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FLASH GENE
Symbol THBS2 contributors: mct/npt/pgu - updated : 21-08-2013
HGNC name thrombospondin 2
HGNC id 11786
Location 6q27      Physical location : 169.615.875 - 169.654.137
Synonym symbol(s) TSP2
DNA
TYPE functioning gene
STRUCTURE 38.26 kb     23 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
23 - 5826 130 1172 - 1999 10364452
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheartvalve    Homo sapiens
Hearing/Equilibriumear   highly
Nervousnerve   highly
Visualeyeanterior segment    Mus musculus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly
Connectivebone  highly
Epithelialbarrier/liningretinal pigment epithelium (RPE)  
Muscularsmooth   
cells
SystemCellPubmedSpeciesStageRna symbol
 fibroblast
cell lineage
cell lines osteosarcoma cell lineage
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a procollagen homology domain
  • three type I (TSP), seven TSP type III domains
  • three EGF-like, type III (Ca++ binding) repeats, with alternatively spliced tissue-specific transcripts
  • one WWF C domain
  • conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to Thbs2
    Homologene
    FAMILY
  • thrombospondin family
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • mediating cell to cell and cell to matrix interactions
  • intervertebral disc extracellular matrix (ECM) proteins that regulate the effective levels of matrix metalloproteinases (MMPs) 2 and 9, which are key effectors of ECM remodeling
  • 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)
  • its diverse functions may also include a role as an intermediary protein that facilitates transcellular receptor-ligand interactions
  • its expression in the heart protects against age-dependent dilated cardiomyopathy
  • enhances Notch signaling and binds to both JAG1 and NOTCH3 ectodomains, potentially bridging two essential extracellular components of NOTCH signaling
  • astrocyte-derived thrombospondin-2 is critical for the repair of the blood-brain barrier
  • highly conserved matricellular protein regulating inflammation, angiogenesis and extracellular matrix remodeling
  • matricellular protein that have been shown to regulate cytoskeleton, cell adhesion, and extracellular matrix remodeling
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • homotrimer, disulfide linked
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • LRP1 and THBS2 stimulate NOTCH activity by driving trans-endocytosis of the NOTCH ectodomain into the signal-sending cell
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    down-regulated at prostate cancer tissues and cell lines, especially at stroma compartment, which could be related to prostate cancer progression
    constitutional     --over  
    mRNA levels were increased in fibro(sclero)tic and stenotic valves
    constitutional     --over  
    circulating levels are elevated in pre-eclampsia
    Susceptibility
  • to myocardial infarction
  • to lumbar-disc herniation
  • to coronary atherosclerosis
  • Variant & Polymorphism SNP
  • increasing the risk of lumbar-disc herniation
  • rs3212556 associated with coronary atherosclerosis
  • Candidate gene
    Marker
  • THBS2 levels could potentially be applied for differential prostate cancer (PCa) and benign prostatic hyperplasia (BPH) diagnosis
  • Therapy target potential therapeutic target in Ewing sarcoma
    ANIMAL & CELL MODELS
  • TSP1-null and TSP2-null mice exhibit lower intraocular pressures
  • TSP2-null mice have an altered brain foreign body response (FBR) characterized by increases in inflammation, extracellular matrix deposition, and leakage of the blood-brain barrier (BBB)