GenomeNet

Database: UniProt
Entry: O95631
LinkDB: O95631
Original site: O95631 
ID   NET1_HUMAN              Reviewed;         604 AA.
AC   O95631; E9KL51;
DT   15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   05-MAY-2009, sequence version 2.
DT   10-APR-2019, entry version 159.
DE   RecName: Full=Netrin-1;
DE   AltName: Full=Epididymis tissue protein Li 131P;
DE   Flags: Precursor;
GN   Name=NTN1; Synonyms=NTN1L;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DCC, TISSUE SPECIFICITY,
RP   AND VARIANTS HIS-351 AND GLU-489.
RC   TISSUE=Brain stem, and Liver;
RX   PubMed=9950216;
RA   Meyerhardt J.A., Caca K., Eckstrand B.C., Hu G., Lengauer C.,
RA   Banavali S., Look A.T., Fearon E.R.;
RT   "Netrin-1: interaction with deleted in colorectal cancer (DCC) and
RT   alterations in brain tumors and neuroblastomas.";
RL   Cell Growth Differ. 10:35-42(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA   Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA   Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA   Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA   Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA   Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA   Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA   Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT   the human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Epididymis;
RX   PubMed=20736409; DOI=10.1074/mcp.M110.001719;
RA   Li J., Liu F., Wang H., Liu X., Liu J., Li N., Wan F., Wang W.,
RA   Zhang C., Jin S., Liu J., Zhu P., Liu Y.;
RT   "Systematic mapping and functional analysis of a family of human
RT   epididymal secretory sperm-located proteins.";
RL   Mol. Cell. Proteomics 9:2517-2528(2010).
RN   [4]
RP   FUNCTION.
RX   PubMed=15343335; DOI=10.1038/nature02788;
RA   Mazelin L., Bernet A., Bonod-Bidaud C., Pays L., Arnaud S.,
RA   Gespach C., Bredesen D.E., Scoazec J.-Y., Mehlen P.;
RT   "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.";
RL   Nature 431:80-84(2004).
RN   [5]
RP   INTERACTION WITH DSCAM.
RX   PubMed=19196994; DOI=10.1073/pnas.0811083106;
RA   Liu G., Li W., Wang L., Kar A., Guan K.L., Rao Y., Wu J.Y.;
RT   "DSCAM functions as a netrin receptor in commissural axon
RT   pathfinding.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:2951-2956(2009).
RN   [6]
RP   FUNCTION.
RX   PubMed=28483977; DOI=10.1523/JNEUROSCI.2617-16.2017;
RA   Shao Q., Yang T., Huang H., Alarmanazi F., Liu G.;
RT   "Uncoupling of UNC5C with Polymerized TUBB3 in Microtubules Mediates
RT   Netrin-1 Repulsion.";
RL   J. Neurosci. 37:5620-5633(2017).
CC   -!- FUNCTION: Netrins control guidance of CNS commissural axons and
CC       peripheral motor axons. Its association with either DCC or some
CC       UNC5 receptors will lead to axon attraction or repulsion,
CC       respectively. Binding to UNC5C might cause dissociation of UNC5C
CC       from polymerized TUBB3 in microtubules and thereby lead to
CC       increased microtubule dynamics and axon repulsion
CC       (PubMed:28483977). Involved in dorsal root ganglion axon
CC       projection towards the spinal cord (PubMed:28483977). It also
CC       serves as a survival factor via its association with its receptors
CC       which prevent the initiation of apoptosis. Involved in
CC       tumorigenesis by regulating apoptosis (PubMed:15343335).
CC       {ECO:0000269|PubMed:15343335, ECO:0000269|PubMed:28483977}.
CC   -!- SUBUNIT: Binds to its receptors; DCC, UNC5A, UNC5B, UNC5C and
CC       probably UNC5D (PubMed:9950216). Binds to its receptor; DSCAM
CC       (PubMed:19196994). Interacts with APP (By similarity).
CC       {ECO:0000250|UniProtKB:O09118, ECO:0000269|PubMed:19196994,
CC       ECO:0000269|PubMed:9950216, ECO:0000303|PubMed:9950216}.
CC   -!- INTERACTION:
CC       P43146:DCC; NbExp=4; IntAct=EBI-2678626, EBI-1222919;
CC       Q8NBI3:DRAXIN; NbExp=3; IntAct=EBI-2678626, EBI-10827752;
CC       Q8IZJ1-2:UNC5B; NbExp=2; IntAct=EBI-2678626, EBI-10832046;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250|UniProtKB:O09118}.
CC   -!- TISSUE SPECIFICITY: Widely expressed in normal adult tissues with
CC       highest levels in heart, small intestine, colon, liver and
CC       prostate. Reduced expression in brain tumors and neuroblastomas.
CC       Expressed in epididymis (at protein level).
CC       {ECO:0000269|PubMed:20736409, ECO:0000269|PubMed:9950216}.
DR   EMBL; U75586; AAD09221.1; -; mRNA.
DR   EMBL; GU727649; ADU87650.1; -; mRNA.
DR   EMBL; AC090610; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC005695; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS11148.1; -.
DR   RefSeq; NP_004813.2; NM_004822.2.
DR   RefSeq; XP_006721658.1; XM_006721595.3.
DR   UniGene; Hs.660885; -.
DR   PDB; 4URT; X-ray; 3.10 A; A=39-453.
DR   PDB; 6FKQ; X-ray; 3.07 A; A=39-453.
DR   PDBsum; 4URT; -.
DR   PDBsum; 6FKQ; -.
DR   ProteinModelPortal; O95631; -.
DR   SMR; O95631; -.
DR   BioGrid; 114816; 6.
DR   DIP; DIP-46273N; -.
DR   IntAct; O95631; 7.
DR   STRING; 9606.ENSP00000173229; -.
DR   GlyConnect; 1542; -.
DR   iPTMnet; O95631; -.
DR   PhosphoSitePlus; O95631; -.
DR   BioMuta; NTN1; -.
DR   jPOST; O95631; -.
DR   MaxQB; O95631; -.
DR   PaxDb; O95631; -.
DR   PeptideAtlas; O95631; -.
DR   PRIDE; O95631; -.
DR   ProteomicsDB; 50967; -.
DR   Ensembl; ENST00000173229; ENSP00000173229; ENSG00000065320.
DR   GeneID; 9423; -.
DR   KEGG; hsa:9423; -.
DR   UCSC; uc002glw.4; human.
DR   CTD; 9423; -.
DR   DisGeNET; 9423; -.
DR   EuPathDB; HostDB:ENSG00000065320.8; -.
DR   GeneCards; NTN1; -.
DR   H-InvDB; HIX0039241; -.
DR   HGNC; HGNC:8029; NTN1.
DR   HPA; HPA056419; -.
DR   MalaCards; NTN1; -.
DR   MIM; 601614; gene.
DR   neXtProt; NX_O95631; -.
DR   OpenTargets; ENSG00000065320; -.
DR   Orphanet; 238722; Familial congenital mirror movements.
DR   PharmGKB; PA31813; -.
DR   eggNOG; KOG3512; Eukaryota.
DR   eggNOG; ENOG410XS7U; LUCA.
DR   GeneTree; ENSGT00940000153882; -.
DR   HOGENOM; HOG000286017; -.
DR   HOVERGEN; HBG006464; -.
DR   InParanoid; O95631; -.
DR   KO; K06843; -.
DR   OMA; DQFLWVR; -.
DR   OrthoDB; 858946at2759; -.
DR   PhylomeDB; O95631; -.
DR   TreeFam; TF352481; -.
DR   Reactome; R-HSA-373752; Netrin-1 signaling.
DR   Reactome; R-HSA-376172; DSCAM interactions.
DR   Reactome; R-HSA-418885; DCC mediated attractive signaling.
DR   Reactome; R-HSA-418886; Netrin mediated repulsion signals.
DR   Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling.
DR   Reactome; R-HSA-428542; Regulation of commissural axon pathfinding by SLIT and ROBO.
DR   SIGNOR; O95631; -.
DR   ChiTaRS; NTN1; human.
DR   GeneWiki; NTN1; -.
DR   GenomeRNAi; 9423; -.
DR   PRO; PR:O95631; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   Bgee; ENSG00000065320; Expressed in 168 organ(s), highest expression level in lower esophagus.
DR   ExpressionAtlas; O95631; baseline and differential.
DR   Genevisible; O95631; HS.
DR   GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0033564; P:anterior/posterior axon guidance; IEA:Ensembl.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0032488; P:Cdc42 protein signal transduction; ISS:UniProtKB.
DR   GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR   GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR   GO; GO:0060603; P:mammary gland duct morphogenesis; IEA:Ensembl.
DR   GO; GO:0030517; P:negative regulation of axon extension; IEA:Ensembl.
DR   GO; GO:1902842; P:negative regulation of netrin-activated signaling pathway; TAS:Reactome.
DR   GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR   GO; GO:0007097; P:nuclear migration; IEA:Ensembl.
DR   GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR   GO; GO:2000147; P:positive regulation of cell motility; ISS:UniProtKB.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
DR   GO; GO:0051963; P:regulation of synapse assembly; IEA:Ensembl.
DR   GO; GO:0006930; P:substrate-dependent cell migration, cell extension; ISS:UniProtKB.
DR   Gene3D; 2.60.120.1490; -; 1.
DR   InterPro; IPR008979; Galactose-bd-like_sf.
DR   InterPro; IPR002049; Laminin_EGF.
DR   InterPro; IPR008211; Laminin_N.
DR   InterPro; IPR038684; Laminin_N_sf.
DR   InterPro; IPR001134; Netrin_domain.
DR   InterPro; IPR018933; Netrin_module_non-TIMP.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   Pfam; PF00053; Laminin_EGF; 3.
DR   Pfam; PF00055; Laminin_N; 1.
DR   Pfam; PF01759; NTR; 1.
DR   SMART; SM00643; C345C; 1.
DR   SMART; SM00180; EGF_Lam; 3.
DR   SMART; SM00136; LamNT; 1.
DR   SUPFAM; SSF49785; SSF49785; 1.
DR   SUPFAM; SSF50242; SSF50242; 1.
DR   PROSITE; PS00022; EGF_1; 2.
DR   PROSITE; PS01248; EGF_LAM_1; 3.
DR   PROSITE; PS50027; EGF_LAM_2; 3.
DR   PROSITE; PS51117; LAMININ_NTER; 1.
DR   PROSITE; PS50189; NTR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Apoptosis; Complete proteome; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Laminin EGF-like domain;
KW   Polymorphism; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL        1     24       {ECO:0000255}.
FT   CHAIN        25    604       Netrin-1.
FT                                /FTId=PRO_0000017082.
FT   DOMAIN       47    284       Laminin N-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00466}.
FT   DOMAIN      285    340       Laminin EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00460}.
FT   DOMAIN      341    403       Laminin EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00460}.
FT   DOMAIN      404    453       Laminin EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00460}.
FT   DOMAIN      472    601       NTR. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00295}.
FT   MOTIF       530    532       Cell attachment site. {ECO:0000255}.
FT   CARBOHYD     95     95       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    116    116       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    131    131       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    417    417       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    119    152       {ECO:0000250}.
FT   DISULFID    285    294       {ECO:0000250}.
FT   DISULFID    287    304       {ECO:0000250}.
FT   DISULFID    306    315       {ECO:0000250}.
FT   DISULFID    318    338       {ECO:0000250}.
FT   DISULFID    341    350       {ECO:0000250}.
FT   DISULFID    343    368       {ECO:0000250}.
FT   DISULFID    371    380       {ECO:0000250}.
FT   DISULFID    383    401       {ECO:0000250}.
FT   DISULFID    404    416       {ECO:0000250}.
FT   DISULFID    406    423       {ECO:0000250}.
FT   DISULFID    425    434       {ECO:0000250}.
FT   DISULFID    437    451       {ECO:0000250}.
FT   DISULFID    472    544       {ECO:0000250}.
FT   DISULFID    491    601       {ECO:0000250}.
FT   VARIANT     351    351       R -> H (in a neuroblastoma sample;
FT                                dbSNP:rs531668666).
FT                                {ECO:0000269|PubMed:9950216}.
FT                                /FTId=VAR_014279.
FT   VARIANT     489    489       K -> E (in a neuroblastoma sample).
FT                                {ECO:0000269|PubMed:9950216}.
FT                                /FTId=VAR_014280.
FT   CONFLICT    299    299       D -> T (in Ref. 1; AAD09221).
FT                                {ECO:0000305}.
FT   STRAND       44     46       {ECO:0000244|PDB:6FKQ}.
FT   TURN         58     61       {ECO:0000244|PDB:6FKQ}.
FT   STRAND       65     67       {ECO:0000244|PDB:6FKQ}.
FT   STRAND       75     83       {ECO:0000244|PDB:6FKQ}.
FT   STRAND       86     94       {ECO:0000244|PDB:6FKQ}.
FT   HELIX        99    101       {ECO:0000244|PDB:6FKQ}.
FT   HELIX       106    109       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      132    153       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      156    166       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      172    179       {ECO:0000244|PDB:6FKQ}.
FT   HELIX       181    185       {ECO:0000244|PDB:6FKQ}.
FT   HELIX       197    199       {ECO:0000244|PDB:4URT}.
FT   STRAND      202    204       {ECO:0000244|PDB:4URT}.
FT   STRAND      212    215       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      217    221       {ECO:0000244|PDB:6FKQ}.
FT   TURN        222    225       {ECO:0000244|PDB:4URT}.
FT   HELIX       232    234       {ECO:0000244|PDB:6FKQ}.
FT   HELIX       236    241       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      243    254       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      257    259       {ECO:0000244|PDB:4URT}.
FT   HELIX       265    269       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      275    285       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      292    296       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      302    305       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      310    312       {ECO:0000244|PDB:6FKQ}.
FT   TURN        344    346       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      350    352       {ECO:0000244|PDB:6FKQ}.
FT   HELIX       354    359       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      366    368       {ECO:0000244|PDB:6FKQ}.
FT   TURN        372    374       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      375    380       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      387    389       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      391    393       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      401    403       {ECO:0000244|PDB:6FKQ}.
FT   TURN        408    410       {ECO:0000244|PDB:6FKQ}.
FT   TURN        418    420       {ECO:0000244|PDB:6FKQ}.
FT   TURN        431    434       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      447    449       {ECO:0000244|PDB:6FKQ}.
FT   STRAND      451    453       {ECO:0000244|PDB:4URT}.
SQ   SEQUENCE   604 AA;  67748 MW;  9827C09D0D783B27 CRC64;
     MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR CIPDFVNAAF
     GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNASDPK KAHPPAFLTD LNNPHNLTCW
     QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ
     CRKMYNRPHR APITKQNEQE AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD
     WVTATDIRVA FSRLHTFGDE NEDDSELARD SYFYAVSDLQ VGGRCKCNGH AARCVRDRDD
     SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC RFNMELYKLS
     GRKSGGVCLN CRHNTAGRHC HYCKEGYYRD MGKPITHRKA CKACDCHPVG AAGKTCNQTT
     GQCPCKDGVT GITCNRCAKG YQQSRSPIAP CIKIPVAPPT TAASSVEEPE DCDSYCKASK
     GKLKINMKKY CKKDYAVQIH ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR
     DIACKCPKIK PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK
     CKKA
//
DBGET integrated database retrieval system