Tumour necrosis factor receptor 21 (IPR022330)

Short name: TNFR_21

Overlapping homologous superfamilies


Family relationships



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 [PMID: 7917108]. The cysteines allow formation of an extended rod-like structure, responsible for ligand binding [PMID: 8387891].

Upon receptor activation, different intracellular signalling complexes are assembled for different members of the TNFR superfamily, depending on their intracellular domains and sequences [PMID: 15500863]. 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 [PMID: 11239407, PMID: 9826575].

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 [PMID: 15500863]. 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 [PMID: 9826574].

TNF receptor 21, also termed death receptor 6 (DR6), is expressed ubiquitously, with high expression in lymphoid organs, heart, brain and pancreas. The receptor plays an important regulatory role in the generation of adaptive immunity and may be involved in tumour cell survival and immune evasion [PMID: 19760075]. It has also been implicated in the pathogenesis of Alzheimer's disease, as activation of the receptor by beta-amyloid precursor protein triggers neuronal death via a caspase-dependent pathway [PMID: 19225519].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.