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Roundabout-like protein 4.


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GeneName robo4
Aliases ENSDARG:ENSDARG00000009387; wu:fa16f09, roundabout homolog 4
Description Roundabout-like protein 4.
GenomicLocation Chromosome 10: 26,698,496-26,734,116 forward strand
ExternalIDs Entrez:560765; EMBL:AF538326; UniGene:75958; ZFIN:ZDB-GENE-020809-1;
TranscriptID ENSDART:ENSDART00000145562; ENSDART:ENSDART00000123267; ENSDART:ENSDART00000004127
mRNA NCBI:XM_684163.5;
GeneDescription Roundabouts (Robos)4 are class of neural guidance receptors that bind to the slit family of guidance cues and primarily mediate axon repulsion signals. Outside the nervous system, slit-robo signaling has been implicated in inhibition of leukocyte migration, kidney induction , and vascular system.
GeneFunction Campbell et al. (2007) through a combination of genetic and in vivo imaging showed that Slit-Robo signaling plays a role in inhibiting arborization in vivo in the vertebrate CNS. Their study shows an inhibitory role for Slit-Robo signaling and shows that in this system slit1a mediates some of its affects on arborization and synaptogenesis independently of robo2.Kaur et al. (2006) demonstrated that on gain of function of robo4, Robo4 activates Cdc42 and Rac1 Rho GTPases in endothelial cells. In addition, robo4 knockdown embryos in vivo display lower amounts of active Cdc42 and Rac1, and angioblasts isolated ex vivo from robo4 knockdown transgenic zebrafish embryos (endothelial specific promoter driving GFP) search actively for directional guidance cues. Cdc42DN blocks Robo4-induced filopodia, as well as cell adhesion and migration, which suggests an important role for Cdc42 and Rac1 activation in Robo4-mediated signaling events. Overall, this study implies Rho GTPases in Robo4-mediated attractive vascular guidance.Barresi et al. (2005) found that in the vertebrate forebrain, Slit-Robo-mediated repulsion is crucial for the appropriate dorsoventral position of the optic chiasm (Rasband et al., 2003). They proposed a model in which slit1a expressed by a glial bridge provides a substrate for axon crossing at the midline, whereas slit2 and slit3 repulsion helps to channel growth cones into commissures.Bedell et al. (2005) demonstrated that roundabout4 is essential for angiogenesis in vivo.
GeneCloning The gene is contained in two BAC clones CH211-164N21 (Vector: pTARBAC2.1) and DKEY-30J19 (Vector: pIndigoBAC-536).
GeneStructure This gene encodes 3 transcripts.Transcript (ENSDART00000004127), which consists of 19 exons and is 3282 bps in length. The protein product (ENSDARP00000006793) consists of 1093 residues.Transcript (ENSDART00000123267), which consists of 11 exons and is 1773 bps in length. The protein product (ENSDARP00000105165) consists of 591 residues. Transcript (ENSDART00000145562), which consists of 19 exons and is 13715 bps in length. The protein product (ENSDARP00000112841) consists of 1134 residues.
Protein ENSDARP:ENSDARP00000112841; ENSDARP:ENSDARP00000105165; ENSDARP:ENSDARP00000006793;
ProteinDomainandFamilies InterPro:IPR003598; InterPro:IPR003961; InterPro:IPR007110; InterPro:IPR013098; InterPro:IPR013783;
Motifs Prosite:PS50835; Prosite:PS50853; PFAM:PF00041; PFAM:PF07679; UniProtKB:Q71B05;
Expression ArrayExpress:ENSDARG00000009387;
GeneOntology GO:0016021; GO:0031226; GO:0001525; GO:0030032; GO:0051057; GO:0030334; GO:0035022; GO:0046847; GO:0001954; GO:0043542; GO:0003674;
Orthologs Entrez:54538;
VariationAndRepeats RSID:rs180133077; RSID:rs180133078; RSID:rs180133080; RSID:rs180133081; RSID:rs180133082; RSID:rs180133083; RSID:rs41173338; RSID:rs180133084; RSID:rs180133085; RSID:rs180133086; RSID:rs180133087; RSID:rs41153632; RSID:rs41069871; RSID:rs3728313; RSID:rs3728312; RSID:rs180133088; RSID:rs41131081; RSID:rs41042188; RSID:rs40901942; RSID:rs180133089; RSID:rs180133076

RelatedPubMedArticles Barresi M. J.; Hutson L. D.; Chien C. B.; Karlstrom R. O.: Hedgehog regulated Slit expression determines commissure and glial cell position in the zebrafish forebrain. Development. 132(16):3643-56. 2005 PMID:16033800 Bedell V. M.; Yeo S. Y.; Park K. W.; Chung J.; Seth P.; Shivalingappa V.; Zhao J.; Obara T.; Sukhatme V. P.; Drummond I. A.; Li D. Y.; Ramchandran R.: roundabout4 is essential for angiogenesis in vivo. Proc Natl Acad Sci U S A. 102(18):6373-8. 2005 PMID:15849270 Ny A.; Autiero M.; Carmeliet P.: Zebrafish and Xenopus tadpoles: small animal models to study angiogenesis and lymphangiogenesis. (Review) Exp Cell Res. 312(5):684-93. 2006. PMID:16309670 Chittenden T. W.; Claes F.; Lanahan A. A.; Autiero M.; Palac R. T.; Tkachenko E. V.; Elfenbein A.; Ruiz de Almodovar C.; Dedkov E.; Tomanek R.; Li W.; Westmore M.; Singh J. P.; Horowitz A.; Mulligan-Kehoe M. J.; Moodie K. L.; Zhuang Z. W.; Carmeliet P.; Simons M.: Selective regulation of arterial branching morphogenesis by synectin. Dev Cell. 10(6):783-95. 2006 PMID:16740480 Campbell D. S.; Stringham S. A.; Timm A.; Xiao T.; Law M. Y.; Baier H.; Nonet M. L.; Chien C. B.: Slit1a inhibits retinal ganglion cell arborization and synaptogenesis via Robo2-dependent and -independent pathways. Neuron. 55(2):231-45. 2007 PMID:17640525 Kaur S.; Abu-Asab M. S.; Singla S.; Yeo S. Y.; Ramchandran R.: Expression pattern for unc5b, an axon guidance gene in embryonic zebrafish development. Gene Expr. ;13(6):321-7. Erratum in: Gene Expr. 2007;14(2):129. Abu-Abab, Mones S [corrected to Abu-Asab, Mones S]. 2007 PMID:17708418 NCBI Resource Coordinators.: Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 41(Database issue):D8-D20. 2013. PMID:23193264
Kersey, P. J.; Allen, J. E.; Christensen, M.; et al.: Ensembl Genomes 2013: scaling up access to genome-wide data. Nucleic Acids Res. 2013. PMID:24163254
Sigrist, C. J. A.; de, Castro, E; Cerutti, L; Cuche, B. A.; Hulo, N.; Bridge, A.; Bougueleret, L. Xenarios, I.: New and continuing developments at PROSITE. Nucleic Acids Res. doi: 10.1093/nar/gks1067. 2012. PMID:23161676
Punta, M.; Coggill, P. C.; Eberhardt, et al.: The Pfam protein families database. Nucleic Acids Res. 40(Database Issue):D290-D301. 2012. PMID:22127870
Hunter, S.; Jones P.; Mitchell A.; et al.: Interpro in 2011: new developments in the family and domain prediction database. Nucleic Acids Res. doi: 10.1093/nar/gkr948. 2011. PMID:22096229
Carbon, S.; Ireland, A.; Mungall, C. J.; Shu, S.; Marshall, B.; Lewis, S.; AMIGO Hub; Web Presence Working Group.: AMIGO: online access to ontology and annotation data. Bioinformatics. 25(2):288-9. 2009. PMID:19033274
Ashburner, M.; Ball, C. A.; Blake, J. A.; et al. The Gene Ontology Consortium.: Gene ontology: tool for the unification of biology. Nat. Genet. 25(1):25-9. 2000. PMID:10802651
Sherry, S. T.; Ward, M. H.; Kholodov, M.; Baker, J.; Phan, L.; Smigielski, E. M.; Sirotkin, K.: dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 1;29(1):308-11. 2001. PMID:11125122
Bradford, Y.; Conlin, T.; Dunn, N.; et al.: ZFIN: enhancements and updates to the zebrafish model organism database. Nucleic Acids Res. 39(suppl 1):D822-D829. 2011. PMID:21036866
Kapushesky, M.; Adamusiak, T.; Burdett, T.; et al.: Gene Expression Atlas update--a value-added database of microarray and sequencing-based functional genomics experiments. Nucleic Acids Res. 40(Database isue):D1077-81. 2012. PMID:22064864

Web resources:
NCBI: http://www.ncbi.nlm.nih.gov/
PFAM: http://pfam.sanger.ac.uk/
PROSITE: http://prosite.expasy.org/
Interpro: http://www.ebi.ac.uk/interpro/
ZFIN: http://zfin.org/
Expression Atlas (EMBL): http://www.ebi.ac.uk/gxa/
Ensembl: http://asia.ensembl.org/Danio_rerio/
Database of Single Nucleotide Polymorphisms (dbSNP). Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine.: http://www.ncbi.nlm.nih.gov/SNP/
PRINTS from Genomenet: http://www.genome.jp/
European Nucleotide Archive: http://www.ebi.ac.uk/ena/home
UNIGENE: http://www.ncbi.nlm.nih.gov/unigene/
AMIGO Gene Ontology: http://amigo.geneontology.org
Topic revision: r4 - 2013-09-03 - SubburajK
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