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TNFR1 (Tumor necrosis factor receptor 1) belongs to the tumor necrosis factor superfamily, and is one of the major TNF-alpha receptors. TNFR1 plays an important role in mediating, in cytokine mediated signaling, positive regulation of the NF-Kb pathway, positive regulation of angiogenesis, and negative regulation of gene expression. The extracellular domain of TNFR1 is also released into the circulatory system as soluble TNFR1 (sTNFR1). In humans, the TNFR1 gene is located on chromosome 12. Anti-apoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with TNFR1, and thus play regulatory roles in the signal transduction mediated by the receptor. Germline mutations of the extracellular domains of TNFR1 were found to be associated with the autosomal dominant periodic fever syndrome, and the impaired receptor clearance is thought to be a mechanism of the disease.
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