View source for Tumor necrosis factor receptor 1

{{Short description|Membrane receptor protein found in humans}}
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{{Infobox_gene}}
'''Tumor necrosis factor receptor 1''' ('''TNFR1'''), also known as '''tumor necrosis factor receptor superfamily member 1A''' ('''TNFRSF1A''') and '''CD120a''', is a ubiquitous membrane receptor that binds [[tumor necrosis factor-alpha]] (TNFα).<ref name="pmid1655358">{{cite journal | vauthors = Baker E, Chen LZ, Smith CA, Callen DF, Goodwin R, Sutherland GR | title = Chromosomal location of the human tumor necrosis factor receptor genes | journal = Cytogenetics and Cell Genetics | volume = 57 | issue = 2–3 | pages = 117–118 | date = November 1991 | pmid = 1655358 | doi = 10.1159/000133127 | authorlink6 = Grant Robert Sutherland }}</ref><ref name="pmid2158863">{{cite journal | vauthors = Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, Gatanaga T, Granger GA, Lentz R, Raab H | title = Molecular cloning and expression of a receptor for human tumor necrosis factor | journal = Cell | volume = 61 | issue = 2 | pages = 361–370 | date = April 1990 | pmid = 2158863 | doi = 10.1016/0092-8674(90)90816-W | s2cid = 36187863 | url = https://www.escholarship.org/uc/item/39j2j0h2 }}</ref><ref>{{cite book | vauthors = Offermanns S, Rosenthal W |title=Encyclopedia of Molecular Pharmacology | volume = 1 |date=2008|publisher=[[Springer Science+Business Media|Springer]]|location=Heidelberg, Germany|page=1248|edition=2nd|url=https://books.google.com/books?id=iwwo5gx8aX8C|isbn=9783540389163}}</ref>

== Function ==
The protein encoded by this gene is a member of the [[tumor necrosis factor receptor]] superfamily, which also contains TNFRSF1B. This protein is one of the major receptors for the [[tumor necrosis factor-alpha]]. This receptor can activate the [[transcription factor]] [[NF-κB]], mediate [[apoptosis]], and function as a regulator of [[inflammation]]. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this receptor, and thus play regulatory roles in the [[signal transduction]] mediated by the receptor.<ref>{{cite web | title = Entrez Gene: TNFRSF1A tumor necrosis factor receptor superfamily, member 1A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7132 }}</ref>

== Clinical significance ==

[[Germline mutation]]s of the extracellular domains of this receptor were found to be associated with the human [[genetic disorder]] called tumor necrosis factor associated periodic syndrome (TRAPS) or [[periodic fever syndrome]].<ref name="pmid19794511">{{cite journal | vauthors = Kümpfel T, Hohlfeld R | title = Multiple sclerosis. TNFRSF1A, TRAPS and multiple sclerosis | journal = Nature Reviews. Neurology | volume = 5 | issue = 10 | pages = 528–529 | date = October 2009 | pmid = 19794511 | doi = 10.1038/nrneurol.2009.154 | s2cid = 40665495 }}</ref>  Impaired receptor clearance is thought to be a mechanism of the disease.

Mutations in the TNFRSF1A gene are associated with elevated risk of multiple sclerosis.<ref>{{cite journal | title = The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study | journal = PLOS ONE | volume = 6 | issue = 4 | pages = e18813 | date = April 2011 | pmid = 21552549 | pmc = 3084233 | doi = 10.1371/journal.pone.0018813 | doi-access = free | bibcode = 2011PLoSO...618813. | author1 = International Multiple Sclerosis Genetics Consortium }}</ref>

Serum levels of TNFRSF1A are elevated in schizophrenia and bipolar disorder,<ref name="pmid19839997">{{cite journal | vauthors = Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA | title = Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor | journal = Bipolar Disorders | volume = 11 | issue = 7 | pages = 726–734 | date = November 2009 | pmid = 19839997 | doi = 10.1111/j.1399-5618.2009.00757.x | hdl-access = free | hdl = 10852/34620 }}</ref> and high levels are associated with more severe psychotic symptoms.<ref name="pmid23403415">{{cite journal | vauthors = Hope S, Ueland T, Steen NE, Dieset I, Lorentzen S, Berg AO, Agartz I, Aukrust P, Andreassen OA | title = Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder | journal = Schizophrenia Research | volume = 145 | issue = 1–3 | pages = 36–42 | date = April 2013 | pmid = 23403415 | doi = 10.1016/j.schres.2012.12.023 | doi-access = free }}</ref>

High serum levels are also associated with cognitive impairment and dementia.<ref name="pmid19070941">{{cite journal | vauthors = Buchhave P, Zetterberg H, Blennow K, Minthon L, Janciauskiene S, Hansson O | title = Soluble TNF receptors are associated with Aβ metabolism and conversion to dementia in subjects with mild cognitive impairment | journal = Neurobiology of Aging | volume = 31 | issue = 11 | pages = 1877–1884 | date = November 2010 | pmid = 19070941 | doi = 10.1016/j.neurobiolaging.2008.10.012 | s2cid = 34595960 }}</ref><ref name="pmid20930310">{{cite journal | vauthors = Diniz BS, Teixeira AL, Ojopi EB, Talib LL, Mendonça VA, Gattaz WF, Forlenza OV | title = Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease | journal = Journal of Alzheimer's Disease | volume = 22 | issue = 4 | pages = 1305–1311 | year = 2010 | pmid = 20930310 | doi = 10.3233/JAD-2010-100921 }}</ref>

== Interactions ==

TNFRSF1A has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[BAG4]],<ref name = pmid9915703>{{cite journal | vauthors = Jiang Y, Woronicz JD, Liu W, Goeddel DV | title = Prevention of constitutive TNF receptor 1 signaling by silencer of death domains | journal = Science | volume = 283 | issue = 5401 | pages = 543–546 | date = January 1999 | pmid = 9915703 | doi = 10.1126/science.283.5401.543 | bibcode = 1999Sci...283..543J }}</ref><ref name = pmid11909948>{{cite journal | vauthors = Miki K, Eddy EM | title = Tumor necrosis factor receptor 1 is an ATPase regulated by silencer of death domain | journal = Molecular and Cellular Biology | volume = 22 | issue = 8 | pages = 2536–2543 | date = April 2002 | pmid = 11909948 | pmc = 133739 | doi = 10.1128/MCB.22.8.2536-2543.2002 }}</ref> 
* [[Caspase 10|CASP10]],<ref name = pmid15659383/><ref name = pmid9045686>{{cite journal | vauthors = Vincenz C, Dixit VM | title = Fas-associated death domain protein interleukin-1beta-converting enzyme 2 (FLICE2), an ICE/Ced-3 homologue, is proximally involved in CD95- and p55-mediated death signaling | journal = The Journal of Biological Chemistry | volume = 272 | issue = 10 | pages = 6578–6583 | date = March 1997 | pmid = 9045686 | doi = 10.1074/jbc.272.10.6578 | doi-access = free }}</ref> 
* [[FADD]],<ref name = pmid15659383>{{cite journal | vauthors = Gajate C, Mollinedo F | title = Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy | journal = The Journal of Biological Chemistry | volume = 280 | issue = 12 | pages = 11641–11647 | date = March 2005 | pmid = 15659383 | doi = 10.1074/jbc.M411781200 | doi-access = free }}</ref><ref name = pmid8565075>{{cite journal | vauthors = Hsu H, Shu HB, Pan MG, Goeddel DV | title = TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways | journal = Cell | volume = 84 | issue = 2 | pages = 299–308 | date = January 1996 | pmid = 8565075 | doi = 10.1016/S0092-8674(00)80984-8 | s2cid = 13171355 | doi-access = free }}</ref> 
* [[IKK2]],<ref name = pmid10755617>{{cite journal | vauthors = Zhang SQ, Kovalenko A, Cantarella G, Wallach D | title = Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation | journal = Immunity | volume = 12 | issue = 3 | pages = 301–311 | date = March 2000 | pmid = 10755617 | doi = 10.1016/S1074-7613(00)80183-1 | doi-access = free }}</ref><ref name = pmid11002417>{{cite journal | vauthors = Chaudhary PM, Eby MT, Jasmin A, Kumar A, Liu L, Hood L | title = Activation of the NF-kappaB pathway by caspase 8 and its homologs | journal = Oncogene | volume = 19 | issue = 39 | pages = 4451–4460 | date = September 2000 | pmid = 11002417 | doi = 10.1038/sj.onc.1203812 | doi-access = free }}</ref> 
* [[Janus kinase 1|JAK1]],<ref name = pmid9510175/><ref name = pmid11801527>{{cite journal | vauthors = Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, Garaci F, Zauli G, Bonvini E, Di Baldassarre A | title = Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells | journal = Cell Growth & Differentiation | volume = 13 | issue = 1 | pages = 13–18 | date = January 2002 | pmid = 11801527 }}</ref> 
* [[Janus kinase 2|JAK2]],<ref name = pmid9510175>{{cite journal | vauthors = Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB | title = Induction of Jak/STAT signaling by activation of the type 1 TNF receptor | journal = Journal of Immunology | volume = 160 | issue = 6 | pages = 2742–2750 | date = March 1998 | pmid = 9510175 | doi = 10.4049/jimmunol.160.6.2742 | doi-access = free }}</ref> 
* [[PIP4K2B]],<ref name = pmid9038203>{{cite journal | vauthors = Castellino AM, Parker GJ, Boronenkov IV, Anderson RA, Chao MV | title = A novel interaction between the juxtamembrane region of the p55 tumor necrosis factor receptor and phosphatidylinositol-4-phosphate 5-kinase | journal = The Journal of Biological Chemistry | volume = 272 | issue = 9 | pages = 5861–5870 | date = February 1997 | pmid = 9038203 | doi = 10.1074/jbc.272.9.5861 | doi-access = free }}</ref> 
* [[PSMD2]],<ref name = pmid7601280>{{cite journal | vauthors = Boldin MP, Mett IL, Wallach D | title = A protein related to a proteasomal subunit binds to the intracellular domain of the p55 TNF receptor upstream to its 'death domain' | journal = FEBS Letters | volume = 367 | issue = 1 | pages = 39–44 | date = June 1995 | pmid = 7601280 | doi = 10.1016/0014-5793(95)00534-G | s2cid = 21442471 | doi-access = free | bibcode = 1995FEBSL.367...39B }}</ref><ref name = pmid9126987>{{cite journal | vauthors = Dunbar JD, Song HY, Guo D, Wu LW, Donner DB | title = Two-hybrid cloning of a gene encoding TNF receptor-associated protein 2, a protein that interacts with the intracellular domain of the type 1 TNF receptor: identity with subunit 2 of the 26S protease | journal = Journal of Immunology | volume = 158 | issue = 9 | pages = 4252–4259 | date = May 1997 | pmid = 9126987 | doi = 10.4049/jimmunol.158.9.4252 | doi-access = free }}</ref> 
* [[RIPK1]],<ref name = pmid8612133/><ref name = pmid11002422>{{cite journal | vauthors = Kim JW, Choi EJ, Joe CO | title = Activation of death-inducing signaling complex (DISC) by pro-apoptotic C-terminal fragment of RIP | journal = Oncogene | volume = 19 | issue = 39 | pages = 4491–4499 | date = September 2000 | pmid = 11002422 | doi = 10.1038/sj.onc.1203796 | doi-access = free }}</ref><ref name = pmid8985253>{{cite journal | vauthors = Duan H, Dixit VM | title = RAIDD is a new 'death' adaptor molecule | journal = Nature | volume = 385 | issue = 6611 | pages = 86–89 | date = January 1997 | pmid = 8985253 | doi = 10.1038/385086a0 | hdl-access = free | s2cid = 4317538 | bibcode = 1997Natur.385...86D | hdl = 2027.42/62739 }}</ref><ref name = pmid18939944>{{cite journal | vauthors = Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D | title = Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1) | journal = The Biochemical Journal | volume = 417 | issue = 1 | pages = 149–160 | date = January 2009 | pmid = 18939944 | doi = 10.1042/BJ20081885 }}</ref><ref name = pmid18724939>{{cite journal | vauthors = Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM | title = Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies | journal = Cell | volume = 134 | issue = 4 | pages = 668–678 | date = August 2008 | pmid = 18724939 | doi = 10.1016/j.cell.2008.07.039 | s2cid = 3955385 | doi-access = free }}</ref><ref name = pmid18621737>{{cite journal | vauthors = Varfolomeev E, Goncharov T, Fedorova AV, Dynek JN, Zobel K, Deshayes K, Fairbrother WJ, Vucic D | title = c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation | journal = The Journal of Biological Chemistry | volume = 283 | issue = 36 | pages = 24295–24299 | date = September 2008 | pmid = 18621737 | pmc = 3259840 | doi = 10.1074/jbc.C800128200 | doi-access = free }}</ref> 
* [[Small ubiquitin-related modifier 1|SUMO1]],<ref name = pmid10187798>{{cite journal | vauthors = Liou ML, Liou HC | title = The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10145–10153 | date = April 1999 | pmid = 10187798 | doi = 10.1074/jbc.274.15.10145 | doi-access = free }}</ref><ref name = pmid8906799>{{cite journal | vauthors = Okura T, Gong L, Kamitani T, Wada T, Okura I, Wei CF, Chang HM, Yeh ET | title = Protection against Fas/APO-1- and tumor necrosis factor-mediated cell death by a novel protein, sentrin | journal = Journal of Immunology | volume = 157 | issue = 10 | pages = 4277–4281 | date = November 1996 | pmid = 8906799 | doi = 10.4049/jimmunol.157.10.4277 | doi-access = free }}</ref>
* [[TRADD]]<ref name = pmid9915703/><ref name = pmid8565075/><ref name = pmid8612133/><ref name = pmid18939944/><ref name = pmid8943045/><ref name = pmid10187805>{{cite journal | vauthors = Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke M | title = Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling | journal = The Journal of Biological Chemistry | volume = 274 | issue = 15 | pages = 10203–10212 | date = April 1999 | pmid = 10187805 | doi = 10.1074/jbc.274.15.10203 | doi-access = free }}</ref><ref name = pmid9082980>{{cite journal | vauthors = Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM | title = The receptor for the cytotoxic ligand TRAIL | journal = Science | volume = 276 | issue = 5309 | pages = 111–113 | date = April 1997 | pmid = 9082980 | doi = 10.1126/science.276.5309.111 | s2cid = 19984057 }}</ref> 
* [[TRAF2]],<ref name = pmid8565075/><ref name = pmid8612133>{{cite journal | vauthors = Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV | title = TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex | journal = Immunity | volume = 4 | issue = 4 | pages = 387–396 | date = April 1996 | pmid = 8612133 | doi = 10.1016/S1074-7613(00)80252-6 | doi-access = free }}</ref><ref name = pmid8943045>{{cite journal | vauthors = Shu HB, Takeuchi M, Goeddel DV | title = The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 24 | pages = 13973–13978 | date = November 1996 | pmid = 8943045 | pmc = 19479 | doi = 10.1073/pnas.93.24.13973 | doi-access = free | bibcode = 1996PNAS...9313973S }}</ref> 
* [[TRPC4AP]],<ref name = pmid14585990>{{cite journal | vauthors = Soond SM, Terry JL, Colbert JD, Riches DW | title = TRUSS, a novel tumor necrosis factor receptor 1 scaffolding protein that mediates activation of the transcription factor NF-kappaB | journal = Molecular and Cellular Biology | volume = 23 | issue = 22 | pages = 8334–8344 | date = November 2003 | pmid = 14585990 | pmc = 262424 | doi = 10.1128/MCB.23.22.8334-8344.2003 }}</ref> 
* [[Tumor necrosis factor-alpha|TNF]],<ref name = pmid14743216>{{cite journal | vauthors = Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nature Cell Biology | volume = 6 | issue = 2 | pages = 97–105 | date = February 2004 | pmid = 14743216 | doi = 10.1038/ncb1086 | s2cid = 11683986 }}</ref><ref name = pmid12887920>{{cite journal | vauthors = Barnhart BC, Peter ME | title = The TNF receptor 1: a split personality complex | journal = Cell | volume = 114 | issue = 2 | pages = 148–150 | date = July 2003 | pmid = 12887914 | doi = 10.1016/s0092-8674(03)00561-0 | s2cid = 11551587 | doi-access = free }}</ref>  and
* [[UBE2I]].<ref name = pmid9563508>{{cite journal | vauthors = Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y | title = hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity | journal = FEBS Letters | volume = 425 | issue = 3 | pages = 431–435 | date = April 1998 | pmid = 9563508 | doi = 10.1016/S0014-5793(98)00287-7 | s2cid = 84816080 | doi-access = free | bibcode = 1998FEBSL.425..431S }}</ref> 
{{Div col end}}

== See also ==
* [[Cluster of differentiation]]
* [[TNF receptor associated periodic syndrome]]
{{Clear}}

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin |35em}}
* {{cite journal | vauthors = Rath PC, Aggarwal BB | title = TNF-induced signaling in apoptosis | journal = Journal of Clinical Immunology | volume = 19 | issue = 6 | pages = 350–364 | date = November 1999 | pmid = 10634209 | doi = 10.1023/A:1020546615229 | s2cid = 23194856 | doi-access = free }}
* {{cite journal | vauthors = Chen G, Goeddel DV | title = TNF-R1 signaling: a beautiful pathway | journal = Science | volume = 296 | issue = 5573 | pages = 1634–1635 | date = May 2002 | pmid = 12040173 | doi = 10.1126/science.1071924 | s2cid = 25321662 | bibcode = 2002Sci...296.1634C }}
* {{cite journal | vauthors = Kollias G, Kontoyiannis D | title = Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments | journal = Cytokine & Growth Factor Reviews | volume = 13 | issue = 4–5 | pages = 315–321 | year = 2003 | pmid = 12220546 | doi = 10.1016/S1359-6101(02)00019-9 | author-link2 = Dimitrios Kontoyiannis }}
* {{cite journal | vauthors = Dodé C, Cuisset L, Delpech M, Grateau G | title = TNFRSF1A-associated periodic syndrome (TRAPS), Muckle-Wells syndrome (MWS) and renal amyloidosis | journal = Journal of Nephrology | volume = 16 | issue = 3 | pages = 435–437 | year = 2003 | pmid = 12832748 }}
* {{cite journal | vauthors = Stojanov S, McDermott MF | title = The tumour necrosis factor receptor-associated periodic syndrome: current concepts | journal = Expert Reviews in Molecular Medicine | volume = 7 | issue = 22 | pages = 1–18 | date = October 2005 | pmid = 16216134 | doi = 10.1017/S1462399405009749 | s2cid = 35803989 }}
* {{cite journal | vauthors = Rezaei N | title = TNF-receptor-associated periodic syndrome (TRAPS): an autosomal dominant multisystem disorder | journal = Clinical Rheumatology | volume = 25 | issue = 6 | pages = 773–777 | date = November 2006 | pmid = 16447098 | doi = 10.1007/s10067-005-0198-6 | s2cid = 41808394 }}
{{refend}}

== External links ==
* {{MeshName|TNFRSF1A+protein,+human}}
* {{PDBe-KB2|P19438|Tumor necrosis factor receptor superfamily member 1A}}

{{NLM content}}
{{PDB Gallery|geneid=7132}}
{{Clusters of differentiation}}
{{Tumor necrosis factor receptor superfamily}}
{{TNF receptor superfamily modulators}}

[[Category:Clusters of differentiation]]
[[Category:TNF receptor family]]