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Gene Review

THBS4  -  thrombospondin 4

Homo sapiens

Synonyms: TSP4, Thrombospondin-4
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Disease relevance of THBS4


High impact information on THBS4


Biological context of THBS4


Anatomical context of THBS4


Associations of THBS4 with chemical compounds

  • Atomic absorption spectroscopy demonstrated that the thrombospondin-4 constructs bind seven less calcium than the thrombospondin-2 construct at 0.6 mM CaCl2 [13].
  • These data indicate that thrombospondin-4 is a pentameric protein that binds to heparin and calcium [8].
  • Thus, alpha(M)beta2 plays a central role in proinflammatory activities of TSP-4 (P387) and may contribute to the prothrombotic phenotype associated with this variant [5].
  • Thrombospondin-4 (TSP-4), a large pentameric glycoprotein of the extracellular matrix, has been described as a neurite outgrowth-promoting molecule [14].
  • BACKGROUND: In a recent large-scale genetic association study, a single nucleotide polymorphism in the thrombospondin-4 (TSP-4) gene, resulting in a proline-for-alanine substitution at position 387, was associated with a significantly increased risk for premature atherosclerosis [15].

Other interactions of THBS4

  • The THBS2 and THBS4 associations have since been replicated [16].
  • The disease-associated polymorphisms lead to single amino acid changes in TSP-4 (A387P) and TSP-1 (N700S) [6].
  • In the human genome, the TSP-1, TSP-3, TSP-4 and TSP-5 genes lie within paralogous regions that provide insight into the ancestral genomic context of vertebrate TSPs [17].

Analytical, diagnostic and therapeutic context of THBS4


  1. Replication of the association between the thrombospondin-4 A387P polymorphism and myocardial infarction. Wessel, J., Topol, E.J., Ji, M., Meyer, J., McCarthy, J.J. Am. Heart J. (2004) [Pubmed]
  2. Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction. Topol, E.J., McCarthy, J., Gabriel, S., Moliterno, D.J., Rogers, W.J., Newby, L.K., Freedman, M., Metivier, J., Cannata, R., O'Donnell, C.J., Kottke-Marchant, K., Murugesan, G., Plow, E.F., Stenina, O., Daley, G.Q. Circulation (2001) [Pubmed]
  3. Thrombospondin-4 Ala387Pro polymorphism is not associated with vascular function and risk of coronary heart disease in US men and women. Asselbergs, F.W., Pai, J.K., Pischon, T., Manson, J.E., Rimm, E.B. Thromb. Haemost. (2006) [Pubmed]
  4. Identification and characterization of thrombospondin-4, a new member of the thrombospondin gene family. Lawler, J., Duquette, M., Whittaker, C.A., Adams, J.C., McHenry, K., DeSimone, D.W. J. Cell Biol. (1993) [Pubmed]
  5. Mechanism and effect of thrombospondin-4 polymorphisms on neutrophil function. Pluskota, E., Stenina, O.I., Krukovets, I., Szpak, D., Topol, E.J., Plow, E.F. Blood (2005) [Pubmed]
  6. Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites. Stenina, O.I., Ustinov, V., Krukovets, I., Marinic, T., Topol, E.J., Plow, E.F. FASEB J. (2005) [Pubmed]
  7. Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73. van Doorn, R., Zoutman, W.H., Dijkman, R., de Menezes, R.X., Commandeur, S., Mulder, A.A., van der Velden, P.A., Vermeer, M.H., Willemze, R., Yan, P.S., Huang, T.H., Tensen, C.P. J. Clin. Oncol. (2005) [Pubmed]
  8. Characterization of human thrombospondin-4. Lawler, J., McHenry, K., Duquette, M., Derick, L. J. Biol. Chem. (1995) [Pubmed]
  9. A thrombospondin homologue in Drosophila melanogaster: cDNA and protein structure. Adolph, K.W. Gene (2001) [Pubmed]
  10. Coronary artery disease and the thrombospondin single nucleotide polymorphisms. Stenina, O.I., Byzova, T.V., Adams, J.C., McCarthy, J.J., Topol, E.J., Plow, E.F. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  11. The C-terminal peptide of thrombospondin-4 stimulates erythroid cell proliferation. Congote, L.F., Difalco, M.R., Gibbs, B.F. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. The thrombospondin-4 gene. Newton, G., Weremowicz, S., Morton, C.C., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Lawler, J. Mamm. Genome (1999) [Pubmed]
  13. Biophysical characterization of the signature domains of thrombospondin-4 and thrombospondin-2. Misenheimer, T.M., Mosher, D.F. J. Biol. Chem. (2005) [Pubmed]
  14. Thrombospondin-4 and matrix three-dimensionality in axon outgrowth and adhesion in the developing retina. Dunkle, E.T., Zaucke, F., Clegg, D.O. Exp. Eye Res. (2007) [Pubmed]
  15. Thrombospondin-4 and its variants: expression and differential effects on endothelial cells. Stenina, O.I., Desai, S.Y., Krukovets, I., Kight, K., Janigro, D., Topol, E.J., Plow, E.F. Circulation (2003) [Pubmed]
  16. Large scale association analysis for identification of genes underlying premature coronary heart disease: cumulative perspective from analysis of 111 candidate genes. McCarthy, J.J., Parker, A., Salem, R., Moliterno, D.J., Wang, Q., Plow, E.F., Rao, S., Shen, G., Rogers, W.J., Newby, L.K., Cannata, R., Glatt, K., Topol, E.J. J. Med. Genet. (2004) [Pubmed]
  17. Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation. McKenzie, P., Chadalavada, S.C., Bohrer, J., Adams, J.C. BMC Evol. Biol. (2006) [Pubmed]
  18. Thrombospondin-4 A387P polymorphism is not associated with coronary artery disease and myocardial infarction in the Chinese Han population. Zhou, X., Huang, J., Chen, J., Zhao, J., Yang, W., Wang, X., Gu, D. Clin. Sci. (2004) [Pubmed]
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