Biology:TSG-6
 Generic protein structure example |
Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein[1] that in humans is encoded by the TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) gene.[2][3]
Structure and function
TSG-6 is a 30 kDa secreted protein that contains a hyaluronan-binding LINK domain a and thus is a member of the hyaluronan-binding protein family, also called hyaladherins. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable, covalent complex with inter-alpha-inhibitor (IαI), and thus enhance the serine protease inhibitory activity of IαI, which is important in the protease network associated with inflammation. The expression of this gene can be induced by a number of signalling molecules, principally tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1). The expression can also be induced by mechanical stimuli in vascular smooth muscle cells, and is found to be correlated with proteoglycan synthesis and aggregation.[3] TSG-6 has been shown to modulate macrophage plasticity and signal the transition of LPS-treated macrophages from pro- to anti-inflammatory phenotype.[4]
TSG-6 also interacts with a number of matrix associated molecules such as aggrecan, versican, thrombospondin (1&2), pentraxin-3 and fibronectin.
References
- ↑ "A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44". The Journal of Cell Biology 116 (2): 545–57. January 1992. doi:10.1083/jcb.116.2.545. PMID 1730767.
- ↑ "Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein". The Journal of Biological Chemistry 268 (9): 6154–60. March 1993. doi:10.1016/S0021-9258(18)53232-4. PMID 8454591.
- ↑ 3.0 3.1 "Entrez Gene: TNFAIP6 tumor necrosis factor, alpha-induced protein 6". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7130.
- ↑ "TNFα-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury". Proceedings of the National Academy of Sciences of the United States of America 113 (50): E8151–E8158. December 2016. doi:10.1073/pnas.1614935113. PMID 27911817. Bibcode: 2016PNAS..113E8151M.
Further reading
- "TSG-6: a multifunctional protein associated with inflammation". Journal of Cell Science 116 (Pt 10): 1863–73. May 2003. doi:10.1242/jcs.00407. PMID 12692188.
- "Inter-alpha-inhibitor, hyaluronan and inflammation". Acta Biochimica Polonica 50 (3): 735–42. 2004. doi:10.18388/abp.2003_3664. PMID 14515153. http://www.actabp.pl/pdf/3_2003/735.pdf.
- "TSG-6: a pluripotent inflammatory mediator?". Biochemical Society Transactions 34 (Pt 3): 446–50. June 2006. doi:10.1042/BST0340446. PMID 16709183.
- "TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor". Biochemistry 33 (23): 7423–9. June 1994. doi:10.1021/bi00189a049. PMID 7516184.
- "NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1". Molecular and Cellular Biology 14 (10): 6561–9. October 1994. doi:10.1128/MCB.14.10.6561. PMID 7935377.
- "TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo". Journal of Immunology 156 (4): 1609–15. February 1996. doi:10.4049/jimmunol.156.4.1609. PMID 8568267.
- "Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration". Cell 86 (5): 767–75. September 1996. doi:10.1016/S0092-8674(00)80151-8. PMID 8797823.
- "TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage". FEBS Letters 428 (3): 171–6. May 1998. doi:10.1016/S0014-5793(98)00523-7. PMID 9654129.
- "Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells". The Journal of Biological Chemistry 276 (17): 13847–51. April 2001. doi:10.1074/jbc.M010556200. PMID 11278699.
- "A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression". The Journal of Biological Chemistry 277 (18): 15354–62. May 2002. doi:10.1074/jbc.M110765200. PMID 11854277.
- "The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner". The Journal of Biological Chemistry 277 (52): 51068–76. December 2002. doi:10.1074/jbc.M205121200. PMID 12401803.
- "The human plasma proteome: a nonredundant list developed by combination of four separate sources". Molecular & Cellular Proteomics 3 (4): 311–26. April 2004. doi:10.1074/mcp.M300127-MCP200. PMID 14718574.
- "The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link". The Journal of Biological Chemistry 280 (12): 11936–42. March 2005. doi:10.1074/jbc.M409016200. PMID 15653696.
- "Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily". The Journal of Biological Chemistry 280 (18): 18189–201. May 2005. doi:10.1074/jbc.M414343200. PMID 15718240.
- "Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line". Biochemical and Biophysical Research Communications 330 (3): 737–45. May 2005. doi:10.1016/j.bbrc.2005.03.040. PMID 15809059.
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