SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P07861

- NEP_RAT

UniProt

P07861 - NEP_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Neprilysin

Gene
Mme
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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

Catalytic activityi

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

Cofactori

Binds 1 zinc ion per subunit.

Enzyme regulationi

Inhibited in a dose dependent manner by sialorphin.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei103 – 1031Substrate carboxyl
Metal bindingi584 – 5841Zinc; catalytic By similarity
Active sitei585 – 5851 By similarity
Metal bindingi588 – 5881Zinc; catalytic By similarity
Metal bindingi647 – 6471Zinc; catalytic By similarity
Active sitei651 – 6511Proton donor By similarity

GO - Molecular functioni

  1. metalloendopeptidase activity Source: UniProtKB
  2. peptide binding Source: RGD
  3. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-amyloid metabolic process Source: UniProtKB
  2. cellular response to cytokine stimulus Source: UniProtKB
  3. cellular response to UV-A Source: UniProtKB
  4. cellular response to UV-B Source: UniProtKB
  5. creatinine metabolic process Source: UniProtKB
  6. kidney development Source: UniProtKB
  7. peptide metabolic process Source: RGD
  8. proteolysis Source: RGD
  9. replicative senescence Source: UniProtKB
  10. sensory perception of pain Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_198807. Metabolism of Angiotensinogen to Angiotensins.

Protein family/group databases

MEROPSiM13.001.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Mme
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 2

Organism-specific databases

RGDi3098. Mme.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 2827Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei29 – 5123Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini52 – 750699Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. axon Source: UniProtKB
  2. brush border Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. dendrite Source: UniProtKB
  5. integral component of membrane Source: UniProtKB-KW
  6. membrane Source: RGD
  7. neuron projection terminus Source: UniProtKB
  8. plasma membrane Source: UniProtKB
  9. synapse Source: UniProtKB
  10. synaptic vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed
Chaini2 – 750749NeprilysinPRO_0000078217Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine By similarity
Disulfide bondi57 ↔ 62 By similarity
Disulfide bondi80 ↔ 735 By similarity
Disulfide bondi88 ↔ 695 By similarity
Disulfide bondi143 ↔ 411 By similarity
Glycosylationi145 – 1451N-linked (GlcNAc...) By similarity
Glycosylationi211 – 2111N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi234 ↔ 242 By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...) Reviewed prediction
Glycosylationi311 – 3111N-linked (GlcNAc...)1 Publication
Glycosylationi325 – 3251N-linked (GlcNAc...) By similarity
Disulfide bondi621 ↔ 747 By similarity
Glycosylationi628 – 6281N-linked (GlcNAc...) By similarity

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

Proteomic databases

PaxDbiP07861.
PRIDEiP07861.

Expressioni

Gene expression databases

GenevestigatoriP07861.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000044578.

Structurei

3D structure databases

ProteinModelPortaliP07861.
SMRiP07861. Positions 55-750.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 238Stop-transfer sequence Reviewed prediction

Sequence similaritiesi

Belongs to the peptidase M13 family.

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00650000093248.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP07861.
KOiK01389.
OMAiVWCGTYR.
OrthoDBiEOG7PZRWQ.
PhylomeDBiP07861.
TreeFamiTF315192.

Family and domain databases

Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P07861-1 [UniParc]FASTAAdd to Basket

« Hide

MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA    50
TYDDGICKSS DCIKSAARLI QNMDASAEPC TDFFKYACGG WLKRNVIPET 100
SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCINESAID 150
SRGGQPLLTL LPDIYGWPVA SQNWEQTYGT SWTAEKSIAQ LNSKYGKKVL 200
INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE ACTAYVDFMI 250
SVARLIRQEQ RLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 300
NKMTLAKLQN NFSLEINGKP FSWSNFTNEI MSTVNINIQN EEEVVVYAPE 350
YLTKLKPILT KYSPRDLQNL MSWRFIMDLV SSLSRNYKES RNAFRKALYG 400
TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV 450
FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIISNE NKLNNEYLEL 500
NYKEEEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR 550
NQIVFPAGIL QPPFFSARQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 600
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFT WDLAGGQHLN GINTLGENIA 650
DNGGIGQAYR AYQNYVKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP 700
EYAVNSIKTD VHSPGNFRII GTLQNSAEFA DAFHCRKNSY MNPERKCRVW 750
Length:750
Mass (Da):85,795
Last modified:January 23, 2007 - v2
Checksum:i609D4716C4B15CBC
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M15944 mRNA. Translation: AAA41116.1.
BC085753 mRNA. Translation: AAH85753.1.
PIRiA29295. HYRTN.
RefSeqiNP_036740.1. NM_012608.2.
XP_006232499.1. XM_006232437.1.
UniGeneiRn.33598.

Genome annotation databases

EnsembliENSRNOT00000042576; ENSRNOP00000044578; ENSRNOG00000009514.
GeneIDi24590.
KEGGirno:24590.
UCSCiRGD:3098. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006232437.1.
UniGenei Rn.33598.

3D structure databases

ProteinModelPortali P07861.
SMRi P07861. Positions 55-750.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000044578.

Chemistry

BindingDBi P07861.
ChEMBLi CHEMBL3369.

Protein family/group databases

MEROPSi M13.001.

Proteomic databases

PaxDbi P07861.
PRIDEi P07861.

Protocols and materials databases

Structural Biology Knowledgebase Search...

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 COG3590.
GeneTreei ENSGT00650000093248.
HOGENOMi HOG000245574.
HOVERGENi HBG005554.
InParanoidi P07861.
KOi K01389.
OMAi VWCGTYR.
OrthoDBi EOG7PZRWQ.
PhylomeDBi P07861.
TreeFami TF315192.

Enzyme and pathway databases

Reactomei REACT_198807. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

NextBioi 603776.
PROi P07861.

Gene expression databases

Genevestigatori P07861.

Family and domain databases

Gene3Di 3.40.390.10. 2 hits.
InterProi IPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view ]
PANTHERi PTHR11733. PTHR11733. 1 hit.
Pfami PF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view ]
PRINTSi PR00786. NEPRILYSIN.
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.

Entry informationi

Entry nameiNEP_RAT
AccessioniPrimary (citable) accession number: P07861
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi