TSG-6

Tumor necrosis factor, alpha-induced protein 6
The LINK domain of TSG-6.[1]
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1O7B​, 1O7C​, 2PF5​, 2WNO​
Identifiers
Symbols	TNFAIP6 ; TSG-6; TSG6
External IDs	OMIM: 600410 MGI: 1195266 HomoloGene: 5162 GeneCards: TNFAIP6 Gene
Gene ontology Molecular function • hyaluronic acid binding Cellular component • extracellular region Biological process • inflammatory response • cell adhesion • signal transduction • cell-cell signaling • negative regulation of inflammatory response Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7130	21930
Ensembl	ENSG00000123610	ENSMUSG00000053475
UniProt	P98066	O08859
RefSeq (mRNA)	NM_007115	NM_009398
RefSeq (protein)	NP_009046	NP_033424
Location (UCSC)	Chr 2: 151.36 – 151.38 Mb	Chr 2: 52.04 – 52.06 Mb
PubMed search

Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein^[2] that in humans is encoded by the TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) gene.^[3][4]

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.^[4]

TSG-6 also interacts with a plethora of matrix associated molecules, such an aggrecan, versican, thrombospondin (1&2), pentraxin-3 and fibronectin.

References

1. PDB: 1o7b​; Blundell CD, Mahoney DJ, Almond A, DeAngelis PL, Kahmann JD, Teriete P, Pickford AR, Campbell ID, Day AJ (December 2003). "The link module from ovulation- and inflammation-associated protein TSG-6 changes conformation on hyaluronan binding". J. Biol. Chem. 278 (49): 49261–70. doi:10.1074/jbc.M309623200. PMID 12972412.
2. Lee TH, Wisniewski HG, Vilcek J (January 1992). "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". J. Cell Biol. 116 (2): 545–57. doi:10.1083/jcb.116.2.545. PMC 2289279. PMID 1730767.
3. Lee TH, Klampfer L, Shows TB, Vilcek J (March 1993). "Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein". J. Biol. Chem. 268 (9): 6154–60. PMID 8454591.
4. "Entrez Gene: TNFAIP6 tumor necrosis factor, alpha-induced protein 6".

Further reading

• Milner CM, Day AJ (2004). "TSG-6: a multifunctional protein associated with inflammation.". J. Cell. Sci. 116 (Pt 10): 1863–73. doi:10.1242/jcs.00407. PMID 12692188.
• Fries E, Kaczmarczyk A (2004). "Inter-alpha-inhibitor, hyaluronan and inflammation.". Acta Biochim. Pol. 50 (3): 735–42. PMID 14515153.
• Milner CM, Higman VA, Day AJ (2006). "TSG-6: a pluripotent inflammatory mediator?". Biochem. Soc. Trans. 34 (Pt 3): 446–50. doi:10.1042/BST0340446. PMID 16709183.
• Wisniewski HG, Burgess WH, Oppenheim JD, Vilcek J (1994). "TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor.". Biochemistry 33 (23): 7423–9. doi:10.1021/bi00189a049. PMID 7516184.
• Klampfer L, Lee TH, Hsu W, et al. (1994). "NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1.". Mol. Cell. Biol. 14 (10): 6561–9. PMC 359186. PMID 7935377.
• Wisniewski HG, Hua JC, Poppers DM, et al. (1996). "TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo.". J. Immunol. 156 (4): 1609–15. PMID 8568267.
• Kohda D, Morton CJ, Parkar AA, et al. (1996). "Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration.". Cell 86 (5): 767–75. doi:10.1016/S0092-8674(00)80151-8. PMID 8797823.
• Parkar AA, Kahmann JD, Howat SL, et al. (1998). "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 Lett. 428 (3): 171–6. doi:10.1016/S0014-5793(98)00523-7. PMID 9654129.
• Lee RT, Yamamoto C, Feng Y, et al. (2001). "Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells.". J. Biol. Chem. 276 (17): 13847–51. doi:10.1074/jbc.M010556200. PMID 11278699.
• Nentwich HA, Mustafa Z, Rugg MS, et al. (2002). "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.". J. Biol. Chem. 277 (18): 15354–62. doi:10.1074/jbc.M110765200. PMID 11854277.
• Getting SJ, Mahoney DJ, Cao T, et al. (2003). "The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner.". J. Biol. Chem. 277 (52): 51068–76. doi:10.1074/jbc.M205121200. PMID 12401803.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Anderson NL, Polanski M, Pieper R, et al. (2004). "The human plasma proteome: a nonredundant list developed by combination of four separate sources.". Mol. Cell Proteomics 3 (4): 311–26. doi:10.1074/mcp.M300127-MCP200. PMID 14718574.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Sanggaard KW, Karring H, Valnickova Z, et al. (2005). "The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link.". J. Biol. Chem. 280 (12): 11936–42. doi:10.1074/jbc.M409016200. PMID 15653696.
• Blundell CD, Almond A, Mahoney DJ, et al. (2005). "Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily.". J. Biol. Chem. 280 (18): 18189–201. doi:10.1074/jbc.M414343200. PMID 15718240.
• Mindrescu C, Le J, Wisniewski HG, Vilcek J (2005). "Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line.". Biochem. Biophys. Res. Commun. 330 (3): 737–45. doi:10.1016/j.bbrc.2005.03.040. PMID 15809059.