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FLASH GENE
Symbol THBS1 contributors: mct/npt/pgu - updated : 20-08-2014
HGNC name thrombospondin 1
HGNC id 11785
Location 15q14      Physical location : 39.873.279 - 39.889.667
Synonym symbol(s) TSP1, THBS, TSP, THBS-1
DNA
TYPE functioning gene
STRUCTURE 16.39 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site   HRE
text structure promoter might have suppressive elements
MAPPING cloned Y linked Y status confirmed
Physical map
THBS1 15q15 thrombospondin 1 FLJ35989 15q14 hypothetical protein FLJ35989 GPR 15q14 putative G protein coupled receptor LOC388113 15 hypothetical gene supported by BC035481 MGC10997 15q13-q14 pseudogene MGC10997 SRP14 15q15.1-q21.1 signal recognition particle 14kDa (homologous Alu RNA binding protein) BMF 15q14 Bcl2 modifying factor BUB1B 15q15 BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast) PAK6 15q14 p21(CDKN1A)-activated kinase 6 LOC390577 15 similar to KIAA1728 protein PLCB2 15q15 phospholipase C, beta 2 LOC390578 15 similar to BLOCK 23 LOC388114 15 LOC388114 LOC388115 15 similar to RIKEN cDNA 2600011L02 LOC146071 15q14 similar to RIKEN cDNA 1810007E14; EST AA238765 DISP2 15q14 dispatched homolog 2 (Drosophila) FLJ14502 15q14 TRAF4 associated factor 1 IVD 15q14-q15 isovaleryl Coenzyme A dehydrogenase KIAA0945 D4ST-1 15q14 isovaleryl Coenzyme A dehydrogenase
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 5820 127.5 1170 - 2008 18757424
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheartvalve    Homo sapiens
Endocrinepancreas     Homo sapiens
Visualeyeanterior segment    Mus musculus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier/liningretinal pigment epithelium (RPE)  
cells
SystemCellPubmedSpeciesStageRna symbol
Endocrineislet cell (alpha,beta...) Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
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