ID O42140_DANRE Unreviewed; 603 AA.
AC O42140; A0A0R4IJU7; A0A0R4IX76;
DT 01-JAN-1998, integrated into UniProtKB/TrEMBL.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 193.
DE RecName: Full=Netrin-1 {ECO:0000256|ARBA:ARBA00015919};
GN Name=ntn1a {ECO:0000313|Ensembl:ENSDARP00000133934,
GN ECO:0000313|RefSeq:NP_571104.1, ECO:0000313|ZFIN:ZDB-GENE-990415-169};
GN Synonyms=net2 {ECO:0000313|RefSeq:NP_571104.1}, zgc:136732
GN {ECO:0000313|RefSeq:NP_571104.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000313|EMBL:CAP71961.1};
RN [1] {ECO:0000313|EMBL:AAC60252.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=9268507; DOI=10.1006/mcne.1997.0624;
RA Lauderdale J.D., Davis N.M., Kuwada J.Y.;
RT "Axon tracts correlate with netrin-1a expression in the zebrafish embryo.";
RL Mol. Cell. Neurosci. 9:293-313(1997).
RN [2] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=9675051;
RA Lauderdale J.D., Pasquali S.K., Fazel R., van Eeden F.J., Schauerte H.E.,
RA Haffter P., Kuwada J.Y.;
RT "Regulation of netrin-1a expression by hedgehog proteins.";
RL Mol. Cell. Neurosci. 11:194-205(1998).
RN [3] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=10207138;
RA Heisenberg C.P., Brennan C., Wilson S.W.;
RT "Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace
RT (fgf8) and coincident defects in CNS development.";
RL Development 126:2129-2140(1999).
RN [4] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=10331983;
RA Chandrasekhar A., Schauerte H.E., Haffter P., Kuwada J.Y.;
RT "The zebrafish detour gene is essential for cranial but not spinal motor
RT neuron induction.";
RL Development 126:2727-2737(1999).
RN [5] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=10027569;
RA Bernhardt R.R.;
RT "Cellular and molecular bases of axonal pathfinding during embryogenesis of
RT the fish central nervous system.";
RL J. Neurobiol. 38:137-160(1999).
RN [6] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=11180840; DOI=10.1007/s004270000073;
RA Shimeld S.;
RT "An amphioxus netrin gene is expressed in midline structures during
RT embryonic and larval development.";
RL Dev. Genes Evol. 210:337-344(2000).
RN [7] {ECO:0000313|EMBL:CAP71961.1}
RP NUCLEOTIDE SEQUENCE.
RA Martin S.and.Wright.G.J.;
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000313|Ensembl:ENSDARP00000133934, ECO:0000313|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000133934};
RX PubMed=23594743; DOI=10.1038/nature12111;
RG Genome Reference Consortium Zebrafish;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [9] {ECO:0000313|Ensembl:ENSDARP00000133934}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000133934};
RG Ensembl;
RL Submitted (NOV-2015) to UniProtKB.
RN [10] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=28392072;
RA Thomas-Jinu S., Gordon P.M., Fielding T., Taylor R., Smith B.N.,
RA Snowden V., Blanc E., Vance C., Topp S., Wong C.H., Bielen H.,
RA Williams K.L., McCann E.P., Nicholson G.A., Pan-Vazquez A., Fox A.H.,
RA Bond C.S., Talbot W.S., Blair I.P., Shaw C.E., Houart C.;
RT "Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts
RT Required for Normal Motor Development.";
RL Neuron 94:322-336(2017).
RN [11] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=28448525;
RA Miyake A., Mekata Y., Fujibayashi H., Nakanishi K., Konishi M., Itoh N.;
RT "Brorin is required for neurogenesis, gliogenesis, and commissural axon
RT guidance in the zebrafish forebrain.";
RL PLoS ONE 12:e0176036-e0176036(2017).
RN [12] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=29417095;
RA Eve A.M.J., Smith J.C.;
RT "Knockdown of Laminin gamma-3 (Lamc3) impairs motoneuron guidance in the
RT zebrafish embryo.";
RL Wellcome Open Res 2:111-111(2017).
RN [13] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=30695021;
RA Turner K.J., Hoyle J., Valdivia L.E., Cerveny K.L., Hart W., Mangoli M.,
RA Geisler R., Rees M., Houart C., Poole R.J., Wilson S.W., Gestri G.;
RT "Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure
RT of cells to transition from proliferation to differentiation, retinal
RT coloboma and midline axon guidance deficits.";
RL PLoS ONE 14:e0211073-e0211073(2019).
RN [14] {ECO:0000313|RefSeq:NP_571104.1}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RX PubMed=30733552;
RA Richardson R., Owen N., Toms M., Young R.M., Tracey-White D., Moosajee M.;
RT "Transcriptome profiling of zebrafish optic fissure fusion.";
RL Sci. Rep. 9:1541-1541(2019).
RN [15] {ECO:0000313|RefSeq:NP_571104.1}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_571104.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- INTERACTION:
CC O42140; A0A0R4IP15: cb333; NbExp=2; IntAct=EBI-42472993, EBI-42471190;
CC O42140; Q4V9H3: draxin; NbExp=3; IntAct=EBI-42472993, EBI-42473401;
CC O42140; E7F6E8: si:dkey-1c11.1; NbExp=2; IntAct=EBI-42472993, EBI-42473772;
CC O42140; A9JR35: unc5h2; NbExp=2; IntAct=EBI-42472993, EBI-2462791;
CC O42140; Q49BB0: zdcc; NbExp=2; IntAct=EBI-42472993, EBI-42472945;
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|PROSITE-ProRule:PRU00460}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL928622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX255899; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF002717; AAC60252.1; -; mRNA.
DR EMBL; CU638812; CAP71961.1; -; mRNA.
DR RefSeq; NP_571104.1; NM_131029.2.
DR IntAct; O42140; 7.
DR STRING; 7955.ENSDARP00000133934; -.
DR PaxDb; 7955-ENSDARP00000124060; -.
DR Ensembl; ENSDART00000157527.2; ENSDARP00000133934.1; ENSDARG00000105112.2.
DR Ensembl; ENSDART00000168882.2; ENSDARP00000141078.1; ENSDARG00000111684.1.
DR GeneID; 30227; -.
DR KEGG; dre:30227; -.
DR AGR; ZFIN:ZDB-GENE-990415-169; -.
DR CTD; 30227; -.
DR ZFIN; ZDB-GENE-990415-169; ntn1a.
DR eggNOG; KOG3512; Eukaryota.
DR HOGENOM; CLU_018213_2_0_1; -.
DR OMA; NSCVACN; -.
DR OrthoDB; 2916807at2759; -.
DR TreeFam; TF352481; -.
DR Proteomes; UP000000437; Alternate scaffold 6.
DR Proteomes; UP000000437; Chromosome 6.
DR Bgee; ENSDARG00000105112; Expressed in swim bladder and 16 other cell types or tissues.
DR GO; GO:0005604; C:basement membrane; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0021960; P:anterior commissure morphogenesis; IMP:ZFIN.
DR GO; GO:0033564; P:anterior/posterior axon guidance; IMP:ZFIN.
DR GO; GO:0048846; P:axon extension involved in axon guidance; IMP:ZFIN.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IGI:ZFIN.
DR GO; GO:0061386; P:closure of optic fissure; IMP:ZFIN.
DR GO; GO:0016358; P:dendrite development; IGI:ZFIN.
DR GO; GO:0003146; P:heart jogging; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:ZFIN.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:ZFIN.
DR GO; GO:0048665; P:neuron fate specification; IMP:ZFIN.
DR GO; GO:0071678; P:olfactory bulb axon guidance; IMP:ZFIN.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IMP:ZFIN.
DR GO; GO:0030516; P:regulation of axon extension; IGI:ZFIN.
DR GO; GO:0030878; P:thyroid gland development; IMP:ZFIN.
DR GO; GO:0009888; P:tissue development; IBA:GO_Central.
DR GO; GO:0001944; P:vasculature development; IMP:ZFIN.
DR GO; GO:0035908; P:ventral aorta development; IMP:ZFIN.
DR CDD; cd00055; EGF_Lam; 3.
DR CDD; cd03579; NTR_netrin-1_like; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 2.10.25.10; Laminin; 2.
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 PANTHER; PTHR10574:SF435; LAMININ SUBUNIT GAMMA-1; 1.
DR PANTHER; PTHR10574; NETRIN/LAMININ-RELATED; 1.
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; SSF57196; EGF/Laminin; 3.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF50242; TIMP-like; 1.
DR PROSITE; PS01248; EGF_LAM_1; 1.
DR PROSITE; PS50027; EGF_LAM_2; 2.
DR PROSITE; PS51117; LAMININ_NTER; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157, ECO:0000256|PROSITE-
KW ProRule:PRU00460};
KW Laminin EGF-like domain {ECO:0000256|ARBA:ARBA00023292,
KW ECO:0000256|PROSITE-ProRule:PRU00460};
KW Reference proteome {ECO:0000313|Proteomes:UP000000437};
KW Secreted {ECO:0000256|ARBA:ARBA00022525};
KW Signal {ECO:0000256|SAM:SignalP, ECO:0000313|RefSeq:NP_571104.1}.
FT SIGNAL 1..23
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 24..603
FT /note="Netrin-1"
FT /evidence="ECO:0000256|SAM:SignalP,
FT ECO:0000313|RefSeq:NP_571104.1"
FT /id="PRO_5035035729"
FT DOMAIN 46..283
FT /note="Laminin N-terminal"
FT /evidence="ECO:0000259|PROSITE:PS51117"
FT DOMAIN 284..339
FT /note="Laminin EGF-like"
FT /evidence="ECO:0000259|PROSITE:PS50027"
FT DOMAIN 403..452
FT /note="Laminin EGF-like"
FT /evidence="ECO:0000259|PROSITE:PS50027"
FT DOMAIN 471..600
FT /note="NTR"
FT /evidence="ECO:0000259|PROSITE:PS50189"
FT DISULFID 286..303
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
FT DISULFID 305..314
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
FT DISULFID 403..415
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
FT DISULFID 405..422
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
FT DISULFID 424..433
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
FT DISULFID 436..450
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU00460"
SQ SEQUENCE 603 AA; 67681 MW; 82EDB32E3E383F37 CRC64;
MLRVSDALVT LVTLCCVLKG TVGGYGMSMF AAQTSPPDPC YDENGHPRRC IPDFVNAAFG
KEVRASSTCG KTPSRYCVVT EKGDERHRNC HTCDASDPKK NHPPAYLTDL NNPHNLTCWQ
SDNYLQYPQN VTLTLSLGKK FEVTYVSLQF CSPRPESMAI FKSMDYGKSW VPFQYYSTQC
RKMYNKPSKA TITKQNEQEA ICTDSHTDMH PLSGGLIAFS TLDGRPSAHD FDNSPVLQDW
VTATDIKVTF SRLHTFGDEN EDDSELARDS YFYAVSDLQV GGRCKCNGHA SRCVKDRDGN
LVCECKHNTA GPECDRCKPF HYDRPWQRAT AREANECVAC NCNLHARRCR FNMELYKLSG
RKSGGVCLNC RHNTAGRHCH YCKEGYYRDM SKPISHRKAC KACDCHPVGA AGKTCNQTTG
QCPCKDGVTG ITCNRCANGY QQSRSPIAPC IKIPIAPPTT TASSTEEPSD CESYCKASKG
KLKINMKKYC KKDYAVQVHI LKADKAGEWW KFTVNIISVY KQGESRIRRG DQFLWVRAKD
VACKCPKIKS GKKYLLLGND EDSPGQSGMV ADKGSLVIQW RDTWARRLRK FQQREKKGKC
KKA
//