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Protein

Neprilysin

Gene

Mme

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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) (PubMed:2966343).By similarity1 Publication

Catalytic activityi

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.1 Publication

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Enzyme regulationi

Inhibited in a dose dependent manner by sialorphin.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei103 – 1031Substrate carboxyl
Metal bindingi584 – 5841Zinc; catalyticPROSITE-ProRule annotation
Active sitei585 – 5851PROSITE-ProRule annotation
Metal bindingi588 – 5881Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi647 – 6471Zinc; catalyticPROSITE-ProRule annotation
Active sitei651 – 6511Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.11. 5301.
ReactomeiREACT_309654. Metabolism of Angiotensinogen to Angiotensins.

Protein family/group databases

MEROPSiM13.001.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi3098. Mme.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 2827CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei29 – 5123Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini52 – 750699ExtracellularSequence AnalysisAdd
BLAST

GO - Cellular componenti

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 glycineBy similarity
Modified residuei4 – 41PhosphoserineBy similarity
Modified residuei6 – 61PhosphoserineBy similarity
Disulfide bondi57 ↔ 62By similarity
Disulfide bondi80 ↔ 735By similarity
Disulfide bondi88 ↔ 695By similarity
Disulfide bondi143 ↔ 411By similarity
Glycosylationi145 – 1451N-linked (GlcNAc...)By similarity
Glycosylationi211 – 2111N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
Glycosylationi311 – 3111N-linked (GlcNAc...)1 Publication
Glycosylationi325 – 3251N-linked (GlcNAc...)By similarity
Disulfide bondi621 ↔ 747By 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, Phosphoprotein

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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 238Stop-transfer sequenceSequence Analysis

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP07861.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
PhylomeDBiP07861.
TreeFamiTF315192.

Family and domain databases

Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR029727. MME/CD10/NEP.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF114. PTHR11733:SF114. 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

        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
Length:750
Mass (Da):85,795
Last modified:January 23, 2007 - v2
Checksum:i609D4716C4B15CBC
GO

Sequence databases

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

Genome annotation databases

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

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliP07861.
SMRiP07861. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000044578.

Chemistry

BindingDBiP07861.
ChEMBLiCHEMBL3369.

Protein family/group databases

MEROPSiM13.001.

Proteomic databases

PaxDbiP07861.
PRIDEiP07861.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4311.
RGDi3098. Mme.

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP07861.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
PhylomeDBiP07861.
TreeFamiTF315192.

Enzyme and pathway databases

BRENDAi3.4.24.11. 5301.
ReactomeiREACT_309654. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

NextBioi603776.
PROiP07861.

Gene expression databases

GenevestigatoriP07861.

Family and domain databases

Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR029727. MME/CD10/NEP.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF114. PTHR11733:SF114. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

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 protease 3.4.24.11 as the major atrial natriuretic factor degrading enzyme in the rat kidney."
    Sonnenberg J.L., Sakane Y., Jeng A.Y., Koehn J.A., Ansell J.A., Wennogle L.P., Ghai R.D.
    Peptides 9:173-180(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "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: CATALYTIC ACTIVITY, ACTIVE SITE ARG-103.
  5. "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: May 27, 2015
This is version 141 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.