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Protein

Neprilysin

Gene

Mme

Organism
Mus musculus (Mouse)
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. Involved in the degradation of atrial natriuretic factor (ANF) (By similarity). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).By similarity1 Publication

Catalytic activityi

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

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei103Substrate carboxylBy similarity1
Metal bindingi584Zinc; catalyticPROSITE-ProRule annotation1
Active sitei585PROSITE-ProRule annotation1
Metal bindingi588Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi647Zinc; catalyticPROSITE-ProRule annotation1
Active sitei651Proton donorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2022377. Metabolism of Angiotensinogen to Angiotensins.
R-MMU-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiM13.001.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:97004. Mme.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 28CytoplasmicSequence analysisAdd BLAST27
Transmembranei29 – 51Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST23
Topological domaini52 – 750ExtracellularSequence analysisAdd BLAST699

GO - Cellular componenti

  • axon Source: MGI
  • brush border Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • dendrite Source: MGI
  • extracellular exosome Source: MGI
  • focal adhesion Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: MGI
  • neuron projection terminus Source: MGI
  • plasma membrane Source: UniProtKB
  • synapse Source: MGI
  • synaptic vesicle Source: MGI

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are overtly normal in appearance and size and do not show obvious abnormalities in motor performance or coordination. Nerve conduction studies reveal no significant differences between mutant and control animals.1 Publication

Chemistry databases

ChEMBLiCHEMBL2642.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000782142 – 750NeprilysinAdd BLAST749

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei4PhosphoserineCombined sources1
Modified residuei6PhosphoserineCombined sources1
Disulfide bondi57 ↔ 62By similarity
Disulfide bondi80 ↔ 735By similarity
Disulfide bondi88 ↔ 695By similarity
Disulfide bondi143 ↔ 411By similarity
Glycosylationi145N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi211N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi311N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi317N-linked (GlcNAc...) asparagine; atypical1 Publication1
Glycosylationi325N-linked (GlcNAc...) asparagineBy similarity1
Disulfide bondi621 ↔ 747By similarity
Glycosylationi628N-linked (GlcNAc...) asparagineBy similarity1

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

MaxQBiQ61391.
PaxDbiQ61391.
PeptideAtlasiQ61391.
PRIDEiQ61391.

PTM databases

iPTMnetiQ61391.
PhosphoSitePlusiQ61391.

Expressioni

Gene expression databases

BgeeiENSMUSG00000027820.
CleanExiMM_MME.
ExpressionAtlasiQ61391. baseline and differential.
GenevisibleiQ61391. MM.

Interactioni

Protein-protein interaction databases

BioGridi201441. 2 interactors.
IntActiQ61391. 3 interactors.
MINTiMINT-4103332.
STRINGi10090.ENSMUSP00000029400.

Chemistry databases

BindingDBiQ61391.

Structurei

Secondary structure

1750
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 12Combined sources4
Beta strandi19 – 21Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2YVCX-ray3.20D/E/F2-23[»]
ProteinModelPortaliQ61391.
SMRiQ61391.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61391.

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 23Stop-transfer sequenceSequence analysis8

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3624. Eukaryota.
COG3590. LUCA.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ61391.
KOiK01389.
OMAiTATWRRC.
OrthoDBiEOG091G025Y.
PhylomeDBiQ61391.
TreeFamiTF315192.

Family and domain databases

CDDicd08662. M13. 1 hit.
Gene3Di3.40.390.10. 2 hits.
InterProiView protein in InterPro
IPR024079. MetalloPept_cat_dom.
IPR029727. MME/CD10/NEP.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF163. PTHR11733:SF163. 1 hit.
PfamiView protein in Pfam
PF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
PRINTSiPR00786. NEPRILYSIN.
PROSITEiView protein in PROSITE
PS00142. ZINC_PROTEASE. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q61391-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA
60 70 80 90 100
TYDDGICKSS DCIKSAARLI QNMDASVEPC TDFFKYACGG WLKRNVIPET
110 120 130 140 150
SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCINESAID
160 170 180 190 200
SRGGQPLLKL LPDIYGWPVA SDNWDQTYGT SWTAEKSIAQ LNSKYGKKVL
210 220 230 240 250
INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
260 270 280 290 300
SVARLIRQEQ SLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY
310 320 330 340 350
NKMTLAKLQN NFSLEVNGKS 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
NYREDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR
560 570 580 590 600
NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
610 620 630 640 650
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFS 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):85,702
Last modified:January 23, 2007 - v3
Checksum:i1FC39A971D98F6FE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti230D → G in AAA37386 (PubMed:1374101).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81591 mRNA. Translation: AAA37386.1.
AK031446 mRNA. Translation: BAC27410.1.
AK033824 mRNA. Translation: BAC28487.1.
BC034092 mRNA. Translation: AAH34092.1.
BC066840 mRNA. Translation: AAH66840.1.
CCDSiCCDS17381.1.
RefSeqiNP_001276391.1. NM_001289462.1.
NP_001276392.1. NM_001289463.1.
NP_032630.2. NM_008604.4.
XP_006501158.1. XM_006501095.3.
XP_006501161.1. XM_006501098.3.
UniGeneiMm.296022.

Genome annotation databases

EnsembliENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.
ENSMUST00000194134; ENSMUSP00000142205; ENSMUSG00000027820.
ENSMUST00000194150; ENSMUSP00000141544; ENSMUSG00000027820.
GeneIDi17380.
KEGGimmu:17380.
UCSCiuc008pjp.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiNEP_MOUSE
AccessioniPrimary (citable) accession number: Q61391
Secondary accession number(s): Q6NXX5, Q8K251
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 156 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families