UniProtKB - P07861 (NEP_RAT)
Neprilysin
Mme
Functioni
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:2966343) (By similarity).
Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:2966343) (By similarity).
Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:2966343) (By similarity).
Involved in the degradation of the atrial natriuretic factor (ANF) (PubMed:2966343).
Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (By similarity).
By similarity1 PublicationCatalytic activityi
- Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.1 Publication EC:3.4.24.11
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 103 | Peptide substrate | 1 | |
Metal bindingi | 584 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 585 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 588 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 647 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 651 | Proton donorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- cardiolipin binding Source: RGD
- endopeptidase activity Source: RGD
- exopeptidase activity Source: RGD
- metalloendopeptidase activity Source: UniProtKB
- oligopeptidase activity Source: RGD
- peptidase activity Source: RGD
- peptide binding Source: RGD
- phosphatidylserine binding Source: RGD
- protein homodimerization activity Source: RGD
- zinc ion binding Source: UniProtKB
GO - Biological processi
- aging Source: RGD
- amyloid-beta clearance Source: ARUK-UCL
- amyloid-beta clearance by cellular catabolic process Source: ARUK-UCL
- amyloid-beta metabolic process Source: UniProtKB
- cellular response to cytokine stimulus Source: UniProtKB
- cellular response to UV-A Source: UniProtKB
- cellular response to UV-B Source: UniProtKB
- creatinine metabolic process Source: UniProtKB
- kidney development Source: RGD
- learning or memory Source: RGD
- lung development Source: RGD
- neuropeptide processing Source: RGD
- peptide metabolic process Source: RGD
- placenta development Source: RGD
- positive regulation of long-term synaptic potentiation Source: RGD
- positive regulation of neurogenesis Source: RGD
- protein processing Source: GO_Central
- proteolysis Source: RGD
- replicative senescence Source: UniProtKB
- sensory perception of pain Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.24.11, 5301 |
Reactomei | R-RNO-2022377, Metabolism of Angiotensinogen to Angiotensins R-RNO-6798695, Neutrophil degranulation |
Protein family/group databases
MEROPSi | M13.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Neprilysin (EC:3.4.24.111 Publication)Alternative name(s): Atriopeptidase Enkephalinase Neutral endopeptidase 24.11 Short name: NEP Short name: Neutral endopeptidase Skin fibroblast elastase Short name: SFE CD_antigen: CD10 |
Gene namesi | Name:Mme |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3098, Mme |
Subcellular locationi
Plasma membrane
Endosome
- early endosome Source: RGD
Golgi apparatus
- trans-Golgi network Source: RGD
Plasma Membrane
- plasma membrane Source: RGD
Other locations
- axon Source: UniProtKB
- brush border Source: UniProtKB
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: RGD
- dendrite Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- membrane Source: RGD
- membrane raft Source: RGD
- neuron projection terminus Source: UniProtKB
- neuronal cell body Source: RGD
- presynapse Source: RGD
- synapse Source: UniProtKB
- synaptic vesicle Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 2 – 28 | CytoplasmicSequence analysisAdd BLAST | 27 | |
Transmembranei | 29 – 51 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 23 | |
Topological domaini | 52 – 750 | ExtracellularSequence analysisAdd BLAST | 699 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Chemistry databases
ChEMBLi | CHEMBL3369 |
DrugCentrali | P07861 |
GuidetoPHARMACOLOGYi | 1611 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed | |||
ChainiPRO_0000078217 | 2 – 750 | NeprilysinAdd BLAST | 749 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Lipidationi | 2 | N-myristoyl glycineBy similarity | 1 | |
Modified residuei | 4 | PhosphoserineBy similarity | 1 | |
Modified residuei | 6 | PhosphoserineCombined sources | 1 | |
Disulfide bondi | 57 ↔ 62 | PROSITE-ProRule annotation | ||
Disulfide bondi | 80 ↔ 735 | PROSITE-ProRule annotation | ||
Disulfide bondi | 88 ↔ 695 | PROSITE-ProRule annotation | ||
Disulfide bondi | 143 ↔ 411 | PROSITE-ProRule annotation | ||
Glycosylationi | 145 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 211 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 234 ↔ 242 | PROSITE-ProRule annotation | ||
Glycosylationi | 285 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 311 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 325 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Disulfide bondi | 621 ↔ 747 | PROSITE-ProRule annotation | ||
Glycosylationi | 628 | N-linked (GlcNAc...) asparagineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, Myristate, PhosphoproteinProteomic databases
PaxDbi | P07861 |
PRIDEi | P07861 |
PTM databases
GlyGeni | P07861, 6 sites |
iPTMneti | P07861 |
PhosphoSitePlusi | P07861 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000009514, Expressed in jejunum and 20 other tissues |
ExpressionAtlasi | P07861, baseline and differential |
Genevisiblei | P07861, RN |
Interactioni
GO - Molecular functioni
- protein homodimerization activity Source: RGD
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000044578 |
Chemistry databases
BindingDBi | P07861 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 56 – 750 | Peptidase M13PROSITE-ProRule annotationAdd BLAST | 695 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 16 – 23 | Stop-transfer sequenceSequence analysis | 8 |
Sequence similaritiesi
Keywords - Domaini
Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3624, Eukaryota |
GeneTreei | ENSGT00940000156745 |
HOGENOMi | CLU_006187_4_1_1 |
InParanoidi | P07861 |
OMAi | GYPDEIM |
OrthoDBi | 282463at2759 |
PhylomeDBi | P07861 |
TreeFami | TF315192 |
Family and domain databases
CDDi | cd08662, M13, 1 hit |
Gene3Di | 1.10.1380.10, 1 hit 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR024079, MetalloPept_cat_dom_sf IPR029727, MME/CD10/NEP IPR000718, Peptidase_M13 IPR018497, Peptidase_M13_C IPR042089, Peptidase_M13_dom_2 IPR008753, Peptidase_M13_N |
PANTHERi | PTHR11733, PTHR11733, 1 hit PTHR11733:SF114, PTHR11733:SF114, 1 hit |
Pfami | View protein in Pfam PF01431, Peptidase_M13, 1 hit PF05649, Peptidase_M13_N, 1 hit |
PRINTSi | PR00786, NEPRILYSIN |
PROSITEi | View protein in PROSITE PS51885, NEPRILYSIN, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA
60 70 80 90 100
TYDDGICKSS DCIKSAARLI QNMDASAEPC TDFFKYACGG WLKRNVIPET
110 120 130 140 150
SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCINESAID
160 170 180 190 200
SRGGQPLLTL LPDIYGWPVA SQNWEQTYGT SWTAEKSIAQ LNSKYGKKVL
210 220 230 240 250
INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
260 270 280 290 300
SVARLIRQEQ RLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY
310 320 330 340 350
NKMTLAKLQN NFSLEINGKP FSWSNFTNEI MSTVNINIQN EEEVVVYAPE
360 370 380 390 400
YLTKLKPILT KYSPRDLQNL MSWRFIMDLV SSLSRNYKES RNAFRKALYG
410 420 430 440 450
TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV
460 470 480 490 500
FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIISNE NKLNNEYLEL
510 520 530 540 550
NYKEEEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR
560 570 580 590 600
NQIVFPAGIL QPPFFSARQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
610 620 630 640 650
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFT WDLAGGQHLN GINTLGENIA
660 670 680 690 700
DNGGIGQAYR AYQNYVKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP
710 720 730 740 750
EYAVNSIKTD VHSPGNFRII GTLQNSAEFA DAFHCRKNSY MNPERKCRVW
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0H2UHX5 | A0A0H2UHX5_RAT | Neprilysin | Mme | 686 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15944 mRNA Translation: AAA41116.1 BC085753 mRNA Translation: AAH85753.1 |
PIRi | A29295, HYRTN |
RefSeqi | NP_036740.1, NM_012608.2 XP_006232499.1, XM_006232437.3 XP_017446118.1, XM_017590629.1 XP_017446119.1, XM_017590630.1 |
Genome annotation databases
Ensembli | ENSRNOT00000042576; ENSRNOP00000044578; ENSRNOG00000009514 |
GeneIDi | 24590 |
KEGGi | rno:24590 |
UCSCi | RGD:3098, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M15944 mRNA Translation: AAA41116.1 BC085753 mRNA Translation: AAH85753.1 |
PIRi | A29295, HYRTN |
RefSeqi | NP_036740.1, NM_012608.2 XP_006232499.1, XM_006232437.3 XP_017446118.1, XM_017590629.1 XP_017446119.1, XM_017590630.1 |
3D structure databases
AlphaFoldDBi | P07861 |
SMRi | P07861 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000044578 |
Chemistry databases
BindingDBi | P07861 |
ChEMBLi | CHEMBL3369 |
DrugCentrali | P07861 |
GuidetoPHARMACOLOGYi | 1611 |
Protein family/group databases
MEROPSi | M13.001 |
PTM databases
GlyGeni | P07861, 6 sites |
iPTMneti | P07861 |
PhosphoSitePlusi | P07861 |
Proteomic databases
PaxDbi | P07861 |
PRIDEi | P07861 |
Genome annotation databases
Ensembli | ENSRNOT00000042576; ENSRNOP00000044578; ENSRNOG00000009514 |
GeneIDi | 24590 |
KEGGi | rno:24590 |
UCSCi | RGD:3098, rat |
Organism-specific databases
CTDi | 4311 |
RGDi | 3098, Mme |
Phylogenomic databases
eggNOGi | KOG3624, Eukaryota |
GeneTreei | ENSGT00940000156745 |
HOGENOMi | CLU_006187_4_1_1 |
InParanoidi | P07861 |
OMAi | GYPDEIM |
OrthoDBi | 282463at2759 |
PhylomeDBi | P07861 |
TreeFami | TF315192 |
Enzyme and pathway databases
BRENDAi | 3.4.24.11, 5301 |
Reactomei | R-RNO-2022377, Metabolism of Angiotensinogen to Angiotensins R-RNO-6798695, Neutrophil degranulation |
Miscellaneous databases
PROi | PR:P07861 |
Gene expression databases
Bgeei | ENSRNOG00000009514, Expressed in jejunum and 20 other tissues |
ExpressionAtlasi | P07861, baseline and differential |
Genevisiblei | P07861, RN |
Family and domain databases
CDDi | cd08662, M13, 1 hit |
Gene3Di | 1.10.1380.10, 1 hit 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR024079, MetalloPept_cat_dom_sf IPR029727, MME/CD10/NEP IPR000718, Peptidase_M13 IPR018497, Peptidase_M13_C IPR042089, Peptidase_M13_dom_2 IPR008753, Peptidase_M13_N |
PANTHERi | PTHR11733, PTHR11733, 1 hit PTHR11733:SF114, PTHR11733:SF114, 1 hit |
Pfami | View protein in Pfam PF01431, Peptidase_M13, 1 hit PF05649, Peptidase_M13_N, 1 hit |
PRINTSi | PR00786, NEPRILYSIN |
PROSITEi | View protein in PROSITE PS51885, NEPRILYSIN, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NEP_RAT | |
Accessioni | P07861Primary (citable) accession number: P07861 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 180 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - SIMILARITY comments
Index of protein domains and families