TNFAIP6
TNFAIP6 (TNF alpha induced protein 6, also known as TSG6 or TSG-6) is a secreted, hyaluronan-binding protein that regulates extracellular matrix organisation during tissue remodelling. It is induced by proinflammatory cytokines and links matrix biology with inflammation. Browse Assay Genie's current range of TNFAIP6 research reagents below, or read on for the biology behind the target.
TNFAIP6 is a major regulator of extracellular matrix organisation during tissue remodelling. It catalyses the transfer of a heavy chain (HC) from the inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. To do this, it cleaves the ester bond between the C-terminus of the HC and the GalNAc residue of the chondroitin sulfate chain, then transesterifies the HC onto hyaluronan. This releases free bikunin and so potentiates the antiprotease function of I-alpha-I. The same activity helps build hyaluronan-HC oligomers and the hyaluronan-rich matrix around the cumulus cell-oocyte complex, a necessary step for oocyte fertilisation.
Beyond matrix assembly, TNFAIP6 organises hyaluronan in pericellular matrices that act as platforms for receptor clustering and signalling. It enables hyaluronan on macrophage surfaces to bind LYVE1 on lymphatic endothelium, facilitating macrophage extravasation. It also alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling. It modulates chemokine interactions with matrix components and proteoglycans, and may limit excessive neutrophil recruitment by antagonising the association of CXCL8 with glycosaminoglycans. In bone, it inhibits BMP2-dependent differentiation of mesenchymal stem cells to osteoblasts and protects against inflammatory bone erosion by inhibiting TNFSF11/RANKL-dependent osteoclast activation.
The TNFAIP6 gene encodes a secretory protein with a hyaluronan-binding domain, placing it in the hyaluronan-binding protein family; this domain is linked to extracellular matrix stability and cell migration. The gene is induced by proinflammatory cytokines such as tumour necrosis factor alpha and interleukin-1, which explains its name. Elevated levels of the protein are found in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.
TNFAIP6 is a major regulator of matrix organisation, transferring heavy chains of inter-alpha-inhibitor onto hyaluronan during tissue remodelling.
It switches CD44 into an active state supporting leukocyte rolling and may limit neutrophil recruitment by antagonising CXCL8 binding to glycosaminoglycans.
Enhanced TNFAIP6 levels occur in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis.
TNFAIP6 inhibits BMP2-driven osteoblast differentiation and RANKL-dependent osteoclast activation, and supports the hyaluronan-rich matrix needed for oocyte fertilisation.
TNFAIP6 catalyses transfer of the heavy chain from the inter-alpha-inhibitor complex to hyaluronan, releasing free bikunin and enhancing antiprotease activity. This builds hyaluronan-rich matrices, including that around the cumulus cell-oocyte complex, and influences CD44 activity, chemokine binding and bone remodelling.
TNFAIP6 is also called TSG6 or TSG-6. Its HGNC name is TNF alpha induced protein 6, previously tumour necrosis factor, alpha-induced protein 6, and UniProt lists it as tumour necrosis factor-inducible gene 6 protein. The names reflect induction by TNF alpha and interleukin-1.
A mouse ortholog, Tnfaip6, exists; check the datasheet of any product for its validated reactivity. Raised TNFAIP6 protein is reported in the synovial fluid of patients with osteoarthritis and rheumatoid arthritis, and it is implicated in inflammation-associated bone erosion.
Other TNF-induced proteins with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P98066; product specifications from Assay Genie datasheets.