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UniProtKB - Q07075 (AMPE_HUMAN)
Protein
Glutamyl aminopeptidase
Gene
ENPEP
Organism
Homo sapiens (Human)
Status
Functioni
Regulates central hypertension through its calcium-modulated preference to cleave N-terminal acidic residues from peptides such as angiotensin II.
1 PublicationCatalytic activityi
- Release of N-terminal glutamate (and to a lesser extent aspartate) from a peptide.2 Publications EC:3.4.11.7
Cofactori
Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication
Activity regulationi
Substrate specificity is modulated by calcium which enhances the enzymatic activity for cleavage of acidic residues while reducing its activity with basic residues. Inhibited by aminopeptidase inhibitors amastatin and bestatin.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 221 | Binds calcium which modulates its enzyme activity1 Publication | 1 | |
Binding sitei | 223 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 393 | Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Active sitei | 394 | Proton acceptorPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 397 | Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 416 | Zinc; catalyticPROSITE-ProRule annotationCombined sources1 Publication | 1 | |
Sitei | 479 | Transition state stabilizerCombined sources1 Publication | 1 | |
Binding sitei | 887 | SubstrateCombined sources1 Publication | 1 |
GO - Molecular functioni
- aminopeptidase activity Source: UniProtKB
- metalloaminopeptidase activity Source: UniProtKB
- peptide binding Source: GO_Central
- zinc ion binding Source: GO_Central
GO - Biological processi
- angiogenesis Source: UniProtKB
- angiotensin maturation Source: UniProtKB
- cell-cell signaling Source: UniProtKB
- cell migration Source: MGI
- cell population proliferation Source: MGI
- glomerulus development Source: UniProtKB
- peptide catabolic process Source: GO_Central
- proteolysis Source: GO_Central
- regulation of blood pressure Source: GO_Central
- regulation of systemic arterial blood pressure by renin-angiotensin Source: UniProtKB
- signal transduction Source: GO_Central
Keywordsi
Molecular function | Aminopeptidase, Hydrolase, Metalloprotease, Protease |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.11.7, 2681 |
PathwayCommonsi | Q07075 |
Reactomei | R-HSA-2022377, Metabolism of Angiotensinogen to Angiotensins |
SignaLinki | Q07075 |
Protein family/group databases
MEROPSi | M01.003 |
Names & Taxonomyi
Protein namesi | Recommended name: Glutamyl aminopeptidase (EC:3.4.11.72 Publications)Short name: EAP Alternative name(s): Aminopeptidase A Short name: AP-A Differentiation antigen gp160 CD_antigen: CD249 |
Gene namesi | Name:ENPEP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3355, ENPEP |
MIMi | 138297, gene |
neXtProti | NX_Q07075 |
VEuPathDBi | HostDB:ENSG00000138792 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type II membrane protein
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Lysosome
- lysosomal membrane Source: UniProtKB
Plasma Membrane
- apical plasma membrane Source: UniProtKB
- external side of plasma membrane Source: UniProtKB
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- apical part of cell Source: UniProtKB
- brush border Source: UniProtKB
- cytoplasm Source: GO_Central
- cytoplasmic vesicle Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 18 | CytoplasmicSequence analysisAdd BLAST | 18 | |
Transmembranei | 19 – 39 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 40 – 957 | ExtracellularSequence analysisAdd BLAST | 918 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 356 | T → V: Reduced enzyme activity. 1 Publication | 1 | |
Mutagenesisi | 887 | R → A: Reduced enzyme activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 2028 |
OpenTargetsi | ENSG00000138792 |
PharmGKBi | PA27790 |
Miscellaneous databases
Pharosi | Q07075, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3439 |
DrugBanki | DB00142, Glutamic acid |
Genetic variation databases
BioMutai | ENPEP |
DMDMi | 296439445 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000095095 | 1 – 957 | Glutamyl aminopeptidaseAdd BLAST | 957 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 98 | N-linked (GlcNAc...) asparagine; atypicalCombined sources1 Publication | 1 | |
Glycosylationi | 124 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 197 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 324 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Glycosylationi | 340 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 554 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 589 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 597 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 607 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 678 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 763 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 | |
Glycosylationi | 773 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 801 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 | |
Glycosylationi | 828 | N-linked (GlcNAc...) asparagineCombined sources1 Publication | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q07075 |
jPOSTi | Q07075 |
MassIVEi | Q07075 |
MaxQBi | Q07075 |
PaxDbi | Q07075 |
PeptideAtlasi | Q07075 |
PRIDEi | Q07075 |
ProteomicsDBi | 58502 |
PTM databases
GlyConnecti | 1940, 8 N-Linked glycans (6 sites) |
GlyGeni | Q07075, 21 sites, 8 N-linked glycans (6 sites), 5 O-linked glycans (4 sites) |
iPTMneti | Q07075 |
PhosphoSitePlusi | Q07075 |
Expressioni
Tissue specificityi
Expressed in choriocarcinoma cancer cell lines (at protein level) (PubMed:10692253). Expressed by epithelial cells of the proximal tubule cells and the glomerulus of the nephron. Also found in a variety of other tissues.1 Publication
Gene expression databases
Bgeei | ENSG00000138792, Expressed in jejunal mucosa and 168 other tissues |
ExpressionAtlasi | Q07075, baseline and differential |
Genevisiblei | Q07075, HS |
Organism-specific databases
HPAi | ENSG00000138792, Tissue enhanced (intestine, kidney) |
Interactioni
Subunit structurei
Homodimer; disulfide-linked.
1 PublicationProtein-protein interaction databases
BioGRIDi | 108342, 6 interactors |
IntActi | Q07075, 5 interactors |
STRINGi | 9606.ENSP00000265162 |
Chemistry databases
BindingDBi | Q07075 |
Miscellaneous databases
RNActi | Q07075, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | Q07075 |
SMRi | Q07075 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 44 – 83 | DisorderedSequence analysisAdd BLAST | 40 | |
Regioni | 357 – 361 | Substrate bindingCombined sources1 Publication | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 57 – 71 | Polar residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Belongs to the peptidase M1 family.Curated
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1046, Eukaryota |
GeneTreei | ENSGT00940000156946 |
HOGENOMi | CLU_003705_0_1_1 |
InParanoidi | Q07075 |
OMAi | FSHGAME |
OrthoDBi | 110058at2759 |
PhylomeDBi | Q07075 |
TreeFami | TF300395 |
Family and domain databases
CDDi | cd09601, M1_APN-Q_like, 1 hit |
Gene3Di | 1.10.390.10, 1 hit 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR033508, Aminopeptidase_A IPR045357, Aminopeptidase_N-like_N IPR042097, Aminopeptidase_N-like_N_sf IPR024571, ERAP1-like_C_dom IPR034016, M1_APN-typ IPR001930, Peptidase_M1 IPR014782, Peptidase_M1_dom IPR027268, Peptidase_M4/M1_CTD_sf |
PANTHERi | PTHR11533:SF242, PTHR11533:SF242, 1 hit |
Pfami | View protein in Pfam PF11838, ERAP1_C, 1 hit PF01433, Peptidase_M1, 1 hit PF17900, Peptidase_M1_N, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SUPFAMi | SSF63737, SSF63737, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q07075-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MNFAEREGSK RYCIQTKHVA ILCAVVVGVG LIVGLAVGLT RSCDSSGDGG
60 70 80 90 100
PGTAPAPSHL PSSTASPSGP PAQDQDICPA SEDESGQWKN FRLPDFVNPV
110 120 130 140 150
HYDLHVKPLL EEDTYTGTVS ISINLSAPTR YLWLHLRETR ITRLPELKRP
160 170 180 190 200
SGDQVQVRRC FEYKKQEYVV VEAEEELTPS SGDGLYLLTM EFAGWLNGSL
210 220 230 240 250
VGFYRTTYTE NGQVKSIVAT DHEPTDARKS FPCFDEPNKK ATYTISITHP
260 270 280 290 300
KEYGALSNMP VAKEESVDDK WTRTTFEKSV PMSTYLVCFA VHQFDSVKRI
310 320 330 340 350
SNSGKPLTIY VQPEQKHTAE YAANITKSVF DYFEEYFAMN YSLPKLDKIA
360 370 380 390 400
IPDFGTGAME NWGLITYRET NLLYDPKESA SSNQQRVATV VAHELVHQWF
410 420 430 440 450
GNIVTMDWWE DLWLNEGFAS FFEFLGVNHA ETDWQMRDQM LLEDVLPVQE
460 470 480 490 500
DDSLMSSHPI IVTVTTPDEI TSVFDGISYS KGSSILRMLE DWIKPENFQK
510 520 530 540 550
GCQMYLEKYQ FKNAKTSDFW AALEEASRLP VKEVMDTWTR QMGYPVLNVN
560 570 580 590 600
GVKNITQKRF LLDPRANPSQ PPSDLGYTWN IPVKWTEDNI TSSVLFNRSE
610 620 630 640 650
KEGITLNSSN PSGNAFLKIN PDHIGFYRVN YEVATWDSIA TALSLNHKTF
660 670 680 690 700
SSADRASLID DAFALARAQL LDYKVALNLT KYLKREENFL PWQRVISAVT
710 720 730 740 750
YIISMFEDDK ELYPMIEEYF QGQVKPIADS LGWNDAGDHV TKLLRSSVLG
760 770 780 790 800
FACKMGDREA LNNASSLFEQ WLNGTVSLPV NLRLLVYRYG MQNSGNEISW
810 820 830 840 850
NYTLEQYQKT SLAQEKEKLL YGLASVKNVT LLSRYLDLLK DTNLIKTQDV
860 870 880 890 900
FTVIRYISYN SYGKNMAWNW IQLNWDYLVN RYTLNNRNLG RIVTIAEPFN
910 920 930 940 950
TELQLWQMES FFAKYPQAGA GEKPREQVLE TVKNNIEWLK QHRNTIREWF
FNLLESG
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0YA67 | H0YA67_HUMAN | Glutamyl aminopeptidase | ENPEP | 144 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030359 | 213 | Q → R4 PublicationsCorresponds to variant dbSNP:rs10004516Ensembl. | 1 | |
Natural variantiVAR_030360 | 218 | V → A1 PublicationCorresponds to variant dbSNP:rs1126483Ensembl. | 1 | |
Natural variantiVAR_057056 | 437 | R → H. Corresponds to variant dbSNP:rs34949711Ensembl. | 1 | |
Natural variantiVAR_057057 | 861 | S → R. Corresponds to variant dbSNP:rs35812243EnsemblClinVar. | 1 | |
Natural variantiVAR_036047 | 887 | R → T in a breast cancer sample; somatic mutation. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L14721 mRNA Translation: AAA35522.1 L12468 mRNA Translation: AAA16876.1 AC017068 Genomic DNA No translation available. AC098798 Genomic DNA No translation available. BC094770 mRNA Translation: AAH94770.1 |
CCDSi | CCDS3691.1 |
PIRi | A47531 |
RefSeqi | NP_001968.3, NM_001977.3 |
Genome annotation databases
Ensembli | ENST00000265162.10; ENSP00000265162.5; ENSG00000138792.10 |
GeneIDi | 2028 |
KEGGi | hsa:2028 |
MANE-Selecti | ENST00000265162.10; ENSP00000265162.5; NM_001977.4; NP_001968.3 |
UCSCi | uc003iab.5, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L14721 mRNA Translation: AAA35522.1 L12468 mRNA Translation: AAA16876.1 AC017068 Genomic DNA No translation available. AC098798 Genomic DNA No translation available. BC094770 mRNA Translation: AAH94770.1 |
CCDSi | CCDS3691.1 |
PIRi | A47531 |
RefSeqi | NP_001968.3, NM_001977.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4KX7 | X-ray | 2.15 | A | 76-957 | [»] | |
4KX8 | X-ray | 2.40 | A | 76-957 | [»] | |
4KX9 | X-ray | 2.25 | A | 76-957 | [»] | |
4KXA | X-ray | 2.40 | A | 76-957 | [»] | |
4KXB | X-ray | 2.40 | A | 76-957 | [»] | |
4KXC | X-ray | 2.40 | A | 76-957 | [»] | |
4KXD | X-ray | 2.15 | A | 76-957 | [»] | |
AlphaFoldDBi | Q07075 | |||||
SMRi | Q07075 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108342, 6 interactors |
IntActi | Q07075, 5 interactors |
STRINGi | 9606.ENSP00000265162 |
Chemistry databases
BindingDBi | Q07075 |
ChEMBLi | CHEMBL3439 |
DrugBanki | DB00142, Glutamic acid |
Protein family/group databases
MEROPSi | M01.003 |
PTM databases
GlyConnecti | 1940, 8 N-Linked glycans (6 sites) |
GlyGeni | Q07075, 21 sites, 8 N-linked glycans (6 sites), 5 O-linked glycans (4 sites) |
iPTMneti | Q07075 |
PhosphoSitePlusi | Q07075 |
Genetic variation databases
BioMutai | ENPEP |
DMDMi | 296439445 |
Proteomic databases
EPDi | Q07075 |
jPOSTi | Q07075 |
MassIVEi | Q07075 |
MaxQBi | Q07075 |
PaxDbi | Q07075 |
PeptideAtlasi | Q07075 |
PRIDEi | Q07075 |
ProteomicsDBi | 58502 |
Protocols and materials databases
Antibodypediai | 979, 516 antibodies from 37 providers |
DNASUi | 2028 |
Genome annotation databases
Ensembli | ENST00000265162.10; ENSP00000265162.5; ENSG00000138792.10 |
GeneIDi | 2028 |
KEGGi | hsa:2028 |
MANE-Selecti | ENST00000265162.10; ENSP00000265162.5; NM_001977.4; NP_001968.3 |
UCSCi | uc003iab.5, human |
Organism-specific databases
CTDi | 2028 |
DisGeNETi | 2028 |
GeneCardsi | ENPEP |
HGNCi | HGNC:3355, ENPEP |
HPAi | ENSG00000138792, Tissue enhanced (intestine, kidney) |
MIMi | 138297, gene |
neXtProti | NX_Q07075 |
OpenTargetsi | ENSG00000138792 |
PharmGKBi | PA27790 |
VEuPathDBi | HostDB:ENSG00000138792 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1046, Eukaryota |
GeneTreei | ENSGT00940000156946 |
HOGENOMi | CLU_003705_0_1_1 |
InParanoidi | Q07075 |
OMAi | FSHGAME |
OrthoDBi | 110058at2759 |
PhylomeDBi | Q07075 |
TreeFami | TF300395 |
Enzyme and pathway databases
BRENDAi | 3.4.11.7, 2681 |
PathwayCommonsi | Q07075 |
Reactomei | R-HSA-2022377, Metabolism of Angiotensinogen to Angiotensins |
SignaLinki | Q07075 |
Miscellaneous databases
BioGRID-ORCSi | 2028, 10 hits in 1073 CRISPR screens |
ChiTaRSi | ENPEP, human |
GenomeRNAii | 2028 |
Pharosi | Q07075, Tchem |
PROi | PR:Q07075 |
RNActi | Q07075, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000138792, Expressed in jejunal mucosa and 168 other tissues |
ExpressionAtlasi | Q07075, baseline and differential |
Genevisiblei | Q07075, HS |
Family and domain databases
CDDi | cd09601, M1_APN-Q_like, 1 hit |
Gene3Di | 1.10.390.10, 1 hit 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR033508, Aminopeptidase_A IPR045357, Aminopeptidase_N-like_N IPR042097, Aminopeptidase_N-like_N_sf IPR024571, ERAP1-like_C_dom IPR034016, M1_APN-typ IPR001930, Peptidase_M1 IPR014782, Peptidase_M1_dom IPR027268, Peptidase_M4/M1_CTD_sf |
PANTHERi | PTHR11533:SF242, PTHR11533:SF242, 1 hit |
Pfami | View protein in Pfam PF11838, ERAP1_C, 1 hit PF01433, Peptidase_M1, 1 hit PF17900, Peptidase_M1_N, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SUPFAMi | SSF63737, SSF63737, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | AMPE_HUMAN | |
Accessioni | Q07075Primary (citable) accession number: Q07075 Secondary accession number(s): Q504U2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1994 |
Last sequence update: | May 18, 2010 | |
Last modified: | May 25, 2022 | |
This is version 197 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Peptidase families
Classification of peptidase families and list of entries - Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families