ID   AMPN_BOVIN              Reviewed;         965 AA.
AC   P79098; Q3MHR1;
DT   23-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 4.
DT   24-JAN-2024, entry version 141.
DE   RecName: Full=Aminopeptidase N {ECO:0000305};
DE            Short=AP-N;
DE            Short=bAPN;
DE            EC=3.4.11.2 {ECO:0000250|UniProtKB:P15144};
DE   AltName: Full=Alanyl aminopeptidase;
DE   AltName: Full=Aminopeptidase M;
DE            Short=AP-M;
DE   AltName: Full=Microsomal aminopeptidase;
DE   AltName: CD_antigen=CD13;
GN   Name=ANPEP; Synonyms=APN;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 648-838.
RC   TISSUE=Intestine;
RX   PubMed=8985407; DOI=10.1128/jvi.71.1.734-737.1997;
RA   Benbacer L., Kut E., Besnardeau L., Laude H., Delmas B.;
RT   "Interspecies aminopeptidase-N chimeras reveal species-specific receptor
RT   recognition by canine coronavirus, feline infectious peritonitis virus, and
RT   transmissible gastroenteritis virus.";
RL   J. Virol. 71:734-737(1997).
CC   -!- FUNCTION: Broad specificity aminopeptidase which plays a role in the
CC       final digestion of peptides generated from hydrolysis of proteins by
CC       gastric and pancreatic proteases. Also involved in the processing of
CC       various peptides including peptide hormones, such as angiotensin III
CC       and IV, neuropeptides, and chemokines. May also be involved the
CC       cleavage of peptides bound to major histocompatibility complex class II
CC       molecules of antigen presenting cells. May have a role in angiogenesis
CC       and promote cholesterol crystallization. May have a role in amino acid
CC       transport by acting as binding partner of amino acid transporter
CC       SLC6A19 and regulating its activity (By similarity).
CC       {ECO:0000250|UniProtKB:P15144, ECO:0000250|UniProtKB:P97449}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal amino acid, Xaa-|-Yaa- from a
CC         peptide, amide or arylamide. Xaa is preferably Ala, but may be most
CC         amino acids including Pro (slow action). When a terminal hydrophobic
CC         residue is followed by a prolyl residue, the two may be released as
CC         an intact Xaa-Pro dipeptide.; EC=3.4.11.2;
CC         Evidence={ECO:0000250|UniProtKB:P15144};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000250|UniProtKB:P15144};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P15144};
CC   -!- SUBUNIT: Homodimer. Interacts with SLC6A19 (By similarity).
CC       {ECO:0000250|UniProtKB:P15144, ECO:0000250|UniProtKB:P97449}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P15144};
CC       Single-pass type II membrane protein {ECO:0000250|UniProtKB:P15144}.
CC       Note=Also found as a soluble form. {ECO:0000250|UniProtKB:P15144}.
CC   -!- PTM: Sulfated. {ECO:0000250|UniProtKB:P15145}.
CC   -!- PTM: N- and O-glycosylated. {ECO:0000250|UniProtKB:P15144}.
CC   -!- PTM: May undergo proteolysis and give rise to a soluble form.
CC       {ECO:0000250|UniProtKB:P15144}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR   EMBL; BC105142; AAI05143.1; -; mRNA.
DR   EMBL; X98240; CAA66896.1; -; mRNA.
DR   RefSeq; NP_001068612.1; NM_001075144.1.
DR   AlphaFoldDB; P79098; -.
DR   SMR; P79098; -.
DR   STRING; 9913.ENSBTAP00000071231; -.
DR   ChEMBL; CHEMBL2010632; -.
DR   MEROPS; M01.001; -.
DR   GlyCosmos; P79098; 10 sites, No reported glycans.
DR   PaxDb; 9913-ENSBTAP00000022456; -.
DR   GeneID; 404191; -.
DR   KEGG; bta:404191; -.
DR   CTD; 290; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   InParanoid; P79098; -.
DR   OrthoDB; 3085317at2759; -.
DR   PRO; PR:P79098; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR   GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR   CDD; cd09601; M1_APN-Q_like; 1.
DR   Gene3D; 1.25.50.20; -; 1.
DR   Gene3D; 2.60.40.1910; -; 1.
DR   Gene3D; 1.10.390.10; Neutral Protease Domain 2; 1.
DR   Gene3D; 2.60.40.1730; tricorn interacting facor f3 domain; 1.
DR   InterPro; IPR045357; Aminopeptidase_N-like_N.
DR   InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR   InterPro; IPR024571; ERAP1-like_C_dom.
DR   InterPro; IPR034016; M1_APN-typ.
DR   InterPro; IPR001930; Peptidase_M1.
DR   InterPro; IPR014782; Peptidase_M1_dom.
DR   InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR   PANTHER; PTHR11533:SF172; AMINOPEPTIDASE N; 1.
DR   PANTHER; PTHR11533; PROTEASE M1 ZINC METALLOPROTEASE; 1.
DR   Pfam; PF11838; ERAP1_C; 1.
DR   Pfam; PF01433; Peptidase_M1; 1.
DR   Pfam; PF17900; Peptidase_M1_N; 1.
DR   PRINTS; PR00756; ALADIPTASE.
DR   SUPFAM; SSF63737; Leukotriene A4 hydrolase N-terminal domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   2: Evidence at transcript level;
KW   Aminopeptidase; Angiogenesis; Cell membrane; Developmental protein;
KW   Differentiation; Disulfide bond; Glycoprotein;
KW   Host cell receptor for virus entry; Hydrolase; Membrane; Metal-binding;
KW   Metalloprotease; Protease; Receptor; Reference proteome; Signal-anchor;
KW   Sulfation; Transmembrane; Transmembrane helix; Zinc.
FT   CHAIN           1..965
FT                   /note="Aminopeptidase N"
FT                   /id="PRO_0000095078"
FT   TOPO_DOM        1..8
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   TRANSMEM        9..32
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        33..965
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   REGION          33..65
FT                   /note="Cytosolic Ser/Thr-rich junction"
FT   REGION          40..65
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          66..965
FT                   /note="Metalloprotease"
FT   COMPBIAS        42..65
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        386
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         349..353
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   BINDING         385
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         389
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         408
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            474
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   MOD_RES         173
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         416
FT                   /note="Sulfotyrosine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        316
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        508
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        569
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        680
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        734
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        738
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        760..767
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   DISULFID        797..833
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
SQ   SEQUENCE   965 AA;  109276 MW;  C730910D173879A8 CRC64;
     MAKGFYISKA LGILAILLGV AAVATIIALS VVYAQEKNKN AERGTAAPTS PTGPTTTSAT
     TLDQSKPWNR YRLPTTLLPD SYRVTLRPYL TPNNNGLYIF TGSSTVRFTC KEPTDVIIIH
     SKKLNYTQHS GHLAALKGVG DTQAPEIDRT ELVLLTEYLV VHLKSSLEAG KTYEMETTFQ
     GELADDLAGF YRSEYMDGNV KKVLATTQMQ STDARKSFPC FDEPAMKATF NITLIHPKDL
     TALSNMPPKG PSVPFDGDSN WSVTEFETTP VMSTYLLAYI VSEFTSVESV APNDVQIRIW
     ARPKATADNH GLYALNVTGP ILNFFANHYN TAYPLPKSDQ IALPDFNAGA MENWGLVTYR
     ENALLYDPQS SSSSNKERVV TVIAHELAHQ WFGNLVTLAW WNDLWLNEGF ASYVEYLGAD
     YAEPTWNLKD LMVPNDVYSV MAVDALVTSH PLTTPANEVN TPAQISEMFD TISYSKGASV
     IRMLSNFLTE DLFKKGLASY LQTFAYQNTT YLNLWEHLQM AVENQLSIRL PDTVSAIMDR
     WTLQMGFPVI TVDTNTGTIS QKHFLLDPNS TVTRPSQFNY LWIVPISSIR NGQPQEHYWL
     RGEERNQNEL FKAAADDWVL LNINVTGYYQ VNYDENNWKK IQNQLMSRRE NIPVINRAQV
     IYDSFNLASA HMVPVTLALN NTLFLKNEME YMPWQAAVSS LNYFKLMFDR TEVYGPMQNY
     LKNQVEPIFL YFENLTKNWT EIPENLMDQY SEINAISTAC SNGLPKCEEL AKTLFNQWMN
     NPNVNPIDPN LRSTIYCNAI AQGGQEEWDF AWNQLQQAEL VNEADKLRSA LACTNHVWLL
     NRYLSYTLNP DLIRKQDATS TITSIASNVI GQSLAWDFIR SNWKKLFEDY GGGSFSFSNL
     IQGVTRRFST EFELQQLEEF KENNMDVGFG SGTRALEQAL EKTKANINWV KENKEVVLNW
     FKDHS
//