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    Robo4 roundabout guidance receptor 4 [ Mus musculus (house mouse) ]

    Gene ID: 74144, updated on 9-Dec-2024

    Summary

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    Official Symbol
    Robo4provided by MGI
    Official Full Name
    roundabout guidance receptor 4provided by MGI
    Primary source
    MGI:MGI:1921394
    See related
    Ensembl:ENSMUSG00000032125 AllianceGenome:MGI:1921394
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    1200012D01Rik
    Summary
    Enables signaling receptor activity. Acts upstream of or within negative regulation of blood vessel endothelial cell migration. Located in external side of plasma membrane. Is expressed in several structures, including forebrain; genitourinary system; neural retina; submandibular gland; and vascular system. Human ortholog(s) of this gene implicated in aortic valve disease 3. Orthologous to human ROBO4 (roundabout guidance receptor 4). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Broad expression in lung adult (RPKM 31.0), subcutaneous fat pad adult (RPKM 26.6) and 19 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Robo4 in Genome Data Viewer
    Location:
    9 A4; 9 20.76 cM
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 9 NC_000075.7 (37313198..37325319)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 9 NC_000075.6 (37401902..37414023)

    Chromosome 9 - NC_000075.7Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 15 Neighboring gene STARR-seq mESC enhancer starr_23800 Neighboring gene predicted gene, 34885 Neighboring gene STARR-positive B cell enhancer ABC_E6724 Neighboring gene STARR-seq mESC enhancer starr_23802 Neighboring gene hepatocyte cell adhesion molecule Neighboring gene STARR-seq mESC enhancer starr_23805 Neighboring gene STARR-positive B cell enhancer ABC_E5061 Neighboring gene roundabout guidance receptor 3 Neighboring gene STARR-seq mESC enhancer starr_23807 Neighboring gene STARR-seq mESC enhancer starr_23808 Neighboring gene STARR-seq mESC enhancer starr_23809 Neighboring gene Myb/SANT-like DNA-binding domain containing 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Roundabout 4 is expressed on hematopoietic stem cells and potentially involved in the niche-mediated regulation of the side population phenotype. Shibata F, et al. Stem Cells, 2009 Jan. PMID 18927479, Free PMC Article
    2. Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches. Smith-Berdan S, et al. Cell Stem Cell, 2011 Jan 7. PMID 21211783, Free PMC Article
    3. Activation of endothelial roundabout receptor 4 reduces the severity of virus-induced keratitis. Mulik S, et al. J Immunol, 2011 Jun 15. PMID 21572022, Free PMC Article
    4. Robo4 inhibits gamma radiation-induced permeability of a murine microvascular endothelial cell by regulating the junctions. Adzraku SY, et al. Cell Mol Biol Lett, 2023 Jan 16. PMID 36647012, Free PMC Article
    5. Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models. Morita M, et al. Proc Natl Acad Sci U S A, 2023 Jan 17. PMID 36634143, Free PMC Article

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.
      Title: Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.
    2. Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.
      Title: Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.
    3. Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models.
      Title: Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models.
    4. Robo4 inhibits gamma radiation-induced permeability of a murine microvascular endothelial cell by regulating the junctions.
      Title: Robo4 inhibits gamma radiation-induced permeability of a murine microvascular endothelial cell by regulating the junctions.
    5. [The destructive role of soluble Robo4 secreted by the M1-polarized-microglia during cerebral ischemia-reperfusion in blood-brain barrier integrity].
      Title: [The destructive role of soluble Robo4 secreted by the M1-polarized-microglia during cerebral ischemia-reperfusion in blood-brain barrier integrity].
    6. ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor.
      Title: ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor.
    7. Robo4-mediated pancreatic endothelial integrity decreases inflammation and islet destruction in autoimmune diabetes.
      Title: Robo4-mediated pancreatic endothelial integrity decreases inflammation and islet destruction in autoimmune diabetes.
    8. a novel functional role for Robo4 in endothelial cell function and metabolic homeostasis in white adipose tissue, with Robo4 deletion protecting against endothelial and metabolic dysfunction associated with a HFD.
      Title: Deletion of Robo4 prevents high-fat diet-induced adipose artery and systemic metabolic dysfunction.
    9. Robo4 inhibits angiogenesis and vessel permeability independently of its cytoplasmic domain. Robo4 deletion enhances permeability and revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous wound healing.
      Title: The Robo4 cytoplasmic domain is dispensable for vascular permeability and neovascularization.
    10. endothelial Robo4 signaling is important for suppressing breast cancer growth and metastasis, and it can be targeted (enhanced) by administrating a small molecular drug.
      Title: Endothelial Robo4 suppresses breast cancer growth and metastasis through regulation of tumor angiogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (22)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (2) 
    • Targeted (8)  1 citation

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables signaling receptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of blood vessel endothelial cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell-cell adhesion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in establishment of endothelial barrier ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within negative regulation of blood vessel endothelial cell migration IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    roundabout homolog 4
    Names
    Magic roundabout

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001309390.2 → NP_001296319.2  roundabout homolog 4 isoform 1 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC138284
      Consensus CDS
      CCDS80976.1
      UniProtKB/Swiss-Prot
      Q8C310, Q9DBW1
      UniProtKB/TrEMBL
      A0A1L1SUF8
      Related
      ENSMUSP00000150722.3, ENSMUST00000214185.3
      Conserved Domains (2) summary
      cd00063
      Location:351 → 436
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      cl11960
      Location:142 → 226
      Ig; Immunoglobulin domain

    2. NM_028783.4 → NP_083059.3  roundabout homolog 4 isoform 2 precursor

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC138284
      Consensus CDS
      CCDS22977.1
      UniProtKB/TrEMBL
      A0A0R4J197
      Related
      ENSMUSP00000159318.2, ENSMUST00000239486.2
      Conserved Domains (2) summary
      cd00063
      Location:351 → 436
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      cl11960
      Location:142 → 226
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000075.7 Reference GRCm39 C57BL/6J

      Range
      37313198..37325319
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006510644.1 → XP_006510707.1  roundabout homolog 4 isoform X1

      UniProtKB/TrEMBL
      D3Z4M4
      Related
      ENSMUSP00000110698.3, ENSMUST00000115046.9
      Conserved Domains (2) summary
      cd00063
      Location:361 → 446
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      cl11960
      Location:152 → 236
      Ig; Immunoglobulin domain

    2. XM_006510645.2 → XP_006510708.1  roundabout homolog 4 isoform X2

      UniProtKB/TrEMBL
      D3Z4M4
      Conserved Domains (2) summary
      cd00063
      Location:361 → 446
      FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
      cl11960
      Location:152 → 236
      Ig; Immunoglobulin domain

    3. XM_036155356.1 → XP_036011249.1  roundabout homolog 4 isoform X3

      UniProtKB/TrEMBL
      D3Z4M4
      Conserved Domains (3) summary
      pfam00041
      Location:348 → 430
      fn3; Fibronectin type III domain
      cd00096
      Location:138 → 141
      Ig; Ig strand A [structural motif]
      cl11960
      Location:138 → 223
      Ig; Immunoglobulin domain

    4. XM_036155358.1 → XP_036011251.1  roundabout homolog 4 isoform X5

      UniProtKB/TrEMBL
      E9QN68, Q6IR38
      Conserved Domains (3) summary
      pfam00041
      Location:158 → 240
      fn3; Fibronectin type III domain
      cd00096
      Location:11 → 19
      Ig; Ig strand F [structural motif]
      cl11960
      Location:1 → 33
      Ig; Immunoglobulin domain

    5. XM_011242615.2 → XP_011240917.1  roundabout homolog 4 isoform X4

      UniProtKB/TrEMBL
      E9QN68, Q6IR38
      Conserved Domains (3) summary
      pfam00041
      Location:158 → 240
      fn3; Fibronectin type III domain
      cd00096
      Location:11 → 19
      Ig; Ig strand F [structural motif]
      cl11960
      Location:1 → 33
      Ig; Immunoglobulin domain

    6. XM_036155357.1 → XP_036011250.1  roundabout homolog 4 isoform X4

      UniProtKB/TrEMBL
      E9QN68, Q6IR38
      Conserved Domains (3) summary
      pfam00041
      Location:158 → 240
      fn3; Fibronectin type III domain
      cd00096
      Location:11 → 19
      Ig; Ig strand F [structural motif]
      cl11960
      Location:1 → 33
      Ig; Immunoglobulin domain

    7. XM_006510647.3 → XP_006510710.1  roundabout homolog 4 isoform X6

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8C310.2 GenPept UniProtKB/Swiss-Prot:Q8C310

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