| Primary Identifier | IPR017371 | Type | Family |
| Short Name | TNFR_11B |
| 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 residuesarranged 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 signalling have potential roles in the prevention and treatment of many diseases, such as viral infections, coronary heart disease, transplant rejection, and immune disease []. TNF receptors 11A and 11B mediate the effects of receptor activator for NF-kappa-B ligand (RANKL), an essential osteoclast regulatory factor. The receptors have opposing effects -activation of TNF receptor 11A by RANKL promotes osteoclast differentiation [], while TNF receptor 11B acts as a soluble decoy receptor for the ligand, thus inhibiting differentiation []. TNF receptor 11B (also known as osteoprotegerin (OPG)) is a secreted protein that contains two death domains within its C-terminal region. Mutations in the TNF receptor 11B gene are associated with the autosomal recessive osteopathy juvenile Paget disease []. The receptor may also be involved in vascular calcification, and high expression levels in serum are a risk factor for the progression of atherosclerosis and the onset of cardiovascular disease []. |
