Tumor necrosis factor receptor 2

<h2 id="function">Function</h2>
The protein encoded by this gene is a member of the <a href="/facts/Tumor_necrosis_factor_receptor/oXUH1YxS">tumor necrosis factor receptor</a> superfamily, which also contains <a href="/facts/TNFRSF1A/vAF53urQ">TNFRSF1A</a>. This protein and <a href="/facts/TNFRSF1A/vAF53urQ">TNF-receptor 1</a> form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, <a href="/facts/BIRC2/RQgFf0La">c-IAP1</a> and <a href="/facts/BIRC3/W4MSnrdC">c-IAP2</a>, which possess <a href="/facts/E3_ubiquitin_ligase/8xmNaWW3">E3 ubiquitin ligase</a> activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced <a href="/facts/Apoptosis/8dVzSm4y">apoptosis</a> by the <a href="/facts/Ubiquitination/hpulmU3m">ubiquitination</a> and degradation of TNF-receptor-associated factor 2 (<a href="/facts/TRAF2/pQALxuu4">TRAF2</a>), which mediates anti-apoptotic signals. <a href="/facts/Gene_knockout/RJTMDbUR">Knockout</a> studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways.<a class="footnote-ref" id="fnref:6" href="#fn:6">6</a>

<h2 id="clinical-significance">Clinical significance</h2>
<h3>CNS</h3>
At least partly because TNFR2 has no intracellular death domain, TNFR2 is <a href="/facts/Neuroprotection/BcbsTfN0">neuroprotective</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7">7</a>
Patients with schizophrenia have increased levels of soluble tumor necrosis factor receptor 2 (<a href="/facts/Soluble_tumor_necrosis_factor_receptor/UkNSuWGp">sTNFR2</a>).<a class="footnote-ref" id="fnref:8" href="#fn:8">8</a>

<h3>Cancer</h3>
Targeting of TNRF2 in tumor cells is associated with increased tumor cell death and decreased progression of tumor cell growth.<a class="footnote-ref" id="fnref:9" href="#fn:9">9</a>
Increased expression of TNFR2 is found in <a href="/facts/Breast_cancer/6hME580v">breast cancer</a>, <a href="/facts/Cervical_cancer/99vngUyd">cervical cancer</a>, <a href="/facts/Colorectal_cancer/nV592sW7">colon cancer</a>, and <a href="/facts/Kidney_cancer/jx6L4829">renal cancer</a>.<a class="footnote-ref" id="fnref:10" href="#fn:10">10</a> A link between the expression of TNRF2 in tumor cells and <a href="/facts/Cancer_staging/d2cFsCtq">late-stage cancer</a> has been discovered.<a class="footnote-ref" id="fnref:11" href="#fn:11">11</a> TNFR2 plays a significant role in tumor cell growth as it has been found that the loss of TNFR2 expression is linked with increased death of associated tumor cells and a significant standstill of further growth.<a class="footnote-ref" id="fnref:12" href="#fn:12">12</a> There is therapeutic potential in the targeting of TNFR2 for cancer treatments through TNFR2 inhibition.<a class="footnote-ref" id="fnref:13" href="#fn:13">13</a>

<h3>Systemic Lupus Erythematous (SLE)</h3>
A small scale study of 289 Japanese patients suggested a minor increased predisposition from an amino acid substitution of the 196 allele at exon 6. Genomic testing of 81 <a href="/facts/SLE/kfHYawre">SLE</a> patients and 207 healthy patients in a Japanese study showed 37% of SLE patients had a polymorphism on position 196 of <a href="/facts/Exon/8KWJtLuN">exon</a> 6 compared to 18.8% of healthy patients. The TNFR2 196R allele polymorphism suggests that even one 196R <a href="/facts/Allele/8FxCS9KA">allele</a> results in increased risk for SLE.<a class="footnote-ref" id="fnref:14" href="#fn:14">14</a>

<h2 id="interactions">Interactions</h2>
TNFRSF1B has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with:

<ul><li><a href="/facts/TRAF2/pQALxuu4">TRAF2</a>,<a class="footnote-ref" id="fnref:15" href="#fn:15">15</a><a class="footnote-ref" id="fnref:16" href="#fn:16">16</a><a class="footnote-ref" id="fnref:17" href="#fn:17">17</a><a class="footnote-ref" id="fnref:18" href="#fn:18">18</a><a class="footnote-ref" id="fnref:19" href="#fn:19">19</a><a class="footnote-ref" id="fnref:20" href="#fn:20">20</a><a class="footnote-ref" id="fnref:21" href="#fn:21">21</a> and</li>
<li><a href="/facts/TTRAP/vbh9vaA7">TTRAP</a>.<a class="footnote-ref" id="fnref:22" href="#fn:22">22</a></li></ul>

<h2 id="further-reading">Further reading</h2>

<ul><li>Kollias G, <a href="/facts/Dimitrios_Kontoyiannis/sAkqb5wT">Kontoyiannis D</a> (2003). "Role of TNF/TNFR in autoimmunity: specific TNF receptor blockade may be advantageous to anti-TNF treatments". Cytokine & Growth Factor Reviews. 13 (4–5): 315–321. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS1359-6101%2802%2900019-9">10.1016/S1359-6101(02)00019-9</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12220546">12220546</a>.</li>
<li>Holtmann MH, Schuchmann M, Zeller G, Galle PR, Neurath MF (2003). "The emerging distinct role of TNF-receptor 2 (p80) signaling in chronic inflammatory disorders". Archivum Immunologiae et Therapiae Experimentalis. 50 (4): 279–288. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12371624">12371624</a>.</li>
<li>Horiuchi T, Kiyohara C, Tsukamoto H, Sawabe T, Furugo I, Yoshizawa S, et al. (March 2007). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856025">"A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case-control study and a meta-analysis"</a>. Annals of the Rheumatic Diseases. 66 (3): 320–324. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1136%2Fard.2006.058917">10.1136/ard.2006.058917</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856025">1856025</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/17028114">17028114</a>.{{cite journal}}: CS1 maint: overridden setting (link)</li></ul>

<h2 id="external-links">External links</h2>
<ul><li><a href="https://meshb.nlm.nih.gov/record/ui?name=CD120b+Antigen">CD120b+Antigen</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li></ul>

<h2 id="references">References</h2>

<ol>
<li id="fn:1">Schall TJ, Lewis M, Koller KJ, Lee A, Rice GC, Wong GH, et al. (April 1990). "Molecular cloning and expression of a receptor for human tumor necrosis factor". Cell. 61 (2): 361–370. doi:10.1016/0092-8674(90)90816-W. PMID 2158863. S2CID 36187863.{{cite journal}}: CS1 maint: overridden setting (link) <a href="https://escholarship.org/uc/item/39j2j0h2" target="_blank">https://escholarship.org/uc/item/39j2j0h2</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></li>
<li id="fn:2">Santee SM, Owen-Schaub LB (August 1996). "Human tumor necrosis factor receptor p75/80 (CD120b) gene structure and promoter characterization". The Journal of Biological Chemistry. 271 (35): 21151–21159. doi:10.1074/jbc.271.35.21151. PMID 8702885. <a href="https://doi.org/10.1074%2Fjbc.271.35.21151" target="_blank">https://doi.org/10.1074%2Fjbc.271.35.21151</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></li>
<li id="fn:3">Wang J, Al-Lamki RS (2013-11-17). "Tumor necrosis factor receptor 2: its contribution to acute cellular rejection and clear cell renal carcinoma". BioMed Research International. 2013: 821310. doi:10.1155/2013/821310. PMC 3848079. PMID 24350291. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848079" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848079</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></li>
<li id="fn:4">Sheng Y, Li F, Qin Z (2018). "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors". Frontiers in Immunology. 9: 1170. doi:10.3389/fimmu.2018.01170. PMC 5985372. PMID 29892300. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></li>
<li id="fn:5">Wang J, Al-Lamki RS (2013-11-17). "Tumor necrosis factor receptor 2: its contribution to acute cellular rejection and clear cell renal carcinoma". BioMed Research International. 2013: 821310. doi:10.1155/2013/821310. PMC 3848079. PMID 24350291. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848079" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848079</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></li>
<li id="fn:6">"Entrez Gene: TNFRSF1B tumor necrosis factor receptor superfamily, member 1B". Retrieved 8 May 2017. <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7133" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7133</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></li>
<li id="fn:7">Chadwick W, Magnus T, Martin B, Keselman A, Mattson MP, Maudsley S (October 2008). "Targeting TNF-alpha receptors for neurotherapeutics". Trends in Neurosciences. 31 (10): 504–511. doi:10.1016/j.tins.2008.07.005. PMC 2574933. PMID 18774186. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574933" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574933</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></li>
<li id="fn:8">Kudo N, Yamamori H, Ishima T, Nemoto K, Yasuda Y, Fujimoto M, et al. (July 2018). "Plasma Levels of Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) Are Associated with Hippocampal Volume and Cognitive Performance in Patients with Schizophrenia". The International Journal of Neuropsychopharmacology. 21 (7): 631–639. doi:10.1093/ijnp/pyy013. PMC 6031046. PMID 29529289.{{cite journal}}: CS1 maint: overridden setting (link) <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031046" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031046</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></li>
<li id="fn:9">Sheng Y, Li F, Qin Z (2018). "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors". Frontiers in Immunology. 9: 1170. doi:10.3389/fimmu.2018.01170. PMC 5985372. PMID 29892300. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></li>
<li id="fn:10">Sheng Y, Li F, Qin Z (2018). "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors". Frontiers in Immunology. 9: 1170. doi:10.3389/fimmu.2018.01170. PMC 5985372. PMID 29892300. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></li>
<li id="fn:11">Sheng Y, Li F, Qin Z (2018). "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors". Frontiers in Immunology. 9: 1170. doi:10.3389/fimmu.2018.01170. PMC 5985372. PMID 29892300. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></li>
<li id="fn:12">Sheng Y, Li F, Qin Z (2018). "TNF Receptor 2 Makes Tumor Necrosis Factor a Friend of Tumors". Frontiers in Immunology. 9: 1170. doi:10.3389/fimmu.2018.01170. PMC 5985372. PMID 29892300. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985372</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></li>
<li id="fn:13">Medler J, Wajant H (April 2019). "Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target". Expert Opinion on Therapeutic Targets. 23 (4): 295–307. doi:10.1080/14728222.2019.1586886. PMID 30856027. S2CID 75139844. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></li>
<li id="fn:14">Komata T, Tsuchiya N, Matsushita M, Hagiwara K, Tokunaga K (June 1999). "Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus". Tissue Antigens. 53 (6): 527–533. doi:10.1034/j.1399-0039.1999.530602.x. PMID 10395102. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></li>
<li id="fn:15">Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.{{cite journal}}: CS1 maint: overridden setting (link) <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></li>
<li id="fn:16">Song HY, Donner DB (August 1995). "Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor". The Biochemical Journal. 309 (3): 825–829. doi:10.1042/bj3090825. PMC 1135706. PMID 7639698. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1135706" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1135706</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></li>
<li id="fn:17">Takeuchi M, Rothe M, Goeddel DV (August 1996). "Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins". The Journal of Biological Chemistry. 271 (33): 19935–19942. doi:10.1074/jbc.271.33.19935. PMID 8702708. <a href="https://doi.org/10.1074%2Fjbc.271.33.19935" target="_blank">https://doi.org/10.1074%2Fjbc.271.33.19935</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></li>
<li id="fn:18">Hostager BS, Bishop GA (April 2002). "Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b". Journal of Immunology. 168 (7): 3318–3322. doi:10.4049/jimmunol.168.7.3318. PMID 11907088. <a href="https://doi.org/10.4049%2Fjimmunol.168.7.3318" target="_blank">https://doi.org/10.4049%2Fjimmunol.168.7.3318</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></li>
<li id="fn:19">Rothe M, Xiong J, Shu HB, Williamson K, Goddard A, Goeddel DV (August 1996). "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction". Proceedings of the National Academy of Sciences of the United States of America. 93 (16): 8241–8246. Bibcode:1996PNAS...93.8241R. doi:10.1073/pnas.93.16.8241. PMC 38654. PMID 8710854. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC38654" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC38654</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></li>
<li id="fn:20">Marsters SA, Ayres TM, Skubatch M, Gray CL, Rothe M, Ashkenazi A (May 1997). "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1". The Journal of Biological Chemistry. 272 (22): 14029–14032. doi:10.1074/jbc.272.22.14029. PMID 9162022. <a href="https://doi.org/10.1074%2Fjbc.272.22.14029" target="_blank">https://doi.org/10.1074%2Fjbc.272.22.14029</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></li>
<li id="fn:21">Carpentier I, Coornaert B, Beyaert R (October 2008). "Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation". Biochemical and Biophysical Research Communications. 374 (4): 752–757. doi:10.1016/j.bbrc.2008.07.103. PMID 18671942. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></li>
<li id="fn:22">Pype S, Declercq W, Ibrahimi A, Michiels C, Van Rietschoten JG, Dewulf N, et al. (June 2000). "TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation". The Journal of Biological Chemistry. 275 (24): 18586–18593. doi:10.1074/jbc.M000531200. PMID 10764746.{{cite journal}}: CS1 maint: overridden setting (link) <a href="https://doi.org/10.1074%2Fjbc.M000531200" target="_blank">https://doi.org/10.1074%2Fjbc.M000531200</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></li>
</ol>

Tumor necrosis factor receptor 2 open-in-new

Tumor necrosis factor receptor 2