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O95631

- NET1_HUMAN

UniProt

O95631 - NET1_HUMAN

Protein

Netrin-1

Gene

NTN1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (05 May 2009)
      Previous versions | rss
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    Functioni

    Netrins control guidance of CNS commissural axons and peripheral motor axons. Its association with either DCC or some UNC5 receptors will lead to axon attraction or repulsion, respectively. It also serve as a survival factor via its association with its receptors which prevent the initiation of apoptosis. Involved in tumorigenesis by regulating apoptosis.1 Publication

    GO - Molecular functioni

    1. protein binding Source: UniProtKB

    GO - Biological processi

    1. anterior/posterior axon guidance Source: Ensembl
    2. apoptotic process Source: UniProtKB-KW
    3. axon guidance Source: Reactome
    4. establishment of nucleus localization Source: Ensembl
    5. inner ear morphogenesis Source: Ensembl
    6. mammary gland duct morphogenesis Source: Ensembl
    7. negative regulation of axon extension Source: Ensembl
    8. neuron migration Source: Ensembl
    9. positive regulation of axon extension Source: Ensembl
    10. positive regulation of cell proliferation Source: Ensembl
    11. regulation of cell migration Source: Ensembl
    12. single organismal cell-cell adhesion Source: Ensembl

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    ReactomeiREACT_22228. Role of second messengers in netrin-1 signaling.
    REACT_22237. Netrin-1 signaling.
    REACT_22351. DCC mediated attractive signaling.
    REACT_22384. Netrin mediated repulsion signals.
    REACT_25299. DSCAM interactions.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Netrin-1
    Alternative name(s):
    Epididymis tissue protein Li 131P
    Gene namesi
    Name:NTN1
    Synonyms:NTN1L
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:8029. NTN1.

    Subcellular locationi

    GO - Cellular componenti

    1. basement membrane Source: Ensembl
    2. cytoplasm Source: Ensembl
    3. extracellular region Source: Reactome

    Keywords - Cellular componenti

    Extracellular matrix, Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31813.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Chaini25 – 604580Netrin-1PRO_0000017082Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi95 – 951N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi119 ↔ 152By similarity
    Glycosylationi131 – 1311N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi285 ↔ 294By similarity
    Disulfide bondi287 ↔ 304By similarity
    Disulfide bondi306 ↔ 315By similarity
    Disulfide bondi318 ↔ 338By similarity
    Disulfide bondi341 ↔ 350By similarity
    Disulfide bondi343 ↔ 368By similarity
    Disulfide bondi371 ↔ 380By similarity
    Disulfide bondi383 ↔ 401By similarity
    Disulfide bondi404 ↔ 416By similarity
    Disulfide bondi406 ↔ 423By similarity
    Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi425 ↔ 434By similarity
    Disulfide bondi437 ↔ 451By similarity
    Disulfide bondi472 ↔ 544By similarity
    Disulfide bondi491 ↔ 601By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiO95631.
    PaxDbiO95631.
    PRIDEiO95631.

    PTM databases

    PhosphoSiteiO95631.

    Expressioni

    Tissue specificityi

    Widely expressed in normal adult tissues with highest levels in heart, small intestine, colon, liver and prostate. Reduced expression in brain tumors and neuroblastomas. Expressed in epididymis (at protein level).2 Publications

    Gene expression databases

    ArrayExpressiO95631.
    BgeeiO95631.
    CleanExiHS_NTN1.
    GenevestigatoriO95631.

    Organism-specific databases

    HPAiHPA056419.

    Interactioni

    Subunit structurei

    Binds to its receptors; DCC, DSCAM, UNC5A, UNC5B, UNC5C and probably UNC5D.

    Protein-protein interaction databases

    BioGridi114816. 2 interactions.
    DIPiDIP-46273N.
    IntActiO95631. 1 interaction.
    STRINGi9606.ENSP00000173229.

    Structurei

    3D structure databases

    ProteinModelPortaliO95631.
    SMRiO95631. Positions 41-446.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini47 – 284238Laminin N-terminalPROSITE-ProRule annotationAdd
    BLAST
    Domaini285 – 34056Laminin EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini341 – 40363Laminin EGF-like 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini404 – 45350Laminin EGF-like 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini472 – 601130NTRPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi530 – 5323Cell attachment siteSequence Analysis

    Sequence similaritiesi

    Contains 3 laminin EGF-like domains.PROSITE-ProRule annotation
    Contains 1 laminin N-terminal domain.PROSITE-ProRule annotation
    Contains 1 NTR domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Laminin EGF-like domain, Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG244580.
    HOGENOMiHOG000286017.
    HOVERGENiHBG006464.
    InParanoidiO95631.
    KOiK06843.
    OMAiDSYYYAV.
    OrthoDBiEOG7SR4KJ.
    PhylomeDBiO95631.
    TreeFamiTF352481.

    Family and domain databases

    Gene3Di2.60.120.260. 1 hit.
    InterProiIPR013032. EGF-like_CS.
    IPR002049. EGF_laminin.
    IPR008979. Galactose-bd-like.
    IPR008211. Laminin_N.
    IPR001134. Netrin_domain.
    IPR018933. Netrin_module_non-TIMP.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view]
    PfamiPF00053. Laminin_EGF. 3 hits.
    PF00055. Laminin_N. 1 hit.
    PF01759. NTR. 1 hit.
    [Graphical view]
    SMARTiSM00643. C345C. 1 hit.
    SM00180. EGF_Lam. 3 hits.
    SM00136. LamNT. 1 hit.
    [Graphical view]
    SUPFAMiSSF49785. SSF49785. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEiPS00022. EGF_1. 2 hits.
    PS01248. EGF_LAM_1. 3 hits.
    PS50027. EGF_LAM_2. 3 hits.
    PS51117. LAMININ_NTER. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O95631-1 [UniParc]FASTAAdd to Basket

    « Hide

    MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR    50
    CIPDFVNAAF GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNASDPK 100
    KAHPPAFLTD LNNPHNLTCW QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ 150
    FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ CRKMYNRPHR APITKQNEQE 200
    AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD WVTATDIRVA 250
    FSRLHTFGDE NEDDSELARD SYFYAVSDLQ VGGRCKCNGH AARCVRDRDD 300
    SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC 350
    RFNMELYKLS GRKSGGVCLN CRHNTAGRHC HYCKEGYYRD MGKPITHRKA 400
    CKACDCHPVG AAGKTCNQTT GQCPCKDGVT GITCNRCAKG YQQSRSPIAP 450
    CIKIPVAPPT TAASSVEEPE DCDSYCKASK GKLKINMKKY CKKDYAVQIH 500
    ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR DIACKCPKIK 550
    PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK 600
    CKKA 604
    Length:604
    Mass (Da):67,748
    Last modified:May 5, 2009 - v2
    Checksum:i9827C09D0D783B27
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti299 – 2991D → T in AAD09221. (PubMed:9950216)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti351 – 3511R → H in a neuroblastoma sample. 1 Publication
    VAR_014279
    Natural varianti489 – 4891K → E in a neuroblastoma sample. 1 Publication
    VAR_014280

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U75586 mRNA. Translation: AAD09221.1.
    GU727649 mRNA. Translation: ADU87650.1.
    AC090610 Genomic DNA. No translation available.
    AC005695 Genomic DNA. No translation available.
    CCDSiCCDS11148.1.
    RefSeqiNP_004813.2. NM_004822.2.
    XP_006721658.1. XM_006721595.1.
    UniGeneiHs.660885.

    Genome annotation databases

    EnsembliENST00000173229; ENSP00000173229; ENSG00000065320.
    GeneIDi9423.
    KEGGihsa:9423.
    UCSCiuc002glw.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U75586 mRNA. Translation: AAD09221.1 .
    GU727649 mRNA. Translation: ADU87650.1 .
    AC090610 Genomic DNA. No translation available.
    AC005695 Genomic DNA. No translation available.
    CCDSi CCDS11148.1.
    RefSeqi NP_004813.2. NM_004822.2.
    XP_006721658.1. XM_006721595.1.
    UniGenei Hs.660885.

    3D structure databases

    ProteinModelPortali O95631.
    SMRi O95631. Positions 41-446.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114816. 2 interactions.
    DIPi DIP-46273N.
    IntActi O95631. 1 interaction.
    STRINGi 9606.ENSP00000173229.

    PTM databases

    PhosphoSitei O95631.

    Proteomic databases

    MaxQBi O95631.
    PaxDbi O95631.
    PRIDEi O95631.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000173229 ; ENSP00000173229 ; ENSG00000065320 .
    GeneIDi 9423.
    KEGGi hsa:9423.
    UCSCi uc002glw.4. human.

    Organism-specific databases

    CTDi 9423.
    GeneCardsi GC17P008924.
    H-InvDB HIX0039241.
    HGNCi HGNC:8029. NTN1.
    HPAi HPA056419.
    MIMi 601614. gene.
    neXtProti NX_O95631.
    PharmGKBi PA31813.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG244580.
    HOGENOMi HOG000286017.
    HOVERGENi HBG006464.
    InParanoidi O95631.
    KOi K06843.
    OMAi DSYYYAV.
    OrthoDBi EOG7SR4KJ.
    PhylomeDBi O95631.
    TreeFami TF352481.

    Enzyme and pathway databases

    Reactomei REACT_22228. Role of second messengers in netrin-1 signaling.
    REACT_22237. Netrin-1 signaling.
    REACT_22351. DCC mediated attractive signaling.
    REACT_22384. Netrin mediated repulsion signals.
    REACT_25299. DSCAM interactions.

    Miscellaneous databases

    GeneWikii NTN1.
    GenomeRNAii 9423.
    NextBioi 35298.
    PROi O95631.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95631.
    Bgeei O95631.
    CleanExi HS_NTN1.
    Genevestigatori O95631.

    Family and domain databases

    Gene3Di 2.60.120.260. 1 hit.
    InterProi IPR013032. EGF-like_CS.
    IPR002049. EGF_laminin.
    IPR008979. Galactose-bd-like.
    IPR008211. Laminin_N.
    IPR001134. Netrin_domain.
    IPR018933. Netrin_module_non-TIMP.
    IPR008993. TIMP-like_OB-fold.
    [Graphical view ]
    Pfami PF00053. Laminin_EGF. 3 hits.
    PF00055. Laminin_N. 1 hit.
    PF01759. NTR. 1 hit.
    [Graphical view ]
    SMARTi SM00643. C345C. 1 hit.
    SM00180. EGF_Lam. 3 hits.
    SM00136. LamNT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49785. SSF49785. 1 hit.
    SSF50242. SSF50242. 1 hit.
    PROSITEi PS00022. EGF_1. 2 hits.
    PS01248. EGF_LAM_1. 3 hits.
    PS50027. EGF_LAM_2. 3 hits.
    PS51117. LAMININ_NTER. 1 hit.
    PS50189. NTR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas."
      Meyerhardt J.A., Caca K., Eckstrand B.C., Hu G., Lengauer C., Banavali S., Look A.T., Fearon E.R.
      Cell Growth Differ. 10:35-42(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DCC, TISSUE SPECIFICITY, VARIANTS HIS-351 AND GLU-489.
      Tissue: Brain stem and Liver.
    2. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
      Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
      , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
      Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins."
      Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W., Zhang C., Jin S., Liu J., Zhu P., Liu Y.
      Mol. Cell. Proteomics 9:2517-2528(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Tissue: Epididymis.
    4. "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis."
      Mazelin L., Bernet A., Bonod-Bidaud C., Pays L., Arnaud S., Gespach C., Bredesen D.E., Scoazec J.-Y., Mehlen P.
      Nature 431:80-84(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "DSCAM functions as a netrin receptor in commissural axon pathfinding."
      Liu G., Li W., Wang L., Kar A., Guan K.L., Rao Y., Wu J.Y.
      Proc. Natl. Acad. Sci. U.S.A. 106:2951-2956(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DSCAM.

    Entry informationi

    Entry nameiNET1_HUMAN
    AccessioniPrimary (citable) accession number: O95631
    Secondary accession number(s): E9KL51
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 15, 2002
    Last sequence update: May 5, 2009
    Last modified: October 1, 2014
    This is version 120 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3