Human Gene ROBO1 (uc003dqe.2)
  Description: Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila) (ROBO1), transcript variant 1, mRNA.
RefSeq Summary (NM_002941): 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 product of this gene is a member of the immunoglobulin gene superfamily and encodes an integral membrane protein that functions in axon guidance and neuronal precursor cell migration. This receptor is activated by SLIT-family proteins, resulting in a repulsive effect on glioma cell guidance in the developing brain. A related gene is located at an adjacent region on chromosome 3. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009].
Transcript (Including UTRs)
   Position: hg19 chr3:78,646,388-79,817,059 Size: 1,170,672 Total Exon Count: 31 Strand: -
Coding Region
   Position: hg19 chr3:78,648,063-79,639,061 Size: 990,999 Coding Exon Count: 30 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:78,646,388-79,817,059)mRNA (may differ from genome)Protein (1651 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer
GeneCardsGeneNetworkH-INVHGNCHPRDLynx
MGIneXtProtOMIMPubMedReactomeUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: ROBO1_HUMAN
DESCRIPTION: RecName: Full=Roundabout homolog 1; AltName: Full=Deleted in U twenty twenty; AltName: Full=H-Robo-1; Flags: Precursor;
FUNCTION: Receptor for SLIT1 and SLIT2 which are thought to act 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. In axon growth cones, the silencing of the attractive effect of NTN1 by SLIT2 may require the formation of a ROBO1-DCC complex. May be required for lung development.
SUBUNIT: Interacts with SLIT1 and SLIT2.
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Potential).
TISSUE SPECIFICITY: Widely expressed, with exception of kidney.
PTM: Ubiquitinated. May be deubiquitinated by USP33 (By similarity).
MISCELLANEOUS: Maps within a region of overlapping homozygous deletions characterized in both small cell lung cancer cell lines (SCLC) and in a breast cancer cell line. The promoter region of ROBO1 shows complete hypermethylation of CpG sites in the BT-20 breast tumor cell lines, some primary invasive breast carcinomasa and some primary clear cell renal cell carcinomas (CC-RCC).
SIMILARITY: Belongs to the immunoglobulin superfamily. ROBO family.
SIMILARITY: Contains 3 fibronectin type-III domains.
SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like) domains.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/ROBO1ID42140ch3p12.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ROBO1
CDC HuGE Published Literature: ROBO1
Positive Disease Associations: Brain imaging in schizophrenia (interaction) , Macular Degeneration , Myocardial Infarction , protein quantitative trait loci
Related Studies:
  1. Brain imaging in schizophrenia (interaction)
    Potkin ,et al. 2008, A Genome-Wide Association Study of Schizophrenia Using Brain Activation as a Quantitative Phenotype, Schizophrenia bulletin 2009 35- 1 : 96-108. [PubMed 19023125]
    Combining imaging and genetic data from a GWAS identified genes related to forebrain development and stress response, already implicated in schizophrenic dysfunction, as affecting prefrontal efficiency.
  2. Macular Degeneration
    , , . [PubMed 0]
  3. Macular Degeneration
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: ROBO1
Diseases sorted by gene-association score: dyslexia (10), reading disorder (8), brain glioma (7), corneal neovascularization (5), breast cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.42 RPKM in Vagina
Total median expression: 211.93 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -52.10208-0.250 Picture PostScript Text
3' UTR -384.681675-0.230 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003961 - Fibronectin_type3
IPR007110 - Ig-like
IPR013783 - Ig-like_fold
IPR013098 - Ig_I-set
IPR003598 - Ig_sub2
IPR003596 - Ig_V-set_subgr

Pfam Domains:
PF00041 - Fibronectin type III domain
PF00047 - Immunoglobulin domain
PF07679 - Immunoglobulin I-set domain
PF07686 - Immunoglobulin V-set domain
PF13895 - Immunoglobulin domain
PF13927 - Immunoglobulin domain

SCOP Domains:
48726 - Immunoglobulin
49265 - Fibronectin type III

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2EO9 - NMR MuPIT 2V9Q - X-ray MuPIT 2V9R - X-ray MuPIT 2V9T - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9Y6N7
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008046 axon guidance receptor activity
GO:0030275 LRR domain binding
GO:0042802 identical protein binding

Biological Process:
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006935 chemotaxis
GO:0007155 cell adhesion
GO:0007156 homophilic cell adhesion via plasma membrane adhesion molecules
GO:0007275 multicellular organism development
GO:0007399 nervous system development
GO:0007411 axon guidance
GO:0007507 heart development
GO:0016199 axon midline choice point recognition
GO:0021836 chemorepulsion involved in postnatal olfactory bulb interneuron migration
GO:0030154 cell differentiation
GO:0030336 negative regulation of cell migration
GO:0033600 negative regulation of mammary gland epithelial cell proliferation
GO:0035025 positive regulation of Rho protein signal transduction
GO:0035385 Roundabout signaling pathway
GO:0043406 positive regulation of MAP kinase activity
GO:0050772 positive regulation of axonogenesis
GO:0050925 negative regulation of negative chemotaxis
GO:0070100 negative regulation of chemokine-mediated signaling pathway
GO:1900748 positive regulation of vascular endothelial growth factor signaling pathway

Cellular Component:
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0042995 cell projection


-  Descriptions from all associated GenBank mRNAs
  AK297481 - Homo sapiens cDNA FLJ59170 complete cds, highly similar to Roundabout homolog 1 precursor.
BC157861 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:189756 IMAGE:9057080), complete cds.
BC171855 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:198570 IMAGE:9054509), complete cds.
BC115020 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:131597 IMAGE:7961997), complete cds.
BC115022 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:131599 IMAGE:7962000), complete cds.
BC112336 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone MGC:133277 IMAGE:40037251), complete cds.
AF040990 - Homo sapiens roundabout 1 (robo1) mRNA, complete cds.
BC029676 - Homo sapiens roundabout, axon guidance receptor, homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:4778395), with apparent retained intron.
AK025535 - Homo sapiens cDNA: FLJ21882 fis, clone HEP02791, highly similar to AF040990 Homo sapiens roundabout 1 (robo1) mRNA.
BC001969 - Homo sapiens, Similar to roundabout (axon guidance receptor, Drosophila) homolog 1, clone IMAGE:3454108, mRNA, partial cds.
BX538319 - Homo sapiens mRNA; cDNA DKFZp686J09169 (from clone DKFZp686J09169).
JD361213 - Sequence 342237 from Patent EP1572962.
JD245311 - Sequence 226335 from Patent EP1572962.
JD236186 - Sequence 217210 from Patent EP1572962.
JD558167 - Sequence 539191 from Patent EP1572962.
JD486655 - Sequence 467679 from Patent EP1572962.
JD237495 - Sequence 218519 from Patent EP1572962.
JD359584 - Sequence 340608 from Patent EP1572962.
JD301350 - Sequence 282374 from Patent EP1572962.
JD131391 - Sequence 112415 from Patent EP1572962.
JD182409 - Sequence 163433 from Patent EP1572962.
JD507912 - Sequence 488936 from Patent EP1572962.
JD275569 - Sequence 256593 from Patent EP1572962.
JD369835 - Sequence 350859 from Patent EP1572962.
JD304137 - Sequence 285161 from Patent EP1572962.
AK299920 - Homo sapiens cDNA FLJ59293 partial cds, highly similar to Roundabout homolog 1 precursor.
AK095256 - Homo sapiens cDNA FLJ37937 fis, clone CTONG2007272, highly similar to Homo sapiens roundabout 1 (robo1) mRNA.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04360 - Axon guidance

Reactome (by CSHL, EBI, and GO)

Protein Q9Y6N7 (Reactome details) participates in the following event(s):

R-HSA-204364 ROBO1 binds SLIT2
R-HSA-9010951 ROBO1 binds NRP1
R-HSA-8986083 USP33 deubiquitinates ROBO1
R-HSA-373715 DCC interaction with ROBO1
R-HSA-376140 Ena/VASP proteins bind ROBO1:SLIT2 complex
R-HSA-376141 Interaction of ABL with ROBO1:SLIT2
R-HSA-376145 SRGAP binds ROBO1:SLIT2
R-HSA-428511 NCK binds ROBO1:SLIT2
R-HSA-428536 ARHGAP39 (Vilse) binds ROBO1:SLIT2
R-HSA-8985591 SLIT2-bound ROBO1 binds MYO9B
R-HSA-8986258 SLIT2:ROBO1 binds CXCR4
R-HSA-9010231 ROBO1 binds FLRT3
R-HSA-8985799 SLIT1 binds ROBO1,(ROBO2)
R-HSA-9014812 ROBOs bind keratan sulfate
R-HSA-9014834 ROBO1,ROBO2 bind SLIT3
R-HSA-428534 Recruitment of Profilin by Ena/VASP proteins
R-HSA-428515 Recruitment of SOS to plasma membrane
R-HSA-428531 Recruitment of PAK to NCK
R-HSA-428883 Recruitment of CAP to ABL
R-HSA-428885 Activation of CLASP
R-HSA-428888 Phosphorylation of ROBO1 by ABL kinase
R-HSA-8985812 NCK2 binds to ROBO1,(ROBO2)
R-HSA-428533 Inactivation of CDC42
R-HSA-428522 Inactivation of RAC1
R-HSA-428535 Activation of RAC1 by SOS
R-HSA-376176 Signaling by ROBO receptors
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-373752 Netrin-1 signaling
R-HSA-428542 Regulation of commissural axon pathfinding by SLIT and ROBO
R-HSA-428890 Role of ABL in ROBO-SLIT signaling
R-HSA-428543 Inactivation of CDC42 and RAC1
R-HSA-428540 Activation of RAC1
R-HSA-8985586 SLIT2:ROBO1 increases RHOA activity
R-HSA-8985801 Regulation of cortical dendrite branching
R-HSA-422475 Axon guidance
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B2RXI1, D3DU36, DUTT1, NM_002941, NP_002932, Q7Z300, Q9BUS7, Q9Y6N7, ROBO1_HUMAN
UCSC ID: uc003dqe.2
RefSeq Accession: NM_002941
Protein: Q9Y6N7 (aka ROBO1_HUMAN or ROB1_HUMAN)
CCDS: CCDS46872.2, CCDS54611.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_002941.3
exon count: 31CDS single in 3' UTR: no RNA size: 6895
ORF size: 4956CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 9909.00frame shift in genome: no % Coverage: 99.19
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.