The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane 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 specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocytes.
The term death receptor refers to those members of the TNF receptor superfamily that contain a death domain, such as TNFR1, Fas receptor, DR4 and DR5. 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.
In the strict sense, the term TNF receptor is often used to refer to the archetypal members of the superfamily, namely TNFR1 and TNFR2, which recognize TNF-alpha.
Members In humans, there are 29 known family members of the TNF receptor superfamily. Historically, the family members have been numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter. Some newer additions to the TNF family remain unnumbered, however, such as the TNF receptor superfamily member EDAR.
Type Protein (member #) Synonyms Gene Ligand(s) 1 Tumor necrosis factor receptor 1 (1A) CD120a TNF (cachectin) Tumor necrosis factor receptor 2 (1B) CD120b 3 Lymphotoxin beta receptor (3) CD18 Lymphotoxin beta (TNF-C) 4 OX40 (4) CD134 OX40L 5 CD40 (5) Bp50 CD154 6 Fas receptor (6) Apo-1, CD95 FasL Decoy receptor 3 (6B) TR6, M68 FasL, LIGHT, TL1A 7 CD27 (7) S152, Tp55 CD70, Siva 8 CD30 (8) Ki-1, TNR8 CD153 9 4-1BB (9) CD137 4-1BB ligand 10 Death receptor 4 (10A) TRAILR1, Apo-2, CD261 TRAIL Death receptor 5 (10B) TRAILR2, CD262 Decoy receptor 1 (10C) TRAILR3, LIT, TRID, CD263 Decoy receptor 2 (10D) TRAILR4, TRUNDD, CD264 11 RANK (11A) CD265 RANKL Osteoprotegerin (11B) OCIF, TR1 12 TWEAK receptor (12A) Fn14, CD266 TWEAK 13 TACI (13B) IGAD2, CD267 APRIL, BAFF, CAMLG BAFF receptor (13C) CD268 BAFF 14 Herpesvirus entry mediator (14) ATAR, TR2, CD270 LIGHT 16 Nerve growth factor receptor (16) p75NTR, CD271 NGF, BDNF, NT-3, NT-4 17 B-cell maturation antigen (17) TNFRSF13A, CD269, BCMA BAFF 18 Glucocorticoid-induced TNFR-related (18) AITR, CD357 GITR ligand 19 TROY (19) TAJ, TRADE unknown19LRELT (19L)FLJ14993RELT 21 Death receptor 6 (21) CD358 25 Death receptor 3 (25) Apo-3, TRAMP, LARD, WS-1 TL1A 27 Ectodysplasin A2 receptor (27) XEDAR EDA-A2EDAREctodysplasin A receptor (EDAR)Downless HomologEDAREDA-A1
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