGGGGACC
CTTTCCCAGGAGCACTTCCTCCTTGACCCCGATTCCAATGTTACCCGCCCCTCAGAATTC
AACTACGTGTGGATTGTGCCCATCACATCCATCAGAGATGGCAGACAGCAGCAGGACTAC
TGGCTGATAGATGTAAGAGCCCAGAACGATCTCTTCAGCACATCAGGCAATGAGTGGGTC
CTGCTGAACCTCAATGTGACGGGCTATTACCGGGTGAACTACGACGAAGAGAACTGGAGG
AAGATTCAGACTCAGCTGCAGAGAGACCACTCGGCCATCCCTGTCATCAATCGGGCACAG
ATCATTAATGACGCCTTCAACCTGGCCAGTGCCCATAAGGTCCCTGTCACTCTGGCGCTG
AACAACACCCTCTTCCTGATTGAAGAGAGACAGTACATGCCCTGGGAGGCCGCCCTGAGC
AGCCTGAGCTACTTCAAGCTCATGTTTGACCGCTCCGAGGTCTATGGCCCCATGAAGAAC
TACCTGAAGAAGCAGGTCACACCCCTCTTCATTCACTTCAGAAATAATACCAACAACTGG
AGGGAGATCCCAGAAAACCTGATGGACCAGTACAGCGAGGTTAATGCCATCAGCACCGCC
TGCTCCAACGGAGTTCCAGAGTGTGAGGAGATGGTCTCTGGCCTTTTCAAGCAGTGGATG
GAGAACCCCAATAATAACCCGATCCACCCCAACCTGCGGTCCACCGTCTACTGCAACGCT
ATCGCCCAGGGCGGGGAGGAGGAGTGGGACTTCGCCTGGGAGCAGTTCCGAAATGCCACA
CTGGTCAATGAGGCTGACAAGCTCCGGGCAGCCCTGGCCTGCAGCAAAGAGTTGTGGATC
CTGAACAGGTACCTGAGCTACACCCTGAACCCGGACTTAATCCGGAAGCAGGACGCCACC
TCTACCATCATCAGCATTACCAACAACGTCATTGGGCAAGGTCTGGTCTGGGACTTTGTC
CAGAGCAACTGGAAGAAGCTTTTTAACGATTATGGTGGTGGCTCGTTCTCCTTCTCCAAC
CTCATCCAGGCAGTGACACGACGATTCTCCACCGAGTATGAGCTGCAGCAGCTGGAGCAG
TTCAAGAAGGACAACGAGGAAACAGGCTTCGGCTCAGGCACCCGGGCCCTGGAGCAAGCC
CTGGAGAAGACGAAAGCCAACATCAAGTGGGTGAAGGAGAACAAGGAGGTGGTGCTCCAG
TGGTTCACAGAAAACAGCAAATAG
Chromosome Location
15
Locus
15q25-q26
External Identifiers
ResourceLink
UniProtKB IDP15144
UniProtKB Entry NameAMPN_HUMAN
GenBank Protein ID28678
GenBank Gene IDX13276
GenAtlas IDANPEP
HGNC IDHGNC:500
General References
  1. Olsen J, Cowell GM, Konigshofer E, Danielsen EM, Moller J, Laustsen L, Hansen OC, Welinder KG, Engberg J, Hunziker W, et al.: Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA. FEBS Lett. 1988 Oct 10;238(2):307-14. [Article]
  2. Look AT, Ashmun RA, Shapiro LH, Peiper SC: Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N. J Clin Invest. 1989 Apr;83(4):1299-307. [Article]
  3. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
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  7. Nunez 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 Lett. 1993 Aug 23;329(1-2):84-8. [Article]
  8. Tokioka-Terao M, Hiwada K, Kokubu T: Purification and characterization of aminopeptidase N from human plasma. Enzyme. 1984;32(2):65-75. [Article]
  9. O'Connell PJ, Gerkis V, d'Apice AJ: Variable O-glycosylation of CD13 (aminopeptidase N). J Biol Chem. 1991 Mar 5;266(7):4593-7. [Article]
  10. 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. 1992 Jun 4;357(6377):420-2. [Article]
  11. 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. Exp Hematol. 1993 Dec;21(13):1695-701. [Article]
  12. Soderberg C, Giugni TD, Zaia JA, Larsson S, Wahlberg JM, Moller E: CD13 (human aminopeptidase N) mediates human cytomegalovirus infection. J Virol. 1993 Nov;67(11):6576-85. [Article]
  13. Kolb AF, Maile J, Heister A, Siddell SG: Characterization of functional domains in the human coronavirus HCV 229E receptor. J Gen Virol. 1996 Oct;77 ( Pt 10):2515-21. [Article]
  14. Noren K, Hansen GH, Clausen H, Noren O, Sjostrom 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. Exp Cell Res. 1997 Feb 25;231(1):112-8. [Article]
  15. Kolb AF, Hegyi A, Siddell SG: Identification of residues critical for the human coronavirus 229E receptor function of human aminopeptidase N. J Gen Virol. 1997 Nov;78 ( Pt 11):2795-802. [Article]
  16. Hegyi A, Kolb AF: Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N. J Gen Virol. 1998 Jun;79 ( Pt 6):1387-91. [Article]
  17. 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. J Immunol. 2000 Jan 1;164(1):129-35. [Article]
  18. 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 Res. 2000 Feb 1;60(3):722-7. [Article]
  19. Seli E, Senturk LM, Bahtiyar OM, Kayisli UA, Arici A: Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen. Fertil Steril. 2001 Jun;75(6):1172-6. [Article]
  20. Wentworth DE, Holmes KV: Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): influence of N-linked glycosylation. J Virol. 2001 Oct;75(20):9741-52. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00973EzetimibeapprovedunknownotherDetails
DB06196Icatibantapproved, investigationalunknowninhibitorDetails
DB06773Human calcitoninapproved, investigationalnosubstrateDetails
DB16627Melphalan flufenamideapproved, withdrawnunknownsubstrateDetails