Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q61391

- NEP_MOUSE

UniProt

Q61391 - NEP_MOUSE

Protein

Neprilysin

Gene

Mme

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 3 (23 Jan 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 similarity1 Publication

    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; 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. peptidase activity Source: MGI
    3. peptide binding Source: UniProtKB
    4. 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

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_196539. 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
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:97004. Mme.

    Subcellular locationi

    GO - Cellular componenti

    1. axon Source: MGI
    2. brush border Source: UniProtKB
    3. cytoplasm Source: UniProtKB
    4. dendrite Source: MGI
    5. integral component of membrane Source: UniProtKB-KW
    6. membrane Source: MGI
    7. neuron projection terminus Source: MGI
    8. plasma membrane Source: UniProtKB
    9. synapse Source: MGI
    10. synaptic vesicle Source: MGI

    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
    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

    Proteomic databases

    MaxQBiQ61391.
    PaxDbiQ61391.
    PRIDEiQ61391.

    PTM databases

    PhosphoSiteiQ61391.

    Expressioni

    Gene expression databases

    ArrayExpressiQ61391.
    BgeeiQ61391.
    CleanExiMM_MME.
    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 – 124

    3D structure databases

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

    Miscellaneous databases

    EvolutionaryTraceiQ61391.

    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.
    InParanoidiQ61391.
    KOiK01389.
    OMAiVWCGTYR.
    OrthoDBiEOG7PZRWQ.
    PhylomeDBiQ61391.
    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.

    Q61391-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGRSESQMDI TDINAPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA    50
    TYDDGICKSS DCIKSAARLI QNMDASVEPC TDFFKYACGG WLKRNVIPET 100
    SSRYSNFDIL RDELEVILKD VLQEPKTEDI VAVQKAKTLY RSCINESAID 150
    SRGGQPLLKL LPDIYGWPVA SDNWDQTYGT SWTAEKSIAQ LNSKYGKKVL 200
    INFFVGTDDK NSTQHIIHFD QPRLGLPSRD YYECTGIYKE ACTAYVDFMI 250
    SVARLIRQEQ SLPIDENQLS LEMNKVMELE KEIANATTKP EDRNDPMLLY 300
    NKMTLAKLQN NFSLEVNGKS FSWSNFTNEI MSTVNINIQN EEEVVVYAPE 350
    YLTKLKPILT KYSPRDLQNL MSWRFIMDLV SSLSRNYKES RNAFRKALYG 400
    TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV 450
    FIQTLDDLTW MDAETKKKAE EKALAIKERI GYPDDIISNE NKLNNEYLEL 500
    NYREDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR 550
    NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 600
    GDLVDWWTQQ SANNFKDQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA 650
    DNGGIGQAYR AYQNYVKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP 700
    EYAVNSIKTD VHSPGNFRII GTLQNSAEFA DAFHCRKNSY MNPERKCRVW 750
    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:
    EMBL
    GenBank
    DDBJ
    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_006501095.1.
    XP_006501161.1. XM_006501098.1.
    XP_006501162.1. XM_006501099.1.
    UniGeneiMm.296022.

    Genome annotation databases

    EnsembliENSMUST00000029400; ENSMUSP00000029400; ENSMUSG00000027820.
    GeneIDi17380.
    KEGGimmu:17380.
    UCSCiuc008pjp.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS17381.1.
    RefSeqi NP_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.
    UniGenei Mm.296022.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2YVC X-ray 3.20 D/E/F 2-23 [» ]
    ProteinModelPortali Q61391.
    SMRi Q61391. Positions 55-750.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201441. 2 interactions.
    IntActi Q61391. 3 interactions.
    MINTi MINT-4103332.

    Chemistry

    BindingDBi Q61391.
    ChEMBLi CHEMBL2642.

    Protein family/group databases

    MEROPSi M13.001.

    PTM databases

    PhosphoSitei Q61391.

    Proteomic databases

    MaxQBi Q61391.
    PaxDbi Q61391.
    PRIDEi Q61391.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000029400 ; ENSMUSP00000029400 ; ENSMUSG00000027820 .
    GeneIDi 17380.
    KEGGi mmu:17380.
    UCSCi uc008pjp.1. mouse.

    Organism-specific databases

    CTDi 4311.
    MGIi MGI:97004. Mme.

    Phylogenomic databases

    eggNOGi COG3590.
    GeneTreei ENSGT00650000093248.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.
    InParanoidi Q61391.
    KOi K01389.
    OMAi VWCGTYR.
    OrthoDBi EOG7PZRWQ.
    PhylomeDBi Q61391.
    TreeFami TF315192.

    Enzyme and pathway databases

    Reactomei REACT_196539. Metabolism of Angiotensinogen to Angiotensins.

    Miscellaneous databases

    EvolutionaryTracei Q61391.
    NextBioi 291980.
    PROi Q61391.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q61391.
    Bgeei Q61391.
    CleanExi MM_MME.
    Genevestigatori Q61391.

    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. "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.
      , 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.

    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: October 1, 2014
    This is version 133 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