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Protein

Neprilysin

Gene

MME

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) (PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).5 Publications

Catalytic activityi

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.2 Publications

Cofactori

Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit.2 Publications

Enzyme regulationi

Inhibited in a dose dependent manner by opiorphin.1 Publication

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
    Active sitei585 – 5851
    Metal bindingi588 – 5881Zinc; catalytic
    Metal bindingi647 – 6471Zinc; catalytic
    Active sitei651 – 6511Proton donorPROSITE-ProRule annotation1 Publication

    GO - Molecular functioni

    • endopeptidase activity Source: UniProtKB
    • exopeptidase activity Source: BHF-UCL
    • metalloendopeptidase activity Source: UniProtKB
    • peptide binding Source: UniProtKB
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    • angiotensin maturation Source: Reactome
    • beta-amyloid metabolic process Source: UniProtKB
    • cellular protein metabolic process Source: Reactome
    • cellular response to cytokine stimulus Source: UniProtKB
    • cellular response to UV-A Source: UniProtKB
    • cellular response to UV-B Source: UniProtKB
    • creatinine metabolic process Source: UniProtKB
    • kidney development Source: UniProtKB
    • peptide metabolic process Source: UniProtKB
    • proteolysis Source: UniProtKB
    • replicative senescence Source: UniProtKB
    • sensory perception of pain Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.24.11. 2681.
    ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.

    Protein family/group databases

    MEROPSiM13.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Neprilysin (EC:3.4.24.112 Publications)
    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 Componenti: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:7154. MME.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini2 – 2827CytoplasmicSequence AnalysisAdd
    BLAST
    Transmembranei29 – 5123Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST
    Topological domaini52 – 750699ExtracellularSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • axon Source: UniProtKB
    • brush border Source: UniProtKB
    • cytoplasm Source: UniProtKB
    • dendrite Source: UniProtKB
    • extracellular exosome Source: UniProtKB
    • focal adhesion Source: UniProtKB
    • integral component of membrane Source: UniProtKB
    • integral component of plasma membrane Source: UniProtKB
    • neuron projection terminus Source: UniProtKB
    • plasma membrane Source: UniProtKB
    • synapse Source: UniProtKB
    • synaptic vesicle Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA30864.

    Chemistry

    DrugBankiDB00616. Candoxatril.
    DB06655. Liraglutide.

    Polymorphism and mutation databases

    BioMutaiMME.
    DMDMi128062.

    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
    Modified residuei4 – 41Phosphoserine1 Publication
    Modified residuei6 – 61Phosphoserine1 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, Phosphoprotein

    Proteomic databases

    MaxQBiP08473.
    PaxDbiP08473.
    PeptideAtlasiP08473.
    PRIDEiP08473.

    PTM databases

    PhosphoSiteiP08473.

    Expressioni

    Gene expression databases

    BgeeiP08473.
    CleanExiHS_MME.
    ExpressionAtlasiP08473. baseline and differential.
    GenevisibleiP08473. HS.

    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. 76 interactions.
    IntActiP08473. 80 interactions.
    STRINGi9606.ENSP00000353679.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    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[»]
    4CTHX-ray2.15A52-750[»]
    ProteinModelPortaliP08473.
    SMRiP08473. Positions 55-750.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08473.

    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.
    GeneTreeiENSGT00760000119162.
    HOGENOMiHOG000245574.
    HOVERGENiHBG005554.
    InParanoidiP08473.
    KOiK01389.
    OMAiSTNHIIH.
    OrthoDBiEOG7PZRWQ.
    PhylomeDBiP08473.
    TreeFamiTF315192.

    Family and domain databases

    Gene3Di3.40.390.10. 2 hits.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR029727. MME/CD10/NEP.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view]
    PANTHERiPTHR11733. PTHR11733. 1 hit.
    PTHR11733:SF114. PTHR11733:SF114. 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

            10         20         30         40         50
    MGKSESQMDI TDINTPKPKK KQRWTPLEIS LSVLVLLLTI IAVTMIALYA
    60 70 80 90 100
    TYDDGICKSS DCIKSAARLI QNMDATTEPC TDFFKYACGG WLKRNVIPET
    110 120 130 140 150
    SSRYGNFDIL RDELEVVLKD VLQEPKTEDI VAVQKAKALY RSCINESAID
    160 170 180 190 200
    SRGGEPLLKL LPDIYGWPVA TENWEQKYGA SWTAEKAIAQ LNSKYGKKVL
    210 220 230 240 250
    INLFVGTDDK NSVNHVIHID QPRLGLPSRD YYECTGIYKE ACTAYVDFMI
    260 270 280 290 300
    SVARLIRQEE RLPIDENQLA LEMNKVMELE KEIANATAKP EDRNDPMLLY
    310 320 330 340 350
    NKMTLAQIQN NFSLEINGKP FSWLNFTNEI MSTVNISITN EEDVVVYAPE
    360 370 380 390 400
    YLTKLKPILT KYSARDLQNL MSWRFIMDLV SSLSRTYKES RNAFRKALYG
    410 420 430 440 450
    TTSETATWRR CANYVNGNME NAVGRLYVEA AFAGESKHVV EDLIAQIREV
    460 470 480 490 500
    FIQTLDDLTW MDAETKKRAE EKALAIKERI GYPDDIVSND NKLNNEYLEL
    510 520 530 540 550
    NYKEDEYFEN IIQNLKFSQS KQLKKLREKV DKDEWISGAA VVNAFYSSGR
    560 570 580 590 600
    NQIVFPAGIL QPPFFSAQQS NSLNYGGIGM VIGHEITHGF DDNGRNFNKD
    610 620 630 640 650
    GDLVDWWTQQ SASNFKEQSQ CMVYQYGNFS WDLAGGQHLN GINTLGENIA
    660 670 680 690 700
    DNGGLGQAYR AYQNYIKKNG EEKLLPGLDL NHKQLFFLNF AQVWCGTYRP
    710 720 730 740 750
    EYAVNSIKTD VHSPGNFRII GTLQNSAEFS EAFHCRKNSY MNPEKKCRVW
    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. Curated

    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:
    EMBLi
    GenBanki
    DDBJi
    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_006713646.2.
    XP_006713710.1. XM_006713647.2.
    XP_011511157.1. XM_011512855.1.
    XP_011511158.1. XM_011512856.1.
    XP_011511159.1. XM_011512857.1.
    XP_011511160.1. XM_011512858.1.
    UniGeneiHs.307734.

    Genome annotation databases

    EnsembliENST00000360490; ENSP00000353679; ENSG00000196549.
    ENST00000460393; ENSP00000418525; ENSG00000196549.
    ENST00000462745; ENSP00000419653; ENSG00000196549.
    ENST00000492661; ENSP00000420389; ENSG00000196549.
    ENST00000493237; ENSP00000417079; ENSG00000196549.
    ENST00000615825; ENSP00000478173; ENSG00000196549.
    GeneIDi4311.
    KEGGihsa:4311.
    UCSCiuc003fab.1. human.

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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_006713646.2.
    XP_006713710.1. XM_006713647.2.
    XP_011511157.1. XM_011512855.1.
    XP_011511158.1. XM_011512856.1.
    XP_011511159.1. XM_011512857.1.
    XP_011511160.1. XM_011512858.1.
    UniGeneiHs.307734.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    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[»]
    4CTHX-ray2.15A52-750[»]
    ProteinModelPortaliP08473.
    SMRiP08473. Positions 55-750.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi110455. 76 interactions.
    IntActiP08473. 80 interactions.
    STRINGi9606.ENSP00000353679.

    Chemistry

    ChEMBLiCHEMBL1944.
    DrugBankiDB00616. Candoxatril.
    DB06655. Liraglutide.
    GuidetoPHARMACOLOGYi1611.

    Protein family/group databases

    MEROPSiM13.001.

    PTM databases

    PhosphoSiteiP08473.

    Polymorphism and mutation databases

    BioMutaiMME.
    DMDMi128062.

    Proteomic databases

    MaxQBiP08473.
    PaxDbiP08473.
    PeptideAtlasiP08473.
    PRIDEiP08473.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000360490; ENSP00000353679; ENSG00000196549.
    ENST00000460393; ENSP00000418525; ENSG00000196549.
    ENST00000462745; ENSP00000419653; ENSG00000196549.
    ENST00000492661; ENSP00000420389; ENSG00000196549.
    ENST00000493237; ENSP00000417079; ENSG00000196549.
    ENST00000615825; ENSP00000478173; ENSG00000196549.
    GeneIDi4311.
    KEGGihsa:4311.
    UCSCiuc003fab.1. human.

    Organism-specific databases

    CTDi4311.
    GeneCardsiGC03P154741.
    HGNCiHGNC:7154. MME.
    HPAiCAB000013.
    MIMi120520. gene.
    neXtProtiNX_P08473.
    PharmGKBiPA30864.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG3590.
    GeneTreeiENSGT00760000119162.
    HOGENOMiHOG000245574.
    HOVERGENiHBG005554.
    InParanoidiP08473.
    KOiK01389.
    OMAiSTNHIIH.
    OrthoDBiEOG7PZRWQ.
    PhylomeDBiP08473.
    TreeFamiTF315192.

    Enzyme and pathway databases

    BRENDAi3.4.24.11. 2681.
    ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.

    Miscellaneous databases

    ChiTaRSiMME. human.
    EvolutionaryTraceiP08473.
    GeneWikiiNeprilysin.
    GenomeRNAii4311.
    NextBioi16959.
    PROiP08473.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP08473.
    CleanExiHS_MME.
    ExpressionAtlasiP08473. baseline and differential.
    GenevisibleiP08473. HS.

    Family and domain databases

    Gene3Di3.40.390.10. 2 hits.
    InterProiIPR024079. MetalloPept_cat_dom.
    IPR029727. MME/CD10/NEP.
    IPR000718. Peptidase_M13.
    IPR018497. Peptidase_M13_C.
    IPR008753. Peptidase_M13_N.
    [Graphical view]
    PANTHERiPTHR11733. PTHR11733. 1 hit.
    PTHR11733:SF114. PTHR11733:SF114. 1 hit.
    PfamiPF01431. Peptidase_M13. 1 hit.
    PF05649. Peptidase_M13_N. 1 hit.
    [Graphical view]
    PRINTSiPR00786. NEPRILYSIN.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    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. "Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site."
      Vanneste Y., Michel A., Dimaline R., Najdovski T., Deschodt-Lanckman M.
      Biochem. J. 254:531-537(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "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.
    11. "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, CATALYTIC ACTIVITY.
    12. "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.
    13. "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, CATALYTIC ACTIVITY.
    14. "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: FUNCTION, INHIBITION BY OPIORPHIN.
    15. "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.
    16. Cited for: MYRISTOYLATION AT GLY-2.
    17. "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.
    18. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4 AND SER-6, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    19. "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.
    20. "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.
    21. "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: July 22, 2015
    This is version 192 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.