Thetumor necrosis factor receptor superfamily (TNFRSF) is aprotein superfamily ofcytokine receptors characterized by the ability to bindtumor necrosis factors (TNFs) via an extracellularcysteine-rich domain.[2][3] With the exception ofnerve growth factor (NGF), all TNFs are homologous to the archetypalTNF-alpha.[4] In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors containtransmembrane domains (TMDs), although some can be cleaved into soluble forms (e.g.TNFR1), and some lack a TMD entirely (e.g.DcR3). In addition, most TNF receptors require specificadaptor protein such asTRADD,TRAF,RIP andFADD for downstream signalling. TNF receptors are primarily involved inapoptosis andinflammation, but they can also take part in othersignal transduction pathways, such asproliferation, survival, anddifferentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially inleukocytes.[4]
The termdeath receptor refers to those members of the TNF receptor superfamily that contain adeath domain, such as TNFR1,Fas receptor,DR4 andDR5.[4] They were named after the fact that they seemed to play an important role in apoptosis (programmed cell death), although they are now known to play other roles as well.[5]
In the strict sense, the term TNF receptor is often used to refer to the archetypal members of the superfamily, namely TNFR1 andTNFR2, which recognize TNF-alpha.
In humans, there are 29 known family members of the TNF receptor superfamily.[6][7] Historically, the family members have been numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter.[2] Some newer additions to the TNF family remain unnumbered, however, such as the TNF receptor superfamily member EDAR.[2][8]
^Banner DW, D'Arcy A, Janes W, et al. (May 1993). "Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation".Cell.73 (3):431–45.doi:10.1016/0092-8674(93)90132-A.PMID8387891.S2CID25155518.
^abcGravestein, LA; Borst, J (December 1998). "Tumor necrosis factor receptor family members in the immune system".Seminars in Immunology.10 (6):423–34.doi:10.1006/smim.1998.0144.PMID9826575.
