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FLASH GENE
Symbol ROBO2 contributors: mct/npt/pgu - updated : 05-10-2015
HGNC name roundabout, axon guidance receptor, homolog 2 (Drosophila)
HGNC id 10250
Corresponding disease
VUR2 vesicoureteral reflux 2
Location 3p12.3      Physical location : 77.089.293 - 77.699.112
Synonym name roundabout homolog 2
Synonym symbol(s) KIAA1568, SAX3
DNA
TYPE functioning gene
STRUCTURE 607.37 kb     26 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC344715 3p14.1 similar to long myosin light chain kinase LOC344716 3p14.1 similar to seven transmembrane helix receptor LOC391548 3 similar to olfactory receptor GA_x6K02T2PVTD-14054886-14053957 LOC339879 3p14.1 similar to mannosyltransferase LOC389130 3 similar to Alkaline sphingomyelinase LOC389131 3 LOC389131 LOC391549 3 similar to chromosome 11 open reading frame2; chromosome  11 open reading frame2 LOC391550 3 similar to seven transmembrane helix receptor LOC285296 3p14.1 similar to unc-93 homolog B1; unc93 (C.elegans) homolog B; unc-93 related protein LOC391551 3 similar to Putative eukaryotic translation initiation factor 3 subunit (eIF-3) LOC391552 3 similar to fetal hypothetical protein LOC285299 3p14.1 similar to FSHD Region Gene 2 protein LOC389132 3 similar to double homeobox protein LOC377064 3p14.1 kruppel-like zinc finger factor X17 LOC152059 3p14.1 similar to Adenylyl cyclase-associated protein 1 (CAP 1) ROBO2 3p12.3 roundabout, axon guidance receptor, homolog 2 (Drosophila) LOC391553 3 similar to Msx2-interacting protein (SMART/HDAC1 associated repressor protein) MRPS17P3 3p12.1 mitochondrial ribosomal protein S17 pseudogene 3 ROBO1 3p12 roundabout, axon guidance receptor, homolog 1 (Drosophila)
RNA
TRANSCRIPTS type messenger
text by alternative splicing
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
25 - 5939 - 1394 - 2006 16829019
also called ROBO2a
26 - 6254 - 1378 ubiquitous except the skeletal muscle 2006 16829019
  • also called ROBO2b
  • 26 exons
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
    Endocrineneuroendocrinepituitary   
     pancreas   highly Homo sapiens
    Nervousbraindiencephalonthalamus moderately Homo sapiensFetal
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandular  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Visualganglion cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text eye, brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five Ig-like domains,
  • three fibronectin-like domains
  • four proline-rich motifs
  • a transmembrane segment
  • a long cytoplasmic tail
  • HOMOLOGY
    interspecies ortholog to Drosophila roundabout axon guidance receptor
    ortholog to zebrafish astray
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • ROBO family, membrane protein receptor family
  • CATEGORY adhesion , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • single-pass type I membrane protein
  • maximal in the late-luteal phase and significantly reduced after luteal rescue
  • displayed nuclear localization
  • basic FUNCTION
  • SLIT receptor retinal axon guidance and control of midline crossing in the establishment of visual projections
  • acting as molecular guidance cue in cellular migration,
  • including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions
    during neuronal development
  • playing a role in formation of the major forebrain commissures that continues through gestation until well after birth
  • playing a key role in mediating Robo-Slit signaling in cell-cell interactions during gangliogenesis, and in vertebrate development
  • control the development of the lateral olfactory tract
  • key role for Robo-Slit signaling in vertebrate longitudinal axon guidance and highlight the importance of context-specific guidance cues during navigation within complex pathways
  • as in other regions of the optic pathway, ROBO2 is the major receptor required for intraretinal axon guidance
  • ROBO1 and ROBO2, are critical for longitudinal axon guidance by the SLIT family of chemorepellents
  • has a distinct function in repelling neuron cell bodies from the floor plate
  • subtype-specific activity of ROBO2 regulates subcircuit morphogenesis in the trigeminal sensory system
  • is involved in the development of embryonic kidneys and the normal expression of ROBO2 can help maintain proper ureteric bud (UB) branching and glomerular morphogenesis (pMID: 22521888)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text neurogenesis, vision
    PATHWAY
    metabolism
    signaling signal transduction , sensory transduction/vision
  • SLIT-ROBO signaling pathway
  • ROBO signaling modulates progenitor cell dynamics in the developing brain
  • a component part of the SLIT/ROBO signaling that is critical during the initial establishment of dopaminergic pathways, with roles in the dorsoventral positioning and precise pathfinding of these ascending longitudinal axons
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SLIT receptor interacting with SLIT2 by its extra cellular domain
  • SLIT1 acts via ROBO2 in dendrites as a branching/growth factor but not in guidance, while ROBO2 and ROBO3 function in concert in axons to mediate axonal interactions and respond to Slits as guidance factors
  • LHX2 influences axon guidance and the topographical sorting of axons by regulating the expression of ROBO1 and ROBO2 guidance receptors, which are essential for these axons to establish correct connections in the cerebral cortex
  • LMO3 is a putative direct transcriptional target of GBX2 (GBX2 regulates the LIM transcriptional codes comprising LHX2, LHX9 and LMO3, which subsequently control the differential expression of ROBO1 and ROBO2 in the thalamus
  • CASP3, CASP9, and MAPK14 interacted with SLIT1-ROBO2 signaling
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) VUR2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in urinary tract anomalies and with risk of vesicoureteral Reflux
    constitutional germinal mutation      
    missense mutation in urinary tract anomalies with risk of vesicoureteral Reflux
    constitutional     --low  
    abnormalities of ROBO2 may lead to autism either by interfering with serotonergic system, or by disrupting neurodevelopment
    tumoral   LOH    
    in primary head and neck cancerous lesions
    constitutional     --over  
    caused reduced ureteric bud (UB) branching and glomerular number, through inhibition of MM (Metanephric mesenchyme) cell migration and clustering
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice lacking robo2, RGC (retinal ganglion cell)axons make qualitatively and quantitatively identical intraretinal pathfinding errors to those reported previously in Slit mutants
  • Slit2 or Robo2 mouse mutants exhibit multilobular kidneys, multiple ureters, and dilatation of the ureter, renal pelvis, and collecting duct system, which lead to vesicoureteral reflux