Tumour necrosis factor receptor 12 (IPR022316)

Short name: TNFR_12

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].

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 12, also known as TWEAK receptor (TWEAKR), fibroblast growth factor-inducible-14 (Fn14) or CD266, is expressed on a wide variety of different cell types and binds the ligand TWEAK (tumor necrosis factor-like weak inducer of apoptosis) to activate several signaling cascades through activation of NF-kappaB signaling mediated by adaptor TRAF proteins [PMID: 18404150]. The FN14/TWEAK pathway controls a range of cellular activities such as proliferation, differentiation, and apoptosis, and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with cardiovascular diseases (CVDs) [PMID: 24478772].

The Fn14 receptor is the smallest TNFR superfamily member described so far. It is initially synthesized as a 129-amino-acid type I transmembrane protein that is then proteolytically processed by signal peptidase. The mature form of TweakR has only 102 amino acids and six cysteine residues in its extracellular region [PMID: 11728344, PMID: 18404150].

Contributing signatures

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