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FLASH GENE
Symbol THBS1 contributors: mct/npt/pgu - updated : 20-08-2014
HGNC name thrombospondin 1
HGNC id 11785
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a procollagen homology domain
  • a motif within the N-terminal domain specifically promotes the proangiogenic activity of endothelial colony-forming cells
  • three type I TSP and seven TSP type III domains
  • three EGF-like and one WWFC domain
  • a peptide RFYVVMWK (4N-1) located in its C-terminal domain, involved in interaction with CD47
    • secondary structure disulfide linked subunits
    conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to murine Thbs1
    Homologene
    FAMILY
  • thrombospondin family
    • CATEGORY adhesion , signaling
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    text matrix protein
    basic FUNCTION
  • matrix protein, involved in platelet aggregation, embryogenesis, morphogenesis, cell adhesion molecule
  • major activator of TGFB1
  • may play an important role in antitumor immunity
  • regulator of tumor growth and metastasis
  • can utilizes a novel pathway for its antiangiogenic effect independent of CD36, and suppresses the cell cycle
  • play a biologically significant role in tumor vascularization in Ewing's sarcoma (EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins)
  • acting by sequestering and consequently inactivating angiogenic activity of VEGFA
  • critical effector of SSTR2 tumor-suppressive activity on pancreatic tumor growth and angiogenesis
  • modulates the angiogenic phenotype of cerebral arteriovenous malformation endothelial cells
  • endothelial-derived THBS1 activates islet TGFB1 of importance for beta-cells (PMID;
  • highly conserved matricellular protein regulating inflammation, angiogenesis and extracellular matrix remodeling
  • role of THBS1 in hyperleptinemia-induced atherosclerotic complications '
  • matricellular protein that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , development
    text homeostasis of the lung
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of the extracellular matrix
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • fibrinogen, fribronectin, laminin, collagen type 5, integrin alpha 5 beta1
  • interacting with PRMT6 (directly regulates the THBS1 promoter activity and THBS1 is a transcriptional repression target of PRMT6)
  • interacting with ADAMTS13 (THBS1 played competitively inhibitory role in ADAMTS13 binding and cleaving of VWF, and the potential competition might happen within A2 and A3 domains)
  • new role for THBS1 and CD36 in the activation of the KDR signaling pathway that requires SYK
  • PTPRJ functions as a receptor for THBS1 and mediates its inhibition of cell growth
  • NOL7 is a tumor suppressor that induces an antiangiogenic phenotype and suppresses tumor growth, in part through upregulation of THBS1
  • negative function of PRMT6 on invasion and migration of cancer cells through up-regulation of THBS1 and down-regulation of MMP2 and MMP9
  • THBS1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus
  • SEMA3F functions as an unconventional SEMA3 that promotes extraembryonic angiogenesis by inhibiting the MYC-regulated synthesis of THBS1 in visceral yolk sac epithelial cells
    • cell & other
  • HMVEC, dermal microvascular endothelial cell
    • REGULATION
    activated by EGF and TGFB1 (role in modulation of angiogenesis and formation of matrices in tumor stroma )
    induced by ELL (ELL directly induces THBS1 expression)
    repressed by NEDD4
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in liver, brain, pancreas, bone cancer in response to EGF and TGFB1
    tumoral     --low  
    low expressed by hypermethylation in gastric carcinoma
    constitutional germinal mutation     loss of function
    in familial pulmonary hypertension
    constitutional     --low  
    in HELLP syndrome
    Susceptibility to thoracic aortic aneurysm (TAA) in hypertensive patients
    Variant & Polymorphism other
  • the 3949T-->G (3prime untranslated region) polymorphism is a risk factor for thoracic aortic aneurysm in hypertensive patients
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbone 
    potential therapeutic target in Ewing sarcoma
    ANIMAL & CELL MODELS
  • TSP1-null and TSP2-null mice exhibit lower intraocular pressures
  • TSP1-deficient mice were glucose intolerant, despite having an increased beta-cell mass