View source for TSG-6

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Tumor necrosis factor-inducible gene 6 protein''' also known as '''TNF-stimulated gene 6 protein''' or '''TSG-6''' is a [[protein]]<ref name="pmid1730767">{{cite journal | vauthors = Lee TH, Wisniewski HG, Vilcek J | title = 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 | journal = The Journal of Cell Biology | volume = 116 | issue = 2 | pages = 545–57 | date = January 1992 | pmid = 1730767 | pmc = 2289279 | doi = 10.1083/jcb.116.2.545 }}</ref> that in humans is encoded by the ''TNFAIP6'' (tumor necrosis factor, alpha-induced protein 6) [[gene]].<ref name="pmid8454591">{{cite journal | vauthors = Lee TH, Klampfer L, Shows TB, Vilcek J | title = Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein | journal = The Journal of Biological Chemistry | volume = 268 | issue = 9 | pages = 6154–60 | date = March 1993 | doi = 10.1016/S0021-9258(18)53232-4 | pmid = 8454591 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TNFAIP6 tumor necrosis factor, alpha-induced protein 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7130}}</ref>
== Structure and function ==
TSG-6 is a 30 [[atomic mass unit|kDa]] secreted protein that contains a [[hyaluronan]]-binding LINK domain a and thus is a member of the hyaluronan-binding protein family, also called [[hyaladherin]]s. 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 ([[ITIH1|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 ([[Tumor necrosis factor-alpha|TNF-α]]) and interleukin-1 ([[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.<ref name="entrez"/> TSG-6 has been shown to modulate macrophage plasticity and signal the transition of LPS-treated macrophages from pro- to anti-inflammatory phenotype.<ref name="Mittal et. al">{{cite journal | vauthors = Mittal M, Tiruppathi C, Nepal S, Zhao YY, Grzych D, Soni D, Prockop DJ, Malik AB | title = TNFα-stimulated gene-6 (TSG6) activates macrophage phenotype transition to prevent inflammatory lung injury | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 113 | issue = 50 | pages = E8151–E8158 | date = December 2016 | pmid = 27911817 | pmc = 5167170 | doi = 10.1073/pnas.1614935113 | bibcode = 2016PNAS..113E8151M | doi-access = free }}</ref>
TSG-6 also interacts with a number of matrix associated molecules such as [[aggrecan]], [[versican]], [[thrombospondin]] (1&2), [[PTX3|pentraxin-3]] and [[fibronectin]].
== References ==
{{reflist}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Milner CM, Day AJ | title = TSG-6: a multifunctional protein associated with inflammation | journal = Journal of Cell Science | volume = 116 | issue = Pt 10 | pages = 1863–73 | date = May 2003 | pmid = 12692188 | doi = 10.1242/jcs.00407 | doi-access = free }}
* {{cite journal | vauthors = Fries E, Kaczmarczyk A | title = Inter-alpha-inhibitor, hyaluronan and inflammation | journal = Acta Biochimica Polonica | volume = 50 | issue = 3 | pages = 735–42 | year = 2004 | doi = 10.18388/abp.2003_3664 | pmid = 14515153 | url = http://www.actabp.pl/pdf/3_2003/735.pdf | doi-access = free }}
* {{cite journal | vauthors = Milner CM, Higman VA, Day AJ | title = TSG-6: a pluripotent inflammatory mediator? | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 3 | pages = 446–50 | date = June 2006 | pmid = 16709183 | doi = 10.1042/BST0340446 }}
* {{cite journal | vauthors = Wisniewski HG, Burgess WH, Oppenheim JD, Vilcek J | title = TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor | journal = Biochemistry | volume = 33 | issue = 23 | pages = 7423–9 | date = June 1994 | pmid = 7516184 | doi = 10.1021/bi00189a049 }}
* {{cite journal | vauthors = Klampfer L, Lee TH, Hsu W, Vilcek J, Chen-Kiang S | title = NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1 | journal = Molecular and Cellular Biology | volume = 14 | issue = 10 | pages = 6561–9 | date = October 1994 | pmid = 7935377 | pmc = 359186 | doi =  10.1128/MCB.14.10.6561}}
* {{cite journal | vauthors = Wisniewski HG, Hua JC, Poppers DM, Naime D, Vilcek J, Cronstein BN | title = TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo | journal = Journal of Immunology | volume = 156 | issue = 4 | pages = 1609–15 | date = February 1996 | doi = 10.4049/jimmunol.156.4.1609 | pmid = 8568267 | s2cid = 22926288 | doi-access = free }}
* {{cite journal | vauthors = Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ | title = Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration | journal = Cell | volume = 86 | issue = 5 | pages = 767–75 | date = September 1996 | pmid = 8797823 | doi = 10.1016/S0092-8674(00)80151-8 | s2cid = 16347386 | doi-access = free }}
* {{cite journal | vauthors = Parkar AA, Kahmann JD, Howat SL, Bayliss MT, Day AJ | title = TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage | journal = FEBS Letters | volume = 428 | issue = 3 | pages = 171–6 | date = May 1998 | pmid = 9654129 | doi = 10.1016/S0014-5793(98)00523-7 | s2cid = 30827372 | doi-access = free }}
* {{cite journal | vauthors = Lee RT, Yamamoto C, Feng Y, Potter-Perigo S, Briggs WH, Landschulz KT, Turi TG, Thompson JF, Libby P, Wight TN | title = Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells | journal = The Journal of Biological Chemistry | volume = 276 | issue = 17 | pages = 13847–51 | date = April 2001 | pmid = 11278699 | doi = 10.1074/jbc.M010556200 | doi-access = free }}
* {{cite journal | vauthors = Nentwich HA, Mustafa Z, Rugg MS, Marsden BD, Cordell MR, Mahoney DJ, Jenkins SC, Dowling B, Fries E, Milner CM, Loughlin J, Day AJ | title = 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 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 18 | pages = 15354–62 | date = May 2002 | pmid = 11854277 | doi = 10.1074/jbc.M110765200 | doi-access = free }}
* {{cite journal | vauthors = Getting SJ, Mahoney DJ, Cao T, Rugg MS, Fries E, Milner CM, Perretti M, Day AJ | title = The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner | journal = The Journal of Biological Chemistry | volume = 277 | issue = 52 | pages = 51068–76 | date = December 2002 | pmid = 12401803 | doi = 10.1074/jbc.M205121200 | doi-access = free }}
* {{cite journal | vauthors = Anderson NL, Polanski M, Pieper R, Gatlin T, Tirumalai RS, Conrads TP, Veenstra TD, Adkins JN, Pounds JG, Fagan R, Lobley A | title = The human plasma proteome: a nonredundant list developed by combination of four separate sources | journal = Molecular & Cellular Proteomics | volume = 3 | issue = 4 | pages = 311–26 | date = April 2004 | pmid = 14718574 | doi = 10.1074/mcp.M300127-MCP200 | doi-access = free }}
* {{cite journal | vauthors = Sanggaard KW, Karring H, Valnickova Z, Thøgersen IB, Enghild JJ | title = The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link | journal = The Journal of Biological Chemistry | volume = 280 | issue = 12 | pages = 11936–42 | date = March 2005 | pmid = 15653696 | doi = 10.1074/jbc.M409016200 | doi-access = free }}
* {{cite journal | vauthors = Blundell CD, Almond A, Mahoney DJ, DeAngelis PL, Campbell ID, Day AJ | title = Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily | journal = The Journal of Biological Chemistry | volume = 280 | issue = 18 | pages = 18189–201 | date = May 2005 | pmid = 15718240 | doi = 10.1074/jbc.M414343200 | doi-access = free }}
* {{cite journal | vauthors = Mindrescu C, Le J, Wisniewski HG, Vilcek J | title = Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line | journal = Biochemical and Biophysical Research Communications | volume = 330 | issue = 3 | pages = 737–45 | date = May 2005 | pmid = 15809059 | doi = 10.1016/j.bbrc.2005.03.040 }}
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{{PDB Gallery|geneid=7130}}
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