TSG-6

The LINK domain of TSG-6
File:PBB Protein TNFAIP6 image.jpg PDB rendering based on 1o7b.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1o7b​, 1o7c​
Identifiers
Symbols	TNFAIP6 ; TSG6
External IDs	Template:OMIM5 Template:MGI HomoloGene: 5162
Gene ontology Molecular function Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE TNFAIP6 206026 s at tn.png
File:PBB GE TNFAIP6 206025 s at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

TSG-6 is the protein product of Tumor necrosis factor alpha simulated gene-6 (also known as Tumor necrosis factor alpha-induced protein 6 or TNFAIP6).

TSG-6 is a 30KDa 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 alpha and interleukin-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.

TSG-6 also interacts with a plethora of matrix associated molecules, such an Aggregcan, Versican, Thrombospondin (1&2), Pentraxin-3 and Fibronectin.

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. doi:035003735 . 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.CS1 maint: Multiple names: authors list (link)
• Lee TH, Wisniewski HG, Vilcek J (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. PMID 1730767.CS1 maint: Multiple names: authors list (link)
• 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. PMID 7516184.CS1 maint: Multiple names: authors list (link)
• 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. PMID 7935377.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 8797823.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 9654129.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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. PMID 15489334.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• 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.CS1 maint: Multiple names: authors list (link)