AMPE_MOUSE
ID AMPE_MOUSE Reviewed; 945 AA.
AC P16406;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 190.
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: Full=BP-1/6C3 antigen;
DE AltName: CD_antigen=CD249;
GN Name=Enpep;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 77-96; 98-102; 624-632;
RP 709-720 AND 930-939, AND TISSUE SPECIFICITY.
RX PubMed=1689065; DOI=10.1073/pnas.87.3.993;
RA Wu Q., Lahti J.M., Air G.M., Burrows P.D., Cooper M.D.;
RT "Molecular cloning of the murine BP-1/6C3 antigen: a member of the zinc-
RT dependent metallopeptidase family.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:993-997(1990).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 -!- TISSUE SPECIFICITY: Early B-lineage cells and certain stromal cell of
CC hemopoietic tissues. Also expressed by capillary endothelial cells,
CC placenta, and epithelial cells of the intestine and proximal renal
CC tubules. {ECO:0000269|PubMed:1689065}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; M29961; AAB47732.1; -; mRNA.
DR CCDS; CCDS17831.1; -.
DR PIR; S30398; S30398.
DR RefSeq; NP_031960.1; NM_007934.3.
DR AlphaFoldDB; P16406; -.
DR SMR; P16406; -.
DR STRING; 10090.ENSMUSP00000029658; -.
DR GuidetoPHARMACOLOGY; 1568; -.
DR MEROPS; M01.003; -.
DR GlyGen; P16406; 9 sites.
DR iPTMnet; P16406; -.
DR PhosphoSitePlus; P16406; -.
DR jPOST; P16406; -.
DR PaxDb; P16406; -.
DR PeptideAtlas; P16406; -.
DR PRIDE; P16406; -.
DR ProteomicsDB; 296283; -.
DR Antibodypedia; 979; 533 antibodies from 37 providers.
DR DNASU; 13809; -.
DR Ensembl; ENSMUST00000029658; ENSMUSP00000029658; ENSMUSG00000028024.
DR GeneID; 13809; -.
DR KEGG; mmu:13809; -.
DR UCSC; uc008rhy.1; mouse.
DR CTD; 2028; -.
DR MGI; MGI:106645; Enpep.
DR VEuPathDB; HostDB:ENSMUSG00000028024; -.
DR eggNOG; KOG1046; Eukaryota.
DR GeneTree; ENSGT00940000156946; -.
DR HOGENOM; CLU_003705_0_1_1; -.
DR InParanoid; P16406; -.
DR OMA; FSHGAME; -.
DR OrthoDB; 110058at2759; -.
DR PhylomeDB; P16406; -.
DR TreeFam; TF300395; -.
DR BRENDA; 3.4.11.7; 3474.
DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR BioGRID-ORCS; 13809; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Enpep; mouse.
DR PRO; PR:P16406; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P16406; protein.
DR Bgee; ENSMUSG00000028024; Expressed in small intestine Peyer's patch and 208 other tissues.
DR ExpressionAtlas; P16406; baseline and differential.
DR Genevisible; P16406; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005903; C:brush border; IDA:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
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:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
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; IEP:UniProtKB.
DR GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
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 GO; GO:0101023; P:vascular endothelial cell proliferation; ISO:MGI.
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; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..945
FT /note="Glutamyl aminopeptidase"
FT /id="PRO_0000095096"
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 43..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 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 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
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 792
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 945 AA; 107956 MW; A93A00CB8635F574 CRC64;
MNFAEEEPSK KYCIKGKHVA IICGVVVAVG LIVGLSVGLT RSCEQDTTPA PSQPPPEAST
ALPPQDQNVC PDSEDESGEW KNFRLPDFIN PVHYDLEVKA LMEEDRYTGI VTISVNLSKP
TRDLWLHIRE TKITKLPELR RPSGEQVPIR RCFEYKKQEY VVIQAAEDLA ATSGDSVYRL
TMEFKGWLNG SLVGFYKTTY MEDGQIRSIA ATDHEPTDAR KSFPCFDEPN KKSTYSISII
HPKEYSALSN MPEEKSEMVD DNWKKTTFVK SVPMSTYLVC FAVHRFTAIE RKSRSGKPLK
VYVQPNQKET AEYAANITQA VFDYFEDYFA MEYALPKLDK IAIPDFGTGA MENWGLVTYR
ETNLLYDPLL SASSNQQRVA SVVAHELVHQ WFGNTVTMDW WDDLWLNEGF ASFFEFLGVN
HAEKDWQMLS QVLLEDVFPV QEDDSLMSSH PVVVTVSTPA EITSVFDGIS YSKGASILRM
LQDWITPEKF QKGCQIYLKK FQFANAKTSD FWDSLQEASN LPVKEVMDTW TSQMGYPVVT
VSGRQNITQK RFLLDSKADP SQPPSELGYT WNIPVRWADN DNSRITVYNR LDKGGITLNA
NLSGDAFLKI NPDHIGFYRV NYEGGTWDWI AEALSSNHTR FSAADRSSFI DDAFALARAQ
LLNYKIALNL TMYLKSEEDF LPWERVISSV SYIISMFEDD RELYPMIETY FQGQVKPVAD
LLGWQDTGSH ITKLLRASIL GFACKMGDRE ALGNASQLFD SWLKGSASIP VNLRLLVYRY
GMQNSGNEAA WNYTLEQYQK TSLAQEKEKL LYGLASVKDV KLLARYLEML KDPNIIKTQD
VFTVIRYISY NSYGKTMAWN WIQLNWDYLV SRFTINDRYL GRIVTIAEPF NTELQLWQMQ
SFFAKYPNAG AGAKPREQVL ETVKNNIEWL NVNRQSIREW FASLP
