Full text data of ANPEP
ANPEP
(APN, CD13, PEPN)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Aminopeptidase N; AP-N; hAPN; 3.4.11.2 (Alanyl aminopeptidase; Aminopeptidase M; AP-M; Microsomal aminopeptidase; Myeloid plasma membrane glycoprotein CD13; gp150; CD13)
Aminopeptidase N; AP-N; hAPN; 3.4.11.2 (Alanyl aminopeptidase; Aminopeptidase M; AP-M; Microsomal aminopeptidase; Myeloid plasma membrane glycoprotein CD13; gp150; CD13)
hRBCD
IPI00221224
IPI00221224 MeMbrane alanine aMinopeptidase precursor Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a integral membrane protein n/a expected molecular weight found in band found in band around 14 kDa
IPI00221224 MeMbrane alanine aMinopeptidase precursor Broad specificity aminopeptidase. Plays a role in the final digestion of peptides generated from hydrolysis of proteins soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a integral membrane protein n/a expected molecular weight found in band found in band around 14 kDa
UniProt
P15144
ID AMPN_HUMAN Reviewed; 967 AA.
AC P15144; Q16728; Q6GT90; Q8IUK3; Q8IVH3; Q9UCE0;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 4.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Aminopeptidase N;
DE Short=AP-N;
DE Short=hAPN;
DE EC=3.4.11.2;
DE AltName: Full=Alanyl aminopeptidase;
DE AltName: Full=Aminopeptidase M;
DE Short=AP-M;
DE AltName: Full=Microsomal aminopeptidase;
DE AltName: Full=Myeloid plasma membrane glycoprotein CD13;
DE AltName: Full=gp150;
DE AltName: CD_antigen=CD13;
GN Name=ANPEP; Synonyms=APN, CD13, PEPN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLN-86 AND MET-603.
RC TISSUE=Intestine;
RX PubMed=2901990; DOI=10.1016/0014-5793(88)80502-7;
RA Olsen J., Cowell G.M., Koenigshoefer E., Danielsen E.M., Moeller J.,
RA Laustsen L., Hansen O.C., Welinder K.G., Engberg J., Hunziker W.,
RA Spiess M., Sjoestroem H., Noren O.;
RT "Complete amino acid sequence of human intestinal aminopeptidase N as
RT deduced from cloned cDNA.";
RL FEBS Lett. 238:307-314(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-21, AND VARIANT
RP GLN-86.
RX PubMed=2564851; DOI=10.1172/JCI114015;
RA Look A.T., Ashmun R.A., Shapiro L.H., Peiper S.C.;
RT "Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical
RT to aminopeptidase N.";
RL J. Clin. Invest. 83:1299-1307(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
RC TISSUE=Intestinal epithelium;
RX PubMed=1675638;
RA Shapiro L.H., Ashmun R.A., Roberts W.M., Look A.T.;
RT "Separate promoters control transcription of the human aminopeptidase
RT N gene in myeloid and intestinal epithelial cells.";
RL J. Biol. Chem. 266:11999-12007(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-479 AND 524-967, AND VARIANT
RP GLN-86.
RC TISSUE=Peripheral blood;
RA Eiz-Vesper B., Fuchs N., Gottschalk D., Mueller K., Reuter S.,
RA Blasczyk R.;
RT "Genomic organisation of aminopeptidase N.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 2-20 AND 70-81.
RX PubMed=7576235;
RA Watanabe Y., Iwaki-Egawa S., Mizukoshi H., Fujimoto Y.;
RT "Identification of an alanine aminopeptidase in human maternal serum
RT as a membrane-bound aminopeptidase N.";
RL Biol. Chem. Hoppe-Seyler 376:397-400(1995).
RN [8]
RP PROTEIN SEQUENCE OF 2-18.
RX PubMed=8102610; DOI=10.1016/0014-5793(93)80199-5;
RA Nunez L., Amigo L., Rigotti A., Puglielli L., Mingrone G., Greco A.V.,
RA Nervi F.;
RT "Cholesterol crystallization-promoting activity of aminopeptidase-N
RT isolated from the vesicular carrier of biliary lipids.";
RL FEBS Lett. 329:84-88(1993).
RN [9]
RP CHARACTERIZATION, AND SUBUNIT.
RX PubMed=6149934;
RA Tokioka-Terao M., Hiwada K., Kokubu T.;
RT "Purification and characterization of aminopeptidase N from human
RT plasma.";
RL Enzyme 32:65-75(1984).
RN [10]
RP GLYCOSYLATION.
RX PubMed=1705556;
RA O'Connell P.J., Gerkis V., d'Apice A.J.F.;
RT "Variable O-glycosylation of CD13 (aminopeptidase N).";
RL J. Biol. Chem. 266:4593-4597(1991).
RN [11]
RP INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN, AND CHARACTERIZATION OF
RP HCOV-229E RECEPTOR FUNCTION.
RX PubMed=1350662; DOI=10.1038/357420a0;
RA Yeager C.L., Ashmun R.A., Williams R.K., Cardellichio C.B.,
RA Shapiro L.H., Look A.T., Holmes K.V.;
RT "Human aminopeptidase N is a receptor for human coronavirus 229E.";
RL Nature 357:420-422(1992).
RN [12]
RP IDENTIFICATION OF SOLUBLE FORM.
RX PubMed=7902291;
RA Favaloro E.J., Browning T., Facey D.;
RT "CD13 (GP150; aminopeptidase-N): predominant functional activity in
RT blood is localized to plasma and is not cell-surface associated.";
RL Exp. Hematol. 21:1695-1701(1993).
RN [13]
RP CHARACTERIZATION OF CMV RECEPTOR FUNCTION.
RX PubMed=8105105;
RA Soderberg C., Giugni T.D., Zaia J.A., Larsson S., Wahlberg J.M.,
RA Moller E.;
RT "CD13 (human aminopeptidase N) mediates human cytomegalovirus
RT infection.";
RL J. Virol. 67:6576-6585(1993).
RN [14]
RP IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR HCOV-229E INFECTION.
RX PubMed=8887485;
RA Kolb A.F., Maile J., Heister A., Siddell S.G.;
RT "Characterization of functional domains in the human coronavirus HCV
RT 229E receptor.";
RL J. Gen. Virol. 77:2515-2521(1996).
RN [15]
RP FUNCTION, AND GLYCOSYLATION.
RX PubMed=9056417; DOI=10.1006/excr.1996.3455;
RA Noren K., Hansen G.H., Clausen H., Noren O., Sjostrom H., Vogel L.K.;
RT "Defectively N-glycosylated and non-O-glycosylated aminopeptidase N
RT (CD13) is normally expressed at the cell surface and has full
RT enzymatic activity.";
RL Exp. Cell Res. 231:112-118(1997).
RN [16]
RP IDENTIFICATION OF RESIDUES CRITICAL FOR HCOV-229E INFECTION.
RX PubMed=9367365;
RA Kolb A.F., Hegyi A., Siddell S.G.;
RT "Identification of residues critical for the human coronavirus 229E
RT receptor function of human aminopeptidase N.";
RL J. Gen. Virol. 78:2795-2802(1997).
RN [17]
RP IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR TGEV INFECTION.
RX PubMed=9634079;
RA Hegyi A., Kolb A.F.;
RT "Characterization of determinants involved in the feline infectious
RT peritonitis virus receptor function of feline aminopeptidase N.";
RL J. Gen. Virol. 79:1387-1391(1998).
RN [18]
RP FUNCTION, AND ENZYMATIC CLEAVAGE OF ANTIGEN PEPTIDES BOUND TO CLASS II
RP MHC.
RX PubMed=10605003;
RA Dong X., An B., Salvucci Kierstead L., Storkus W.J., Amoscato A.A.,
RA Salter R.D.;
RT "Modification of the amino terminus of a class II epitope confers
RT resistance to degradation by CD13 on dendritic cells and enhances
RT presentation to T cells.";
RL J. Immunol. 164:129-135(2000).
RN [19]
RP ROLE IN ANGIOGENESIS, AND CHARACTERIZATION OF RECEPTOR FOR
RP TUMOR-HOMING PEPTIDES FUNCTION.
RX PubMed=10676659;
RA Pasqualini R., Koivunen E., Kain R., Lahdenranta J., Sakamoto M.,
RA Stryhn A., Ashmun R.A., Shapiro L.H., Arap W., Ruoslahti E.;
RT "Aminopeptidase N is a receptor for tumor-homing peptides and a target
RT for inhibiting angiogenesis.";
RL Cancer Res. 60:722-727(2000).
RN [20]
RP FUNCTION, AND INDUCTION BY ESTRADIOL AND IL8.
RX PubMed=11384645; DOI=10.1016/S0015-0282(01)01779-4;
RA Seli E., Senturk L.M., Bahtiyar O.M., Kayisli U.A., Arici A.;
RT "Expression of aminopeptidase N in human endometrium and regulation of
RT its activity by estrogen.";
RL Fertil. Steril. 75:1172-1176(2001).
RN [21]
RP MUTAGENESIS OF 288-ASP--SER-295 AND ASN-818.
RX PubMed=11559807; DOI=10.1128/JVI.75.20.9741-9752.2001;
RA Wentworth D.E., Holmes K.V.;
RT "Molecular determinants of species specificity in the coronavirus
RT receptor aminopeptidase N (CD13): influence of N-linked
RT glycosylation.";
RL J. Virol. 75:9741-9752(2001).
RN [22]
RP FUNCTION OF SOLUBLE FORM.
RX PubMed=12473585;
RA van Hensbergen Y., Broxterman H.J., Hanemaaijer R., Jorna A.S.,
RA van Lent N.A., Verheul H.M., Pinedo H.M., Hoekman K.;
RT "Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions
RT and intratumoral fluid.";
RL Clin. Cancer Res. 8:3747-3754(2002).
RN [23]
RP INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN.
RX PubMed=12551991; DOI=10.1128/JVI.77.4.2530-2538.2003;
RA Bonavia A., Zelus B.D., Wentworth D.E., Talbot P.J., Holmes K.V.;
RT "Identification of a receptor-binding domain of the spike glycoprotein
RT of human coronavirus HCoV-229E.";
RL J. Virol. 77:2530-2538(2003).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265, AND MASS
RP SPECTROMETRY.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H.,
RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265;
RP ASN-681 AND ASN-818, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [26]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265;
RP ASN-573; ASN-681 AND ASN-818, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 66-967 IN COMPLEX WITH
RP ANGIOTENSIN-4 AND INHIBITORS, CATALYTIC ACTIVITY, COFACTOR,
RP SUBSTRATE-BINDING REGION, ZINC-BINDING SITES, ACTIVE SITE,
RP GLYCOSYLATION AT ASN-128; ASN-234; ASN-265; ASN-319; ASN-527; ASN-625;
RP ASN-681 AND ASN-818, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=22932899; DOI=10.1074/jbc.M112.398842;
RA Wong A.H., Zhou D., Rini J.M.;
RT "The X-ray crystal structure of human aminopeptidase N reveals a novel
RT dimer and the basis for peptide processing.";
RL J. Biol. Chem. 287:36804-36813(2012).
RN [29]
RP VARIANTS TYR-242 AND PRO-243.
RX PubMed=9452074;
RA Lendeckel U., Wex T., Arndt M., Frank K., Franke A., Ansorge S.;
RT "Identification of point mutations in the aminopeptidase N gene by
RT SSCP analysis and sequencing.";
RL Hum. Mutat. Suppl. 1:S158-S160(1998).
CC -!- FUNCTION: Broad specificity aminopeptidase. Plays a role in the
CC final digestion of peptides generated from hydrolysis of proteins
CC by gastric and pancreatic proteases. May play a critical role in
CC the pathogenesis of cholesterol gallstone disease. May be involved
CC in the metabolism of regulatory peptides of diverse cell types,
CC responsible for the processing of peptide hormones, such as
CC angiotensin III and IV, neuropeptides, and chemokines. Found to
CC cleave antigen peptides bound to major histocompatibility complex
CC class II molecules of presenting cells and to degrade
CC neurotransmitters at synaptic junctions. Is also implicated as a
CC regulator of IL-8 bioavailability in the endometrium, and
CC therefore may contribute to the regulation of angiogenesis. Is
CC used as a marker for acute myeloid leukemia and plays a role in
CC tumor invasion. In case of human coronavirus 229E (HCoV-229E)
CC infection, serves as receptor for HCoV-229E spike glycoprotein.
CC Mediates as well human cytomegalovirus (HCMV) infection.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Xaa-|-
CC Yaa- from a peptide, amide or arylamide. Xaa is preferably Ala,
CC but may be most amino acids including Pro (slow action). When a
CC terminal hydrophobic residue is followed by a prolyl residue, the
CC two may be released as an intact Xaa-Pro dipeptide.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Homodimer. Interacts with the S1 domain of HCoV-229E
CC spike protein.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Cytoplasm, cytosol (Potential). Note=A soluble form has
CC also been detected.
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells of the kidney,
CC intestine, and respiratory tract; granulocytes, monocytes,
CC fibroblasts, endothelial cells, cerebral pericytes at the blood-
CC brain barrier, synaptic membranes of cells in the CNS. Also
CC expressed in endometrial stromal cells, but not in the endometrial
CC glandular cells. Found in the vasculature of tissues that undergo
CC angiogenesis and in malignant gliomas and lymph node metastases
CC from multiple tumor types but not in blood vessels of normal
CC tissues. A soluble form has been found in plasma. It is found to
CC be elevated in plasma and effusions of cancer patients.
CC -!- INDUCTION: Estradiol and IL8/interleukin-8 decrease enzymatic
CC activity in vitro in endometrial stromal cells by 40% and 30%,
CC respectively.
CC -!- DOMAIN: Amino acids 260-353 are essential to mediate
CC susceptibility to infection with HCoV-229E (in porcine/human
CC chimeric studies) and more specifically amino acids 288-295
CC (mutagenesis studies).
CC -!- PTM: Sulfated (By similarity).
CC -!- PTM: N- and O-glycosylated.
CC -!- PTM: May undergo proteolysis and give rise to a soluble form.
CC -!- MISCELLANEOUS: Found to serve as a receptor for tumor-homing
CC peptides, more specifically NGR peptides. It could serve thus as a
CC target for delivering drugs into tumors. Concentration in human
CC hepatic bile, varies from 17.3 to 57.6 micrograms/ml.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
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DR EMBL; X13276; CAA31640.1; -; mRNA.
DR EMBL; M22324; AAA51719.1; -; mRNA.
DR EMBL; AC018988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058928; AAH58928.1; -; mRNA.
DR EMBL; M55522; AAA83399.1; -; Genomic_DNA.
DR EMBL; AJ421875; CAD19098.2; -; Genomic_DNA.
DR EMBL; AJ421876; CAD19098.2; JOINED; Genomic_DNA.
DR EMBL; AJ426050; CAD19802.1; -; Genomic_DNA.
DR EMBL; AJ427985; CAD20931.1; -; Genomic_DNA.
DR EMBL; AJ427986; CAD20931.1; JOINED; Genomic_DNA.
DR EMBL; AJ427987; CAD20931.1; JOINED; Genomic_DNA.
DR EMBL; AJ427988; CAD20931.1; JOINED; Genomic_DNA.
DR PIR; A30325; A30325.
DR RefSeq; NP_001141.2; NM_001150.2.
DR RefSeq; XP_005254949.1; XM_005254892.1.
DR UniGene; Hs.1239; -.
DR PDB; 4FYQ; X-ray; 1.90 A; A=66-967.
DR PDB; 4FYR; X-ray; 1.91 A; A=66-967.
DR PDB; 4FYS; X-ray; 2.01 A; A=66-967.
DR PDB; 4FYT; X-ray; 1.85 A; A=66-967.
DR PDBsum; 4FYQ; -.
DR PDBsum; 4FYR; -.
DR PDBsum; 4FYS; -.
DR PDBsum; 4FYT; -.
DR ProteinModelPortal; P15144; -.
DR SMR; P15144; 66-967.
DR IntAct; P15144; 5.
DR STRING; 9606.ENSP00000300060; -.
DR BindingDB; P15144; -.
DR ChEMBL; CHEMBL1907; -.
DR DrugBank; DB00973; Ezetimibe.
DR MEROPS; M01.001; -.
DR PhosphoSite; P15144; -.
DR DMDM; 143811362; -.
DR PaxDb; P15144; -.
DR PRIDE; P15144; -.
DR DNASU; 290; -.
DR Ensembl; ENST00000300060; ENSP00000300060; ENSG00000166825.
DR GeneID; 290; -.
DR KEGG; hsa:290; -.
DR UCSC; uc002bop.4; human.
DR CTD; 290; -.
DR GeneCards; GC15M090328; -.
DR H-InvDB; HIX0038141; -.
DR HGNC; HGNC:500; ANPEP.
DR HPA; CAB002417; -.
DR MIM; 151530; gene.
DR neXtProt; NX_P15144; -.
DR PharmGKB; PA24815; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG006616; -.
DR InParanoid; P15144; -.
DR KO; K11140; -.
DR OMA; WVLLNLN; -.
DR OrthoDB; EOG754HNR; -.
DR PhylomeDB; P15144; -.
DR BRENDA; 3.4.11.2; 2681.
DR Reactome; REACT_17015; Metabolism of proteins.
DR SABIO-RK; P15144; -.
DR GeneWiki; Alanine_aminopeptidase; -.
DR GenomeRNAi; 290; -.
DR NextBio; 1183; -.
DR PRO; PR:P15144; -.
DR ArrayExpress; P15144; -.
DR Bgee; P15144; -.
DR CleanEx; HS_ANPEP; -.
DR Genevestigator; P15144; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0004872; F:receptor activity; TAS:ProtInc.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0002003; P:angiotensin maturation; TAS:Reactome.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; IEA:GOC.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Angiogenesis; Cell membrane;
KW Complete proteome; Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Receptor; Reference proteome; Signal-anchor; Sulfation; Transmembrane;
KW Transmembrane helix; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 967 Aminopeptidase N.
FT /FTId=PRO_0000095081.
FT TOPO_DOM 2 8 Cytoplasmic.
FT TRANSMEM 9 32 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 33 967 Extracellular.
FT REGION 33 68 Cytosolic Ser/Thr-rich junction.
FT REGION 69 967 Metalloprotease.
FT REGION 260 353 Interaction with HCoV-229E.
FT REGION 352 356 Substrate binding.
FT ACT_SITE 389 389 Proton acceptor.
FT METAL 388 388 Zinc; catalytic.
FT METAL 392 392 Zinc; catalytic.
FT METAL 411 411 Zinc; catalytic.
FT SITE 477 477 Transition state stabilizer.
FT MOD_RES 176 176 Sulfotyrosine (Potential).
FT MOD_RES 419 419 Sulfotyrosine (Potential).
FT MOD_RES 424 424 Sulfotyrosine (Potential).
FT MOD_RES 913 913 Sulfotyrosine (Potential).
FT CARBOHYD 128 128 N-linked (GlcNAc...).
FT CARBOHYD 234 234 N-linked (GlcNAc...).
FT CARBOHYD 265 265 N-linked (GlcNAc...).
FT CARBOHYD 319 319 N-linked (GlcNAc...).
FT CARBOHYD 527 527 N-linked (GlcNAc...).
FT CARBOHYD 573 573 N-linked (GlcNAc...).
FT CARBOHYD 625 625 N-linked (GlcNAc...).
FT CARBOHYD 681 681 N-linked (GlcNAc...).
FT CARBOHYD 735 735 N-linked (GlcNAc...).
FT CARBOHYD 818 818 N-linked (GlcNAc...).
FT DISULFID 761 768
FT DISULFID 798 834
FT VARIANT 20 20 V -> M (in dbSNP:rs10152474).
FT /FTId=VAR_031262.
FT VARIANT 86 86 R -> Q (in dbSNP:rs25653).
FT /FTId=VAR_014736.
FT VARIANT 242 242 D -> Y.
FT /FTId=VAR_006727.
FT VARIANT 243 243 L -> P.
FT /FTId=VAR_006728.
FT VARIANT 311 311 A -> V (in dbSNP:rs17240268).
FT /FTId=VAR_031263.
FT VARIANT 321 321 T -> M (in dbSNP:rs8179199).
FT /FTId=VAR_031264.
FT VARIANT 603 603 I -> K (in dbSNP:rs17240212).
FT /FTId=VAR_031265.
FT VARIANT 603 603 I -> M (in dbSNP:rs8192297).
FT /FTId=VAR_031266.
FT VARIANT 752 752 S -> N (in dbSNP:rs25651).
FT /FTId=VAR_014737.
FT MUTAGEN 288 295 DYVEKQAS->QSVEETAQ: No change in receptor
FT activity and HCoV-229E infection.
FT MUTAGEN 288 295 DYVEKQAS->QSVNEQAQ: No change in receptor
FT activity and HCoV-229E infection.
FT MUTAGEN 288 295 DYVEKQAS->QSVNETAQ: Complete loss of
FT receptor activity and blocks HCoV-229E
FT infection. No loss of enzymatic activity.
FT MUTAGEN 291 293 EKQ->NKT: Complete loss of receptor
FT activity and blocks HCoV-229E infection.
FT No loss of enzymatic activity.
FT MUTAGEN 291 291 E->N: No change of receptor activity and
FT HCoV-229E infection.
FT MUTAGEN 293 293 Q->T: No change of receptor activity and
FT HCoV-229E infection.
FT MUTAGEN 818 818 N->E: Very low receptor activity and
FT HCoV-229E infection.
FT CONFLICT 536 536 V -> E (in Ref. 1; CAA31640).
FT CONFLICT 887 887 L -> P (in Ref. 1; CAA31640).
FT HELIX 70 72
FT STRAND 73 75
FT STRAND 78 91
FT STRAND 102 115
FT STRAND 118 123
FT STRAND 135 142
FT STRAND 150 156
FT TURN 157 160
FT STRAND 161 168
FT STRAND 175 185
FT STRAND 188 200
FT STRAND 203 211
FT TURN 213 216
FT HELIX 217 219
FT STRAND 231 240
FT STRAND 243 249
FT STRAND 251 253
FT STRAND 256 258
FT STRAND 261 269
FT HELIX 277 279
FT STRAND 282 285
FT STRAND 288 293
FT STRAND 299 304
FT HELIX 306 310
FT TURN 311 314
FT HELIX 315 331
FT STRAND 338 348
FT STRAND 350 354
FT STRAND 359 363
FT HELIX 364 367
FT TURN 371 373
FT HELIX 376 394
FT TURN 396 398
FT STRAND 399 403
FT HELIX 404 407
FT HELIX 408 425
FT HELIX 427 429
FT HELIX 431 434
FT HELIX 435 438
FT HELIX 440 447
FT HELIX 459 461
FT HELIX 465 470
FT HELIX 474 491
FT HELIX 493 507
FT STRAND 510 512
FT HELIX 514 527
FT HELIX 536 544
FT STRAND 550 555
FT TURN 556 559
FT STRAND 560 565
FT TURN 579 582
FT STRAND 586 588
FT STRAND 590 592
FT STRAND 600 602
FT STRAND 604 608
FT HELIX 610 612
FT STRAND 620 623
FT HELIX 624 626
FT STRAND 631 634
FT HELIX 636 649
FT HELIX 650 652
FT HELIX 655 670
FT HELIX 676 681
FT HELIX 682 688
FT HELIX 692 709
FT HELIX 715 736
FT TURN 737 741
FT HELIX 747 762
FT HELIX 766 781
FT HELIX 790 792
FT HELIX 793 803
FT HELIX 806 817
FT HELIX 822 832
FT HELIX 838 848
FT TURN 851 853
FT HELIX 856 858
FT HELIX 859 868
FT HELIX 872 882
FT HELIX 884 890
FT TURN 891 894
FT HELIX 898 906
FT HELIX 912 924
FT TURN 925 928
FT HELIX 931 933
FT HELIX 934 965
SQ SEQUENCE 967 AA; 109540 MW; 37B6BC1BF0D6B1F2 CRC64;
MAKGFYISKS LGILGILLGV AAVCTIIALS VVYSQEKNKN ANSSPVASTT PSASATTNPA
SATTLDQSKA WNRYRLPNTL KPDSYRVTLR PYLTPNDRGL YVFKGSSTVR FTCKEATDVI
IIHSKKLNYT LSQGHRVVLR GVGGSQPPDI DKTELVEPTE YLVVHLKGSL VKDSQYEMDS
EFEGELADDL AGFYRSEYME GNVRKVVATT QMQAADARKS FPCFDEPAMK AEFNITLIHP
KDLTALSNML PKGPSTPLPE DPNWNVTEFH TTPKMSTYLL AFIVSEFDYV EKQASNGVLI
RIWARPSAIA AGHGDYALNV TGPILNFFAG HYDTPYPLPK SDQIGLPDFN AGAMENWGLV
TYRENSLLFD PLSSSSSNKE RVVTVIAHEL AHQWFGNLVT IEWWNDLWLN EGFASYVEYL
GADYAEPTWN LKDLMVLNDV YRVMAVDALA SSHPLSTPAS EINTPAQISE LFDAISYSKG
ASVLRMLSSF LSEDVFKQGL ASYLHTFAYQ NTIYLNLWDH LQEAVNNRSI QLPTTVRDIM
NRWTLQMGFP VITVDTSTGT LSQEHFLLDP DSNVTRPSEF NYVWIVPITS IRDGRQQQDY
WLIDVRAQND LFSTSGNEWV LLNLNVTGYY RVNYDEENWR KIQTQLQRDH SAIPVINRAQ
IINDAFNLAS AHKVPVTLAL NNTLFLIEER QYMPWEAALS SLSYFKLMFD RSEVYGPMKN
YLKKQVTPLF IHFRNNTNNW REIPENLMDQ YSEVNAISTA CSNGVPECEE MVSGLFKQWM
ENPNNNPIHP NLRSTVYCNA IAQGGEEEWD FAWEQFRNAT LVNEADKLRA ALACSKELWI
LNRYLSYTLN PDLIRKQDAT STIISITNNV IGQGLVWDFV QSNWKKLFND YGGGSFSFSN
LIQAVTRRFS TEYELQQLEQ FKKDNEETGF GSGTRALEQA LEKTKANIKW VKENKEVVLQ
WFTENSK
//
ID AMPN_HUMAN Reviewed; 967 AA.
AC P15144; Q16728; Q6GT90; Q8IUK3; Q8IVH3; Q9UCE0;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-APR-2007, sequence version 4.
DT 22-JAN-2014, entry version 167.
DE RecName: Full=Aminopeptidase N;
DE Short=AP-N;
DE Short=hAPN;
DE EC=3.4.11.2;
DE AltName: Full=Alanyl aminopeptidase;
DE AltName: Full=Aminopeptidase M;
DE Short=AP-M;
DE AltName: Full=Microsomal aminopeptidase;
DE AltName: Full=Myeloid plasma membrane glycoprotein CD13;
DE AltName: Full=gp150;
DE AltName: CD_antigen=CD13;
GN Name=ANPEP; Synonyms=APN, CD13, PEPN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLN-86 AND MET-603.
RC TISSUE=Intestine;
RX PubMed=2901990; DOI=10.1016/0014-5793(88)80502-7;
RA Olsen J., Cowell G.M., Koenigshoefer E., Danielsen E.M., Moeller J.,
RA Laustsen L., Hansen O.C., Welinder K.G., Engberg J., Hunziker W.,
RA Spiess M., Sjoestroem H., Noren O.;
RT "Complete amino acid sequence of human intestinal aminopeptidase N as
RT deduced from cloned cDNA.";
RL FEBS Lett. 238:307-314(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-21, AND VARIANT
RP GLN-86.
RX PubMed=2564851; DOI=10.1172/JCI114015;
RA Look A.T., Ashmun R.A., Shapiro L.H., Peiper S.C.;
RT "Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical
RT to aminopeptidase N.";
RL J. Clin. Invest. 83:1299-1307(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
RC TISSUE=Intestinal epithelium;
RX PubMed=1675638;
RA Shapiro L.H., Ashmun R.A., Roberts W.M., Look A.T.;
RT "Separate promoters control transcription of the human aminopeptidase
RT N gene in myeloid and intestinal epithelial cells.";
RL J. Biol. Chem. 266:11999-12007(1991).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-479 AND 524-967, AND VARIANT
RP GLN-86.
RC TISSUE=Peripheral blood;
RA Eiz-Vesper B., Fuchs N., Gottschalk D., Mueller K., Reuter S.,
RA Blasczyk R.;
RT "Genomic organisation of aminopeptidase N.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PROTEIN SEQUENCE OF 2-20 AND 70-81.
RX PubMed=7576235;
RA Watanabe Y., Iwaki-Egawa S., Mizukoshi H., Fujimoto Y.;
RT "Identification of an alanine aminopeptidase in human maternal serum
RT as a membrane-bound aminopeptidase N.";
RL Biol. Chem. Hoppe-Seyler 376:397-400(1995).
RN [8]
RP PROTEIN SEQUENCE OF 2-18.
RX PubMed=8102610; DOI=10.1016/0014-5793(93)80199-5;
RA Nunez L., Amigo L., Rigotti A., Puglielli L., Mingrone G., Greco A.V.,
RA Nervi F.;
RT "Cholesterol crystallization-promoting activity of aminopeptidase-N
RT isolated from the vesicular carrier of biliary lipids.";
RL FEBS Lett. 329:84-88(1993).
RN [9]
RP CHARACTERIZATION, AND SUBUNIT.
RX PubMed=6149934;
RA Tokioka-Terao M., Hiwada K., Kokubu T.;
RT "Purification and characterization of aminopeptidase N from human
RT plasma.";
RL Enzyme 32:65-75(1984).
RN [10]
RP GLYCOSYLATION.
RX PubMed=1705556;
RA O'Connell P.J., Gerkis V., d'Apice A.J.F.;
RT "Variable O-glycosylation of CD13 (aminopeptidase N).";
RL J. Biol. Chem. 266:4593-4597(1991).
RN [11]
RP INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN, AND CHARACTERIZATION OF
RP HCOV-229E RECEPTOR FUNCTION.
RX PubMed=1350662; DOI=10.1038/357420a0;
RA Yeager C.L., Ashmun R.A., Williams R.K., Cardellichio C.B.,
RA Shapiro L.H., Look A.T., Holmes K.V.;
RT "Human aminopeptidase N is a receptor for human coronavirus 229E.";
RL Nature 357:420-422(1992).
RN [12]
RP IDENTIFICATION OF SOLUBLE FORM.
RX PubMed=7902291;
RA Favaloro E.J., Browning T., Facey D.;
RT "CD13 (GP150; aminopeptidase-N): predominant functional activity in
RT blood is localized to plasma and is not cell-surface associated.";
RL Exp. Hematol. 21:1695-1701(1993).
RN [13]
RP CHARACTERIZATION OF CMV RECEPTOR FUNCTION.
RX PubMed=8105105;
RA Soderberg C., Giugni T.D., Zaia J.A., Larsson S., Wahlberg J.M.,
RA Moller E.;
RT "CD13 (human aminopeptidase N) mediates human cytomegalovirus
RT infection.";
RL J. Virol. 67:6576-6585(1993).
RN [14]
RP IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR HCOV-229E INFECTION.
RX PubMed=8887485;
RA Kolb A.F., Maile J., Heister A., Siddell S.G.;
RT "Characterization of functional domains in the human coronavirus HCV
RT 229E receptor.";
RL J. Gen. Virol. 77:2515-2521(1996).
RN [15]
RP FUNCTION, AND GLYCOSYLATION.
RX PubMed=9056417; DOI=10.1006/excr.1996.3455;
RA Noren K., Hansen G.H., Clausen H., Noren O., Sjostrom H., Vogel L.K.;
RT "Defectively N-glycosylated and non-O-glycosylated aminopeptidase N
RT (CD13) is normally expressed at the cell surface and has full
RT enzymatic activity.";
RL Exp. Cell Res. 231:112-118(1997).
RN [16]
RP IDENTIFICATION OF RESIDUES CRITICAL FOR HCOV-229E INFECTION.
RX PubMed=9367365;
RA Kolb A.F., Hegyi A., Siddell S.G.;
RT "Identification of residues critical for the human coronavirus 229E
RT receptor function of human aminopeptidase N.";
RL J. Gen. Virol. 78:2795-2802(1997).
RN [17]
RP IDENTIFICATION OF RECEPTOR FUNCTIONAL DOMAINS FOR TGEV INFECTION.
RX PubMed=9634079;
RA Hegyi A., Kolb A.F.;
RT "Characterization of determinants involved in the feline infectious
RT peritonitis virus receptor function of feline aminopeptidase N.";
RL J. Gen. Virol. 79:1387-1391(1998).
RN [18]
RP FUNCTION, AND ENZYMATIC CLEAVAGE OF ANTIGEN PEPTIDES BOUND TO CLASS II
RP MHC.
RX PubMed=10605003;
RA Dong X., An B., Salvucci Kierstead L., Storkus W.J., Amoscato A.A.,
RA Salter R.D.;
RT "Modification of the amino terminus of a class II epitope confers
RT resistance to degradation by CD13 on dendritic cells and enhances
RT presentation to T cells.";
RL J. Immunol. 164:129-135(2000).
RN [19]
RP ROLE IN ANGIOGENESIS, AND CHARACTERIZATION OF RECEPTOR FOR
RP TUMOR-HOMING PEPTIDES FUNCTION.
RX PubMed=10676659;
RA Pasqualini R., Koivunen E., Kain R., Lahdenranta J., Sakamoto M.,
RA Stryhn A., Ashmun R.A., Shapiro L.H., Arap W., Ruoslahti E.;
RT "Aminopeptidase N is a receptor for tumor-homing peptides and a target
RT for inhibiting angiogenesis.";
RL Cancer Res. 60:722-727(2000).
RN [20]
RP FUNCTION, AND INDUCTION BY ESTRADIOL AND IL8.
RX PubMed=11384645; DOI=10.1016/S0015-0282(01)01779-4;
RA Seli E., Senturk L.M., Bahtiyar O.M., Kayisli U.A., Arici A.;
RT "Expression of aminopeptidase N in human endometrium and regulation of
RT its activity by estrogen.";
RL Fertil. Steril. 75:1172-1176(2001).
RN [21]
RP MUTAGENESIS OF 288-ASP--SER-295 AND ASN-818.
RX PubMed=11559807; DOI=10.1128/JVI.75.20.9741-9752.2001;
RA Wentworth D.E., Holmes K.V.;
RT "Molecular determinants of species specificity in the coronavirus
RT receptor aminopeptidase N (CD13): influence of N-linked
RT glycosylation.";
RL J. Virol. 75:9741-9752(2001).
RN [22]
RP FUNCTION OF SOLUBLE FORM.
RX PubMed=12473585;
RA van Hensbergen Y., Broxterman H.J., Hanemaaijer R., Jorna A.S.,
RA van Lent N.A., Verheul H.M., Pinedo H.M., Hoekman K.;
RT "Soluble aminopeptidase N/CD13 in malignant and nonmalignant effusions
RT and intratumoral fluid.";
RL Clin. Cancer Res. 8:3747-3754(2002).
RN [23]
RP INTERACTION WITH HCOV-229E SPIKE GLYCOPROTEIN.
RX PubMed=12551991; DOI=10.1128/JVI.77.4.2530-2538.2003;
RA Bonavia A., Zelus B.D., Wentworth D.E., Talbot P.J., Holmes K.V.;
RT "Identification of a receptor-binding domain of the spike glycoprotein
RT of human coronavirus HCoV-229E.";
RL J. Virol. 77:2530-2538(2003).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265, AND MASS
RP SPECTROMETRY.
RC TISSUE=Bile;
RX PubMed=15084671; DOI=10.1074/mcp.M400015-MCP200;
RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H.,
RA Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.;
RT "A proteomic analysis of human bile.";
RL Mol. Cell. Proteomics 3:715-728(2004).
RN [25]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265;
RP ASN-681 AND ASN-818, AND MASS SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [26]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265;
RP ASN-573; ASN-681 AND ASN-818, AND MASS SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 66-967 IN COMPLEX WITH
RP ANGIOTENSIN-4 AND INHIBITORS, CATALYTIC ACTIVITY, COFACTOR,
RP SUBSTRATE-BINDING REGION, ZINC-BINDING SITES, ACTIVE SITE,
RP GLYCOSYLATION AT ASN-128; ASN-234; ASN-265; ASN-319; ASN-527; ASN-625;
RP ASN-681 AND ASN-818, SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=22932899; DOI=10.1074/jbc.M112.398842;
RA Wong A.H., Zhou D., Rini J.M.;
RT "The X-ray crystal structure of human aminopeptidase N reveals a novel
RT dimer and the basis for peptide processing.";
RL J. Biol. Chem. 287:36804-36813(2012).
RN [29]
RP VARIANTS TYR-242 AND PRO-243.
RX PubMed=9452074;
RA Lendeckel U., Wex T., Arndt M., Frank K., Franke A., Ansorge S.;
RT "Identification of point mutations in the aminopeptidase N gene by
RT SSCP analysis and sequencing.";
RL Hum. Mutat. Suppl. 1:S158-S160(1998).
CC -!- FUNCTION: Broad specificity aminopeptidase. Plays a role in the
CC final digestion of peptides generated from hydrolysis of proteins
CC by gastric and pancreatic proteases. May play a critical role in
CC the pathogenesis of cholesterol gallstone disease. May be involved
CC in the metabolism of regulatory peptides of diverse cell types,
CC responsible for the processing of peptide hormones, such as
CC angiotensin III and IV, neuropeptides, and chemokines. Found to
CC cleave antigen peptides bound to major histocompatibility complex
CC class II molecules of presenting cells and to degrade
CC neurotransmitters at synaptic junctions. Is also implicated as a
CC regulator of IL-8 bioavailability in the endometrium, and
CC therefore may contribute to the regulation of angiogenesis. Is
CC used as a marker for acute myeloid leukemia and plays a role in
CC tumor invasion. In case of human coronavirus 229E (HCoV-229E)
CC infection, serves as receptor for HCoV-229E spike glycoprotein.
CC Mediates as well human cytomegalovirus (HCMV) infection.
CC -!- CATALYTIC ACTIVITY: Release of an N-terminal amino acid, Xaa-|-
CC Yaa- from a peptide, amide or arylamide. Xaa is preferably Ala,
CC but may be most amino acids including Pro (slow action). When a
CC terminal hydrophobic residue is followed by a prolyl residue, the
CC two may be released as an intact Xaa-Pro dipeptide.
CC -!- COFACTOR: Binds 1 zinc ion per subunit.
CC -!- SUBUNIT: Homodimer. Interacts with the S1 domain of HCoV-229E
CC spike protein.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type II membrane
CC protein. Cytoplasm, cytosol (Potential). Note=A soluble form has
CC also been detected.
CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells of the kidney,
CC intestine, and respiratory tract; granulocytes, monocytes,
CC fibroblasts, endothelial cells, cerebral pericytes at the blood-
CC brain barrier, synaptic membranes of cells in the CNS. Also
CC expressed in endometrial stromal cells, but not in the endometrial
CC glandular cells. Found in the vasculature of tissues that undergo
CC angiogenesis and in malignant gliomas and lymph node metastases
CC from multiple tumor types but not in blood vessels of normal
CC tissues. A soluble form has been found in plasma. It is found to
CC be elevated in plasma and effusions of cancer patients.
CC -!- INDUCTION: Estradiol and IL8/interleukin-8 decrease enzymatic
CC activity in vitro in endometrial stromal cells by 40% and 30%,
CC respectively.
CC -!- DOMAIN: Amino acids 260-353 are essential to mediate
CC susceptibility to infection with HCoV-229E (in porcine/human
CC chimeric studies) and more specifically amino acids 288-295
CC (mutagenesis studies).
CC -!- PTM: Sulfated (By similarity).
CC -!- PTM: N- and O-glycosylated.
CC -!- PTM: May undergo proteolysis and give rise to a soluble form.
CC -!- MISCELLANEOUS: Found to serve as a receptor for tumor-homing
CC peptides, more specifically NGR peptides. It could serve thus as a
CC target for delivering drugs into tumors. Concentration in human
CC hepatic bile, varies from 17.3 to 57.6 micrograms/ml.
CC -!- SIMILARITY: Belongs to the peptidase M1 family.
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DR EMBL; X13276; CAA31640.1; -; mRNA.
DR EMBL; M22324; AAA51719.1; -; mRNA.
DR EMBL; AC018988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC079075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC058928; AAH58928.1; -; mRNA.
DR EMBL; M55522; AAA83399.1; -; Genomic_DNA.
DR EMBL; AJ421875; CAD19098.2; -; Genomic_DNA.
DR EMBL; AJ421876; CAD19098.2; JOINED; Genomic_DNA.
DR EMBL; AJ426050; CAD19802.1; -; Genomic_DNA.
DR EMBL; AJ427985; CAD20931.1; -; Genomic_DNA.
DR EMBL; AJ427986; CAD20931.1; JOINED; Genomic_DNA.
DR EMBL; AJ427987; CAD20931.1; JOINED; Genomic_DNA.
DR EMBL; AJ427988; CAD20931.1; JOINED; Genomic_DNA.
DR PIR; A30325; A30325.
DR RefSeq; NP_001141.2; NM_001150.2.
DR RefSeq; XP_005254949.1; XM_005254892.1.
DR UniGene; Hs.1239; -.
DR PDB; 4FYQ; X-ray; 1.90 A; A=66-967.
DR PDB; 4FYR; X-ray; 1.91 A; A=66-967.
DR PDB; 4FYS; X-ray; 2.01 A; A=66-967.
DR PDB; 4FYT; X-ray; 1.85 A; A=66-967.
DR PDBsum; 4FYQ; -.
DR PDBsum; 4FYR; -.
DR PDBsum; 4FYS; -.
DR PDBsum; 4FYT; -.
DR ProteinModelPortal; P15144; -.
DR SMR; P15144; 66-967.
DR IntAct; P15144; 5.
DR STRING; 9606.ENSP00000300060; -.
DR BindingDB; P15144; -.
DR ChEMBL; CHEMBL1907; -.
DR DrugBank; DB00973; Ezetimibe.
DR MEROPS; M01.001; -.
DR PhosphoSite; P15144; -.
DR DMDM; 143811362; -.
DR PaxDb; P15144; -.
DR PRIDE; P15144; -.
DR DNASU; 290; -.
DR Ensembl; ENST00000300060; ENSP00000300060; ENSG00000166825.
DR GeneID; 290; -.
DR KEGG; hsa:290; -.
DR UCSC; uc002bop.4; human.
DR CTD; 290; -.
DR GeneCards; GC15M090328; -.
DR H-InvDB; HIX0038141; -.
DR HGNC; HGNC:500; ANPEP.
DR HPA; CAB002417; -.
DR MIM; 151530; gene.
DR neXtProt; NX_P15144; -.
DR PharmGKB; PA24815; -.
DR eggNOG; COG0308; -.
DR HOVERGEN; HBG006616; -.
DR InParanoid; P15144; -.
DR KO; K11140; -.
DR OMA; WVLLNLN; -.
DR OrthoDB; EOG754HNR; -.
DR PhylomeDB; P15144; -.
DR BRENDA; 3.4.11.2; 2681.
DR Reactome; REACT_17015; Metabolism of proteins.
DR SABIO-RK; P15144; -.
DR GeneWiki; Alanine_aminopeptidase; -.
DR GenomeRNAi; 290; -.
DR NextBio; 1183; -.
DR PRO; PR:P15144; -.
DR ArrayExpress; P15144; -.
DR Bgee; P15144; -.
DR CleanEx; HS_ANPEP; -.
DR Genevestigator; P15144; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; IDA:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR GO; GO:0004872; F:receptor activity; TAS:ProtInc.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0002003; P:angiotensin maturation; TAS:Reactome.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0009615; P:response to virus; IEA:GOC.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_N.
DR PANTHER; PTHR11533; PTHR11533; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Angiogenesis; Cell membrane;
KW Complete proteome; Cytoplasm; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Polymorphism; Protease;
KW Receptor; Reference proteome; Signal-anchor; Sulfation; Transmembrane;
KW Transmembrane helix; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 967 Aminopeptidase N.
FT /FTId=PRO_0000095081.
FT TOPO_DOM 2 8 Cytoplasmic.
FT TRANSMEM 9 32 Helical; Signal-anchor for type II
FT membrane protein; (Potential).
FT TOPO_DOM 33 967 Extracellular.
FT REGION 33 68 Cytosolic Ser/Thr-rich junction.
FT REGION 69 967 Metalloprotease.
FT REGION 260 353 Interaction with HCoV-229E.
FT REGION 352 356 Substrate binding.
FT ACT_SITE 389 389 Proton acceptor.
FT METAL 388 388 Zinc; catalytic.
FT METAL 392 392 Zinc; catalytic.
FT METAL 411 411 Zinc; catalytic.
FT SITE 477 477 Transition state stabilizer.
FT MOD_RES 176 176 Sulfotyrosine (Potential).
FT MOD_RES 419 419 Sulfotyrosine (Potential).
FT MOD_RES 424 424 Sulfotyrosine (Potential).
FT MOD_RES 913 913 Sulfotyrosine (Potential).
FT CARBOHYD 128 128 N-linked (GlcNAc...).
FT CARBOHYD 234 234 N-linked (GlcNAc...).
FT CARBOHYD 265 265 N-linked (GlcNAc...).
FT CARBOHYD 319 319 N-linked (GlcNAc...).
FT CARBOHYD 527 527 N-linked (GlcNAc...).
FT CARBOHYD 573 573 N-linked (GlcNAc...).
FT CARBOHYD 625 625 N-linked (GlcNAc...).
FT CARBOHYD 681 681 N-linked (GlcNAc...).
FT CARBOHYD 735 735 N-linked (GlcNAc...).
FT CARBOHYD 818 818 N-linked (GlcNAc...).
FT DISULFID 761 768
FT DISULFID 798 834
FT VARIANT 20 20 V -> M (in dbSNP:rs10152474).
FT /FTId=VAR_031262.
FT VARIANT 86 86 R -> Q (in dbSNP:rs25653).
FT /FTId=VAR_014736.
FT VARIANT 242 242 D -> Y.
FT /FTId=VAR_006727.
FT VARIANT 243 243 L -> P.
FT /FTId=VAR_006728.
FT VARIANT 311 311 A -> V (in dbSNP:rs17240268).
FT /FTId=VAR_031263.
FT VARIANT 321 321 T -> M (in dbSNP:rs8179199).
FT /FTId=VAR_031264.
FT VARIANT 603 603 I -> K (in dbSNP:rs17240212).
FT /FTId=VAR_031265.
FT VARIANT 603 603 I -> M (in dbSNP:rs8192297).
FT /FTId=VAR_031266.
FT VARIANT 752 752 S -> N (in dbSNP:rs25651).
FT /FTId=VAR_014737.
FT MUTAGEN 288 295 DYVEKQAS->QSVEETAQ: No change in receptor
FT activity and HCoV-229E infection.
FT MUTAGEN 288 295 DYVEKQAS->QSVNEQAQ: No change in receptor
FT activity and HCoV-229E infection.
FT MUTAGEN 288 295 DYVEKQAS->QSVNETAQ: Complete loss of
FT receptor activity and blocks HCoV-229E
FT infection. No loss of enzymatic activity.
FT MUTAGEN 291 293 EKQ->NKT: Complete loss of receptor
FT activity and blocks HCoV-229E infection.
FT No loss of enzymatic activity.
FT MUTAGEN 291 291 E->N: No change of receptor activity and
FT HCoV-229E infection.
FT MUTAGEN 293 293 Q->T: No change of receptor activity and
FT HCoV-229E infection.
FT MUTAGEN 818 818 N->E: Very low receptor activity and
FT HCoV-229E infection.
FT CONFLICT 536 536 V -> E (in Ref. 1; CAA31640).
FT CONFLICT 887 887 L -> P (in Ref. 1; CAA31640).
FT HELIX 70 72
FT STRAND 73 75
FT STRAND 78 91
FT STRAND 102 115
FT STRAND 118 123
FT STRAND 135 142
FT STRAND 150 156
FT TURN 157 160
FT STRAND 161 168
FT STRAND 175 185
FT STRAND 188 200
FT STRAND 203 211
FT TURN 213 216
FT HELIX 217 219
FT STRAND 231 240
FT STRAND 243 249
FT STRAND 251 253
FT STRAND 256 258
FT STRAND 261 269
FT HELIX 277 279
FT STRAND 282 285
FT STRAND 288 293
FT STRAND 299 304
FT HELIX 306 310
FT TURN 311 314
FT HELIX 315 331
FT STRAND 338 348
FT STRAND 350 354
FT STRAND 359 363
FT HELIX 364 367
FT TURN 371 373
FT HELIX 376 394
FT TURN 396 398
FT STRAND 399 403
FT HELIX 404 407
FT HELIX 408 425
FT HELIX 427 429
FT HELIX 431 434
FT HELIX 435 438
FT HELIX 440 447
FT HELIX 459 461
FT HELIX 465 470
FT HELIX 474 491
FT HELIX 493 507
FT STRAND 510 512
FT HELIX 514 527
FT HELIX 536 544
FT STRAND 550 555
FT TURN 556 559
FT STRAND 560 565
FT TURN 579 582
FT STRAND 586 588
FT STRAND 590 592
FT STRAND 600 602
FT STRAND 604 608
FT HELIX 610 612
FT STRAND 620 623
FT HELIX 624 626
FT STRAND 631 634
FT HELIX 636 649
FT HELIX 650 652
FT HELIX 655 670
FT HELIX 676 681
FT HELIX 682 688
FT HELIX 692 709
FT HELIX 715 736
FT TURN 737 741
FT HELIX 747 762
FT HELIX 766 781
FT HELIX 790 792
FT HELIX 793 803
FT HELIX 806 817
FT HELIX 822 832
FT HELIX 838 848
FT TURN 851 853
FT HELIX 856 858
FT HELIX 859 868
FT HELIX 872 882
FT HELIX 884 890
FT TURN 891 894
FT HELIX 898 906
FT HELIX 912 924
FT TURN 925 928
FT HELIX 931 933
FT HELIX 934 965
SQ SEQUENCE 967 AA; 109540 MW; 37B6BC1BF0D6B1F2 CRC64;
MAKGFYISKS LGILGILLGV AAVCTIIALS VVYSQEKNKN ANSSPVASTT PSASATTNPA
SATTLDQSKA WNRYRLPNTL KPDSYRVTLR PYLTPNDRGL YVFKGSSTVR FTCKEATDVI
IIHSKKLNYT LSQGHRVVLR GVGGSQPPDI DKTELVEPTE YLVVHLKGSL VKDSQYEMDS
EFEGELADDL AGFYRSEYME GNVRKVVATT QMQAADARKS FPCFDEPAMK AEFNITLIHP
KDLTALSNML PKGPSTPLPE DPNWNVTEFH TTPKMSTYLL AFIVSEFDYV EKQASNGVLI
RIWARPSAIA AGHGDYALNV TGPILNFFAG HYDTPYPLPK SDQIGLPDFN AGAMENWGLV
TYRENSLLFD PLSSSSSNKE RVVTVIAHEL AHQWFGNLVT IEWWNDLWLN EGFASYVEYL
GADYAEPTWN LKDLMVLNDV YRVMAVDALA SSHPLSTPAS EINTPAQISE LFDAISYSKG
ASVLRMLSSF LSEDVFKQGL ASYLHTFAYQ NTIYLNLWDH LQEAVNNRSI QLPTTVRDIM
NRWTLQMGFP VITVDTSTGT LSQEHFLLDP DSNVTRPSEF NYVWIVPITS IRDGRQQQDY
WLIDVRAQND LFSTSGNEWV LLNLNVTGYY RVNYDEENWR KIQTQLQRDH SAIPVINRAQ
IINDAFNLAS AHKVPVTLAL NNTLFLIEER QYMPWEAALS SLSYFKLMFD RSEVYGPMKN
YLKKQVTPLF IHFRNNTNNW REIPENLMDQ YSEVNAISTA CSNGVPECEE MVSGLFKQWM
ENPNNNPIHP NLRSTVYCNA IAQGGEEEWD FAWEQFRNAT LVNEADKLRA ALACSKELWI
LNRYLSYTLN PDLIRKQDAT STIISITNNV IGQGLVWDFV QSNWKKLFND YGGGSFSFSN
LIQAVTRRFS TEYELQQLEQ FKKDNEETGF GSGTRALEQA LEKTKANIKW VKENKEVVLQ
WFTENSK
//
MIM
151530
*RECORD*
*FIELD* NO
151530
*FIELD* TI
*151530 ALANYL AMINOPEPTIDASE; ANPEP
;;AMINOPEPTIDASE N; PEPN;;
CD13 ANTIGEN; CD13;;
read moreLEUKOCYTE SURFACE ANTIGEN GP150; GP150
*FIELD* TX
DESCRIPTION
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).
CLONING
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.
GENE FUNCTION
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.
MAPPING
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.
ANIMAL MODEL
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.
*FIELD* RF
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Watt, V. M.; Willard, H. F.: The human aminopeptidase N gene:
isolation, chromosome localization, and DNA polymorphism analysis. Hum.
Genet. 85: 651-654, 1990.
8. 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.
9. 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.
*FIELD* CN
Paul J. Converse - updated: 7/24/2008
Marla J. F. O'Neill - updated: 4/30/2007
Patricia A. Hartz - updated: 3/15/2007
*FIELD* CD
Victor A. McKusick: 9/14/1988
*FIELD* ED
mgross: 08/18/2008
terry: 7/24/2008
wwang: 4/30/2007
wwang: 3/21/2007
terry: 3/15/2007
psherman: 9/29/1999
carol: 9/22/1993
carol: 7/2/1992
carol: 6/23/1992
supermim: 3/16/1992
carol: 12/5/1990
supermim: 3/20/1990
*RECORD*
*FIELD* NO
151530
*FIELD* TI
*151530 ALANYL AMINOPEPTIDASE; ANPEP
;;AMINOPEPTIDASE N; PEPN;;
CD13 ANTIGEN; CD13;;
read moreLEUKOCYTE SURFACE ANTIGEN GP150; GP150
*FIELD* TX
DESCRIPTION
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).
CLONING
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.
GENE FUNCTION
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.
MAPPING
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.
ANIMAL MODEL
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.
*FIELD* RF
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Watt, V. M.; Willard, H. F.: The human aminopeptidase N gene:
isolation, chromosome localization, and DNA polymorphism analysis. Hum.
Genet. 85: 651-654, 1990.
8. 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.
9. 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.
*FIELD* CN
Paul J. Converse - updated: 7/24/2008
Marla J. F. O'Neill - updated: 4/30/2007
Patricia A. Hartz - updated: 3/15/2007
*FIELD* CD
Victor A. McKusick: 9/14/1988
*FIELD* ED
mgross: 08/18/2008
terry: 7/24/2008
wwang: 4/30/2007
wwang: 3/21/2007
terry: 3/15/2007
psherman: 9/29/1999
carol: 9/22/1993
carol: 7/2/1992
carol: 6/23/1992
supermim: 3/16/1992
carol: 12/5/1990
supermim: 3/20/1990