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Q61391 (NEP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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 By similarity. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers. Ref.6

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit.

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 term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-amyloid metabolic process

Inferred from direct assay PubMed 12074840. Source: MGI

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 sequence or structural similarity. Source: UniProtKB

proteolysis

Inferred from sequence or structural similarity. Source: UniProtKB

replicative senescence

Inferred from sequence or structural similarity. Source: UniProtKB

sensory perception of pain

Inferred from mutant phenotype PubMed 9751784. Source: UniProtKB

   Cellular_componentaxon

Inferred from direct assay PubMed 12074840. Source: MGI

brush border

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 12074840. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 15944124. Source: MGI

neuron projection terminus

Inferred from direct assay PubMed 12074840. Source: MGI

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from direct assay PubMed 12074840. Source: MGI

synaptic vesicle

Inferred from direct assay PubMed 12074840. Source: MGI

   Molecular_functionmetalloendopeptidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

peptidase activity

Inferred from direct assay PubMed 15944124. Source: MGI

peptide binding

Inferred from sequence or structural similarity. Source: UniProtKB

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 By similarity
Chain2 – 750749Neprilysin
PRO_0000078214

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 By similarity

Amino acid modifications

Lipidation21N-myristoyl glycine By similarity
Glycosylation1451N-linked (GlcNAc...) Ref.5
Glycosylation2111N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Ref.5
Glycosylation3111N-linked (GlcNAc...) Ref.5
Glycosylation3171N-linked (GlcNAc...); atypical Ref.5
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

Experimental info

Sequence conflict2301D → G in AAA37386. Ref.1

Secondary structure

... 750
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q61391 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 1FC39A971D98F6FE

FASTA75085,702
        10         20         30         40         50         60 
MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA TYDDGICKSS 

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

       130        140        150        160        170        180 
VLQEPKTEDI VAVQKAKTLY RSCINESAID SRGGQPLLKL LPDIYGWPVA SDNWDQTYGT 

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

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

       310        320        330        340        350        360 
NKMTLAKLQN NFSLEVNGKS 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 NYREDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA 

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

       610        620        630        640        650        660 
GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFS 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]"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(1992) [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. expand/collapse author list , 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(2005) [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(2004) [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 (JAN-2009) 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(2009) [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(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS SKIN FIBROBLAST ELASTASE, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17381.1.
RefSeqNP_001276391.1. NM_001289462.1.
NP_001276392.1. NM_001289463.1.
NP_032630.2. NM_008604.4.
XP_006501158.1. XM_006501095.1.
XP_006501161.1. XM_006501098.1.
XP_006501162.1. XM_006501099.1.
UniGeneMm.296022.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2YVCX-ray3.20D/E/F2-23[»]
ProteinModelPortalQ61391.
SMRQ61391. Positions 55-750.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201441. 2 interactions.
IntActQ61391. 3 interactions.
MINTMINT-4103332.

Chemistry

BindingDBQ61391.
ChEMBLCHEMBL2642.

Protein family/group databases

MEROPSM13.001.

PTM databases

PhosphoSiteQ61391.

Proteomic databases

MaxQBQ61391.
PaxDbQ61391.
PRIDEQ61391.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.
GeneID17380.
KEGGmmu:17380.
UCSCuc008pjp.1. mouse.

Organism-specific databases

CTD4311.
MGIMGI:97004. Mme.

Phylogenomic databases

eggNOGCOG3590.
GeneTreeENSGT00650000093248.
HOGENOMHOG000245574.
HOVERGENHBG005554.
InParanoidQ61391.
KOK01389.
OMAVWCGTYR.
OrthoDBEOG7PZRWQ.
PhylomeDBQ61391.
TreeFamTF315192.

Gene expression databases

ArrayExpressQ61391.
BgeeQ61391.
CleanExMM_MME.
GenevestigatorQ61391.

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

EvolutionaryTraceQ61391.
NextBio291980.
PROQ61391.
SOURCESearch...

Entry information

Entry nameNEP_MOUSE
AccessionPrimary (citable) accession number: Q61391
Secondary accession number(s): Q6NXX5, Q8K251
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 131 of the entry and version 3 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot