NET1_MOUSE
ID NET1_MOUSE Reviewed; 604 AA.
AC O09118; B1ARR0; Q60832; Q9QY50;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Netrin-1;
DE Flags: Precursor;
GN Name=Ntn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Embryonic brain;
RX PubMed=8978605; DOI=10.1016/s0092-8674(00)81795-x;
RA Serafini T., Colamarino S.A., Leonardo E.D., Wang H., Beddington R.,
RA Skarnes W.C., Tessier-Lavigne M.;
RT "Netrin-1 is required for commissural axon guidance in the developing
RT vertebrate nervous system.";
RL Cell 87:1001-1014(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10381568; DOI=10.1016/s0925-4773(99)00035-0;
RA Pueschel A.W.;
RT "Divergent properties of mouse netrins.";
RL Mech. Dev. 83:65-75(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 352-398, AND SUBCELLULAR LOCATION.
RX PubMed=7604039; DOI=10.1073/pnas.92.14.6592;
RA Skarnes W.C., Moss J.E., Hurtley S.M., Beddington R.S.;
RT "Capturing genes encoding membrane and secreted proteins important for
RT mouse development.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:6592-6596(1995).
RN [7]
RP INTERACTION WITH DSCAM.
RX PubMed=18585357; DOI=10.1016/j.cell.2008.05.030;
RA Ly A., Nikolaev A., Suresh G., Zheng Y., Tessier-Lavigne M., Stein E.;
RT "DSCAM is a netrin receptor that collaborates with DCC in mediating turning
RT responses to netrin-1.";
RL Cell 133:1241-1254(2008).
RN [8]
RP INTERACTION WITH APP.
RX PubMed=27068745; DOI=10.1074/jbc.m115.698092;
RA Hashimoto Y., Toyama Y., Kusakari S., Nawa M., Matsuoka M.;
RT "An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor
RT Uncoordinated-5C-induced Signaling That Merges with Amyloid beta Precursor
RT Protein Signaling.";
RL J. Biol. Chem. 291:12282-12293(2016).
RN [9]
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 UNC5
CC receptors will lead to axon attraction or repulsion, respectively.
CC Binding to UNC5C might cause dissociation of UNC5C from polymerized
CC TUBB3 in microtubules and thereby lead to increased microtubule
CC dynamics and axon repulsion (PubMed:28483977). Involved in dorsal root
CC ganglion axon projection towards the spinal cord (PubMed:28483977). It
CC also serves as a survival factor via its association with its receptors
CC which prevent the initiation of apoptosis. Involved in colorectal
CC tumorigenesis by regulating apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:O95631, ECO:0000269|PubMed:10381568,
CC ECO:0000269|PubMed:28483977, ECO:0000269|PubMed:8978605}.
CC -!- SUBUNIT: Binds to its receptors; DCC, UNC5A, UNC5B, UNC5C and probably
CC UNC5D (By similarity). Binds to its receptor; DSCAM (PubMed:18585357).
CC Interacts with APP (PubMed:27068745). {ECO:0000250|UniProtKB:O95631,
CC ECO:0000269|PubMed:18585357, ECO:0000269|PubMed:27068745}.
CC -!- INTERACTION:
CC O09118; Q8K1S3-1: Unc5b; NbExp=4; IntAct=EBI-1798844, EBI-11658250;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7604039}. Cytoplasm
CC {ECO:0000250|UniProtKB:O95631}. Note=Mainly secreted.
CC {ECO:0000269|PubMed:7604039}.
CC -!- TISSUE SPECIFICITY: In the embryo, widely expressed in the developing
CC nervous system and in mesodermal tissues.
CC {ECO:0000269|PubMed:10381568}.
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DR EMBL; U65418; AAC52971.1; -; mRNA.
DR EMBL; AF128865; AAD28602.1; -; mRNA.
DR EMBL; AL606831; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662894; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669842; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466601; EDL10446.1; -; Genomic_DNA.
DR EMBL; BC141294; AAI41295.1; -; mRNA.
DR EMBL; U23505; AAA87938.1; -; mRNA.
DR CCDS; CCDS24864.1; -.
DR RefSeq; NP_032770.2; NM_008744.2.
DR PDB; 4OVE; X-ray; 2.64 A; A=23-457.
DR PDBsum; 4OVE; -.
DR AlphaFoldDB; O09118; -.
DR SMR; O09118; -.
DR BioGRID; 201866; 7.
DR IntAct; O09118; 4.
DR STRING; 10090.ENSMUSP00000104314; -.
DR GlyConnect; 2531; 1 N-Linked glycan (1 site).
DR GlyGen; O09118; 4 sites, 1 N-linked glycan (1 site).
DR PhosphoSitePlus; O09118; -.
DR MaxQB; O09118; -.
DR PaxDb; O09118; -.
DR PeptideAtlas; O09118; -.
DR PRIDE; O09118; -.
DR ProteomicsDB; 287480; -.
DR Antibodypedia; 24762; 359 antibodies from 41 providers.
DR DNASU; 18208; -.
DR Ensembl; ENSMUST00000021284; ENSMUSP00000021284; ENSMUSG00000020902.
DR Ensembl; ENSMUST00000108674; ENSMUSP00000104314; ENSMUSG00000020902.
DR GeneID; 18208; -.
DR KEGG; mmu:18208; -.
DR UCSC; uc007jnm.1; mouse.
DR CTD; 9423; -.
DR MGI; MGI:105088; Ntn1.
DR VEuPathDB; HostDB:ENSMUSG00000020902; -.
DR eggNOG; KOG3512; Eukaryota.
DR GeneTree; ENSGT00940000153882; -.
DR HOGENOM; CLU_018213_2_0_1; -.
DR InParanoid; O09118; -.
DR OMA; YFSQFSM; -.
DR OrthoDB; 858946at2759; -.
DR PhylomeDB; O09118; -.
DR TreeFam; TF352481; -.
DR Reactome; R-MMU-373752; Netrin-1 signaling.
DR Reactome; R-MMU-418885; DCC mediated attractive signaling.
DR BioGRID-ORCS; 18208; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ntn1; mouse.
DR PRO; PR:O09118; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O09118; protein.
DR Bgee; ENSMUSG00000020902; Expressed in brain white matter and 250 other tissues.
DR ExpressionAtlas; O09118; baseline and differential.
DR Genevisible; O09118; MM.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031012; C:extracellular matrix; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0033564; P:anterior/posterior axon guidance; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; IDA:MGI.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0019724; P:B cell mediated immunity; ISS:UniProtKB.
DR GO; GO:0042100; P:B cell proliferation; ISS:UniProtKB.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IGI:MGI.
DR GO; GO:0061643; P:chemorepulsion of axon; IDA:UniProtKB.
DR GO; GO:0016358; P:dendrite development; IBA:GO_Central.
DR GO; GO:0014009; P:glial cell proliferation; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0030879; P:mammary gland development; IGI:MGI.
DR GO; GO:0060603; P:mammary gland duct morphogenesis; IGI:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0097475; P:motor neuron migration; IMP:MGI.
DR GO; GO:0030517; P:negative regulation of axon extension; IDA:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0007097; P:nuclear migration; IDA:MGI.
DR GO; GO:0045773; P:positive regulation of axon extension; IDA:MGI.
DR GO; GO:2000147; P:positive regulation of cell motility; ISS:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IDA:MGI.
DR GO; GO:1903975; P:regulation of glial cell migration; IMP:MGI.
DR GO; GO:0051963; P:regulation of synapse assembly; IDA:SynGO.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; ISS:UniProtKB.
DR GO; GO:0002456; P:T cell mediated immunity; ISS:UniProtKB.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR CDD; cd00055; EGF_Lam; 3.
DR Gene3D; 2.40.50.120; -; 1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR008211; Laminin_N.
DR InterPro; IPR002049; LE_dom.
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; Cytoplasm; Disulfide bond; Glycoprotein;
KW Laminin EGF-like domain; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..604
FT /note="Netrin-1"
FT /id="PRO_0000017083"
FT DOMAIN 47..284
FT /note="Laminin N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00466"
FT DOMAIN 285..340
FT /note="Laminin EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 341..403
FT /note="Laminin EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 404..453
FT /note="Laminin EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00460"
FT DOMAIN 472..601
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT MOTIF 530..532
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 119..152
FT /evidence="ECO:0000250"
FT DISULFID 285..294
FT /evidence="ECO:0000250"
FT DISULFID 287..304
FT /evidence="ECO:0000250"
FT DISULFID 306..315
FT /evidence="ECO:0000250"
FT DISULFID 318..338
FT /evidence="ECO:0000250"
FT DISULFID 341..350
FT /evidence="ECO:0000250"
FT DISULFID 343..368
FT /evidence="ECO:0000250"
FT DISULFID 371..380
FT /evidence="ECO:0000250"
FT DISULFID 383..401
FT /evidence="ECO:0000250"
FT DISULFID 404..416
FT /evidence="ECO:0000250"
FT DISULFID 406..423
FT /evidence="ECO:0000250"
FT DISULFID 425..434
FT /evidence="ECO:0000250"
FT DISULFID 437..451
FT /evidence="ECO:0000250"
FT DISULFID 472..544
FT /evidence="ECO:0000250"
FT DISULFID 491..601
FT /evidence="ECO:0000250"
FT CONFLICT 24
FT /note="Missing (in Ref. 1; AAC52971)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="L -> V (in Ref. 1; AAC52971 and 2; AAD28602)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="V -> A (in Ref. 2; AAD28602)"
FT /evidence="ECO:0000305"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 132..153
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 157..166
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 227..234
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 236..241
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 243..253
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 275..285
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 312..315
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 348..352
FT /evidence="ECO:0007829|PDB:4OVE"
FT HELIX 354..359
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 366..370
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:4OVE"
FT TURN 431..434
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 441..443
FT /evidence="ECO:0007829|PDB:4OVE"
FT STRAND 451..453
FT /evidence="ECO:0007829|PDB:4OVE"
SQ SEQUENCE 604 AA; 67810 MW; 135120DB6F0482F3 CRC64;
MMRAVWEALA ALAAVACLVG AVRGGPGLSM FAGQAAQPDP CSDENGHPRR CIPDFVNAAF
GKDVRVSSTC GRPPARYCVV SERGEERLRS CHLCNSSDPK KAHPPAFLTD LNNPHNLTCW
QSENYLQFPH NVTLTLSLGK KFEVTYVSLQ FCSPRPESMA IYKSMDYGRT WVPFQFYSTQ
CRKMYNRPHR APITKQNEQE AVCTDSHTDM RPLSGGLIAF STLDGRPSAH DFDNSPVLQD
WVTATDIRVA FSRLHTFGDE NEDDSELARD SYYYAVSDLQ VGGRCKCNGH AARCVRDRDD
SLVCDCRHNT AGPECDRCKP FHYDRPWQRA TAREANECVA CNCNLHARRC RFNMELYKLS
GRKSGGVCLN CRHNTAGRHC HYCKEGFYRD MGKPITHRKA CKACDCHPVG AAGKTCNQTT
GQCPCKDGVT GITCNRCAKG YQQSRSPIAP CIKIPVAPPT TAASSVEEPE DCDSYCKASK
GKLKMNMKKY CRKDYAVQIH ILKADKAGDW WKFTVNIISV YKQGTSRIRR GDQSLWIRSR
DIACKCPKIK PLKKYLLLGN AEDSPDQSGI VADKSSLVIQ WRDTWARRLR KFQQREKKGK
CKKA
