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P08049

- NEP_RABIT

UniProt

P08049 - NEP_RABIT

Protein

Neprilysin

Gene

MME

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (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 By similarity. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers By similarity.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.

    Sites

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

    GO - Molecular functioni

    1. metalloendopeptidase activity Source: UniProtKB
    2. peptide binding Source: UniProtKB
    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: UniProtKB
    8. proteolysis Source: UniProtKB
    9. replicative senescence Source: UniProtKB
    10. sensory perception of pain Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    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
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    ProteomesiUP000001811: Unplaced

    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. neuron projection terminus Source: UniProtKB
    7. plasma membrane Source: UniProtKB
    8. synapse Source: UniProtKB
    9. 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_0000078216Add
    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
    Disulfide bondi234 ↔ 242By similarity
    Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi311 – 3111N-linked (GlcNAc...)By similarity
    Glycosylationi325 – 3251N-linked (GlcNAc...)By similarity
    Disulfide bondi621 ↔ 747By similarity
    Glycosylationi628 – 6281N-linked (GlcNAc...)

    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

    Interactioni

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000021723.

    Structurei

    3D structure databases

    ProteinModelPortaliP08049.
    SMRiP08049. 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.
    HOGENOMiHOG000245574.
    HOVERGENiHBG005554.

    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.

    P08049-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGRSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTV IAVTMIALYA    50
    TYDDGICKSS DCIKSAARLI QNMDATAEPC TDFFKYACGG WLKRNVIPET 100
    SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCVNETAID 150
    SRGGQPLLKL LPDVYGWPVA TQNWEQTYGT SWSAEKSIAQ LNSNYGKKVL 200
    INFFVGTDDK NSMNHIIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI 250
    AVAKLIRQEE GLPIDENQIS VEMNKVMELE KEIANATTKS EDRNDPMLLY 300
    NKMTLAQIQN NFSLEINGKP FSWSNFTNEI MSTVNINIPN EEDVVVYAPE 350
    YLIKLKPILT KYFPRDFQNL FSWRFIMDLV SSLSRTYKDS RNAFRKALYG 400
    TTSESATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV 450
    FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIVSND NKLNNEYLEL 500
    NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWITGAA IVNAFYSSGR 550
    NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 600
    GDLVDWWTQQ SANNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA 650
    DNGGIGQAYR AYQNYVKKNG EEKLLPGIDL NHKQLFFLNF AQVWCGTYRP 700
    EYAVNSIKTD VHSPGNFRII GSLQNSVEFS EAFQCPKNSY MNPEKKCRVW 750
    Length:750
    Mass (Da):85,582
    Last modified:January 23, 2007 - v2
    Checksum:i0F26AF7316BB9D12
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X05338 mRNA. Translation: CAA28950.1.
    M16593 mRNA. Translation: AAA53694.1.
    PIRiA29451. HYRBN.
    RefSeqiNP_001095155.1. NM_001101685.1.
    UniGeneiOcu.2011.

    Genome annotation databases

    GeneIDi100009251.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X05338 mRNA. Translation: CAA28950.1 .
    M16593 mRNA. Translation: AAA53694.1 .
    PIRi A29451. HYRBN.
    RefSeqi NP_001095155.1. NM_001101685.1.
    UniGenei Ocu.2011.

    3D structure databases

    ProteinModelPortali P08049.
    SMRi P08049. Positions 55-750.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9986.ENSOCUP00000021723.

    Chemistry

    BindingDBi P08049.
    ChEMBLi CHEMBL3768.

    Protein family/group databases

    MEROPSi M13.001.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100009251.

    Organism-specific databases

    CTDi 4311.

    Phylogenomic databases

    eggNOGi COG3590.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.

    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. "Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA."
      Devault A., Lazure C., Nault C., le Moual H., Seidah N.G., Chretien M., Kahn P., Powell J., Mallet J., Beaumont A., Roques B.P., Crine P., Boileau G.
      EMBO J. 6:1317-1322(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Kidney.
    2. "An antibody purified with a lambda GT11 fusion protein precipitates enkephalinase activity."
      Kahn P.H., Powell J.F., Beaumont A., Roques B.P., Mallet J.J.
      Biochem. Biophys. Res. Commun. 145:488-493(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 206-274.
    3. "Exploration of the catalytic site of endopeptidase 24.11 by site-directed mutagenesis. Histidine residues 583 and 587 are essential for catalysis."
      Devault A., Sales V., Nault C., Beaumont A., Roques B., Crine P., Boileau G.
      FEBS Lett. 231:54-58(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS.

    Entry informationi

    Entry nameiNEP_RABIT
    AccessioniPrimary (citable) accession number: P08049
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 117 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