P15144 (AMPN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aminopeptidase N
Short name=AP-N
Short name=hAPN
EC=3.4.11.2

Alternative name(s):
Alanyl aminopeptidase
Aminopeptidase M
Short name=AP-M
Microsomal aminopeptidase
Myeloid plasma membrane glycoprotein CD13
gp150
CD_antigen=CD13

Gene names

Name:	ANPEP
Synonyms:	APN, CD13, PEPN

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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, 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. Ref.11 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22
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. Ref.28
Cofactor	Binds 1 zinc ion per subunit. Ref.28
Subunit structure	Homodimer. Interacts with the S1 domain of HCoV-229E spike protein. Ref.9 Ref.11 Ref.23 Ref.28
Subcellular location	Cell membrane; Single-pass type II membrane protein. Cytoplasm › cytosol Potential. 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 IL8/interleukin-8 decrease enzymatic activity in vitro in endometrial stromal cells by 40% and 30%, respectively. Ref.20
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). Ref.14 Ref.17
Post-translational modification	Sulfated By similarity. N- and O-glycosylated. Ref.10 Ref.15 Ref.28 May undergo proteolysis and give rise to a soluble form.
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

Keywords
Biological process	Angiogenesis Differentiation Host-virus interaction
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Aminopeptidase Developmental protein Host cell receptor for virus entry Hydrolase Metalloprotease Protease Receptor
PTM	Disulfide bond Glycoprotein Sulfation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from direct assay PubMed 15308636. Source: UniProtKB external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.2. Source: ProtInc
Molecular_function	aminopeptidase activity Traceable author statement PubMed 10734069. Source: ProtInc metallopeptidase activity Traceable author statement Ref.2. Source: ProtInc receptor activity Traceable author statement Ref.11. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2 Ref.7 Ref.8

Chain

2 – 967

966

Aminopeptidase N

PRO_0000095081

Regions

Topological domain

2 – 8

7

Cytoplasmic

Transmembrane

9 – 32

24

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

33 – 967

935

Extracellular

Region

33 – 68

36

Cytosolic Ser/Thr-rich junction

Region

69 – 967

899

Metalloprotease

Region

260 – 353

94

Interaction with HCoV-229E

Region

352 – 356

5

Substrate binding

Sites

Active site

389

1

Proton acceptor Ref.28

Metal binding

388

1

Zinc; catalytic

Metal binding

392

1

Zinc; catalytic

Metal binding

411

1

Zinc; catalytic

Site

477

1

Transition state stabilize

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

Glycosylation

128

1

N-linked (GlcNAc...) Ref.25 Ref.26 Ref.28

Glycosylation

234

1

N-linked (GlcNAc...) Ref.25 Ref.26 Ref.28

Glycosylation

265

1

N-linked (GlcNAc...) Ref.24 Ref.25 Ref.26 Ref.28

Glycosylation

319

1

N-linked (GlcNAc...) Ref.28

Glycosylation

527

1

N-linked (GlcNAc...) Ref.28

Glycosylation

573

1

N-linked (GlcNAc...) Ref.26

Glycosylation

625

1

N-linked (GlcNAc...) Ref.28

Glycosylation

681

1

N-linked (GlcNAc...) Ref.25 Ref.26 Ref.28

Glycosylation

735

1

N-linked (GlcNAc...)

Glycosylation

818

1

N-linked (GlcNAc...) Ref.25 Ref.26 Ref.28

Disulfide bond

761 ↔ 768

Ref.28

Disulfide bond

798 ↔ 834

Ref.28

Natural variations

Natural variant

20

1

V → M.
Corresponds to variant rs10152474 [ dbSNP | Ensembl ].

VAR_031262

Natural variant

86

1

R → Q. Ref.1 Ref.2 Ref.6
Corresponds to variant rs25653 [ dbSNP | Ensembl ].

VAR_014736

Natural variant

242

1

D → Y. Ref.29

VAR_006727

Natural variant

243

1

L → P. Ref.29

VAR_006728

Natural variant

311

1

A → V.
Corresponds to variant rs17240268 [ dbSNP | Ensembl ].

VAR_031263

Natural variant

321

1

T → M.
Corresponds to variant rs8179199 [ dbSNP | Ensembl ].

VAR_031264

Natural variant

603

1

I → K.
Corresponds to variant rs17240212 [ dbSNP | Ensembl ].

VAR_031265

Natural variant

603

1

I → M. Ref.1
Corresponds to variant rs8192297 [ dbSNP | Ensembl ].

VAR_031266

Natural variant

752

1

S → N.
Corresponds to variant rs25651 [ dbSNP | Ensembl ].

VAR_014737

Experimental info

Mutagenesis

288 – 295

8

DYVEKQAS → QSVEETAQ: No change in receptor activity and HCoV-229E infection. Ref.21

Mutagenesis

288 – 295

8

DYVEKQAS → QSVNEQAQ: No change in receptor activity and HCoV-229E infection. Ref.21

Mutagenesis

288 – 295

8

DYVEKQAS → QSVNETAQ: Complete loss of receptor activity and blocks HCoV-229E infection. No loss of enzymatic activity. Ref.21

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. Ref.21

Sequence conflict

536

1

V → E in CAA31640. Ref.1

Sequence conflict

887

1

L → P in CAA31640. Ref.1

Secondary structure

1

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967

Helix Strand Turn

Details...

Helix

70 – 72

3

Beta strand

73 – 75

3

Beta strand

78 – 91

14

Beta strand

102 – 115

14

Beta strand

118 – 123

6

Beta strand

135 – 142

8

Beta strand

150 – 156

7

Turn

157 – 160

4

Beta strand

161 – 168

8

Beta strand

175 – 185

11

Beta strand

188 – 200

13

Beta strand

203 – 211

9

Turn

213 – 216

4

Helix

217 – 219

3

Beta strand

231 – 240

10

Beta strand

243 – 249

7

Beta strand

251 – 253

3

Beta strand

256 – 258

3

Beta strand

261 – 269

9

Helix

277 – 279

3

Beta strand

282 – 285

4

Beta strand

288 – 293

6

Beta strand

299 – 304

6

Helix

306 – 310

5

Turn

311 – 314

4

Helix

315 – 331

17

Beta strand

338 – 348

11

Beta strand

350 – 354

5

Beta strand

359 – 363

5

Helix

364 – 367

4

Turn

371 – 373

3

Helix

376 – 394

19

Turn

396 – 398

3

Beta strand

399 – 403

5

Helix

404 – 407

4

Helix

408 – 425

18

Helix

427 – 429

3

Helix

431 – 434

4

Helix

435 – 438

4

Helix

440 – 447

8

Helix

459 – 461

3

Helix

465 – 470

6

Helix

474 – 491

18

Helix

493 – 507

15

Beta strand

510 – 512

3

Helix

514 – 527

14

Helix

536 – 544

9

Beta strand

550 – 555

6

Turn

556 – 559

4

Beta strand

560 – 565

6

Turn

579 – 582

4

Beta strand

586 – 588

3

Beta strand

590 – 592

3

Beta strand

600 – 602

3

Beta strand

604 – 608

5

Helix

610 – 612

3

Beta strand

620 – 623

4

Helix

624 – 626

3

Beta strand

631 – 634

4

Helix

636 – 649

14

Helix

650 – 652

3

Helix

655 – 670

16

Helix

676 – 681

6

Helix

682 – 688

7

Helix

692 – 709

18

Helix

715 – 736

22

Turn

737 – 741

5

Helix

747 – 762

16

Helix

766 – 781

16

Helix

790 – 792

3

Helix

793 – 803

11

Helix

806 – 817

12

Helix

822 – 832

11

Helix

838 – 848

11

Turn

851 – 853

3

Helix

856 – 858

3

Helix

859 – 868

10

Helix

872 – 882

11

Helix

884 – 890

7

Turn

891 – 894

4

Helix

898 – 906

9

Helix

912 – 924

13

Turn

925 – 928

4

Helix

931 – 933

3

Helix

934 – 965

32

Sequences

	Sequence		Length	Mass (Da)
	P15144 [UniParc]. Last modified April 3, 2007. Version 4. Checksum: 37B6BC1BF0D6B1F2	FASTA	967	109,540
	10 20 30 40 50 60 MAKGFYISKS LGILGILLGV AAVCTIIALS VVYSQEKNKN ANSSPVASTT PSASATTNPA 70 80 90 100 110 120 SATTLDQSKA WNRYRLPNTL KPDSYRVTLR PYLTPNDRGL YVFKGSSTVR FTCKEATDVI 130 140 150 160 170 180 IIHSKKLNYT LSQGHRVVLR GVGGSQPPDI DKTELVEPTE YLVVHLKGSL VKDSQYEMDS 190 200 210 220 230 240 EFEGELADDL AGFYRSEYME GNVRKVVATT QMQAADARKS FPCFDEPAMK AEFNITLIHP 250 260 270 280 290 300 KDLTALSNML PKGPSTPLPE DPNWNVTEFH TTPKMSTYLL AFIVSEFDYV EKQASNGVLI 310 320 330 340 350 360 RIWARPSAIA AGHGDYALNV TGPILNFFAG HYDTPYPLPK SDQIGLPDFN AGAMENWGLV 370 380 390 400 410 420 TYRENSLLFD PLSSSSSNKE RVVTVIAHEL AHQWFGNLVT IEWWNDLWLN EGFASYVEYL 430 440 450 460 470 480 GADYAEPTWN LKDLMVLNDV YRVMAVDALA SSHPLSTPAS EINTPAQISE LFDAISYSKG 490 500 510 520 530 540 ASVLRMLSSF LSEDVFKQGL ASYLHTFAYQ NTIYLNLWDH LQEAVNNRSI QLPTTVRDIM 550 560 570 580 590 600 NRWTLQMGFP VITVDTSTGT LSQEHFLLDP DSNVTRPSEF NYVWIVPITS IRDGRQQQDY 610 620 630 640 650 660 WLIDVRAQND LFSTSGNEWV LLNLNVTGYY RVNYDEENWR KIQTQLQRDH SAIPVINRAQ 670 680 690 700 710 720 IINDAFNLAS AHKVPVTLAL NNTLFLIEER QYMPWEAALS SLSYFKLMFD RSEVYGPMKN 730 740 750 760 770 780 YLKKQVTPLF IHFRNNTNNW REIPENLMDQ YSEVNAISTA CSNGVPECEE MVSGLFKQWM 790 800 810 820 830 840 ENPNNNPIHP NLRSTVYCNA IAQGGEEEWD FAWEQFRNAT LVNEADKLRA ALACSKELWI 850 860 870 880 890 900 LNRYLSYTLN PDLIRKQDAT STIISITNNV IGQGLVWDFV QSNWKKLFND YGGGSFSFSN 910 920 930 940 950 960 LIQAVTRRFS TEYELQQLEQ FKKDNEETGF GSGTRALEQA LEKTKANIKW VKENKEVVLQ WFTENSK

References

	« Hide 'large scale' referencesShow '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] [Europe PMC] [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] [Europe PMC] [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. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION BY ESTRADIOL AND IL8.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265; ASN-681 AND ASN-818, MASS SPECTROMETRY. Tissue: Plasma.
[26]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128; ASN-234; ASN-265; ASN-573; ASN-681 AND ASN-818, MASS SPECTROMETRY. Tissue: Liver.
[27]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]	"The X-ray crystal structure of human aminopeptidase N reveals a novel dimer and the basis for peptide processing." Wong A.H., Zhou D., Rini J.M. J. Biol. Chem. 287:36804-36813(2012) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 66-967 IN COMPLEX WITH ANGIOTENSIN-4 AND INHIBITORS, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE-BINDING REGION, ZINC-BINDING SITES, ACTIVE SITE, GLYCOSYLATION AT ASN-128; ASN-234; ASN-265; ASN-319; ASN-527; ASN-625; ASN-681 AND ASN-818, SUBUNIT, DISULFIDE BONDS.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS TYR-242 AND PRO-243.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X13276 mRNA. Translation: CAA31640.1.
M22324 mRNA. Translation: AAA51719.1.
AC018988 Genomic DNA. No translation available.
AC079075 Genomic DNA. No translation available.
BC058928 mRNA. Translation: AAH58928.1.
M55522 Genomic DNA. Translation: AAA83399.1.
AJ421875, AJ421876 Genomic DNA. Translation: CAD19098.2.
AJ426050 Genomic DNA. Translation: CAD19802.1.
AJ427985 , AJ427986, AJ427987, AJ427988 Genomic DNA. Translation: CAD20931.1.

IPI

IPI00221224.

PIR

A30325.

RefSeq

NP_001141.2. NM_001150.2.

UniGene

Hs.1239.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4FYQ	X-ray	1.90	A	66-967	[»]
4FYR	X-ray	1.91	A	66-967	[»]
4FYS	X-ray	2.01	A	66-967	[»]
4FYT	X-ray	1.85	A	66-967	[»]

ProteinModelPortal

P15144.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15144. 4 interactions.

STRING

9606.ENSP00000300060.

Protein family/group databases

MEROPS

M01.001.

PTM databases

PhosphoSite

P15144.

Polymorphism databases

DMDM

143811362.

Proteomic databases

PaxDb

P15144.

PRIDE

P15144.

Protocols and materials databases

DNASU

290.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000300060; ENSP00000300060; ENSG00000166825.

GeneID

290.

KEGG

hsa:290.

UCSC

uc002bop.4. human.

Organism-specific databases

CTD

290.

GeneCards

GC15M090328.

H-InvDB

HIX0038141.

HGNC

HGNC:500. ANPEP.

HPA

CAB002417.

MIM

151530. gene.

neXtProt

NX_P15144.

PharmGKB

PA24815.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0308.

HOVERGEN

HBG006616.

InParanoid

P15144.

KO

K11140.

OMA

SSNKERV.

OrthoDB

EOG4B5P4K.

PhylomeDB

P15144.

Enzyme and pathway databases

BRENDA

3.4.11.2. 2681.

Reactome

REACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpress

P15144.

Bgee

P15144.

CleanEx

HS_ANPEP.

Genevestigator

P15144.

GermOnline

ENSG00000166825. Homo sapiens.

Family and domain databases

InterPro

IPR024571. DUF3358.
IPR001930. Peptidase_M1.
IPR014782. Peptidase_M1_N.
[Graphical view]

PANTHER

PTHR11533. PTHR11533. 1 hit.

Pfam

PF11838. DUF3358. 1 hit.
PF01433. Peptidase_M1. 1 hit.
[Graphical view]

PRINTS

PR00756. ALADIPTASE.

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P15144.

ChEMBL

CHEMBL1907.

DrugBank

DB00973. Ezetimibe.

GenomeRNAi

290.

NextBio

1183.

SOURCE

Search...

Entry information

Entry name

AMPN_HUMAN

Accession

Primary (citable) accession number: P15144
Secondary accession number(s): Q16728 , Q6GT90, Q8IUK3, Q8IVH3, Q9UCE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 3, 2007
Last modified:	May 1, 2013
This is version 160 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.