TNF receptor superfamily

TNFR/NGFR cysteine-rich region
Structure of the soluble human 55 kd TNF receptor-human TNF beta complex.[1]
Identifiers
Symbol	TNFR_c6
Pfam	PF00020
Pfam clan	CL0607
ECOD	389.1.3
InterPro	IPR011614
PROSITE	PDOC00561
SCOP2	1tnr / SCOPe / SUPFAM
Membranome	6
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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]

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 (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, BCMA	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

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. S2CID 25155518.
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. S2CID 7657797.
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

• Kavurma MM, Tan NY, Bennett MR (2008). "Death receptors and their ligands in atherosclerosis". Arterioscler Thromb Vasc Biol. 28 (10): 1694–702. doi:10.1161/ATVBAHA.107.155143. PMID 18669890.
• Hatano, E. (2007). "Tumor necrosis factor signaling in hepatocyte apoptosis". J Gastroenterol Hepatol. 22: S43–44. doi:10.1111/j.1440-1746.2006.04645.x. PMID 17567463.

External links

• Tumor+Necrosis+Factor+Receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)