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Gene Review

THBS1  -  thrombospondin 1

Homo sapiens

Synonyms: THBS, THBS-1, TSP, TSP-1, TSP1, ...
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Disease relevance of THBS1


Psychiatry related information on THBS1


High impact information on THBS1


Chemical compound and disease context of THBS1


Biological context of THBS1


Anatomical context of THBS1


Associations of THBS1 with chemical compounds

  • In contrast to THBS1, CTGF is required for mesangial synthesis of fibronectin stimulated by high glucose or glycated albumin, and is thus a potential therapeutic target [20].
  • Determination of THBS1 gene structure has revealed that the type I repeat modules are encoded by symmetrical exons and that the heparin-binding domain is encoded by a single exon [23].
  • A recombinant piece of TSP2 containing this sequence replicated the alpha4beta1 integrin-dependent activities of TSP1 [24].
  • The enhanced spreading induced by TS1 and 4N1K and the constitutive spreading on higher density VN are both blocked by calphostin C (100 nM), wortmannin (10 nM), and tyrosine kinase inhibitors [25].
  • With this assay we assessed the binding of TS in solution to proteins adsorbed to polystyrene microtiter plates [26].
  • New research has identified components downstream of NO as the primary target of the endogenous angiogenesis inhibitor thrombospondin-1 and has shown that circulating levels of thrombospondin-1 are sufficient to limit angiogenic responses by antagonizing NO signaling [27].
  • The formation of cis and trans dimers of the TSPN-1 domain with relatively short segments of heparin further enhances the ability of TSP-1 to participate in high affinity binding to glycosaminoglycans [28].

Physical interactions of THBS1

  • Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein [29].
  • We have shown previously that HRGP binds with high affinity to thrombospondin-1 (TSP-1), a homotrimeric glycoprotein that is a potent inhibitor of angiogenesis [5].
  • PAS-IV bound to TSP with similar characteristics except that maximum binding was consistently approximately 50% of that of GPIIIb and binding was not inhibited by EDTA [30].
  • We investigated the mechanism by which TS-bound IAP modulates the affinity of platelet integrin, alphaIIbbeta3 [31].
  • Peptides spanning aa 19-36 (RWIESKHKSDFGKFVLSS) blocked hep I-stimulated focal adhesion disassembly, indicating that the TSP/hep I-binding site is located to this sequence in calreticulin [32].
  • Gel shift and antibody supershift studies indicated that ATF-1 was involved in DNA binding to the TSP-1-CRE site [33].

Enzymatic interactions of THBS1


Regulatory relationships of THBS1


Other interactions of THBS1


Analytical, diagnostic and therapeutic context of THBS1


  1. CpG island methylator phenotype in colorectal cancer. Toyota, M., Ahuja, N., Ohe-Toyota, M., Herman, J.G., Baylin, S.B., Issa, J.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  2. Thrombin modulates the expression of a set of genes including thrombospondin-1 in human microvascular endothelial cells. McLaughlin, J.N., Mazzoni, M.R., Cleator, J.H., Earls, L., Perdigoto, A.L., Brooks, J.D., Muldowney, J.A., Vaughan, D.E., Hamm, H.E. J. Biol. Chem. (2005) [Pubmed]
  3. Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Li, Q., Ahuja, N., Burger, P.C., Issa, J.P. Oncogene (1999) [Pubmed]
  4. Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects. Ramis, J.M., Franssen-van Hal, N.L., Kramer, E., Llado, I., Bouillaud, F., Palou, A., Keijer, J. Cell. Mol. Life Sci. (2002) [Pubmed]
  5. Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. Simantov, R., Febbraio, M., Crombie, R., Asch, A.S., Nachman, R.L., Silverstein, R.L. J. Clin. Invest. (2001) [Pubmed]
  6. Extracellular matrix protein expression in cerebrospinal fluid from patients with tropical spastic paraparesis associated with HTLV-I and Creutzfeldt-Jakob disease. Cartier, L., García, L., Kettlun, A.M., Castañeda, P., Collados, L., Vásquez, F., Giraudon, P., Belin, M.F., Valenzuela, M.A. Scand. J. Clin. Lab. Invest. (2004) [Pubmed]
  7. Temperature-dependent sex determination and gonadal differentiation in reptiles. Pieau, C., Dorizzi, M., Richard-Mercier, N. EXS. (2001) [Pubmed]
  8. Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer's disease. Buée, L., Hof, P.R., Roberts, D.D., Delacourte, A., Morrison, J.H., Fillit, H.M. Am. J. Pathol. (1992) [Pubmed]
  9. Neuropsychological assessment in HTLV-1 infection: a comparative study among TSP/HAM, asymptomatic carriers, and healthy controls. Silva, M.T., Mattos, P., Alfano, A., Araújo, A.Q. J. Neurol. Neurosurg. Psychiatr. (2003) [Pubmed]
  10. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Yoshida, M. Annu. Rev. Immunol. (2001) [Pubmed]
  11. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Baruch, D.I., Pasloske, B.L., Singh, H.B., Bi, X., Ma, X.C., Feldman, M., Taraschi, T.F., Howard, R.J. Cell (1995) [Pubmed]
  12. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Larsen, E., Celi, A., Gilbert, G.E., Furie, B.C., Erban, J.K., Bonfanti, R., Wagner, D.D., Furie, B. Cell (1989) [Pubmed]
  13. CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Oquendo, P., Hundt, E., Lawler, J., Seed, B. Cell (1989) [Pubmed]
  14. Thrombospondins I and II messenger RNA expression in lung carcinoma: relationship with p53 alterations, angiogenic growth factors, and vascular density. Fontanini, G., Boldrini, L., Calcinai, A., Chinè, S., Lucchi, M., Mussi, A., Angeletti, C.A., Basolo, F., Bevilacqua, G. Clin. Cancer Res. (1999) [Pubmed]
  15. Adhesion of osteosarcoma cells to the 70-kDa core region of thrombospondin-1 is mediated by the alpha 4 beta 1 integrin. Decker, S., van Valen, F., Vischer, P. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Effects of 17beta-estradiol, progesterone, synthetic progestins, tibolone, and raloxifene on vascular endothelial growth factor and Thrombospondin-1 messengerRNA in breast cancer cells. Mirkin, S., Wong, B.C., Archer, D.F. Int. J. Gynecol. Cancer (2006) [Pubmed]
  17. Induction of thrombospondin-1 by all-trans retinoic acid modulates growth and differentiation of HL-60 myeloid leukemia cells. Touhami, M., Fauvel-Lafève, F., Da Silva, N., Chomienne, C., Legrand, C. Leukemia (1997) [Pubmed]
  18. Thrombospondin 1 protein expression relates to good prognostic indices in ductal carcinoma in situ of the breast. Rice, A.J., Steward, M.A., Quinn, C.M. J. Clin. Pathol. (2002) [Pubmed]
  19. Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Toyota, M., Ohe-Toyota, M., Ahuja, N., Issa, J.P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  20. Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli. Wahab, N.A., Schaefer, L., Weston, B.S., Yiannikouris, O., Wright, A., Babelova, A., Schaefer, R., Mason, R.M. Diabetologia (2005) [Pubmed]
  21. Vitamin d analogs modulate the expression of plasminogen activator inhibitor-1, thrombospondin-1 and thrombomodulin in human aortic smooth muscle cells. Wu-Wong, J.R., Nakane, M., Ma, J. J. Vasc. Res. (2007) [Pubmed]
  22. Thrombospondin-1 expression in bladder cancer: association with p53 alterations, tumor angiogenesis, and tumor progression. Grossfeld, G.D., Ginsberg, D.A., Stein, J.P., Bochner, B.H., Esrig, D., Groshen, S., Dunn, M., Nichols, P.W., Taylor, C.R., Skinner, D.G., Cote, R.J. J. Natl. Cancer Inst. (1997) [Pubmed]
  23. Structure and chromosomal localization of the human thrombospondin gene. Wolf, F.W., Eddy, R.L., Shows, T.B., Dixit, V.M. Genomics (1990) [Pubmed]
  24. Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior. Li, Z., Calzada, M.J., Sipes, J.M., Cashel, J.A., Krutzsch, H.C., Annis, D.S., Mosher, D.F., Roberts, D.D. J. Cell Biol. (2002) [Pubmed]
  25. Thrombospondin modulates alpha v beta 3 function through integrin-associated protein. Gao, A.G., Lindberg, F.P., Dimitry, J.M., Brown, E.J., Frazier, W.A. J. Cell Biol. (1996) [Pubmed]
  26. Interactions of thrombospondin with extracellular matrix proteins: selective binding to type V collagen. Mumby, S.M., Raugi, G.J., Bornstein, P. J. Cell Biol. (1984) [Pubmed]
  27. Nitric oxide and its gatekeeper thrombospondin-1 in tumor angiogenesis. Roberts, D.D., Isenberg, J.S., Ridnour, L.A., Wink, D.A. Clin. Cancer Res. (2007) [Pubmed]
  28. Heparin-induced cis- and trans-dimerization modes of the thrombospondin-1 N-terminal domain. Tan, K., Duquette, M., Liu, J.H., Shanmugasundaram, K., Joachimiak, A., Gallagher, J.T., Rigby, A.C., Wang, J.H., Lawler, J. J. Biol. Chem. (2008) [Pubmed]
  29. Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein. Silverstein, R.L., Leung, L.L., Harpel, P.C., Nachman, R.L. J. Clin. Invest. (1985) [Pubmed]
  30. Epithelial membrane glycoprotein PAS-IV is related to platelet glycoprotein IIIb binding to thrombospondin but not to malaria-infected erythrocytes. Catimel, B., McGregor, J.L., Hasler, T., Greenwalt, D.E., Howard, R.J., Leung, L.L. Blood (1991) [Pubmed]
  31. Thrombospondin-bound integrin-associated protein (CD47) physically and functionally modifies integrin alphaIIbbeta3 by its extracellular domain. Fujimoto, T.T., Katsutani, S., Shimomura, T., Fujimura, K. J. Biol. Chem. (2003) [Pubmed]
  32. The anti-adhesive activity of thrombospondin is mediated by the N-terminal domain of cell surface calreticulin. Goicoechea, S., Pallero, M.A., Eggleton, P., Michalak, M., Murphy-Ullrich, J.E. J. Biol. Chem. (2002) [Pubmed]
  33. Activating transcription factor-1-mediated hepatocyte growth factor-induced down-regulation of thrombospondin-1 expression leads to thyroid cancer cell invasion. Ghoneim, C., Soula-Rothhut, M., Blanchevoye, C., Martiny, L., Antonicelli, F., Rothhut, B. J. Biol. Chem. (2007) [Pubmed]
  34. Thrombospondin is a tight-binding competitive inhibitor of neutrophil elastase. Hogg, P.J., Owensby, D.A., Mosher, D.F., Misenheimer, T.M., Chesterman, C.N. J. Biol. Chem. (1993) [Pubmed]
  35. Conformational regulation of the fibronectin binding and alpha 3beta 1 integrin-mediated adhesive activities of thrombospondin-1. Rodrigues, R.G., Guo , N., Zhou, L., Sipes, J.M., Williams, S.B., Templeton, N.S., Gralnick, H.R., Roberts, D.D. J. Biol. Chem. (2001) [Pubmed]
  36. Mechanism of CD47-induced alpha4beta1 integrin activation and adhesion in sickle reticulocytes. Brittain, J.E., Han, J., Ataga, K.I., Orringer, E.P., Parise, L.V. J. Biol. Chem. (2004) [Pubmed]
  37. Tissue plasminogen activator and urokinase enhance the binding of plasminogen to thrombospondin. Silverstein, R.L., Harpel, P.C., Nachman, R.L. J. Biol. Chem. (1986) [Pubmed]
  38. A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor. Manns, J.M., Uknis, A.B., Rico, M.C., Agelan, A., Castaneda, J., Arango, I., Barbe, M.F., Safadi, F.F., Popoff, S.N., DeLa Cadena, R.A. Arthritis Rheum. (2006) [Pubmed]
  39. Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator. Silverstein, R.L., Leung, L.L., Harpel, P.C., Nachman, R.L. J. Clin. Invest. (1984) [Pubmed]
  40. Human brain glial cells synthesize thrombospondin. Asch, A.S., Leung, L.L., Shapiro, J., Nachman, R.L. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
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