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FLASH GENE
Symbol SOSTDC1 contributors: mct/npt/pgu - updated : 09-09-2013
HGNC name sclerostin domain containing 1
HGNC id 21748
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a CTCK (C-terminal cystine knot-like) domain
    • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to rattus Usag1
    ortholog to murine Sostdc1
    intraspecies paralog to SOST
    Homologene
    FAMILY
  • sclerostin family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
    text secreted
    basic FUNCTION
  • may be involved in the onset of endometrial receptivity for implantation/sensitization for the decidual cell reaction
  • enhancing Wnt signaling
  • inhibiting TGF-beta signaling
  • directly antagonizing activity of BMP2, BMP4, BMP6 and BMP7 in a dose-dependent manner, in the developing and adult kidney
  • negatively regulates the renoprotective action of BMP7
  • with MEOX2, may have a role in the progression of Wilms tumorigenesis
  • modulate Wnt signaling and also inhibit BMP signals, and modulation of Wnt signaling activity is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands
  • having multiple functions at the molecular level, suggesting a possible role in balancing Wnt and BMP signals
  • plays crucial roles in tooth morphogenesis
  • uncovers the role of dental mesenchyme in limiting tooth induction
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    enhancing Wnt signaling ; inhibiting TGF-beta signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • BMP2
  • BMP4
  • BMP6
  • BMP7
  • BMP antagonist
  • binds LRP6 through one of three loops formed by the cystine knot
  • HR repressed the expression of Wnt inhibitors, including SOSTDC1, DKKL1, SFRP1, and SFRP2
  • interplay between LRP4 and SOSTDC1 in inhibiting Wnt/CTNNB1 signaling, providing an insight into how modulation of Wnt/CTNNB1 signaling controls cellular processes important for skin placode formation
  • SOST and its paralog SOSTDC1 coordinate digit number in a GLI3-dependent manner
  • VDR-mediated control of DKKL1, SOSTDC1, and HR gene expression in keratinocytes
    • cell & other
  • binds to neighboring cells and/or the extracellular matrix
    • REGULATION
    induced by by IHH is independent of GLI1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in Wilms tumor
    tumoral     --low  
    in renal clear cell carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    suppressing proliferation of renal carcinoma cells, restoration of SOSTDC1 signaling may represent a novel target in treatment of renal clear cell carcinoma
    ANIMAL & CELL MODELS
  • Wise-null mice phenocopied a subset of the Lrp4 mammary defects and Wise overexpression reduced the number of mammary precursor cells