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FLASH GENE

Symbol

ROBO1

contributors: mct/npt/pgu - updated : 22-05-2015

HGNC name	roundabout, axon guidance receptor, homolog 1 (Drosophila)
HGNC id	10249

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002941 30 - 6895 NP_002932 181 1651 - 2009 19104841 also called variant 1/isoform a or H-ROBO1 variant 3 - - 7568 isoform 3 177 1612 - 2009 19104841 also called variant 3/isoform b or DUTT1 alternative N terminus NM_001145845 - - 7385 NP_001139317 169.5 1551 - 2009 19104841 also called variant 4/isoform d NM_133631 29 - 7550 NM_002941 175.7 1606 - 2009 19104841 also called variant 2/isoform b

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth       highly Endocrine pancreas         Homo sapiens Hearing/Equilibrium ear       highly Nervous brain diencephalon thalamus     Homo sapiens Fetal Respiratory lung         Visual eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid         Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Endocrine islet cell (alpha,beta...) Homo sapiens Visual ganglion cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	five Ig-like domains
	three fibronectin-like domains
	a transmembrane segment and a long cytoplasmic tail

HOMOLOGY

interspecies	ortholog to Drosophila roundabout axon guidance receptor
	homolog to C.elegans sax3
	homolog to murine Robo1

Homologene

FAMILY	immunoglobulin superfamily
	ROBO family

CATEGORY

adhesion

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	translocation to the nucleus of cancer cells
	could be found in the plasma membrane and cytosolic compartments typical for receptors of soluble ligands

basic FUNCTION	involved in axon guidance and controlling midline crossing
	candidate tumor suppressor for lung and potentially kidney and breast cancers
	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
	control the development of the lateral olfactory tract
	essential for ROBO4-mediated filopodia induction
	in cancer cells, may function beyond the receptor as a signaling molecule through stepwise cleavages and translocation to the nucleus
	ROBO1 and ROBO2, are critical for longitudinal axon guidance by the SLIT family of chemorepellents
	predominant receptor for guiding axons in ventral tracts and prevents midline crossing
	normal crossing of the auditory pathways requires an adequate ROBO1 expression level
	regulates the correct positioning of layers II/III pyramidal neurons in the neocortex

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	neurogenesis

PATHWAY

metabolism

signaling

signal transduction

	SLIT/ROBO1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation
	ROBO signaling modulates progenitor cell dynamics in the developing brain

a component

forms a heterodimeric complex with ROBO4

INTERACTION

DNA

RNA

small molecule

protein	SLIT receptor interacting with SLIT* by its extra cellular domain
	interacting with SRGAP* by its intra cellular domain CC3
	interact with ROBO4 and share molecules such as SLIT2, ENAH and ARHGAP1 (specific components of the Robo signaling apparatus that work together to guide directional migration of endothelial cells)
	interacts with USP33 (required for Slit-induced ROBO1 redistribution to the plasma membrane without affecting the total ROBO1 protein level
	interacting with DCC
	TGFB1 induces ROBO1 expression specifically in the basal layer, functioning together with SLIT2 to restrict branch formation in basal cell of branching morphogenesis
	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
	GDI1 controls axonal midline crossing by regulating ROBO1 surface expression

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     of the U-twenty-twenty cell line of small cell lung carcinoma tumoral   LOH     in breast carcinoma with promoter methylation constitutional     --low   abnormalities of ROBO1 may lead to autism either by interfering with serotonergic system, or by disrupting neurodevelopment tumoral   LOH     in primary head and neck cancerous lesions tumoral       loss of function in human cancers and may regulate apoptosis and metastasis

Susceptibility

to autism

Variant & Polymorphism

Candidate gene	for susceptibility to dyslexia
	inactivation of ROBO1 could be used as molecular signature for early detection and prognosis of the head and neck cancer
Marker
Therapy target

ANIMAL & CELL MODELS

bronchial hyperplasia and dysplasia in knockout mice