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P07861

- NEP_RAT

UniProt

P07861 - NEP_RAT

Protein

Neprilysin

Gene

Mme

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 2 (23 Jan 2007)
      Previous versions | rss
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    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).By similarity

    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; 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. 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

    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

    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

    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
    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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini2 – 2827CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini52 – 750699ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei29 – 5123Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    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.
    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

    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: October 1, 2014
    This is version 134 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