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P08473

- NEP_HUMAN

UniProt

P08473 - NEP_HUMAN

Protein

Neprilysin

Gene

MME

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 182 (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. Involved in the degradation of atrial natriuretic factor (ANF). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers.3 Publications

    Catalytic activityi

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

    Cofactori

    Binds 1 zinc ion per subunit.2 Publications

    Enzyme regulationi

    Inhibited in a dose dependent manner by opiorphin.

    Kineticsi

    1. KM=55.1 µM for angiotensin-11 Publication
    2. KM=179 µM for angiotensin-21 Publication
    3. KM=111.4 µM for angiotensin 1-91 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei103 – 1031Substrate carboxylBy similarity
    Metal bindingi584 – 5841Zinc; catalytic
    Metal bindingi588 – 5881Zinc; catalytic
    Active sitei591 – 5911
    Metal bindingi647 – 6471Zinc; catalytic
    Active sitei651 – 6511Proton donor1 PublicationPROSITE-ProRule annotation

    GO - Molecular functioni

    1. endopeptidase activity Source: UniProtKB
    2. metalloendopeptidase activity Source: UniProtKB
    3. peptide binding Source: UniProtKB
    4. protein binding Source: IntAct
    5. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. angiotensin maturation Source: Reactome
    2. beta-amyloid metabolic process Source: UniProtKB
    3. cellular protein metabolic process Source: Reactome
    4. cellular response to cytokine stimulus Source: UniProtKB
    5. cellular response to UV-A Source: UniProtKB
    6. cellular response to UV-B Source: UniProtKB
    7. creatinine metabolic process Source: UniProtKB
    8. kidney development Source: UniProtKB
    9. peptide metabolic process Source: UniProtKB
    10. proteolysis Source: UniProtKB
    11. replicative senescence Source: UniProtKB
    12. sensory perception of pain Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_147707. 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
    Common acute lymphocytic leukemia antigen
    Short name:
    CALLA
    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
    Synonyms:EPN
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:7154. MME.

    Subcellular locationi

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. brush border Source: UniProtKB
    3. cytoplasm Source: UniProtKB
    4. dendrite Source: UniProtKB
    5. extracellular vesicular exosome Source: UniProt
    6. integral component of membrane Source: UniProtKB
    7. integral component of plasma membrane Source: UniProtKB
    8. neuron projection terminus Source: UniProtKB
    9. plasma membrane Source: UniProtKB
    10. synapse Source: UniProtKB
    11. synaptic vesicle Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30864.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed
    Chaini2 – 750749NeprilysinPRO_0000078213Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycine1 Publication
    Disulfide bondi57 ↔ 62
    Disulfide bondi80 ↔ 735
    Disulfide bondi88 ↔ 695
    Disulfide bondi143 ↔ 411
    Glycosylationi145 – 1451N-linked (GlcNAc...)4 Publications
    Disulfide bondi234 ↔ 242
    Glycosylationi285 – 2851N-linked (GlcNAc...)1 Publication
    Glycosylationi325 – 3251N-linked (GlcNAc...)3 Publications
    Disulfide bondi621 ↔ 747
    Glycosylationi628 – 6281N-linked (GlcNAc...)4 Publications

    Post-translational modificationi

    Myristoylation is a determinant of membrane targeting.1 Publication
    Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.5 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Lipoprotein, Myristate

    Proteomic databases

    MaxQBiP08473.
    PaxDbiP08473.
    PeptideAtlasiP08473.
    PRIDEiP08473.

    PTM databases

    PhosphoSiteiP08473.

    Expressioni

    Gene expression databases

    ArrayExpressiP08473.
    BgeeiP08473.
    CleanExiHS_MME.
    GenevestigatoriP08473.

    Organism-specific databases

    HPAiCAB000013.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CD9P219266EBI-353759,EBI-4280101
    HSPA1BP081073EBI-353759,EBI-629985
    HSPB1P047924EBI-353759,EBI-352682

    Protein-protein interaction databases

    BioGridi110455. 77 interactions.
    IntActiP08473. 80 interactions.
    STRINGi9606.ENSP00000353679.

    Structurei

    Secondary structure

    1
    750
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi60 – 7213
    Turni79 – 813
    Helixi83 – 9412
    Beta strandi102 – 1054
    Helixi106 – 12217
    Helixi131 – 14414
    Helixi146 – 1516
    Turni152 – 1543
    Helixi155 – 1584
    Helixi161 – 1644
    Helixi168 – 1703
    Beta strandi171 – 1733
    Helixi174 – 1774
    Turni178 – 1814
    Helixi184 – 19512
    Beta strandi200 – 2089
    Beta strandi211 – 22010
    Beta strandi225 – 2284
    Helixi229 – 2335
    Helixi236 – 2383
    Helixi239 – 25921
    Helixi266 – 28621
    Helixi290 – 2923
    Helixi296 – 2994
    Beta strandi302 – 3043
    Helixi305 – 3117
    Beta strandi316 – 3194
    Helixi323 – 3319
    Helixi332 – 3343
    Beta strandi343 – 3475
    Helixi349 – 35911
    Helixi364 – 37916
    Helixi380 – 3823
    Helixi385 – 3895
    Helixi392 – 3998
    Helixi407 – 41812
    Helixi420 – 43112
    Helixi436 – 45419
    Helixi455 – 4573
    Beta strandi459 – 4613
    Helixi463 – 47412
    Beta strandi477 – 4815
    Helixi485 – 4884
    Helixi490 – 4967
    Turni497 – 4993
    Helixi507 – 52317
    Turni524 – 5274
    Beta strandi545 – 5473
    Turni548 – 5514
    Beta strandi552 – 5565
    Helixi557 – 5593
    Turni562 – 5643
    Beta strandi567 – 5693
    Helixi571 – 5766
    Helixi578 – 58710
    Helixi588 – 5903
    Turni592 – 5954
    Helixi609 – 62719
    Helixi632 – 6343
    Beta strandi636 – 6383
    Turni641 – 6444
    Helixi645 – 66925
    Helixi682 – 69211
    Beta strandi696 – 6983
    Helixi700 – 70910
    Helixi715 – 72410
    Helixi727 – 7326

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DL9model-A508-750[»]
    1DMTX-ray2.10A55-750[»]
    1QVDmodel-A55-750[»]
    1R1HX-ray1.95A55-750[»]
    1R1IX-ray2.60A55-750[»]
    1R1JX-ray2.35A55-750[»]
    1Y8JX-ray2.25A55-750[»]
    2QPJX-ray2.05A55-750[»]
    2YB9X-ray2.40A55-750[»]
    ProteinModelPortaliP08473.
    SMRiP08473. Positions 55-750.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08473.

    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.
    InParanoidiP08473.
    KOiK01389.
    OMAiVWCGTYR.
    OrthoDBiEOG7PZRWQ.
    PhylomeDBiP08473.
    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.

    P08473-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA    50
    TYDDGICKSS DCIKSAARLI QNMDATTEPC TDFFKYACGG WLKRNVIPET 100
    SSRYGNFDIL RDELEVVLKD VLQEPKTEDI VAVQKAKALY RSCINESAID 150
    SRGGEPLLKL LPDIYGWPVA TENWEQKYGA SWTAEKAIAQ LNSKYGKKVL 200
    INLFVGTDDK NSVNHVIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI 250
    SVARLIRQEE RLPIDENQLA LEMNKVMELE KEIANATAKP EDRNDPMLLY 300
    NKMTLAQIQN NFSLEINGKP FSWLNFTNEI MSTVNISITN EEDVVVYAPE 350
    YLTKLKPILT KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG 400
    TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV 450
    FIQTLDDLTW MDAETKKRAE EKALAIKERI GYPDDIVSND NKLNNEYLEL 500
    NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR 550
    NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD 600
    GDLVDWWTQQ SASNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA 650
    DNGGLGQAYR AYQNYIKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP 700
    EYAVNSIKTD VHSPGNFRII GTLQNSAEFS EAFHCRKNSY MNPEKKCRVW 750
    Length:750
    Mass (Da):85,514
    Last modified:January 23, 2007 - v2
    Checksum:iBCF3827C39898630
    GO

    Sequence cautioni

    The sequence CAA30157.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti26 – 261P → R in AAA51915. (PubMed:14702039)Curated
    Sequence conflicti44 – 441T → R in AAA51915. (PubMed:14702039)Curated
    Sequence conflicti81 – 811T → R in AAA51915. (PubMed:14702039)Curated
    Sequence conflicti304 – 3041T → R in AAA51915. (PubMed:14702039)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y00811 mRNA. Translation: CAA68752.1.
    J03779 mRNA. Translation: AAA51915.1.
    M26628
    , M26607, M26608, M26609, M26610, M26611, M26612, M26613, M26614, M26615, M26616, M26617, M26618, M26619, M26620, M26621, M26622, M26623, M26624, M26625, M26626, M26627 Genomic DNA. Translation: AAA52294.1.
    AK291761 mRNA. Translation: BAF84450.1.
    EU326307 Genomic DNA. Translation: ACA05913.1.
    CH471052 Genomic DNA. Translation: EAW78754.1.
    CH471052 Genomic DNA. Translation: EAW78755.1.
    CH471052 Genomic DNA. Translation: EAW78756.1.
    CH471052 Genomic DNA. Translation: EAW78757.1.
    CH471052 Genomic DNA. Translation: EAW78758.1.
    BC101632 mRNA. Translation: AAI01633.1.
    BC101658 mRNA. Translation: AAI01659.1.
    X07166 mRNA. Translation: CAA30157.1. Different initiation.
    CCDSiCCDS3172.1.
    PIRiA41387. HYHUN.
    RefSeqiNP_000893.2. NM_000902.3.
    NP_009218.2. NM_007287.2.
    NP_009219.2. NM_007288.2.
    NP_009220.2. NM_007289.2.
    XP_006713709.1. XM_006713646.1.
    XP_006713710.1. XM_006713647.1.
    UniGeneiHs.307734.

    Genome annotation databases

    EnsembliENST00000360490; ENSP00000353679; ENSG00000196549.
    ENST00000460393; ENSP00000418525; ENSG00000196549.
    ENST00000462745; ENSP00000419653; ENSG00000196549.
    ENST00000492661; ENSP00000420389; ENSG00000196549.
    ENST00000493237; ENSP00000417079; ENSG00000196549.
    GeneIDi4311.
    KEGGihsa:4311.
    UCSCiuc003fab.1. human.

    Polymorphism databases

    DMDMi128062.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y00811 mRNA. Translation: CAA68752.1 .
    J03779 mRNA. Translation: AAA51915.1 .
    M26628
    , M26607 , M26608 , M26609 , M26610 , M26611 , M26612 , M26613 , M26614 , M26615 , M26616 , M26617 , M26618 , M26619 , M26620 , M26621 , M26622 , M26623 , M26624 , M26625 , M26626 , M26627 Genomic DNA. Translation: AAA52294.1 .
    AK291761 mRNA. Translation: BAF84450.1 .
    EU326307 Genomic DNA. Translation: ACA05913.1 .
    CH471052 Genomic DNA. Translation: EAW78754.1 .
    CH471052 Genomic DNA. Translation: EAW78755.1 .
    CH471052 Genomic DNA. Translation: EAW78756.1 .
    CH471052 Genomic DNA. Translation: EAW78757.1 .
    CH471052 Genomic DNA. Translation: EAW78758.1 .
    BC101632 mRNA. Translation: AAI01633.1 .
    BC101658 mRNA. Translation: AAI01659.1 .
    X07166 mRNA. Translation: CAA30157.1 . Different initiation.
    CCDSi CCDS3172.1.
    PIRi A41387. HYHUN.
    RefSeqi NP_000893.2. NM_000902.3.
    NP_009218.2. NM_007287.2.
    NP_009219.2. NM_007288.2.
    NP_009220.2. NM_007289.2.
    XP_006713709.1. XM_006713646.1.
    XP_006713710.1. XM_006713647.1.
    UniGenei Hs.307734.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DL9 model - A 508-750 [» ]
    1DMT X-ray 2.10 A 55-750 [» ]
    1QVD model - A 55-750 [» ]
    1R1H X-ray 1.95 A 55-750 [» ]
    1R1I X-ray 2.60 A 55-750 [» ]
    1R1J X-ray 2.35 A 55-750 [» ]
    1Y8J X-ray 2.25 A 55-750 [» ]
    2QPJ X-ray 2.05 A 55-750 [» ]
    2YB9 X-ray 2.40 A 55-750 [» ]
    ProteinModelPortali P08473.
    SMRi P08473. Positions 55-750.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110455. 77 interactions.
    IntActi P08473. 80 interactions.
    STRINGi 9606.ENSP00000353679.

    Chemistry

    BindingDBi P08473.
    ChEMBLi CHEMBL1944.
    DrugBanki DB00616. Candoxatril.
    GuidetoPHARMACOLOGYi 1611.

    Protein family/group databases

    MEROPSi M13.001.

    PTM databases

    PhosphoSitei P08473.

    Polymorphism databases

    DMDMi 128062.

    Proteomic databases

    MaxQBi P08473.
    PaxDbi P08473.
    PeptideAtlasi P08473.
    PRIDEi P08473.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000360490 ; ENSP00000353679 ; ENSG00000196549 .
    ENST00000460393 ; ENSP00000418525 ; ENSG00000196549 .
    ENST00000462745 ; ENSP00000419653 ; ENSG00000196549 .
    ENST00000492661 ; ENSP00000420389 ; ENSG00000196549 .
    ENST00000493237 ; ENSP00000417079 ; ENSG00000196549 .
    GeneIDi 4311.
    KEGGi hsa:4311.
    UCSCi uc003fab.1. human.

    Organism-specific databases

    CTDi 4311.
    GeneCardsi GC03P154741.
    HGNCi HGNC:7154. MME.
    HPAi CAB000013.
    MIMi 120520. gene.
    neXtProti NX_P08473.
    PharmGKBi PA30864.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3590.
    HOGENOMi HOG000245574.
    HOVERGENi HBG005554.
    InParanoidi P08473.
    KOi K01389.
    OMAi VWCGTYR.
    OrthoDBi EOG7PZRWQ.
    PhylomeDBi P08473.
    TreeFami TF315192.

    Enzyme and pathway databases

    Reactomei REACT_147707. Metabolism of Angiotensinogen to Angiotensins.

    Miscellaneous databases

    EvolutionaryTracei P08473.
    GeneWikii Neprilysin.
    GenomeRNAii 4311.
    NextBioi 16959.
    PROi P08473.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08473.
    Bgeei P08473.
    CleanExi HS_MME.
    Genevestigatori P08473.

    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. "Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase."
      Letarte M., Vera S., Tran R., Addis J.B.L., Onizuka R.J., Quackenbush E.J., Jongeneel C.V., McInnes R.R.
      J. Exp. Med. 168:1247-1253(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Kidney.
    2. "Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein."
      Shipp M.A., Richardson N.E., Sayre P.H., Brown N.R., Masteller E.L., Clayton L.K., Ritz J., Reinherz E.L.
      Proc. Natl. Acad. Sci. U.S.A. 85:4819-4823(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions."
      D'Adamio L., Shipp M.A., Masteller E.L., Reinherz E.L.
      Proc. Natl. Acad. Sci. U.S.A. 86:7103-7107(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Placenta.
    5. NHLBI resequencing and genotyping service (RS&G)
      Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "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: Brain.
    8. "Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase)."
      Malfroy B., Kuang W.-J., Seeburg P.H., Mason A.J., Schofield P.R.
      FEBS Lett. 229:206-210(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-750.
      Tissue: Placenta.
    9. "Endopeptidase-24.11 in human plasma degrades atrial natriuretic factor (ANF) to ANF(99-105/106-126)."
      Yandle T.G., Brennan S.O., Espiner E.A., Nicholls M.G., Richards A.M.
      Peptides 10:891-894(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN THE DEGRADATION OF ANF.
    10. "Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11."
      Le Moual H., Dion N., Roques B.P., Crine P., Boileau G.
      Eur. J. Biochem. 221:475-480(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACTIVE SITE ASP-651.
    11. "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry."
      Zhang H., Li X.-J., Martin D.B., Aebersold R.
      Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-145 AND ASN-285.
    12. "Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism."
      Rice G.I., Thomas D.A., Grant P.J., Turner A.J., Hooper N.M.
      Biochem. J. 383:45-51(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ANGIOTENSIN PEPTIDE METABOLISM, BIOPHYSICOCHEMICAL PROPERTIES.
    13. "Human opiorphin, a natural antinociceptive modulator of opioid-dependent pathways."
      Wisner A., Dufour E., Messaoudi M., Nejdi A., Marcel A., Ungeheuer M.-N., Rougeot C.
      Proc. Natl. Acad. Sci. U.S.A. 103:17979-17984(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INHIBITION BY OPIORPHIN.
    14. "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.
    15. Cited for: MYRISTOYLATION AT GLY-2.
    16. "The human CD10 lacking an N-glycan at Asn(628) is deficient in surface expression and neutral endopeptidase activity."
      Sato B., Katagiri Y.U., Iijima K., Yamada H., Ito S., Kawasaki N., Okita H., Fujimoto J., Kiyokawa N.
      Biochim. Biophys. Acta 1820:1715-1723(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-628.
    17. "Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon."
      Oefner C., D'Arcy A., Hennig M., Winkler F.K., Dale G.E.
      J. Mol. Biol. 296:341-349(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), GLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.
    18. "Structural analysis of neprilysin with various specific and potent inhibitors."
      Oefner C., Roques B.P., Fournie-Zaluski M.-C., Dale G.E.
      Acta Crystallogr. D 60:392-396(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 55-750 IN COMPLEXES WITH ZINC IONS AND SYNTHETIC INHIBITORS, DISULFIDE BONDS, COFACTOR, GLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.
    19. "Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV."
      Oefner C., Pierau S., Schulz H., Dale G.E.
      Acta Crystallogr. D 63:975-981(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 55-750 IN COMPLEX WITH ZINC IONS AND THE SYNTHETIC INHIBITOR MCB3937, DISULFIDE BONDS, COFACTOR, GLYCOSYLATION AT ASN-145; ASN-325 AND ASN-628.

    Entry informationi

    Entry nameiNEP_HUMAN
    AccessioniPrimary (citable) accession number: P08473
    Secondary accession number(s): A8K6U6, D3DNJ9, Q3MIX4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 182 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3