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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei103 – 1031Substrate carboxylBy similarity
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

  1. endopeptidase activity Source: MGI
  2. exopeptidase activity Source: MGI
  3. metalloendopeptidase activity Source: UniProtKB
  4. peptidase activity Source: MGI
  5. peptide binding Source: UniProtKB
  6. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. beta-amyloid metabolic process Source: MGI
  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: UniProtKB
  8. proteolysis Source: UniProtKB
  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_281604. Metabolism of Angiotensinogen to Angiotensins.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:97004. 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

  1. axon Source: MGI
  2. brush border Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. dendrite Source: MGI
  5. extracellular vesicular exosome Source: MGI
  6. focal adhesion Source: MGI
  7. integral component of membrane Source: UniProtKB-KW
  8. membrane Source: MGI
  9. neuron projection terminus Source: MGI
  10. plasma membrane Source: UniProtKB
  11. synapse Source: MGI
  12. synaptic vesicle Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 750749NeprilysinPRO_0000078214Add
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...)1 Publication
Glycosylationi211 – 2111N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi234 ↔ 242By similarity
Glycosylationi285 – 2851N-linked (GlcNAc...)1 Publication
Glycosylationi311 – 3111N-linked (GlcNAc...)1 Publication
Glycosylationi317 – 3171N-linked (GlcNAc...); atypical1 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

MaxQBiQ61391.
PaxDbiQ61391.
PRIDEiQ61391.

PTM databases

PhosphoSiteiQ61391.

Expressioni

Gene expression databases

BgeeiQ61391.
CleanExiMM_MME.
ExpressionAtlasiQ61391. baseline and differential.
GenevestigatoriQ61391.

Interactioni

Protein-protein interaction databases

BioGridi201441. 2 interactions.
IntActiQ61391. 3 interactions.
MINTiMINT-4103332.

Structurei

Secondary structure

1
750
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi9 – 124Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YVCX-ray3.20D/E/F2-23[»]
ProteinModelPortaliQ61391.
SMRiQ61391. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ61391.

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.
InParanoidiQ61391.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
PhylomeDBiQ61391.
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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti230 – 2301D → G in AAA37386 (PubMed:1374101).Curated

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_006501095.2.
XP_006501161.1. XM_006501098.2.
UniGeneiMm.296022.

Genome annotation databases

EnsembliENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.
ENSMUST00000194134; ENSMUSP00000142205; ENSMUSG00000027820.
ENSMUST00000194150; ENSMUSP00000141544; ENSMUSG00000027820.
GeneIDi17380.
KEGGimmu:17380.
UCSCiuc008pjp.1. mouse.

Cross-referencesi

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_006501095.2.
XP_006501161.1. XM_006501098.2.
UniGeneiMm.296022.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2YVCX-ray3.20D/E/F2-23[»]
ProteinModelPortaliQ61391.
SMRiQ61391. Positions 55-750.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201441. 2 interactions.
IntActiQ61391. 3 interactions.
MINTiMINT-4103332.

Chemistry

BindingDBiQ61391.
ChEMBLiCHEMBL2642.

Protein family/group databases

MEROPSiM13.001.

PTM databases

PhosphoSiteiQ61391.

Proteomic databases

MaxQBiQ61391.
PaxDbiQ61391.
PRIDEiQ61391.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.
ENSMUST00000194134; ENSMUSP00000142205; ENSMUSG00000027820.
ENSMUST00000194150; ENSMUSP00000141544; ENSMUSG00000027820.
GeneIDi17380.
KEGGimmu:17380.
UCSCiuc008pjp.1. mouse.

Organism-specific databases

CTDi4311.
MGIiMGI:97004. Mme.

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ61391.
KOiK01389.
OMAiLQNLMSW.
OrthoDBiEOG7PZRWQ.
PhylomeDBiQ61391.
TreeFamiTF315192.

Enzyme and pathway databases

ReactomeiREACT_281604. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

EvolutionaryTraceiQ61391.
NextBioi291980.
PROiQ61391.
SOURCEiSearch...

Gene expression databases

BgeeiQ61391.
CleanExiMM_MME.
ExpressionAtlasiQ61391. baseline and differential.
GenevestigatoriQ61391.

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. "Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase 24.11). Molecular characterization, chromosomal localization, and modeling of the active site."
    Chen C.Y., Salles G., Seldin M.F., Kister A.E., Reinher E.L., Shipp M.A.
    J. Immunol. 148:2817-2825(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Epididymis and Testis.
  3. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and FVB/N.
    Tissue: Embryonic germ cell and Mammary tumor.
  4. Lubec G., Sunyer B., Chen W.-Q.
    Submitted (DEC-2008) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 473-479, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: OF1.
    Tissue: Hippocampus.
  5. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
    Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
    Nat. Biotechnol. 27:378-386(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-145; ASN-285; ASN-311 AND ASN-317.
  6. "Neprilysin is identical to skin fibroblast elastase: its role in skin aging and UV responses."
    Morisaki N., Moriwaki S., Sugiyama-Nakagiri Y., Haketa K., Takema Y., Imokawa G.
    J. Biol. Chem. 285:39819-39827(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION AS SKIN FIBROBLAST ELASTASE, FUNCTION.

Entry informationi

Entry nameiNEP_MOUSE
AccessioniPrimary (citable) accession number: Q61391
Secondary accession number(s): Q6NXX5, Q8K251
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: April 1, 2015
This is version 139 of the entry and version 3 of the sequence. [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

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.