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FLASH GENE
Symbol RSPO2 contributors: mct/npt/pgu - updated : 26-08-2016
HGNC name R-spondin 2 homolog (Xenopus laevis)
HGNC id 28583
Location 8q23.1      Physical location : 108.911.544 - 109.095.913
Synonym name Roof plate-specific spondin-2
Synonym symbol(s) MGC43342, CRISTIN2, MGC35555
DNA
TYPE functioning gene
STRUCTURE 184.37 kb     6 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 3149 - 243 - 2011 21160497
- - - - - - 2011 21160497
  • derivative containing only the two furin-like domains
  • having potent activity and synergized strongly with WNT3A in a beta-catenin reporter assay (Li 2009)
  • 5 - 2777 - 179 - 2011 21160497
    5 - 2498 - 176 - 2011 21160497
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea   Homo sapiensFetal
    Nervousbrain    
    Reproductivemale systemtestis   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Hearing / Equilibriumcochlea cell Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • R-spondin family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • functioning in a positive feedback loop to stimulate the Wnt/beta-catenin cascade
  • having essential roles in vertebrate development and its ligand-type activities overlap substantially with those of the canonical Wnt ligands in that both RSPO and canonical Wnt signaling result in the activation of beta-catenin
  • required for normal laryngeal-tracheal, lung and limb morphogenesis
  • modulate the Wnt pathway by a common mechanism and coexpression with specific Wnt ligands and DKK1 may determine their biological specificity
  • may regulates midfacial, limb, and lung morphogenesis during development through the Wnt/CTNNB signaling
  • RSPO1, RSPO2, RSPO3, RSPO4 can stimulate the proliferation of intestinal crypt stem cells, through enhancement of Wnt/CTNNB signaling
  • mesenchyme-derived factor that plays critical roles in regulating first branchial arch (BA1) patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate
  • in cochlea is required to limit the number of outer hair cells to three rows and for optimal arrangement of peripheral nerve fibers
  • may promote hepatic stellate cells (HSCs) activation by enhancing the canonical Wnt pathway
  • activates WNT/CTNNB1 signaling to reduce COL2A1 and SOX9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage
  • secreted agonist of canonical WNT-CTNNB signaling
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • potentiate Wnt/CTNNB signaling by actually functioning as ligands of LGR4 and LGR5
  • each of the four R-spondins, secreted Wnt pathway agonists, can bind to LGR4, LGR5 and LGR6 (Pubmed 21727895)
  • LGR4 acted as a key receptor for RSPO2 to promote osteogenesis
  • RSPO2 and its receptor LGR5 are WNT-dependent and agrin-independent regulators of acetylcholine receptor (ACHR) clustering at the neuromuscular junction (NMJ)
  • inhibited expression of genes encoding early chondrocyte differentiation markers by activating WNT-CTNNB1 signaling
  • TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in human colorectal cancers (CRCs) due to promoter hypermethylation
    Susceptibility to ossification of the posterior longitudinal ligament of the spine (OPLL)
    Variant & Polymorphism SNP SNP (rs374810) in the RSPO2 promoter causes deceased binding of C/EBPB, which leads to decreased RSPO2 expression, decreased Wnt-CTNNB1 signal, and eventually OPLL
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • CLP with mild facial skeletal defects in Rspo2(-/-) mice which also exhibited distal limb loss and lung hypoplasia, and died immediately after birth with respiratory failure; apparent reduction of Wnt/Ctnnb1 signaling activity at the branchial arch and the apical ectodermal ridge in Rspo2(-/-)mice
  • in Rspo2(-/-) mouse, loss of Rspo2 results in an additional single row of outer hair cells and disruption of peripheral innervation pattern
  • mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate