ROBO1

ROBO1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EO9, 2V9Q, 2V9T, 4HLJ
Identifiers
Aliases	ROBO1 , DUTT1, SAX3, roundabout guidance receptor 1
External IDs	OMIM: 602430; MGI: 1274781; HomoloGene: 2206; GeneCards: ROBO1; OMA:ROBO1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p12.3 Start 78,597,239 bp [1] End 79,767,998 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16|16 C3.1 Start 72,105,194 bp [2] End 72,842,983 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence tibia human penis Achilles tendon periodontal fiber gingival epithelium lateral nuclear group of thalamus skin of hip urethra Top expressed in genital tubercle cumulus cell Gonadal ridge habenula vestibular membrane of cochlear duct hair follicle olfactory tubercle maxillary prominence left lung lobe migratory enteric neural crest cell More reference expression data BioGPS n/a
Gene ontology Molecular function LRR domain binding protein binding identical protein binding axon guidance receptor activity Cellular component cytoplasm integral component of membrane cell projection membrane integral component of plasma membrane cell surface axon plasma membrane endoplasmic reticulum-Golgi intermediate compartment membrane Biological process positive regulation of Rho protein signal transduction negative regulation of chemokine-mediated signaling pathway cell differentiation negative regulation of mammary gland epithelial cell proliferation Roundabout signaling pathway positive regulation of axonogenesis nervous system development cell migration involved in sprouting angiogenesis axon guidance multicellular organism development chemotaxis heart development cell adhesion negative regulation of cell migration negative regulation of negative chemotaxis axon midline choice point recognition activation of cysteine-type endopeptidase activity involved in apoptotic process chemorepulsion involved in postnatal olfactory bulb interneuron migration homophilic cell adhesion via plasma membrane adhesion molecules positive regulation of MAP kinase activity positive regulation of vascular endothelial growth factor signaling pathway outflow tract septum morphogenesis aortic valve morphogenesis pulmonary valve morphogenesis endocardial cushion formation positive regulation of gene expression negative regulation of gene expression positive regulation of Notch signaling pathway involved in heart induction aorta development ventricular septum morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6091 19876 Ensembl ENSG00000169855 ENSMUSG00000022883 UniProt Q9Y6N7 O89026 RefSeq (mRNA) NM_001145845 NM_002941 NM_133631 NM_019413 RefSeq (protein) NP_001139317 NP_002932 NP_598334 NP_062286 Location (UCSC) Chr 3: 78.6 – 79.77 Mb Chr 16: 72.11 – 72.84 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Roundabout homolog 1 is a protein that in humans is encoded by the ROBO1 gene. ^{[5] [6] [7]}

Function

Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The protein encoded by ROBO1 is structurally similar to a Drosophila integral membrane protein which is encoded by the Drosophila roundabout gene (a member of the immunoglobulin gene superfamily) and is both an axon guidance receptor and a cell adhesion receptor, known to be involved in the decision by axons to cross the central nervous system midline. Two transcript variants encoding different isoforms have been found for ROBO1. ^[7]

Clinical significance

ROBO1 was implicated in a communication disorder based on a Finnish pedigree with severe dyslexia. Analyses revealed a translocation had occurred disrupting ROBO1. ^[8] Study of the phonological memory component of the language acquisition system suggests that ROBO1 polymorphisms are associated with functioning in this system. ^[9] The gene is thought to be related to the brain's ability to represent quantities, and is correlated with better math scores of young children in one limited study. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000169855 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022883 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, Tear G (Feb 1998). "Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors". Cell. 92 (2): 205–15. doi: 10.1016/S0092-8674(00)80915-0 . PMID   9458045. S2CID   2036419.
6. Sundaresan V, Roberts I, Bateman A, Bankier A, Sheppard M, Hobbs C, Xiong J, Minna J, Latif F, Lerman M, Rabbitts P (Aug 1998). "The DUTT1 gene, a novel NCAM family member is expressed in developing murine neural tissues and has an unusually broad pattern of expression". Mol Cell Neurosci. 11 (1–2): 29–35. doi:10.1006/mcne.1998.0672. PMID   9608531. S2CID   7168171.
7. "Entrez Gene: ROBO1 roundabout, axon guidance receptor, homolog 1 (Drosophila)".
8. Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, Eklund R, Nopola-Hemmi J, Kääriäinen H, Kere J (October 2005). "The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia". PLOS Genet. 1 (4): e50. doi: 10.1371/journal.pgen.0010050 . PMC   1270007 . PMID   16254601.
9. Bates TC, Luciano M, Medland SE, Montgomery GW, Wright MJ, Martin NG (January 2011). "Genetic variance in a component of the language acquisition device: ROBO1 polymorphisms associated with phonological buffer deficits". Behav. Genet. 41 (1): 50–7. doi:10.1007/s10519-010-9402-9. PMID   20949370. S2CID   13129473.
10. "How genetic variation gives rise to differences in mathematical ability".

Further reading

• Sundaresan V, Chung G, Heppell-Parton A, et al. (1998). "Homozygous deletions at 3p12 in breast and lung cancer". Oncogene. 17 (13): 1723–9. doi: 10.1038/sj.onc.1202103 . PMID   9796701.
• Zhao XC, Zhang LM, Li Q, Tong DY, Fan LC, An P, Wu XY, Chen WM, Zhao P, Wang J (2013). "Isoflurane post-conditioning protects primary cultures of cortical neurons against oxygen and glucose deprivation injury via upregulation of Slit2/Robo1". Brain Res. 1537: 283–9. doi:10.1016/j.brainres.2013.08.036. PMC   3820100 . PMID   23994690.
• Brose K, Bland KS, Wang KH, et al. (1999). "Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance". Cell. 96 (6): 795–806. doi: 10.1016/S0092-8674(00)80590-5 . PMID   10102268. S2CID   16301178.
• Yuan W, Zhou L, Chen JH, et al. (1999). "The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance". Dev. Biol. 212 (2): 290–306. doi: 10.1006/dbio.1999.9371 . PMID   10433822.
• Bashaw GJ, Kidd T, Murray D, et al. (2000). "Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor". Cell. 101 (7): 703–15. doi: 10.1016/S0092-8674(00)80883-1 . PMID   10892742. S2CID   2715852.
• Nguyen Ba-Charvet KT, Brose K, Ma L, et al. (2001). "Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance". J. Neurosci. 21 (12): 4281–9. doi: 10.1523/JNEUROSCI.21-12-04281.2001 . PMC   6762758 . PMID   11404413.
• Wong K, Ren XR, Huang YZ, et al. (2001). "Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway". Cell. 107 (2): 209–21. doi: 10.1016/S0092-8674(01)00530-X . PMID   11672528. S2CID   2458943.
• Dallol A, Forgacs E, Martinez A, et al. (2002). "Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers". Oncogene. 21 (19): 3020–8. doi: 10.1038/sj.onc.1205421 . PMID   12082532.
• Latil A, Chêne L, Cochant-Priollet B, et al. (2003). "Quantification of expression of netrins, slits and their receptors in human prostate tumors". Int. J. Cancer. 103 (3): 306–15. doi: 10.1002/ijc.10821 . PMID   12471613. S2CID   22859295.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Hivert B, Liu Z, Chuang CY, et al. (2003). "Robo1 and Robo2 are homophilic binding molecules that promote axonal growth". Mol. Cell. Neurosci. 21 (4): 534–45. doi:10.1006/mcne.2002.1193. PMID   12504588. S2CID   19664833.
• Wang B, Xiao Y, Ding BB, et al. (2004). "Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity". Cancer Cell. 4 (1): 19–29. doi: 10.1016/S1535-6108(03)00164-8 . PMID   12892710.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, et al. (2006). "The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia". PLOS Genet. 1 (4): e50. doi: 10.1371/journal.pgen.0010050 . PMC   1270007 . PMID   16254601.
• Werbowetski-Ogilvie TE, Seyed Sadr M, Jabado N, et al. (2006). "Inhibition of medulloblastoma cell invasion by Slit". Oncogene. 25 (37): 5103–12. doi:10.1038/sj.onc.1209524. PMC   2072874 . PMID   16636676.
• Muzny DM, Scherer SE, Kaul R, et al. (2006). "The DNA sequence, annotation and analysis of human chromosome 3". Nature. 440 (7088): 1194–8. Bibcode:2006Natur.440.1194M. doi: 10.1038/nature04728 . PMID   16641997.
• Gröne J, Doebler O, Loddenkemper C, et al. (2007). "Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer". Oncol. Rep. 15 (6): 1437–43. doi: 10.3892/or.15.6.1437 . PMID   16685377.
• Ito H, Funahashi S, Yamauchi N, et al. (2007). "Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target". Clin. Cancer Res. 12 (11 Pt 1): 3257–64. doi: 10.1158/1078-0432.CCR-05-2787 . PMID   16740745.