TSG-6

Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein[5] that in humans is encoded by the TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) gene.[6][7]

TNFAIP6
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTNFAIP6, TSG-6, TSG6, TNF alpha induced protein 6
External IDsOMIM: 600410 MGI: 1195266 HomoloGene: 5162 GeneCards: TNFAIP6
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2q23.3Start151,357,592 bp[1]
End151,380,046 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 2: 52.04 – 52.06 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7] TSG-6 has been shown to modulate macrophage plasticity and signal the transition of LPS-treated macrophages from pro- to anti-inflammatory phenotype.[8]

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

References
  1. GRCh38: Ensembl release 89: ENSG00000123610 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000053475 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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". The Journal of Cell Biology. 116 (2): 545–57. doi:10.1083/jcb.116.2.545. PMC 2289279. PMID 1730767.
  6. 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". The Journal of Biological Chemistry. 268 (9): 6154–60. PMID 8454591.
  7. "Entrez Gene: TNFAIP6 tumor necrosis factor, alpha-induced protein 6".
  8. Mittal M, Tiruppathi C, Nepal S, Zhao YY, Grzych D, Soni D, Prockop DJ, Malik AB (December 2016). "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. doi:10.1073/pnas.1614935113. PMC 5167170. PMID 27911817.

Further reading
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