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FLASH GENE
Symbol RSPO3 contributors: mct/npt/pgu - updated : 18-12-2023
HGNC name R-spondin 3 homolog (Xenopus laevis)
HGNC id 20866
Location 6q22.33      Physical location : 127.440.047 - 127.518.182
Synonym name
  • thrombospondin-like gene
  • thrombospondin, type I domain-containing 2
  • R-spondin 3
  • protein with TSP type-1 repeat
  • roof plate-specific spondin-3
    • Synonym symbol(s) FLJ14440, PWTSR, THSD2, CRISTIN1
    DNA
    TYPE functioning gene
    STRUCTURE 78.14 kb     5 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 4815 - 272 - 2006 16357527
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Nervousbrain    
    Reproductivefemale systemplacenta   
     female systemovary   
     male systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveboneperiosteum   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text brain, placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a thrombospondin type I repeat (TSR) domain
  • two furin-like cysteine-rich region
  • two putative C-mannosylation sites at Trp(153) and Trp(156), and C-mannosylation of RSPO3 promotes its secretion and activates Wnt/CTNNB1 signaling
    • HOMOLOGY
    Homologene
    FAMILY
  • thrombospondin type I repeat supergene family (hPWTSR)
  • R-spondin family
    • CATEGORY transport carrier
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • may have a peptidase activity
  • enhances oncogenicity
  • 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
  • potentiate Wnt/beta-catenin signaling, an important pathway in embryonic development that is constitutively active in many cancers
  • modulate the Wnt pathway by a common mechanism and coexpression with specific Wnt ligands and DKK1 may determine their biological specificity
  • essential for regulating the balance between angioblast and blood cell specification
  • novel, evolutionarily conserved angiogenic factor in embryogenesis
  • RSPO1, RSPO2, RSPO3, RSPO4 can stimulate the proliferation of intestinal crypt stem cells, through enhancement of Wnt/CTNNB signaling
  • SDC4 and RSPO3 are essential for two Wnt/PCP-driven processes-gastrulation movements and head cartilage morphogenesis
  • RSPO3 is a key angiocrine factor that controls metabolic zonation of liver hepatocytes
  • acts as an agonist of canonical Wnt/CTNNB1 signaling that plays an important role in embryonic development and homeostasis
  • RSPO3 is a potent driver of intestinal cancer
  • matricellular protein RSPO3 is a mediator of endothelial hyperpermeability that can act in synergy with the inflammatory mediator IL1B
  • RSPO3 is an important determinant of peripheral adipose tissue (AT) storage capacity.
  • RSPO3 regulates vertebral trabecular bone mass and fracture risk in humans
  • RSPO3 is likely a paracrine factor that may positively participate in the myogenesis processes of myoblasts and satellite cells
  • RSPO3 consistently promotes the proliferation and invasion of breast cancer cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • iron ion binding
    • protein
  • interacting with FZD8
  • binds syndecan 4 (SDC4) and that together they activate Wnt/PCP signaling
  • 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)
  • RSPO1 and RSPO3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis
  • LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in a TP53-deficient mammary epithelial cell line
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    as a candidate target for therapy in patients with colorectal cancer harbouring RSPO3 fusions
    cancerreproductivebreast
    RSPO3 itself is likely a valuable therapeutic target in breast cancer
    ANIMAL & CELL MODELS