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UniProtKB/Swiss-Prot P15144 (AMPN_HUMAN)
Last modified
November 25, 2008.
Version 112.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended name: Aminopeptidase N Short name=hAPN EC=3.4.11.2 Alternative name(s): Alanyl aminopeptidase Microsomal aminopeptidase Aminopeptidase M gp150 Myeloid plasma membrane glycoprotein CD13 CD_antigen=CD13 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 967 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| 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 including small intestinal and tubular epithelial cells, macrophages, granulocytes and synaptic membranes from the CNS. 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. |
| Catalytic activity | Release of an N-terminal amino acid, Xaa-|-Yaa- from a peptide, amide or arylamide. Xaa is preferably Ala, but may be most amino acids including Pro (slow action). When a terminal hydrophobic residue is followed by a prolyl residue, the two may be released as an intact Xaa-Pro dipeptide. |
| Cofactor | Binds 1 zinc ion per subunit By similarity. |
| Subunit structure | Homodimer. Interacts with the S1 domain of HCoV-229E spike protein. |
| Subcellular location | Cell membrane; Single-pass type II membrane protein. Cytoplasm › cytosolPotential. Note= A soluble form has also been detected. |
| Tissue specificity | Expressed in epithelial cells of the kidney, intestine, and respiratory tract; granulocytes, monocytes, fibroblasts, endothelial cells, cerebral pericytes at the blood-brain barrier, synaptic membranes of cells in the CNS. Also expressed in endometrial stromal cells, but not in the endometrial glandular cells. Found in the vasculature of tissues that undergo angiogenesis and in malignant gliomas and lymph node metastases from multiple tumor types but not in blood vessels of normal tissues. A soluble form has been found in plasma. It is found to be elevated in plasma and effusions of cancer patients. |
| Induction | Estradiol and IL-8 decrease enzymatic activity in vitro in endometrial stromal cells by 40% and 30%, respectively. |
| Domain | Amino acids 260-353 are essential to mediate susceptibility to infection with HCoV-229E (in porcine/human chimeric studies) and more specifically amino acids 288-295 (mutagenesis studies). |
| Post-translational modification | Sulfated By similarity. N- and O-glycosylated. May undergo proteolysis and give rise to a soluble form. |
| Involvement in disease | Defects in ANPEP may be a cause of various types of leukemia or lymphoma. |
| Miscellaneous | Found to serve as a receptor for tumor-homing peptides, more specifically NGR peptides. It could serve thus as a target for delivering drugs into tumors. Concentration in human hepatic bile, varies from 17.3 to 57.6 micrograms/ml. |
| Sequence similarities | Belongs to the peptidase M1 family. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 967 | 966 | Aminopeptidase N | PRO_0000095081 | |||||
Regions | |||||||||
| Topological domain | 2 – 8 | 7 | Cytoplasmic | ||||||
| Transmembrane | 9 – 32 | 24 | Signal-anchor for type II membrane protein Potential | ||||||
| Region | 33 – 68 | 36 | Cytosolic Ser/Thr-rich junction | ||||||
| Region | 69 – 967 | 899 | Metalloprotease | ||||||
| Region | 260 – 353 | 94 | Interaction with HCoV-229E | ||||||
Sites | |||||||||
| Active site | 389 | 1 | By similarity | ||||||
| Active site | 477 | 1 | Proton donor Potential | ||||||
| Metal binding | 388 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 392 | 1 | Zinc; catalytic By similarity | ||||||
| Metal binding | 411 | 1 | Zinc; catalytic By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 176 | 1 | Sulfotyrosine Potential | ||||||
| Modified residue | 419 | 1 | Sulfotyrosine Potential | ||||||
| Modified residue | 424 | 1 | Sulfotyrosine Potential | ||||||
| Modified residue | 913 | 1 | Sulfotyrosine Potential | ||||||
| Modified residue | 928 | 1 | Phosphothreonine | ||||||
| Glycosylation | 128 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 234 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 265 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 319 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 527 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 573 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 625 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 681 | 1 | N-linked (GlcNAc...) | ||||||
| Glycosylation | 735 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 818 | 1 | N-linked (GlcNAc...) | ||||||
Natural variations | |||||||||
| Natural variant | 20 | 1 | V → M: dbSNP rs10152474. | VAR_031262 | |||||
| Natural variant | 86 | 1 | R → Q: dbSNP rs25653. | VAR_014736 | |||||
| Natural variant | 242 | 1 | D → Y | VAR_006727 | |||||
| Natural variant | 243 | 1 | L → P | VAR_006728 | |||||
| Natural variant | 311 | 1 | A → V: dbSNP rs17240268. | VAR_031263 | |||||
| Natural variant | 321 | 1 | T → M: dbSNP rs8179199. | VAR_031264 | |||||
| Natural variant | 603 | 1 | I → K: dbSNP rs17240212. | VAR_031265 | |||||
| Natural variant | 603 | 1 | I → M: dbSNP rs8192297. | VAR_031266 | |||||
| Natural variant | 752 | 1 | S → N: dbSNP rs25651. | VAR_014737 | |||||
Experimental info | |||||||||
| Mutagenesis | 288 – 295 | 8 | DYVEKQAS → QSVEETAQ: No change in receptor activity and HCoV-229E infection | ||||||
| Mutagenesis | 288 – 295 | 8 | DYVEKQAS → QSVNEQAQ: No change in receptor activity and HCoV-229E infection | ||||||
| Mutagenesis | 288 – 295 | 8 | DYVEKQAS → QSVNETAQ: Complete loss of receptor activity and blocks HCoV-229E infection. No loss of enzymatic activity | ||||||
| Mutagenesis | 291 – 293 | 3 | EKQ → NKT: Complete loss of receptor activity and blocks HCoV-229E infection. No loss of enzymatic activity | ||||||
| Mutagenesis | 291 | 1 | E → N: No change of receptor activity and HCoV-229E infection | ||||||
| Mutagenesis | 293 | 1 | Q → T: No change of receptor activity and HCoV-229E infection | ||||||
| Mutagenesis | 818 | 1 | N → E: Very low receptor activity and HCoV-229E infection | ||||||
| Sequence conflict | 536 | 1 | V → E in CAA31640. Ref.1 | ||||||
| Sequence conflict | 887 | 1 | L → P in CAA31640. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA." Olsen J., Cowell G.M., Koenigshoefer E., Danielsen E.M., Moeller J., Laustsen L., Hansen O.C., Welinder K.G., Engberg J., Hunziker W., Spiess M., Sjoestroem H., Noren O. FEBS Lett. 238:307-314(1988) [PubMed: 2901990] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLN-86 AND MET-603. Tissue: Intestine. |
| [2] | "Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase N." Look A.T., Ashmun R.A., Shapiro L.H., Peiper S.C. J. Clin. Invest. 83:1299-1307(1989) [PubMed: 2564851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-21, VARIANT GLN-86. |
| [3] | "Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. Nusbaum C.Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas. |
| [5] | "Separate promoters control transcription of the human aminopeptidase N gene in myeloid and intestinal epithelial cells." Shapiro L.H., Ashmun R.A., Roberts W.M., Look A.T. J. Biol. Chem. 266:11999-12007(1991) [PubMed: 1675638] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15. Tissue: Intestinal epithelium. |
| [6] | "Genomic organisation of aminopeptidase N." Eiz-Vesper B., Fuchs N., Gottschalk D., Mueller K., Reuter S., Blasczyk R. Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-479 AND 524-967, VARIANT GLN-86. Tissue: Peripheral blood. |
| [7] | "Identification of an alanine aminopeptidase in human maternal serum as a membrane-bound aminopeptidase N." Watanabe Y., Iwaki-Egawa S., Mizukoshi H., Fujimoto Y. Biol. Chem. Hoppe-Seyler 376:397-400(1995) [PubMed: 7576235] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-20 AND 70-81. |
| [8] | "Cholesterol crystallization-promoting activity of aminopeptidase-N isolated from the vesicular carrier of biliary lipids." Nunez L., Amigo L., Rigotti A., Puglielli L., Mingrone G., Greco A.V., Nervi F. FEBS Lett. 329:84-88(1993) [PubMed: 8102610] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-18. |
| [9] | "Purification and characterization of aminopeptidase N from human plasma." Tokioka-Terao M., Hiwada K., Kokubu T. Enzyme 32:65-75(1984) [PubMed: 6149934] [Abstract] Cited for: CHARACTERIZATION, SUBUNIT. |
| [10] | "Variable O-glycosylation of CD13 (aminopeptidase N)." O'Connell P.J., Gerkis V., d'Apice A.J.F. J. Biol. Chem. 266:4593-4597(1991) [PubMed: 1705556] [Abstract] Cited for: GLYCOSYLATION. |
| [11] | "Human aminopeptidase N is a receptor for human coronavirus 229E." Yeager C.L., Ashmun R.A., Williams R.K., Cardellichio C.B., Shapiro L.H., Look A.T., Holmes K.V. Nature 357:420-422(1992) [PubMed: 1350662] [Abstract] Cited for: INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN, CHARACTERIZATION OF HCOV-229E RECEPTOR FUNCTION. |
| [12] | "CD13 (GP150; aminopeptidase-N): predominant functional activity in blood is localized to plasma and is not cell-surface associated." Favaloro E.J., Browning T., Facey D. Exp. Hematol. 21:1695-1701(1993) [PubMed: 7902291] [Abstract] Cited for: IDENTIFICATION OF SOLUBLE FORM. |
| [13] | "CD13 (human aminopeptidase N) mediates human cytomegalovirus infection." Soderberg C., Giugni T.D., Zaia J.A., Larsson S., Wahlberg J.M., Moller E. J. Virol. 67:6576-6585(1993) [PubMed: 8105105] [Abstract] Cited for: CHARACTERIZATION OF CMV RECEPTOR FUNCTION. |
| [14] | "Characterization of functional domains in the human coronavirus HCV 229E receptor." Kolb A.F., Maile J., Heister A., Siddell S.G. J. Gen. Virol. 77:2515-2521(1996) [PubMed: 8887485] [Abstract] Cited for: IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR HCOV-229E INFECTION. |
| [15] | "Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity." Noren K., Hansen G.H., Clausen H., Noren O., Sjostrom H., Vogel L.K. Exp. Cell Res. 231:112-118(1997) [PubMed: 9056417] [Abstract] Cited for: FUNCTION, GLYCOSYLATION. |
| [16] | "Identification of residues critical for the human coronavirus 229E receptor function of human aminopeptidase N." Kolb A.F., Hegyi A., Siddell S.G. J. Gen. Virol. 78:2795-2802(1997) [PubMed: 9367365] [Abstract] Cited for: IDENTIFICATION OF RESIDUES CRITICAL FOR HCOV-229E INFECTION. |
| [17] | "Characterization of determinants involved in the feline infectious peritonitis virus receptor function of feline aminopeptidase N." Hegyi A., Kolb A.F. J. Gen. Virol. 79:1387-1391(1998) [PubMed: 9634079] [Abstract] Cited for: IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR TGEV INFECTION. |
| [18] | "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." Dong X., An B., Salvucci Kierstead L., Storkus W.J., Amoscato A.A., Salter R.D. J. Immunol. 164:129-135(2000) [PubMed: 10605003] [Abstract] Cited for: FUNCTION, ENZYMATIC CLEAVAGE OF ANTIGEN PEPTIDES BOUND TO CLASS II MHC. |
| [19] | "Aminopeptidase N is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis." Pasqualini R., Koivunen E., Kain R., Lahdenranta J., Sakamoto M., Stryhn A., Ashmun R.A., Shapiro L.H., Arap W., Ruoslahti E. Cancer Res. 60:722-727(2000) [PubMed: 10676659] [Abstract] Cited for: ROLE IN ANGIOGENESIS, CHARACTERIZATION OF RECEPTOR FOR TUMOR-HOMING PEPTIDES FUNCTION. |
| [20] | "Expression of aminopeptidase N in human endometrium and regulation of its activity by estrogen." Seli E., Senturk L.M., Bahtiyar O.M., Kayisli U.A., Arici A. Fertil. Steril. 75:1172-1176(2001) [PubMed: 11384645] [Abstract] Cited for: FUNCTION, INDUCTION BY ESTRADIOL AND IL-8. |
| [21] | "Molecular determinants of species specificity in the coronavirus receptor aminopeptidase N (CD13): influence of N-linked glycosylation." Wentworth D.E., Holmes K.V. J. Virol. 75:9741-9752(2001) [PubMed: 11559807] [Abstract] Cited for: MUTAGENESIS OF 288-ASP--SER-295 AND ASN-818. |
| [22] | "Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions and intratumoral fluid." van Hensbergen Y., Broxterman H.J., Hanemaaijer R., Jorna A.S., van Lent N.A., Verheul H.M., Pinedo H.M., Hoekman K. Clin. Cancer Res. 8:3747-3754(2002) [PubMed: 12473585] [Abstract] Cited for: FUNCTION OF SOLUBLE FORM. |
| [23] | "Identification of a receptor-binding domain of the spike glycoprotein of human coronavirus HCoV-229E." Bonavia A., Zelus B.D., Wentworth D.E., Talbot P.J., Holmes K.V. J. Virol. 77:2530-2538(2003) [PubMed: 12551991] [Abstract] Cited for: INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN. |
| [24] | "A proteomic analysis of human bile." Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A. Mol. Cell. Proteomics 3:715-728(2004) [PubMed: 15084671] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265, MASS SPECTROMETRY. Tissue: Bile. |
| [25] | "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265; ASN-681 AND ASN-818, MASS SPECTROMETRY. Tissue: Plasma. |
| [26] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-928, MASS SPECTROMETRY. Tissue: Epithelium. |
| [27] | "Identification of point mutations in the aminopeptidase N gene by SSCP analysis and sequencing." Lendeckel U., Wex T., Arndt M., Frank K., Franke A., Ansorge S. Hum. Mutat. Suppl. 1:S158-S160(1998) [PubMed: 9452074] [Abstract] Cited for: VARIANTS TYR-242 AND PRO-243. |
| + | Additional computationally mapped references. |

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