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 24-JAN-2024, entry version 132. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U66371; AAB07141.1; -; mRNA. DR RefSeq; NP_999182.1; NM_214017.1. DR AlphaFoldDB; Q95334; -. DR SMR; Q95334; -. DR STRING; 9823.ENSSSCP00000064005; -. DR BindingDB; Q95334; -. DR ChEMBL; CHEMBL4868; -. DR MEROPS; M01.003; -. DR GlyCosmos; Q95334; 14 sites, No reported glycans. DR PaxDb; 9823-ENSSSCP00000009739; -. DR PeptideAtlas; Q95334; -. DR Ensembl; ENSSSCT00055031803.1; ENSSSCP00055025312.1; ENSSSCG00055016116.1. DR Ensembl; ENSSSCT00065093299.1; ENSSSCP00065040826.1; ENSSSCG00065067948.1. DR GeneID; 397080; -. DR KEGG; ssc:397080; -. DR CTD; 2028; -. DR eggNOG; KOG1046; Eukaryota. DR InParanoid; Q95334; -. DR OrthoDB; 3085317at2759; -. DR Reactome; R-SSC-2022377; Metabolism of Angiotensinogen to Angiotensins. DR SABIO-RK; Q95334; -. DR Proteomes; UP000008227; Unplaced. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. 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 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:SF242; GLUTAMYL AMINOPEPTIDASE; 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; 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 //