AMPN_RABIT
ID AMPN_RABIT Reviewed; 966 AA.
AC P15541;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Aminopeptidase N {ECO:0000305};
DE Short=AP-N;
DE Short=rbAPN;
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;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=7903857; DOI=10.1139/o93-042;
RA Yang X.F., Milhiet P.E., Gaudoux F., Crine P., Boileau G.;
RT "Complete sequence of rabbit kidney aminopeptidase N and mRNA localization
RT in rabbit kidney by in situ hybridization.";
RL Biochem. Cell Biol. 71:278-287(1993).
RN [2]
RP PROTEIN SEQUENCE OF 6-19.
RX PubMed=6120002; DOI=10.1016/0005-2736(82)90057-8;
RA Feracci H., Maroux S., Bonicel J., Desnuelle P.;
RT "The amino acid sequence of the hydrophobic anchor of rabbit intestinal
RT brush border aminopeptidase N.";
RL Biochim. Biophys. Acta 684:133-136(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 178-966.
RX PubMed=2574692; DOI=10.1016/0014-5793(89)81506-6;
RA Noren O., Dabelsteen E., Hoeyer P.E., Olsen J., Sjoestroem H., Hansen G.H.;
RT "Onset of transcription of the aminopeptidase N (leukemia antigen CD 13)
RT gene at the crypt/villus transition zone during rabbit enterocyte
RT differentiation.";
RL FEBS Lett. 259:107-112(1989).
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; S68687; AAB29534.1; -; mRNA.
DR EMBL; X51508; CAA35873.1; -; mRNA.
DR PIR; S07099; S07099.
DR RefSeq; NP_001075795.1; NM_001082326.1.
DR AlphaFoldDB; P15541; -.
DR SMR; P15541; -.
DR STRING; 9986.ENSOCUP00000015166; -.
DR MEROPS; M01.001; -.
DR PRIDE; P15541; -.
DR GeneID; 100009167; -.
DR KEGG; ocu:100009167; -.
DR CTD; 290; -.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; P15541; -.
DR OrthoDB; 110058at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 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 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; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Angiogenesis; Cell membrane; Developmental protein;
KW Differentiation; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Phosphoprotein;
KW Protease; Reference proteome; Signal-anchor; Sulfation; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..966
FT /note="Aminopeptidase N"
FT /id="PRO_0000095084"
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..966
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT REGION 33..65
FT /note="Cytosolic Ser/Thr-rich junction"
FT REGION 40..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..966
FT /note="Metalloprotease"
FT ACT_SITE 385
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 348..352
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 384
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 407
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 473
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 415
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 420
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 852
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P97449"
FT MOD_RES 912
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 552
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
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 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 817
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"
FT CONFLICT 10
FT /note="S -> A (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 16
FT /note="I -> F (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="Q -> QMQ (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="M -> S (in Ref. 3; CAA35873)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="P -> L (in Ref. 3; CAA35873)"
FT /evidence="ECO:0000305"
FT CONFLICT 593..594
FT /note="LE -> QQ (in Ref. 3; CAA35873)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 966 AA; 109318 MW; ED12832072B0DB52 CRC64;
MAKGFYISKS LGILGILLGV AALCTIVALS VVYRQEKNKN TSQSPSMAPL NPTATSSPAT
TLDQNLPWNR YRLPKTLIPD SYNVVLRPYL SPNSQGLYIF TGSSTVRFTC QEATNVIIIH
SKKLNYTITQ GHRVVLRGVR GSQPPAIAST ELVELTEYLV VHLQGQLVAG SQYEMDTQFQ
GELADDLAGF YRSEYMEGNV RKVVATTQMQ AADARKSFPC FDEPAMKATF NITPIHPRDY
TALSNMLPRS STALPEDPNW TVTEFHTTPK MSTYLLAYIV SEFTNIEAQS PNNVQIRIWA
RPSAISEGHG QYALNVTGPI LNFFANHYNT PYPLEKSDQI GLPDFNAGAM ENWGLVTYRE
SALLFDPLVS SISNKERVVT VVAHELAHQW FGNLVTVDWW NDLWLNEGFA SYVEYLGADY
AEPTWNLKDL IVLNELHSVM AVDALASSHP LSSPADEVNT PAQISELFDS ITYSKGASVL
RMLSSFLTED LFKEGLASYL HTFAYQNTIY LDLWEHLQQA VNSQSAIQLP ASVRDIMDRW
ILQMGFPVVT VNTTNGIISQ HHFLLDPTSN VTRPSDFNYL WIVPVSSMRN GVLEQEFWLE
GVEQTQNSLF RVEGDNNWIL ANLNVTGYYQ VNYDEGNWKK LQTQLQTNPS VIPVINRAQI
IHDAFNLASA QKVPVTLALD NTLFLIRETE YMPWQAALSS LNYFKLMFDR SEVYGPMKNY
LSKQVRPLFE HFKNITNDWT RRPDTLMDQY NEINAISTAC SNGIQECETL VSDLFKQWMD
DPSNNPIHPN LRTTVYCNAI ALGGEREWDF AWEQFRNATL VNEADKLRSA LACSNEVWIL
NRYLSYTLNP DYIRRQDATS TINSIASNVI GQTLVWDFVQ SNWKKLFEDF GGGSFSFANL
IRAVTRRFST EYELQQLEQF RLNNLDTGFG SGTRALEQAL EQTRANIKWV QENKEAVLAW
FTANSA
