TNF receptor superfamily

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.[2][3] With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha.[4] 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.[4]

TNFR/NGFR cysteine-rich region
Structure of the soluble human 55 kd TNF receptor-human TNF beta complex.[1]
Identifiers
SymbolTNFR_c6
PfamPF00020
InterProIPR011614
PROSITEPDOC00561
SCOPe1tnr / SUPFAM
Membranome6

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.[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 and TNFR2, which recognize TNF-alpha.

Members

There are 27 family members, numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter.[2]

Type Protein (member #) Synonyms Gene Ligand(s)
1 Tumor necrosis factor receptor 1 (1A) CD120a TNFRSF1A TNF-alpha (cachectin)
Tumor necrosis factor receptor 2 (1B) CD120b TNFRSF1B
3 Lymphotoxin beta receptor (3) CD18 LTBR Lymphotoxin beta (TNF-C)
4 OX40 (4) CD134 TNFRSF4 OX40L
5 CD40 (5) Bp50 CD40 CD154
6 Fas receptor (6) Apo-1, CD95 FAS FasL
Decoy receptor 3 (6B) TR6, M68 TNFRSF6B FasL, LIGHT, TL1A
7 CD27 (7) S152, Tp55 CD27 CD70, Siva
8 CD30 (8) Ki-1, TNR8 TNFRSF8 CD153
9 4-1BB (9) CD137 TNFRSF9 4-1BB ligand
10 Death receptor 4 (10A) TRAILR1, Apo-2, CD261 TNFRSF10A TRAIL
Death receptor 5 (10B) TRAILR2, CD262 TNFRSF10B
Decoy receptor 1 (10C) TRAILR3, LIT, TRID, CD263 TNFRSF10C
Decoy receptor 2 (10D) TRAILR4, TRUNDD, CD264 TNFRSF10D
11 RANK (11A) CD265 TNFRSF11A RANKL
Osteoprotegerin (11B) OCIF, TR1 TNFRSF11B
12 TWEAK receptor (12A) Fn14, CD266 TNFRSF12A TWEAK
13 TACI (13B) IGAD2, CD267 TNFRSF13B APRIL, BAFF, CAMLG
BAFF receptor (13C) CD268 TNFRSF13C BAFF
14 Herpesvirus entry mediator (14) ATAR, TR2, CD270 TNFRSF14 LIGHT
16 Nerve growth factor receptor (16) p75NTR, CD271 NGFR NGF, BDNF, NT-3, NT-4
17 B-cell maturation antigen (17) TNFRSF13A, CD269 TNFRSF17 BAFF
18 Glucocorticoid-induced TNFR-related (18) AITR, CD357 TNFRSF18 GITR ligand
19 TROY (19) TAJ, TRADE TNFRSF19 unknown
21 Death receptor 6 (21) CD358 TNFRSF21
25 Death receptor 3 (25) Apo-3, TRAMP, LARD, WS-1 TNFRSF25 TL1A
27 Ectodysplasin A2 receptor (27) XEDAR EDA2R EDA-A2
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References
  1. 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. PMID 8387891.
  2. Locksley RM, Killeen N, Lenardo MJ (2001). "The TNF and TNF receptor superfamilies: integrating mammalian biology". Cell. 104 (4): 487–501. doi:10.1016/S0092-8674(01)00237-9. PMID 11239407.
  3. Hehlgans T, Pfeffer K (2005). "The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games". Immunology. 115 (1): 1–20. doi:10.1111/j.1365-2567.2005.02143.x. PMC 1782125. PMID 15819693.
  4. Gravestein, 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. PMID 9826575.
  5. Ashkenazi, A.; Dixit, VM (1998). "Death Receptors: Signaling and Modulation". Science. 281 (5381): 1305–8. doi:10.1126/science.281.5381.1305. PMID 9721089.

Further reading
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