ID   AMPN_CHICK              Reviewed;         972 AA.
AC   O57579; A0A1D5NWZ2; D2KKL5;
DT   15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 2.
DT   27-MAR-2024, entry version 125.
DE   RecName: Full=Aminopeptidase Ey {ECO:0000303|PubMed:9734335};
DE            EC=3.4.11.20 {ECO:0000269|PubMed:7684960, ECO:0000269|PubMed:8205380};
DE   AltName: Full=Aminopeptidase N {ECO:0000312|EMBL:ACZ95799.1};
GN   Name=ANPEP; Synonyms=APDE;
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 224-234; 296-363;
RP   378-405; 496-526 AND 954-966.
RC   TISSUE=Egg yolk {ECO:0000269|PubMed:9734335}, and Liver
RC   {ECO:0000269|PubMed:9734335};
RX   PubMed=9734335; DOI=10.1016/s0305-0491(98)00012-1;
RA   Midorikawa T., Abe R., Yamagata Y., Nakajima T., Ichishima E.;
RT   "Isolation and characterization of cDNA encoding chicken egg yolk
RT   aminopeptidase Ey.";
RL   Comp. Biochem. Physiol. 119:513-520(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Embryonic kidney {ECO:0000312|EMBL:ACZ95799.1};
RA   Xin Y., Ping W., Bo M.X.;
RT   "Soluble high-expression and biological function of chicken aminopeptidase
RT   N.";
RL   Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Red jungle fowl;
RX   PubMed=15592404; DOI=10.1038/nature03154;
RA   Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA   Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA   Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA   Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA   McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA   Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA   Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA   Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA   Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA   Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA   Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA   Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA   Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA   Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA   Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA   Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA   Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA   Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA   Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA   Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA   Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA   Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA   Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA   Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA   Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA   Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA   Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA   Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA   Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA   Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA   Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA   Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA   Wilson R.K.;
RT   "Sequence and comparative analysis of the chicken genome provide unique
RT   perspectives on vertebrate evolution.";
RL   Nature 432:695-716(2004).
RN   [4]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RA   Ichishima E., Yamagata Y., Chiba H., Sawaguchi K., Tanaka T.;
RT   "Soluble and bound forms of aminopeptidase in hen's egg yolk.";
RL   Agric. Biol. Chem. 53:1867-1872(1989).
RN   [5]
RP   SUBUNIT.
RA   Tanaka T., Oshida K., Ichishima E.;
RT   "Electron microscopic analysis of dimeric form of aminopeptidase Ey from
RT   hen's egg yolk.";
RL   Agric. Biol. Chem. 55:2179-2181(1991).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=7684960; DOI=10.1016/0305-0491(93)90175-5;
RA   Tanaka T., Ichishima E.;
RT   "Substrate specificity of aminopeptidase Ey from hen's (Gallus domesticus)
RT   egg yolk.";
RL   Comp. Biochem. Physiol. 105:105-110(1993).
RN   [7]
RP   COFACTOR.
RX   PubMed=8288037; DOI=10.1016/0020-711x(93)90528-m;
RA   Tanaka T., Ichishima E.;
RT   "Molecular properties of aminopeptidase Ey as a zinc-metalloenzyme.";
RL   Int. J. Biochem. 25:1681-1688(1993).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=8205380; DOI=10.1016/0305-0491(94)90181-3;
RA   Tanaka T., Ichishima E.;
RT   "Inactivation of chemotactic peptides by aminopeptidase Ey from hen's
RT   (Gallus gallus domesticus) egg yolk.";
RL   Comp. Biochem. Physiol. 107B:533-538(1994).
CC   -!- FUNCTION: Broad specificity aminopeptidase. Degrades a variety of
CC       peptides possessing various N-terminal amino acids including
CC       hydrophobic, basic and acidic amino acids. Preferentially hydrolyzes
CC       small peptides consisting of 4 or 5 amino acids. Hydrolyzes the N-
CC       terminal Xaa-Pro bonds in the chicken brain peptide Leu-Pro-Leu-Arg-
CC       PheNH2, the substance P fragment Arg-Pro-Lys-Pro and the bradykinin
CC       fragment Arg-Pro-Pro-Gly-Phe. Hydrolyzes the N-formylated peptides
CC       fMet-Leu-Phe, fMet-Ala-Gly-Ser-Glu and fMet-Nle-Leu-Phe-Nle-Tyr-Lys,
CC       but does not hydrolyze peptides with acetylation or pyroglutamic acid
CC       at N-terminus. Does not hydrolyze large peptides such as complete
CC       substance P, bradykinin or schistoFLRFamide.
CC       {ECO:0000269|PubMed:7684960, ECO:0000269|PubMed:8205380,
CC       ECO:0000269|Ref.4}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Differs from other aminopeptidases in broad specificity for
CC         amino acids in the P1 position and the ability to hydrolyze peptides
CC         of four or five residues that contain Pro in the P1' position.;
CC         EC=3.4.11.20; Evidence={ECO:0000269|PubMed:7684960,
CC         ECO:0000269|PubMed:8205380};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:8288037};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:8288037};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.58 mM for Leu-Pro-Leu-Arg-PheNH2 {ECO:0000269|PubMed:7684960,
CC         ECO:0000269|PubMed:8205380};
CC         KM=1.23 mM for fMet-Leu-Phe {ECO:0000269|PubMed:7684960,
CC         ECO:0000269|PubMed:8205380};
CC         KM=1.53 mM for fMet-Ala-Gly-Ser-Glu {ECO:0000269|PubMed:7684960,
CC         ECO:0000269|PubMed:8205380};
CC         KM=1.72 mM for fMet-Nle-Leu-Phe-Nle-Tyr-Lys
CC         {ECO:0000269|PubMed:7684960, ECO:0000269|PubMed:8205380};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.5}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|Ref.4}; Single-pass
CC       type II membrane protein {ECO:0000250|UniProtKB:P15144}. Note=Also
CC       found as a soluble form. {ECO:0000269|Ref.4}.
CC   -!- TISSUE SPECIFICITY: Detected in the plasma and granule fractions of egg
CC       yolk (at protein level). {ECO:0000269|Ref.4}.
CC   -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000255}.
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DR   EMBL; D87992; BAA24263.1; -; mRNA.
DR   EMBL; GU223212; ACZ95799.1; -; mRNA.
DR   EMBL; AADN04000131; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_990192.1; NM_204861.1.
DR   RefSeq; XP_015147557.1; XM_015292071.1.
DR   AlphaFoldDB; O57579; -.
DR   SMR; O57579; -.
DR   STRING; 9031.ENSGALP00000044885; -.
DR   MEROPS; M01.016; -.
DR   GlyCosmos; O57579; 14 sites, No reported glycans.
DR   PaxDb; 9031-ENSGALP00000040682; -.
DR   Ensembl; ENSGALT00000064511; ENSGALP00000044885; ENSGALG00000027501.
DR   GeneID; 395667; -.
DR   KEGG; gga:395667; -.
DR   CTD; 290; -.
DR   VEuPathDB; HostDB:geneid_395667; -.
DR   eggNOG; KOG1046; Eukaryota.
DR   InParanoid; O57579; -.
DR   PhylomeDB; O57579; -.
DR   BRENDA; 3.4.11.20; 1306.
DR   Reactome; R-GGA-6798695; Neutrophil degranulation.
DR   SABIO-RK; O57579; -.
DR   PRO; PR:O57579; -.
DR   Proteomes; UP000000539; Chromosome 10.
DR   Bgee; ENSGALG00000027501; Expressed in liver and 11 other cell types or tissues.
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:0008270; F:zinc ion binding; IBA:GO_Central.
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   1: Evidence at protein level;
KW   Aminopeptidase; Cell membrane; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW   Protease; Reference proteome; Signal-anchor; Transmembrane;
KW   Transmembrane helix; Zinc.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   CHAIN           2..972
FT                   /note="Aminopeptidase Ey"
FT                   /id="PRO_0000394749"
FT   TOPO_DOM        2..10
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        11..31
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        32..972
FT                   /note="Extracellular"
FT   REGION          33..72
FT                   /note="Cytosolic Ser/Thr-rich junction"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   REGION          37..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          73..967
FT                   /note="Metalloprotease"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   COMPBIAS        37..75
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        392
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         355..359
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   BINDING         391
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         395
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         414
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            480
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P15144"
FT   CARBOHYD        38
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        110
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        147
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        269
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        513
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        574
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        584
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        628
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        684
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        742
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        785
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        764..771
FT                   /evidence="ECO:0000250"
FT   DISULFID        801..837
FT                   /evidence="ECO:0000250"
FT   CONFLICT        56..60
FT                   /note="Missing (in Ref. 1; BAA24263 and 2; ACZ95799)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        248
FT                   /note="T -> K (in Ref. 2; ACZ95799)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        255
FT                   /note="V -> A (in Ref. 2; ACZ95799)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        538
FT                   /note="S -> T (in Ref. 2; ACZ95799)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        614
FT                   /note="D -> N (in Ref. 1; BAA24263 and 2; ACZ95799)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        675..678
FT                   /note="QQVS -> HNVN (in Ref. 1; BAA24263)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        923
FT                   /note="Q -> H (in Ref. 1; BAA24263)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   972 AA;  109132 MW;  701F1BC0BCE1F852 CRC64;
     MAAGFFISKS VGIVGIVLAL GAVATIIALS VVYAQEKNKS SGGSGGSDTT STTTASTTTT
     STTTASTTAA PNNPWNRWRL PTALKPESYE VTLQPFLTPD DNNMYIFKGN SSVVFLCEEA
     TDLILIHSNK LNYTLQGGFH ASLHAVNGST PPTISNTWLE TNTQYLVLQL AGPLQQGQHY
     RLFSIFTGEL ADDLAGFYRS EYTEGNVTKV VATTQMQAPD ARKAFPCFDE PAMKAVFTVT
     MIHPSDHTAI SNMPVHSTYQ LQMDGQSWNV TQFDPTPRMS TYLLAFIVSQ FDYVENNTGK
     VQIRIWGRPA AIAEGQGEYA LEKTGPILSF FERHYNTAYP LPKSDQVGLP DFNAGAMENW
     GLVTYRENSL LYDNAYSSIG NKERVVTVIA HELAHQWFGN LVTLRWWNDL WLNEGFASYV
     EYLGADSAEP TWDIKDLMVL NELYTVMATD ALTTSHPLTF REDEINTPAQ ISEVFDSIAY
     SKGASVLRML SDFLTEDVFK EGLQSYLHDF SYNNTVYTDL WDHLQEAVNK NSVPLPDSIG
     AIMDRWTLQM GFPVVTVNTL TGSVQQSHFL LDSNSTVERP SVFNYTWIVP ITWMTPSRTG
     DRYWLVDVSA TNSDFSVGSS TWLLLNLNVS GYFRVNYNQE NWDQLLQQLS NNHQAIPVIN
     RAQIIDDAFN LARAQQVSVT LALNTTRFLS GETAYMPWQA ALNNLQYFQL MFDRSEVFGA
     MTKYIQKQVT PLFEYYRTAT NNWTAIPSAL MDQYNEINAI STACSYGIAE CQQLATALYQ
     QWRQNVSNNP IAPNLRSAIY CSAVATGGEE VWDFIWERFL EAPVVSEADK LRTALTCSTE
     TWILQRYLQY TIDPTKIRKQ DATSTINSIA SNVVGQPLAW DFIRSNWRTL FGQYGGGSFS
     FSRLISAVTQ RFNTEFELKQ LEQFKADNQD IGFGSGTRAL EQALERTRTN INWVKENKEV
     VHAWFRAETA SS
//