TNFR1, a type I membrane protein, is a prototype of the TNF receptor superfamily. TNF binds with high affinity to two members of the TNFRSF family, TNFR1 (P55) which is activated by both membrane-anchored TNF (tmTNF) and soluble TNF, and TNFR2 (P75) which is activated mainly by tmTMF
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|Synonym:||CD120a, TNFRSF1A, FPF, MGC19588, p55, p55-R, p60, TBP1, TNF-R, TNF-R-I, TNF-R55, TNFAR, TNFR55, TNFR60|
|Tag:||Mouse IgG2a Fc|
|Construction:||Human TNFR1 (I22-T211)-Mouse IgG2a Fc|
|MW (calculated):||48,463 Kd|
|MW (SDS-PAGE):||50 Kd|
|Abs 0.1% (= 1 mg/ml):||1.006|
TNFR1, a type I membrane protein, is a prototype of the TNF receptor superfamily. TNF binds with high affinity to two members of the TNFRSF family, TNFR1 (P55) which is activated by both membrane-anchored TNF (tmTNF) and soluble TNF, and TNFR2 (P75) which is activated mainly by tmTMF. Most of the biological activity of TNF is mediated by TNFR1. The extracellular domain of the TNFR1 contains 4 cysteine-rich domains (CRD1-4). The CRD1 contains the pre-ligand assembly domain (PLAD) which is thought to play a role in dimerization of the CRD2 domain that is critical for high affinity ligand binding.
TNFR1 binds to two ligands, TNF and lymphotoxin-alpha (LT-alpha), both of which also bind to the closely related receptor, the TNFR2. TNFR1-deficient mice are highly sensitive to bacterial and viral infections. The systemic inflammation triggered by elevated circulating TNF that may lead to death is primarily mediated by TNFR1. Chronically overexposure to TNF leads to arthritis and inflammatory bowel diseases, both are TNFR1 dependent. Lastly the antitumor effect of TNF is entirely mediated by TNFR1.
The extracellular domain of TNFR1 can be proteolyzed by TACI and release as soluble protein, which just like P020F, is capable of interacting with TNF and LT-alpha. A splice variant of TNFR1, TNFR-D6, which misses both transmembrane and intracellular domain is associated with multiple sclerosis (MS). The soluble TNFR1-D6 protein behaves as a decoy receptor and mimics the effect of TNF-blockers.
Amino Acid Sequence.
References1. Chen G, Goeddel DV. (2002) TNF-R1 signaling: a beautiful pathway. Science 296:1634–1635
2. Chan FK, Chun HJ, Zheng L, Siegel RM, Bui KL, Lenardo MJ. (2000) A domain in TNF receptors that mediates ligand-independent receptor assembly and signaling. Science 288:2351–2354.
3. Kontoyiannis D, Pasparakis M, Pizarro TT, Cominelli F, Kollias G. ( 1999) Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10:387–398
4. Gregory AP, Dendrou CA, Attfield KE, Haghikia A, Xifara DK, Butter F, et al. (2011) TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature 488:508–511.