UniProtKB - P08049 (NEP_RABIT)
Protein
Neprilysin
Gene
MME
Organism
Oryctolagus cuniculus (Rabbit)
Status
Functioni
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids. Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.By similarity
Catalytic activityi
- Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.By similarity EC:3.4.24.11
Cofactori
Zn2+Note: Binds 1 zinc ion per subunit.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 103 | Substrate carboxylBy similarity | 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
- metalloendopeptidase activity Source: UniProtKB
- peptide binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- 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: UniProtKB
- peptide metabolic process Source: UniProtKB
- proteolysis Source: UniProtKB
- replicative senescence Source: UniProtKB
- sensory perception of pain Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Protein family/group databases
MEROPSi | M13.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Neprilysin (EC:3.4.24.11By similarity)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 | Oryctolagus cuniculus (Rabbit) |
Taxonomic identifieri | 9986 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Proteomesi |
|
Subcellular locationi
Plasma membrane
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- axon Source: UniProtKB
- brush border Source: UniProtKB
- cytoplasm Source: UniProtKB
- dendrite Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- neuron projection terminus Source: UniProtKB
- 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, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed | |||
ChainiPRO_0000078216 | 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 | PhosphoserineBy similarity | 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 | |
Disulfide bondi | 234 ↔ 242 | PROSITE-ProRule annotation | ||
Glycosylationi | 285 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 311 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 325 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Disulfide bondi | 621 ↔ 747 | PROSITE-ProRule annotation | ||
Glycosylationi | 628 | N-linked (GlcNAc...) asparagine | 1 |
Post-translational modificationi
Myristoylation is a determinant of membrane targeting.By similarity
Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.By similarity
Keywords - PTMi
Disulfide bond, Glycoprotein, Lipoprotein, Myristate, PhosphoproteinInteractioni
Protein-protein interaction databases
STRINGi | 9986.ENSOCUP00000024871 |
Chemistry databases
BindingDBi | P08049 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P08049 |
ModBasei | Search... |
PDBe-KBi | Search... |
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 |
InParanoidi | P08049 |
OrthoDBi | 282463at2759 |
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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P08049-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MGRSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTV IAVTMIALYA
60 70 80 90 100
TYDDGICKSS DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET
110 120 130 140 150
SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCVNETAID
160 170 180 190 200
SRGGQPLLKL LPDVYGWPVA TQNWEQTYGT SWSAEKSIAQ LNSNYGKKVL
210 220 230 240 250
INFFVGTDDK NSMNHIIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
260 270 280 290 300
AVAKLIRQEE GLPIDENQIS VEMNKVMELE KEIANATTKS EDRNDPMLLY
310 320 330 340 350
NKMTLAQIQN NFSLEINGKP FSWSNFTNEI MSTVNINIPN EEDVVVYAPE
360 370 380 390 400
YLIKLKPILT KYFPRDFQNL FSWRFIMDLV SSLSRTYKDS RNAFRKALYG
410 420 430 440 450
TTSESATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV
460 470 480 490 500
FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIVSND NKLNNEYLEL
510 520 530 540 550
NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWITGAA IVNAFYSSGR
560 570 580 590 600
NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
610 620 630 640 650
GDLVDWWTQQ SANNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA
660 670 680 690 700
DNGGIGQAYR AYQNYVKKNG EEKLLPGIDL NHKQLFFLNF AQVWCGTYRP
710 720 730 740 750
EYAVNSIKTD VHSPGNFRII GSLQNSVEFS EAFQCPKNSY MNPEKKCRVW
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X05338 mRNA Translation: CAA28950.1 M16593 mRNA Translation: AAA53694.1 |
PIRi | A29451, HYRBN |
RefSeqi | NP_001095155.1, NM_001101685.1 |
Genome annotation databases
GeneIDi | 100009251 |
KEGGi | ocu:100009251 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X05338 mRNA Translation: CAA28950.1 M16593 mRNA Translation: AAA53694.1 |
PIRi | A29451, HYRBN |
RefSeqi | NP_001095155.1, NM_001101685.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4XBH | X-ray | 2.11 | A/B | 55-750 | [»] | |
4ZR5 | X-ray | 2.80 | A/B | 55-750 | [»] | |
5V48 | X-ray | 3.00 | A/B | 55-750 | [»] | |
SMRi | P08049 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 9986.ENSOCUP00000024871 |
Chemistry databases
BindingDBi | P08049 |
ChEMBLi | CHEMBL3768 |
DrugCentrali | P08049 |
Protein family/group databases
MEROPSi | M13.001 |
Genome annotation databases
GeneIDi | 100009251 |
KEGGi | ocu:100009251 |
Organism-specific databases
CTDi | 4311 |
Phylogenomic databases
eggNOGi | KOG3624, Eukaryota |
InParanoidi | P08049 |
OrthoDBi | 282463at2759 |
Miscellaneous databases
PROi | PR:P08049 |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NEP_RABIT | |
Accessioni | P08049Primary (citable) accession number: P08049 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1988 |
Last sequence update: | January 23, 2007 | |
Last modified: | December 2, 2020 | |
This is version 151 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
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Peptidase families
Classification of peptidase families and list of entries