AMPE_RAT
ID AMPE_RAT Reviewed; 945 AA.
AC P50123; Q64200; Q9JLQ7; Q9JLQ9; Q9QV24;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Glutamyl aminopeptidase;
DE Short=EAP;
DE EC=3.4.11.7;
DE AltName: Full=Aminopeptidase A;
DE Short=AP-A;
DE AltName: CD_antigen=CD249;
GN Name=Enpep;
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] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=10666143; DOI=10.1152/ajpregu.2000.278.2.r413;
RA Troyanovskaya M., Jayaraman G., Song L., Healy D.P.;
RT "Aminopeptidase-A. I. cDNA cloning and expression and localization in rat
RT tissues.";
RL Am. J. Physiol. 278:R413-R424(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RX PubMed=10978538; DOI=10.1016/s0167-4781(00)00183-4;
RA Lee H.-J., Tomioka M., Takaki Y., Masumoto H., Saido T.C.;
RT "Molecular cloning and expression of aminopeptidase A isoforms from rat
RT hippocampus.";
RL Biochim. Biophys. Acta 1493:273-278(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 265-397, PROTEIN SEQUENCE OF 714-731 (ISOFORM
RP 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=7943354; DOI=10.1152/ajprenal.1994.267.4.f546;
RA Song L., Ye M., Troyanovskaya M., Wilk E., Wilk S., Healy D.P.;
RT "Rat kidney glutamyl aminopeptidase (aminopeptidase A): molecular identity
RT and cellular localization.";
RL Am. J. Physiol. 267:F546-F557(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 482-606 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
RX PubMed=8613196; DOI=10.1161/01.hyp.27.3.518;
RA Troyanovskaya M., Song L., Jayaraman G., Healy D.P.;
RT "Expression of aminopeptidase A, an angiotensinase, in glomerular mesangial
RT cells.";
RL Hypertension 27:518-522(1996).
CC -!- FUNCTION: Regulates central hypertension through its calcium-modulated
CC preference to cleave N-terminal acidic residues from peptides such as
CC angiotensin II. {ECO:0000250|UniProtKB:Q07075}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal glutamate (and to a lesser extent
CC aspartate) from a peptide.; EC=3.4.11.7;
CC Evidence={ECO:0000250|UniProtKB:Q07075};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q07075};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q07075};
CC -!- ACTIVITY REGULATION: Substrate specificity is modulated by calcium
CC which enhances the enzymatic activity for cleavage of acidic residues
CC while reducing its activity with basic residues. Inhibited by
CC aminopeptidase inhibitors amastatin and bestatin.
CC {ECO:0000250|UniProtKB:Q07075}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:Q07075}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q07075};
CC Single-pass type II membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=APAL;
CC IsoId=P50123-1; Sequence=Displayed;
CC Name=2; Synonyms=APAS;
CC IsoId=P50123-2; Sequence=VSP_007844, VSP_007845;
CC -!- TISSUE SPECIFICITY: Highest expression in kidney proximal tubules and
CC ileum enterocytes. High expression also detected in liver and
CC pituitary. Lower levels in heart, adrenal gland and brain. Not detected
CC in aorta, lung or spleen. In heart, higher levels in ventricle than in
CC atrium. Also expressed in glomerular mesangial cells.
CC {ECO:0000269|PubMed:10666143, ECO:0000269|PubMed:10978538,
CC ECO:0000269|PubMed:7943354, ECO:0000269|PubMed:8613196}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; AF146044; AAF66704.1; -; mRNA.
DR EMBL; AF146518; AAF66710.1; -; mRNA.
DR EMBL; BC066663; AAH66663.1; -; mRNA.
DR EMBL; AF214568; AAF37622.1; -; mRNA.
DR RefSeq; NP_071587.2; NM_022251.2.
DR AlphaFoldDB; P50123; -.
DR SMR; P50123; -.
DR BioGRID; 248936; 1.
DR IntAct; P50123; 1.
DR STRING; 10116.ENSRNOP00000064188; -.
DR MEROPS; M01.003; -.
DR GlyGen; P50123; 12 sites.
DR iPTMnet; P50123; -.
DR PhosphoSitePlus; P50123; -.
DR PaxDb; P50123; -.
DR PRIDE; P50123; -.
DR GeneID; 64017; -.
DR KEGG; rno:64017; -.
DR UCSC; RGD:621228; rat. [P50123-1]
DR CTD; 2028; -.
DR RGD; 621228; Enpep.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; P50123; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; P50123; -.
DR BRENDA; 3.4.11.7; 5301.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR PRO; PR:P50123; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0005903; C:brush border; ISO:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; 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; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032835; P:glomerulus development; ISO:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA: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:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; ISS:UniProtKB.
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; IPR033508; Aminopeptidase_A.
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:SF242; PTHR11533:SF242; 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; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Aminopeptidase; Calcium; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..945
FT /note="Glutamyl aminopeptidase"
FT /id="PRO_0000095098"
FT TOPO_DOM 1..18
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 19..39
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 40..945
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 45..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 386
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT BINDING 349..353
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
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 BINDING 878
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT SITE 213
FT /note="Binds calcium which modulates its enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT SITE 471
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
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 546
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 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 640
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 669
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 754
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 766
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 792
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 569..573
FT /note="YTWNI -> NHFEC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10978538"
FT /id="VSP_007844"
FT VAR_SEQ 574..945
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10978538"
FT /id="VSP_007845"
FT CONFLICT 256
FT /note="K -> E (in Ref. 2; AAF66704/AAF66710)"
FT /evidence="ECO:0000305"
FT CONFLICT 306
FT /note="N -> K (in Ref. 2; AAF66704/AAF66710)"
FT /evidence="ECO:0000305"
FT CONFLICT 748
FT /note="A -> D (in Ref. 2; AAF66704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 945 AA; 107995 MW; 5A74F1A537DC5937 CRC64;
MNFAEEEPSK KYCIKGKHVA IICATVVAVG LIVGLSVGLT RSCEPGTTPA PSNPPPHTST
ALPPQDQNVC PDSDDESGEW KNFRLPDFIQ PVHYDLEVKV LMEEDRYTGI VSISVNLSKD
TRDLWLHIRE TRITKLPELR RPSGEQVPIR RCFEYKKQEY VVIQAEEDLA ATSGDSVYRL
TIEFEGWLNG SLVGFYRTTY TEDGQTKSIA ATDHEPTDAR KSFPCFDEPN KKATYNISLI
HPKEYSALSN MPVEKKETLD NDWKKTTFMK SVPMSTYLVC FAVHQFTSIQ RTSRSGKPLT
VYVQPNQKQT AEYAANITKA VFDFFEDYFA MEYSLPKLDK IAIPDFGTGA MENWGLVTYR
ETNLLYDPLL SASSNQQRVA SVVAHELVHQ WFGNIVTMDW WDDLWLNEGF ASFFEFLGVN
HAEADWQMLS QVLLEDVLPV QEDDSLMSSH PVVVTVSTPA EITSVFDGIS YSKGASILRM
LQDWITPEKF QKGCQIYLEN FKFKNAKTSD FWDSLEKASN QPVKEVMDTW TSQMGYPVVT
VSGKQNVTQK RFLLDYKADP SQPPSALGYT WNIPIKWTEN GNSNITVYYR SNREGITLNA
NLSGDGFLKI NPDHIGFYRV NYEAETWDWI AETLSSNHMN FSSADRSSFI DDAFALARAQ
LLDYEKALNL TRYLTSEKDF LPWERVISAV SYIISMFEDD RELYPLIETY FRSQVKPIAD
SLGWQDTGSH ITKLLRASVL GFACKMGAGE ALGNASQLFE AWLKGNESIP VNLRLLVYRY
GMQNSGNEAA WNYTLEQYQK TSLAQEKEKL LYGLASVKDV TLLARYLEML KDPNIIKTQD
VFTVIRYISY NSYGKSMAWN WIQLNWDYLV NRFTINDRYL GRIVTIAEPF NTELQLWQMQ
SFFAKYPNAG AGAKPREQVL ETVKNNIEWL KLNRKSISEW FTSMP
