TNFR1 (CY/Fc-Fusion)

While TNFR1 and TNFR2 share similar extracellular CRD regions and can bind to both TNF and LT-α the intracellular domains of these two receptors share little homology indicating each bears distinct signaling mechanism. TNFR1 contains the characteristic death domain that provides interface for interacting with death domain of TRADD, which, in turn, recruits components such as TRAFs, RIPK1, and FADD and forms the signaling complex.

Interacting protein(s): TNF, LT-a
Related products: TNF-Receptor Superfamily

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Quick Specs

Description

While TNFR1 and TNFR2 share similar extracellular CRD regions and can bind to both TNF and LT-α the intracellular domains of these two receptors share little homology indicating each bears distinct signaling mechanism. TNFR1 contains the characteristic death domain that provides interface for interacting with death domain of TRADD, which, in turn, recruits components such as TRAFs, RIPK1, and FADD and forms the signaling complex.

This complex activates at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Soluble TNFR1 that is fully active for binding TNF can be found in blood and urine of healthy individual and its level is elevated in patients with infection, immunological disorders or cancers. At physiological pH, soluble TNFR1 can form parallel dimers or anti-parallel dimers. Binding of TNF is occluded from the anti-parallel dimers. Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS).

In addition, point mutations in TNFRSF1A gene is associated with susceptibility to the type 5 multiple sclerosis (MS5), a multifactorial, inflammatory, demyelinating disease of the central nervous system.

Amino Acid Sequence.

References

1. Siegmund D, Wajant H. TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond. Nat Rev Rheumatol. 2023;19(9):576-91. Epub 20230804. doi: 10.1038/s41584-023-01002-7. PubMed PMID: 37542139.

2. Molecular cloning and expression of a receptor for human tumor necrosis factor. Schall T.J., Lewis M., Koller K.J., Lee A., Rice G.C., Wong G.H.W., Getanaga T., Granger G.A., Lentz R., Raab H., Kohr W.J., Goeddel D.V. Cell 61:361-370 (1990) 

3. Soluble forms of tumor necrosis factor receptors (TNF-Rs). The cDNA for the type I TNF-R, cloned using amino acid sequence data of its soluble form, encodes both the cell surface and a soluble form of the receptor. Nophar Y., Kemper O., Brakebusch C., Engelmann H., Zwang R., Aderka D., Holtmann H., Wallach D. EMBO J. 9:3269-3278 (1990) 

4. Prevention of constitutive TNF receptor 1 signaling by silencer of death domains. Jiang Y., Woronicz J.D., Liu W., Goeddel D.V. Science 283:543-546 (1999)