{{Short description|Protein superfamily of cytokine receptors}} {{Infobox protein family | Symbol = TNFR_c6 | Name = TNFR/NGFR cysteine-rich region | image = PDB 1tnr EBI.jpg | width = | caption = Structure of the soluble human 55 kd TNF receptor-human TNF beta complex.<ref name="pmid8387891">{{cite journal |author=Banner DW |title=Crystal structure of the soluble human 55 kd TNF receptor-human TNF beta complex: implications for TNF receptor activation |journal=Cell |volume=73 |issue=3 |pages=431–45 |date=May 1993 |pmid=8387891 |doi= 10.1016/0092-8674(93)90132-A|name-list-style=vanc|author2=D'Arcy A |author3=Janes W |display-authors=3 |last4=Gentz |first4=Reiner |last5=Schoenfeld |first5=Hans-Joachim |last6=Broger |first6=Clemens |last7=Loetscher |first7=Hansruedi |last8=Lesslauer |first8=Werner|s2cid=25155518 }}</ref> | Pfam= PF00020 | Pfam_clan = CL0607 | ECOD = 389.1.3 | InterPro= IPR011614 | SMART= | PROSITE = PDOC00561 | SCOP = 1tnr | TCDB = | PDB= | Membranome superfamily =6 }} 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.<ref name="pmid11239407">{{cite journal |vauthors=Locksley RM, Killeen N, Lenardo MJ | title = The TNF and TNF receptor superfamilies: integrating mammalian biology | journal = Cell | volume = 104 | issue = 4 | pages = 487–501 | year = 2001 | pmid = 11239407 | doi = 10.1016/S0092-8674(01)00237-9 | s2cid = 7657797 | doi-access = free }}</ref><ref name="pmid15819693">{{cite journal |vauthors=Hehlgans T, Pfeffer K | title = The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games | journal = Immunology | volume = 115 | issue = 1 | pages = 1–20 | year = 2005 | pmid = 15819693 | doi = 10.1111/j.1365-2567.2005.02143.x | pmc = 1782125 }}</ref> With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha.<ref name="Gravestein">{{cite journal|last1=Gravestein|first1=LA|last2=Borst|first2=J|title=Tumor necrosis factor receptor family members in the immune system.|journal=Seminars in Immunology|date=December 1998|volume=10|issue=6|pages=423–34|pmid=9826575|doi=10.1006/smim.1998.0144}}</ref> 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.<ref name="Gravestein" />
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.<ref name="Gravestein" /> 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.<ref>{{cite journal|doi=10.1126/science.281.5381.1305|title=Death Receptors: Signaling and Modulation|year=1998|last1=Ashkenazi|first1=A.|journal=Science|volume=281|issue=5381|pages=1305–8|pmid=9721089|last2=Dixit|first2=VM}}</ref>
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.<ref>{{Cite journal |last=Wallach |first=David |date=2018-10-01 |title=The Tumor Necrosis Factor Family: Family Conventions and Private Idiosyncrasies |url=https://cshperspectives.cshlp.org/content/10/10/a028431 |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=10 |issue=10 |article-number=a028431 |doi=10.1101/cshperspect.a028431 |issn=1943-0264 |pmc=6169814 |pmid=28847899}}</ref><ref>{{Cite web |title=Gene group {{!}} HUGO Gene Nomenclature Committee |url=https://genenames.org/data/genegroup/#!/group/782 |access-date=2025-01-13 |website=genenames.org}}</ref> Historically, the family members have been numerically classified as TNFRSF#, where # denotes the member number, sometimes followed a letter.<ref name="pmid11239407"/> Some newer additions to the TNF family remain unnumbered, however, such as the TNF receptor superfamily member EDAR.<ref name="pmid11239407" /><ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/Q9UNE0/entry#names_and_taxonomy |access-date=2025-01-13 |website=www.uniprot.org}}</ref>
{| class="wikitable sortable" border="3" style="text-align:center" |- ! Type ! Protein (member #) ! Synonyms ! Gene ! Ligand(s) |- | rowspan="2" style="width:20px" | 1 | style="width:250px" | Tumor necrosis factor receptor 1 (1A) | style="width:200px" | CD120a | style="width:100px" | {{gene|TNFRSF1A}} | rowspan="2" style="width:200px" | TNF (cachectin) |- | Tumor necrosis factor receptor 2 (1B) | CD120b | {{gene|TNFRSF1B}} |- | 3 | Lymphotoxin beta receptor (3) | CD18 | {{gene|LTBR}} | Lymphotoxin beta (TNF-C) |- | 4 | OX40 (4) | CD134 | {{gene|TNFRSF4}} | OX40L |- | 5 | CD40 (5) | Bp50 | {{gene|CD40}} | CD154 |- | rowspan="2" | 6 | Fas receptor (6) | Apo-1, CD95 | {{gene|FAS}} | FasL |- | Decoy receptor 3 (6B) | TR6, M68 | {{gene|TNFRSF6B}} | FasL, LIGHT, TL1A |- | 7 | CD27 (7) | S152, Tp55 | {{gene|CD27}} | CD70, Siva |- | 8 | CD30 (8) | Ki-1, TNR8 | {{gene|TNFRSF8}} | CD153 |- | 9 | 4-1BB (9) | CD137 | {{gene|TNFRSF9}} | 4-1BB ligand |- | rowspan="4" | 10 | Death receptor 4 (10A) | TRAILR1, Apo-2, CD261 | {{gene|TNFRSF10A}} | rowspan="4" | TRAIL |- | Death receptor 5 (10B) | TRAILR2, CD262 | {{gene|TNFRSF10B}} |- | Decoy receptor 1 (10C) | TRAILR3, LIT, TRID, CD263 | {{gene|TNFRSF10C}} |- | Decoy receptor 2 (10D) | TRAILR4, TRUNDD, CD264 | {{gene|TNFRSF10D}} |- | rowspan="2" | 11 | RANK (11A) | CD265 | {{gene|TNFRSF11A}} | rowspan="2" | RANKL |- | Osteoprotegerin (11B) | OCIF, TR1 | {{gene|TNFRSF11B}} |- | 12 | TWEAK receptor (12A) | Fn14, CD266 | {{gene|TNFRSF12A}} | TWEAK |- | rowspan="2" | 13 | TACI (13B) | IGAD2, CD267 | {{gene|TNFRSF13B}} | APRIL, BAFF, CAMLG |- | BAFF receptor (13C) | CD268 | {{gene|TNFRSF13C}} | BAFF |- | 14 | Herpesvirus entry mediator (14) | ATAR, TR2, CD270 | {{gene|TNFRSF14}} | LIGHT |- | 16 | Nerve growth factor receptor (16) | p75NTR, CD271 | {{gene|NGFR}} | NGF, BDNF, NT-3, NT-4 |- | 17 | B-cell maturation antigen (17) | TNFRSF13A, CD269, BCMA | {{gene|TNFRSF17}} | BAFF |- | 18 | Glucocorticoid-induced TNFR-related (18) | AITR, CD357 | {{gene|TNFRSF18}} | GITR ligand |- | 19 | TROY (19) | TAJ, TRADE | {{gene|TNFRSF19}} | rowspan="3" | ''unknown'' |- |19L<ref>{{Cite web |title=Gene symbol report {{!}} HUGO Gene Nomenclature Committee |url=https://genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13764 |access-date=2025-01-13 |website=genenames.org}}</ref> |RELT (19L) |FLJ14993 |''[https://genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13764 RELT]'' |- | 21 | Death receptor 6 (21) | CD358 | {{gene|TNFRSF21}} |- | 25 | Death receptor 3 (25) | Apo-3, TRAMP, LARD, WS-1 | {{gene|TNFRSF25}} | TL1A |- | 27 | Ectodysplasin A2 receptor (27) | XEDAR | {{gene|EDA2R}} | EDA-A2 |- |EDAR<ref>{{Cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/Q9UNE0/entry#names_and_taxonomy |access-date=2025-01-13 |website=www.uniprot.org}}</ref> |Ectodysplasin A receptor (EDAR) |Downless Homolog |''[https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2895 EDAR]'' |EDA-A1 |}
==References== {{Reflist|2}}
==Further reading== *{{cite journal |vauthors=Kavurma MM, Tan NY, Bennett MR |title=Death receptors and their ligands in atherosclerosis|journal=Arterioscler Thromb Vasc Biol |volume=28 |issue= 10 |pages= 1694–702 |year= 2008 |pmid= 18669890 |doi=10.1161/ATVBAHA.107.155143 |doi-access=free }} *{{cite journal | author=Hatano, E.|title=Tumor necrosis factor signaling in hepatocyte apoptosis|journal= J Gastroenterol Hepatol |volume=22 |pages= S43–44 |year= 2007 |pmid= 17567463 |doi=10.1111/j.1440-1746.2006.04645.x }}
==External links== * {{MeshName|Tumor+Necrosis+Factor+Receptor}}
{{Cell surface receptors}} {{Cytokine receptors}} {{Apoptosis signaling pathway}} {{TNF receptor superfamily modulators}}
Category:TNF receptor family Category:Apoptosis Category:Protein superfamilies Category:Single-pass transmembrane proteins