| Primary Identifier | IPR020419 | Type | Family |
| Short Name | TNFR_1A |
| description | The tumour necrosis factor (TNF) receptor (TNFR) superfamily comprises more than 20 type-I transmembrane proteins. Family members are defined based on similarity in their extracellular domain - a region that contains many cysteine residues arranged in a specific repetitive pattern []. The cysteines allow formation of an extended rod-like structure, responsible for ligand binding []. Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences []. Activation of TNFRs can therefore induce a range of disparate effects, including cell proliferation, differentiation, survival, or apoptotic cell death, depending upon the receptor involved [, ]. TNFRs are widely distributed and play important roles in many crucial biological processes, such as lymphoid and neuronal development, innate and adaptive immunity, and maintenance of cellular homeostasis []. Drugs that manipulate their signaling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease []. TNF receptor 1A (also known as TNF-R1 and CD120a antigen) contains a death domain within its C-terminal region that mediates interactions with several proteins involved in signaling the downstream effects of TNF. Activation of the receptor may induce either cell survival or apoptosis, the latter proceeding via recruitment of the adaptor protein FADD and caspase-8 to the receptor complex []. Defects in TNF receptor 1A are the cause of familial hibernian fever (FHF) - an autosomal dominant disease characterised by recurrent fever, abdominal pain, localised tender skin lesions and myalgia. |
