AMPE_PIG
ID AMPE_PIG Reviewed; 942 AA.
AC Q95334;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT.
RX PubMed=9062131; DOI=10.1021/bi962401q;
RA Hesp J.R., Hooper N.M.;
RT "Proteolytic fragmentation reveals the oligomeric and domain structure of
RT porcine aminopeptidase A.";
RL Biochemistry 36:3000-3007(1997).
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:0000269|PubMed:9062131}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q07075};
CC Single-pass type II membrane protein.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; U66371; AAB07141.1; -; mRNA.
DR RefSeq; NP_999182.1; NM_214017.1.
DR AlphaFoldDB; Q95334; -.
DR SMR; Q95334; -.
DR STRING; 9823.ENSSSCP00000009739; -.
DR BindingDB; Q95334; -.
DR ChEMBL; CHEMBL4868; -.
DR MEROPS; M01.003; -.
DR PeptideAtlas; Q95334; -.
DR PRIDE; Q95334; -.
DR Ensembl; ENSSSCT00055031803; ENSSSCP00055025312; ENSSSCG00055016116.
DR Ensembl; ENSSSCT00065093299; ENSSSCP00065040826; ENSSSCG00065067948.
DR GeneID; 397080; -.
DR KEGG; ssc:397080; -.
DR CTD; 2028; -.
DR eggNOG; KOG1046; Eukaryota.
DR InParanoid; Q95334; -.
DR OrthoDB; 110058at2759; -.
DR Reactome; R-SSC-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SABIO-RK; Q95334; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; ISS:UniProtKB.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; ISS:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; IBA:GO_Central.
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 Aminopeptidase; Calcium; Cell membrane; Disulfide bond; Glycoprotein;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix;
KW Zinc.
FT CHAIN 1..942
FT /note="Glutamyl aminopeptidase"
FT /id="PRO_0000095097"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..35
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 36..942
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 40..74
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 384
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT BINDING 347..351
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
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 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 877
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT SITE 211
FT /note="Binds calcium which modulates its enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT SITE 469
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q07075"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 579
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 587
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 597
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 668
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 753
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 786
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 791
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 942 AA; 108284 MW; C531E639A588EF2E CRC64;
MSTDSKRYCI KTKHVAIICA AVVAVGLIVG LSVGLTRSCD SKDGGQGTTQ SPSHLPPTSS
PPQDQGVCPA SEDESGNWRD FRLPDFINPV HYDLQVKPLL EQDTYTGTVN ISINVTSPTQ
HLWLHLRETR ITQLPVLWRP SGEQVQVRRC FEYKKQEYVV VEAEEELAPN SGEGLYHLTM
EFAGWLNGSL VGFYRTTYVE KGQIKSIAAT DHEPTDARKS FPCFDEPNKK ATYTISIIHP
KEYKALSNMP VEKEESVDDI WTQTTFQKSV PMSTYLVCFA VHQFDSVTRT SRSGKPLTIY
VQPEQKHTAE YAANITKSVF DYFEDYFAME YSLPKLDKIA IPDFGTGAME NWGLITYRET
NLLYDPNESA SSNQQRVAAV VAHELVHQWF GNIVTMEWWE DLWLNEGFAS FFEFLGVDHA
EKEWQMRDQI LLEDVLPVQE DDSLISSHPI VVTVSTPAEI TSVFDGISYS KGASILRMLE
DWITPEKFQK GCQEYLKKFE FKNAKTSDFW EALEEASNLP VKEVMDTWTN QMGYPVLNVE
DMRIISQKRF LLDPNANSSE PHSVFGYTWN IPVRWTNDNE STITIYNRSE TGGITLNSSN
PNGNAFLKIN PDHIGFYRVN YEVSTWEWIA TNLSLNHKDF STADRASLID DAFALARAQL
LNYKEALNLT KYLKMEDEYL PWQRVISAVT YIISMFEDDK ELYPMIEKYF RDQVKPIADS
LGWNDNGDHL TKLLRASVLG FACKMGDSNA LNNASHLFEQ WLTGTVSLPV NLRLLVYRYG
MQNSGNETSW NYTLKQYQET SLAQEKEKLL YGLASVKNVA LLSRYLDLLK DPNVIKSQDV
FTVIRYISYN SYGKTMAWNW IQLNWEYLVN RYTLNDRNLG RIVTIAEPFN TELQLWQMES
FFKRYPEAGA GEKPREQVLE TVKNNIEWLK QNRDTIRDWF FN
