AMPN_RAT
ID AMPN_RAT Reviewed; 965 AA.
AC P15684; Q9JHP4;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Aminopeptidase N {ECO:0000305};
DE Short=AP-N;
DE Short=rAPN;
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=Kidney Zn peptidase;
DE Short=KZP;
DE AltName: Full=Microsomal aminopeptidase;
DE AltName: CD_antigen=CD13;
GN Name=Anpep;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=2564389; DOI=10.1016/s0021-9258(18)83570-0;
RA Watt V.M., Yip C.C.;
RT "Amino acid sequence deduced from a rat kidney cDNA suggests it encodes the
RT Zn-peptidase aminopeptidase N.";
RL J. Biol. Chem. 264:5480-5487(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=2567164; DOI=10.1016/0006-291x(89)91586-6;
RA Malfroy B., Kado-Fong H., Gros C., Giros B., Schwartz J.C., Hellmiss R.;
RT "Molecular cloning and amino acid sequence of rat kidney aminopeptidase M:
RT a member of a super family of zinc-metallohydrolases.";
RL Biochem. Biophys. Res. Commun. 161:236-241(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 198-754.
RA Gal-Gaber O.;
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 2-19; 68-84; 206-215; 286-299 AND 364-371.
RX PubMed=1673322; DOI=10.1152/ajplung.1991.260.4.l274;
RA Funkhouser J.D., Tangada S.D., Jones M., O S.J., Peterson R.D.;
RT "p146 type II alveolar epithelial cell antigen is identical to
RT aminopeptidase N.";
RL Am. J. Physiol. 260:L274-L279(1991).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=11672613; DOI=10.1016/s0306-4522(01)00185-3;
RA Noble F., Banisadr G., Jardinaud F., Popovici T., Lai-Kuen R., Chen H.,
RA Bischoff L., Parsadaniantz S.M., Fournie-Zaluski M.-C., Roques B.P.;
RT "First discrete autoradiographic distribution of aminopeptidase N in
RT various structures of rat brain and spinal cord using the selective
RT iodinated inhibitor 125IRB 129.";
RL Neuroscience 105:479-488(2001).
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:0000269|PubMed:2564389};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P15144}.
CC Note=Also found as a soluble form. {ECO:0000250|UniProtKB:P15144}.
CC -!- TISSUE SPECIFICITY: Widely distributed throughout the CNS. Particularly
CC abundant in kidney and intestinal microvilli, also detected in lung and
CC liver. Weakly expressed in heart and aorta.
CC {ECO:0000269|PubMed:11672613, ECO:0000269|PubMed:2564389}.
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; M25073; AAA41502.1; -; mRNA.
DR EMBL; M26710; AAA57129.1; -; mRNA.
DR EMBL; Y18765; CAB93958.1; -; mRNA.
DR PIR; A32852; A32852.
DR RefSeq; NP_112274.1; NM_031012.1.
DR AlphaFoldDB; P15684; -.
DR SMR; P15684; -.
DR BioGRID; 249541; 3.
DR IntAct; P15684; 1.
DR STRING; 10116.ENSRNOP00000020002; -.
DR BindingDB; P15684; -.
DR ChEMBL; CHEMBL3259; -.
DR DrugCentral; P15684; -.
DR MEROPS; M01.001; -.
DR GlyGen; P15684; 9 sites.
DR iPTMnet; P15684; -.
DR PhosphoSitePlus; P15684; -.
DR PaxDb; P15684; -.
DR PRIDE; P15684; -.
DR GeneID; 81641; -.
DR KEGG; rno:81641; -.
DR UCSC; RGD:2991; rat.
DR CTD; 290; -.
DR RGD; 2991; Anpep.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; P15684; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; P15684; -.
DR BioCyc; MetaCyc:MON-9982; -.
DR BRENDA; 3.4.11.2; 5301.
DR BRENDA; 3.4.11.7; 5301.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR SABIO-RK; P15684; -.
DR PRO; PR:P15684; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
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:0035814; P:negative regulation of renal sodium excretion; IMP:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IMP:RGD.
DR GO; GO:0016485; P:protein processing; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
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 INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1673322"
FT CHAIN 2..965
FT /note="Aminopeptidase N"
FT /id="PRO_0000095085"
FT TOPO_DOM 2..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..68
FT /note="Cytosolic Ser/Thr-rich junction"
FT REGION 44..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..965
FT /note="Metalloprotease"
FT ACT_SITE 388
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 351..355
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
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 410
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 476
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P15144"
FT MOD_RES 176
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000255"
FT MOD_RES 852
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P97449"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 555
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 606
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 780
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 558
FT /note="T -> A (in Ref. 3; CAB93958)"
FT /evidence="ECO:0000305"
FT CONFLICT 582
FT /note="Y -> L (in Ref. 3; CAB93958)"
FT /evidence="ECO:0000305"
FT CONFLICT 590..598
FT /note="YLKNGKEDH -> VSQKWKGGS (in Ref. 3; CAB93958)"
FT /evidence="ECO:0000305"
FT CONFLICT 802..804
FT /note="FGG -> SC (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 807
FT /note="E -> A (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 813..818
FT /note="EQFRKA -> ATVPER (in Ref. 2; AAA57129)"
FT /evidence="ECO:0000305"
FT CONFLICT 831..833
FT /note="LAC -> VGR (in Ref. 2; AAA57129)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 965 AA; 109449 MW; 03A9A14AEFCCE31C CRC64;
MAKGFYISKT LGILGILLGV AAVCTIIALS VVYAQEKNRN AENSAIAPTL PGSTSATTST
TNPAIDESKP WNQYRLPKTL IPDSYQVTLR PYLTPNEQGL YIFKGSSTVR FTCNETTNVI
IIHSKKLNYT NKGNHRVALR ALGDTPAPNI DTTELVERTE YLVVHLQGSL VKGHQYEMDS
EFQGELADDL AGFYRSEYME GGNKKVVATT QMQAADARKS FPCFDEPAMK ASFNITLIHP
NNLTALSNML PKDSRTLQED PSWNVTEFHP TPKMSTYLLA YIVSEFKYVE AVSPNRVQIR
IWARPSAIDE GHGDYALQVT GPILNFFAQH YNTAYPLEKS DQIALPDFNA GAMENWGLVT
YRESALVFDP QSSSISNKER VVTVIAHELA HQWFGNLVTV DWWNDLWLNE GFASYVEFLG
ADYAEPTWNL KDLIVLNDVY RVMAVDALAS SHPLSSPANE VNTPAQISEL FDSITYSKGA
SVLRMLSSFL TEDLFKKGLS SYLHTFQYSN TIYLDLWEHL QQAVDSQTAI KLPASVSTIM
DRWILQMGFP VITVNTSTGE IYQEHFLLDP TSKPTRPSDF NYLWIVPIPY LKNGKEDHYW
LETEKNQSAE FQTSSNEWLL LNINVTGYYQ VNYDENNWRK IQNQLQTDLS VIPVINRAQI
IHDSFNLASA GKLSITLPLS NTLFLASETE YMPWEAALSS LNYFKLMFDR SEVYGPMKRY
LKKQVTPLFA YFKIKTNNWL DRPPTLMEQY NEINAISTAC SSGLEECRDL VVGLYSQWMN
NSDNNPIHPN LRSTVYCNAI AFGGEEEWNF AWEQFRKATL VNEADKLRSA LACSNEVWIL
NRYLSYTLNP DYIRKQDATS TIVSIANNVV GQTLVWDFVR SNWKKLFEDY GGGSFSFANL
IQGVTRRFSS EFELQQLEQF KEDNSATGFG SGTRALEQAL EKTKANIKWV KENKDVVLKW
FTENS
