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P07861 (NEP_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neprilysin

EC=3.4.24.11
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 names
Name:Mme
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length750 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Displays UV-inducible elastase activity toward skin preelastic and elastic fibers By similarity. Involved in the degradation of atrial natriuretic factor (ANF).

Catalytic activity

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.

Cofactor

Binds 1 zinc ion per subunit.

Enzyme regulation

Inhibited in a dose dependent manner by sialorphin.

Subcellular location

Cell membrane; Single-pass type II membrane protein.

Post-translational modification

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.

Sequence similarities

Belongs to the peptidase M13 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Myristate
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-amyloid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to UV-A

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to UV-B

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to cytokine stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

creatinine metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

kidney development

Inferred from sequence or structural similarity. Source: UniProtKB

peptide metabolic process

Inferred from mutant phenotype PubMed 10642323. Source: RGD

proteolysis

Inferred from direct assay PubMed 15308303. Source: RGD

replicative senescence

Inferred from sequence or structural similarity. Source: UniProtKB

sensory perception of pain

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

brush border

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 15308303. Source: RGD

neuron projection terminus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from sequence or structural similarity. Source: UniProtKB

synaptic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionmetalloendopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

peptide binding

Inferred from direct assay PubMed 15308303. Source: RGD

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 750749Neprilysin
PRO_0000078217

Regions

Topological domain2 – 2827Cytoplasmic Potential
Transmembrane29 – 5123Helical; Signal-anchor for type II membrane protein; Potential
Topological domain52 – 750699Extracellular Potential
Motif16 – 238Stop-transfer sequence Potential

Sites

Active site5851 By similarity
Active site6511Proton donor By similarity
Metal binding5841Zinc; catalytic By similarity
Metal binding5881Zinc; catalytic By similarity
Metal binding6471Zinc; catalytic By similarity
Binding site1031Substrate carboxyl

Amino acid modifications

Lipidation21N-myristoyl glycine By similarity
Glycosylation1451N-linked (GlcNAc...) By similarity
Glycosylation2111N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3111N-linked (GlcNAc...) Ref.1
Glycosylation3251N-linked (GlcNAc...) By similarity
Glycosylation6281N-linked (GlcNAc...) By similarity
Disulfide bond57 ↔ 62 By similarity
Disulfide bond80 ↔ 735 By similarity
Disulfide bond88 ↔ 695 By similarity
Disulfide bond143 ↔ 411 By similarity
Disulfide bond234 ↔ 242 By similarity
Disulfide bond621 ↔ 747 By similarity

Sequences

Sequence LengthMass (Da)Tools
P07861 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 609D4716C4B15CBC

FASTA75085,795
        10         20         30         40         50         60 
MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 

        70         80         90        100        110        120 
DCIKSAARLI QNMDASAEPC TDFFKYACGG WLKRNVIPET SSRYSNFDIL RDELEVILKD 

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGQPLLTL LPDIYGWPVA SQNWEQTYGT 

       190        200        210        220        230        240 
SWTAEKSIAQ LNSKYGKKVL INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE 

       250        260        270        280        290        300 
ACTAYVDFMI SVARLIRQEQ RLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 

       310        320        330        340        350        360 
NKMTLAKLQN NFSLEINGKP FSWSNFTNEI MSTVNINIQN EEEVVVYAPE YLTKLKPILT 

       370        380        390        400        410        420 
KYSPRDLQNL MSWRFIMDLV SSLSRNYKES RNAFRKALYG TTSETATWRR CANYVNGNME 

       430        440        450        460        470        480 
NAVGRLYVEA AFAGESKHVV EDLIAQIREV FIQTLDDLTW MDAETKKKAE EKALAIKERI 

       490        500        510        520        530        540 
GYPDDIISNE NKLNNEYLEL NYKEEEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 

       550        560        570        580        590        600 
VVNAFYSSGR NQIVFPAGIL QPPFFSARQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 

       610        620        630        640        650        660 
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFT WDLAGGQHLN GINTLGENIA DNGGIGQAYR 

       670        680        690        700        710        720 
AYQNYVKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP EYAVNSIKTD VHSPGNFRII 

       730        740        750 
GTLQNSAEFA DAFHCRKNSY MNPERKCRVW 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and amino acid sequence of rat enkephalinase."
Malfroy B., Schofield P.R., Kuang W.-J., Seeburg P.H., Mason A.J., Henzel W.J.
Biochem. Biophys. Res. Commun. 144:59-66(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[3]"Identification of the active-site arginine in rat neutral endopeptidase 24.11 (enkephalinase) as arginine 102 and analysis of a glutamine 102 mutant."
Bateman R.C. Jr., Jackson D., Slaughter C.A., Unnithan S., Chai Y.G., Moomaw C., Hersh L.B.
J. Biol. Chem. 264:6151-6157(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE ARG-103.
[4]"Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity."
Rougeot C., Messaoudi M., Hermitte V., Rigault A.G., Blisnick T., Dugave C., Desor D., Rougeon F.
Proc. Natl. Acad. Sci. U.S.A. 100:8549-8554(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY SIALORPHIN.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M15944 mRNA. Translation: AAA41116.1.
BC085753 mRNA. Translation: AAH85753.1.
PIRHYRTN. A29295.
RefSeqNP_036740.1. NM_012608.2.
XP_006232499.1. XM_006232437.1.
UniGeneRn.33598.

3D structure databases

ProteinModelPortalP07861.
SMRP07861. Positions 55-750.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000044578.

Chemistry

BindingDBP07861.
ChEMBLCHEMBL3369.

Protein family/group databases

MEROPSM13.001.

Proteomic databases

PaxDbP07861.
PRIDEP07861.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000042576; ENSRNOP00000044578; ENSRNOG00000009514.
GeneID24590.
KEGGrno:24590.
UCSCRGD:3098. rat.

Organism-specific databases

CTD4311.
RGD3098. Mme.

Phylogenomic databases

eggNOGCOG3590.
GeneTreeENSGT00650000093248.
HOGENOMHOG000245574.
HOVERGENHBG005554.
InParanoidP07861.
KOK01389.
OMAVWCGTYR.
OrthoDBEOG7PZRWQ.
PhylomeDBP07861.
TreeFamTF315192.

Gene expression databases

GenevestigatorP07861.

Family and domain databases

Gene3D3.40.390.10. 2 hits.
InterProIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERPTHR11733. PTHR11733. 1 hit.
PfamPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSPR00786. NEPRILYSIN.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio603776.
PROP07861.

Entry information

Entry nameNEP_RAT
AccessionPrimary (citable) accession number: P07861
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries