Property Summary

NCBI Gene PubMed Count 67
PubMed Score 168.79
PubTator Score 124.94

Knowledge Summary


No data available


  Disease (3)

Disease Target Count Z-score Confidence
Arthritis 248 4.07 2.0
Ulceroglandular tularemia 2 3.796 1.9


Gene RIF (54)

27143355 The current study describes a novel mechanism linking the TSG-6 transfer of the newly described HC5 to the HA-dependent control of cell phenotype. The interaction of HC5 with cell surface HA was essential for TGFbeta1-dependent differentiation of fibroblasts to myofibroblasts, highlighting its importance as a novel potential therapeutic target.
26685054 Data postulate that the molecular cross-linking enhanced by the multiple binding modes of the Link module might be critical for remodeling the ECM during inflammation/ovulation and might contribute to other functions of TSG-6.
26468290 the well characterized hyaluronan-binding site in the TSG-6 Link module is not used for recognition during transfer of HCs onto HA.
25661977 TSG-6 exhibited anti-inflammatory effects during the wound healing process and cicatrization and significantly diminished hypertrophic scar formation in a rabbit ear model
25561734 Heavy chain transfer by tumor necrosis factor-stimulated gene 6 to the bikunin proteoglycan.
25329668 results suggest that systemic administration of hASC or TSG-6 may be novel approaches to reverse CS-induced myelosuppression.
25325979 TSG-6 activity in tissues, was examined.
24742347 HIV-1 gp120 upregulates the expression of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in human B cells
24667918 HIV-1 gp120 upregulates the expression of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in human B cells
24501198 TSG-6 suppresses CXCL8-mediated chemotaxis of neutrophils; this lower potency effect might be important at sites where there is high local expression of TSG-6.
24403066 the HA-binding site defined here may not play a role in TSG-6-mediated transfer of heavy chains from inter-alpha-inhibitor onto HA, a process known to be essential for ovulation.
24213015 data suggest that TSG-6 expression might be essential in endometrial matrix organization and feto-maternal communication during the implantation process.
24162774 HIV-1 gp120 upregulates the expression of tumor necrosis factor, alpha-induced protein 6 (TNFAIP6) in human B cells
24005673 Data indicate that TSG-6-mediated cross-linking of hyaluronan (HA) films is impaired in the presence of inter-alpha-inhibitor (IalphaI) and that this effect suppresses the TSG-6-mediated enhancement of HA binding to CD44-positive cells.
23921952 This study provides insight into what we believe to be a previously undescribed multifaceted role of mesenchymal stem cell-released TSG-6 in wound healing.
23166324 analysis of irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6
23129777 TSG-6 increases the accumulation of HA in the cell-associated matrix, partially by preventing its dissolution from the cell-associated matrix into the conditioned medium, but primarily by inducing HA synthesis
23017666 The protein product of tumor necrosis factor-alpha stimulated gene-6 strongly correlated with ossification markers and hyaluronidase in calcified human aortic valves.
22922154 This review discusses TSG-6 as a potential molecular marker of oocyte maturation.
22267482 TSG-6 reverts the inhibitory effects exerted by PTX3 on FGF2-mediated angiogenesis through competition of FGF2/PTX3 interaction.
21864707 TSG-6 was central to EMT through effects on HA macromolecular structure and through CD44-dependent triggering of cell responses.
21596748 TSG-6 is a potent HA cross-linking agent
21569482 TSG-6 expression by hMSCs was induced 12 h after oropharyngeal delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects.
21566135 TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
21239672 negative correlation between TSG-6 expression levels and severity of capsular contracture (CC) suggests a possible protective role for TSG-6 in the context of CC formation, and this may have a clinically relevant role in prevention of breast CC
20628624 Meta-analysis of gene-disease association. (HuGE Navigator)
20602615 Observational study of gene-disease association. (HuGE Navigator)
20463016 TSG-6/HC2 link heavy chains randomly on the chondroitin sulfate chain of bikunin, in contrast to the ordered attachment observed during the biosynthesis.
20237496 Observational study of gene-disease association. (HuGE Navigator)
19389798 myelomonocytic cells and MoDC are a major source of TSG-6 and that PTX3 and TSG-6 are coregulated
19383344 up-regulation in human colorectal cancer is correlated with upregulation of the TIMP-1 transcript
19344623 Observational study of gene-disease association. (HuGE Navigator)
18820257 TSG-6 transfers proteins between glycosaminoglycans via a Ser28-mediated covalent catalytic mechanism
18586671 TSG-6 has dual roles in bone remodeling: it inhibits RANKL-induced bone erosion in inflammatory diseases, and its interactions with BMP-2 and RANKL help to balance mineralization by osteoblasts and bone resorption by osteoclasts
18448433 The transfer of heavy chains from bikunin proteins to hyaluronan requires both TSG-6 and HC2.
18260761 3 genes were upregulated in patients with chronic EBV infection: guanylate binding protein 1, tumor necrosis factor-induced protein 6, and guanylate binding protein 5; they may be associated with the inflammatory reaction or with cell proliferation.
18042364 TSG-6 is a high affinity ligand that can mediate fibronectin interactions with other matrix components and modulate some interactions of fibronectin with cells
17585936 Crystallography data on the free protein, and (15)N NMR relaxation data for the uncomplexed and HA(8)-bound forms of Link_TSG6, is presented.
16873769 TSG-6 may play an important protective role in bronchial epithelium by increasing the antiprotease screen on the airway lumen.
16771708 TSG-6 is down-regulated during osteoblastic differentiation, and suppressed osteoblastic differentiation induced by both BMP-2 and osteogenic differentiation medium.
16709183 Evidence is cited in this review that TSG-6 can regulate the expression of various molecules that have important roles in the control of inflammation.
16687630 hyaluronan synthase 2 and TSG-6 have roles in hyaluronan distribution and function in proximal tubular epithelial cells
16467113 The tumor necrosis factor alpha induced protein 6 is a potential marker that could be used for early diagnosis and prognosis of cancerous or precancerous lesions.
16453284 Observational study of gene-disease association. (HuGE Navigator)
16006654 Results suggest a physiological function of thrombospondin-1 binding to TSG-6 in regulation of hyaluronan metabolism at sites of inflammation.
15917224 heparin with the Link module significantly increases the anti-plasmin activity of the TSG-6.IalphaI complex; TSG-6 is likely to contribute to matrix remodeling, at least in part, through down-regulation of the protease network
15840581 TSG-6 acts as cofactor and catalyst in the production of IalphaI heavy chain x hyaluronan complexes
15809059 TSG-6 treatment also resulted in a rapid increase in cyclooxygenase-2 (COX-2) mRNA levels, suggesting that TSG-6 up-regulates COX-2 gene expression
15718240 This TSG-6 model reveals the residues most likely to be involved in stabilizing the inter-Link module interface, which are highly conserved across the Link protein/ chondroitin sulfate proteoglycan subfamily.
15653696 The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link.
14515153 Tumor necrosis factor, alpha-induced protein 6 activates an anti-inflammatory agent- inter-alpha-inhibitor[review].
12692188 TSG-6 is a multifunctional protein associated with inflammation [review]
11854277 Observational study of gene-disease association. (HuGE Navigator)
11854277 polymorphism in osteoarthritis; chromosome location given here (chromosome 2)

AA Sequence


Text Mined References (68)

PMID Year Title
27143355 2016 Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)-mediated Interactions with the Inter-?-inhibitor Heavy Chain 5 Facilitate Tumor Growth Factor ?1 (TGF?1)-dependent Fibroblast to Myofibroblast Differentiation.
27044744 2016 The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by Inhibiting Chemokine/Glycosaminoglycan Interactions.
26685054 2016 Nuclear Magnetic Resonance Insight into the Multiple Glycosaminoglycan Binding Modes of the Link Module from Human TSG-6.
26468290 2015 Metal Ion-dependent Heavy Chain Transfer Activity of TSG-6 Mediates Assembly of the Cumulus-Oocyte Matrix.
25661977 2015 Anti-inflammatory cytokine TSG-6 inhibits hypertrophic scar formation in a rabbit ear model.
25561734 2015 Heavy chain transfer by tumor necrosis factor-stimulated gene 6 to the bikunin proteoglycan.
25329668 2015 Human adipose-derived stem cells ameliorate cigarette smoke-induced murine myelosuppression via secretion of TSG-6.
25325979 2015 Analysis of the heavy-chain modification and TSG-6 activity in pathological hyaluronan matrices.
24501198 2014 TSG-6 inhibits neutrophil migration via direct interaction with the chemokine CXCL8.
24403066 2014 A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function.
24213015 2014 Modulation of tumor necrosis factor-stimulated gene-6 (TSG-6) expression in human endometrium.
24005673 2013 Inter-?-inhibitor impairs TSG-6-induced hyaluronan cross-linking.
23921952 2014 TSG-6 released from intradermally injected mesenchymal stem cells accelerates wound healing and reduces tissue fibrosis in murine full-thickness skin wounds.
23166324 2013 Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6.
23143601 2012 Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.
23129777 2013 Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by airway smooth muscle cells.
23017666 2012 Hyaluronan turnover and hypoxic brown adipocytic differentiation are co-localized with ossification in calcified human aortic valves.
22922154 2012 [TSG-6 protein and its role during maturation of ovarian follicles].
22267482 2012 Long pentraxin 3/tumor necrosis factor-stimulated gene-6 interaction: a biological rheostat for fibroblast growth factor 2-mediated angiogenesis.
21864707 2011 Tumour necrosis factor-stimulated gene (TSG)-6 controls epithelial-mesenchymal transition of proximal tubular epithelial cells.
21596748 2011 The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers.
21569482 2011 Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-?-induced protein 6.
21566135 2011 TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
21239672 2011 Hyaluronan, TSG-6, and inter-?-inhibitor in periprosthetic breast capsules: reduced levels of free hyaluronan and TSG-6 expression in contracted capsules.
20628624 2010 Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot".
20602615 2010 Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol?
20463016 2010 The TSG-6/HC2-mediated transfer is a dynamic process shuffling heavy chains between glycosaminoglycans.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
19389798 2009 Coregulation in human leukocytes of the long pentraxin PTX3 and TSG-6.
19383344 2008 TIMP-1 expression in human colorectal cancer is associated with TGF-B1, LOXL2, INHBA1, TNF-AIP6 and TIMP-2 transcript profiles.
19344623 2009 Polymorphisms in the tumour necrosis factor alpha-induced protein 3 (TNFAIP3) gene are associated with chronic rhinosinusitis.
18820257 2008 TSG-6 transfers proteins between glycosaminoglycans via a Ser28-mediated covalent catalytic mechanism.
18586671 2008 TSG-6 regulates bone remodeling through inhibition of osteoblastogenesis and osteoclast activation.
18448433 2008 The transfer of heavy chains from bikunin proteins to hyaluronan requires both TSG-6 and HC2.
18260761 2008 Oligonucleotide microarray analysis of gene expression profiles followed by real-time reverse-transcriptase polymerase chain reaction assay in chronic active Epstein-Barr virus infection.
18042364 2008 TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly.
17585936 2007 Plasticity of the TSG-6 HA-binding loop and mobility in the TSG-6-HA complex revealed by NMR and X-ray crystallography.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16873769 2007 TSG-6 potentiates the antitissue kallikrein activity of inter-alpha-inhibitor through bikunin release.
16771708 2006 Tumour necrosis factor alpha-stimulated gene-6 inhibits osteoblastic differentiation of human mesenchymal stem cells induced by osteogenic differentiation medium and BMP-2.
16709183 2006 TSG-6: a pluripotent inflammatory mediator?
16687630 2006 Overexpression of hyaluronan synthase 2 alters hyaluronan distribution and function in proximal tubular epithelial cells.
16467113 2006 2-Methoxyestradiol inhibits prostate tumor development in transgenic adenocarcinoma of mouse prostate: role of tumor necrosis factor-alpha-stimulated gene 6.
16453284 2006 Reproducible genetic associations between candidate genes and clinical knee osteoarthritis in men and women.
16006654 2005 The N-terminal module of thrombospondin-1 interacts with the link domain of TSG-6 and enhances its covalent association with the heavy chains of inter-alpha-trypsin inhibitor.
15917224 2005 Characterization of the interaction between tumor necrosis factor-stimulated gene-6 and heparin: implications for the inhibition of plasmin in extracellular matrix microenvironments.
15840581 2005 Characterization of complexes formed between TSG-6 and inter-alpha-inhibitor that act as intermediates in the covalent transfer of heavy chains onto hyaluronan.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15809059 2005 Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line.
15718240 2005 Towards a structure for a TSG-6.hyaluronan complex by modeling and NMR spectroscopy: insights into other members of the link module superfamily.
15653696 2005 The TSG-6 and I alpha I interaction promotes a transesterification cleaving the protein-glycosaminoglycan-protein (PGP) cross-link.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15060082 2004 TSG-6 modulates the interaction between hyaluronan and cell surface CD44.
14718574 2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources.
14515153 2003 Inter-alpha-inhibitor, hyaluronan and inflammation.
12692188 2003 TSG-6: a multifunctional protein associated with inflammation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12401803 2002 The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner.
11854277 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.
11375929 2001 Diverse transcriptional initiation revealed by fine, large-scale mapping of mRNA start sites.
11278699 2001 Mechanical strain induces specific changes in the synthesis and organization of proteoglycans by vascular smooth muscle cells.
9654129 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.
8797823 1996 Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration.
8568267 1996 TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo.
8454591 1993 Transcriptional regulation of TSG6, a tumor necrosis factor- and interleukin-1-inducible primary response gene coding for a secreted hyaluronan-binding protein.
7935377 1994 NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1.
7516184 1994 TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor.
1730767 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.