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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
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