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to content main menu main menu move to sidebar hide navigation main page contents current events random article about wikipedia contact us contribute help learn to edit community portal recent changes upload file special pages search search appearance donate create account log in personal tools donate create account log in contents move to sidebar hide top 1 function 2 clinical significance 3 as a drug or drug target 4 interactions 5 references 6 external links 7 further reading toggle the table of contents tnfrsf4 7 languages čeština cymraeg español فارسی русский татарча tatarça українська edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia redirected from ox40 protein coding gene in humans tnfrsf4 identifiers aliases tnfrsf4 act35 cd134 imd16 ox40 txgp1l tumor necrosis factor receptor superfamily member 4 tnf receptor superfamily member 4 external ids omim 600315 mgi 104512 genecards tnfrsf4 available structures pdb ortholog search pdbe rcsb list of pdb id codes 1d0a 2hev 2hey gene location human chr chromosome 1 human 1 band 1p36 33 start 1 211 340 bp 1 end 1 214 153 bp 1 rna expression pattern bgee human mouse ortholog top expressed in apex of heart granulocyte gonad spleen lymph node cartilage tissue mucosa of transverse colon upper lobe of left lung blood appendix n a more reference expression data biogps more reference expression data gene ontology molecular function virus receptor activity tumor necrosis factor activated receptor activity protein binding cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane cell surface external side of plasma membrane biological process regulation of apoptotic process tumor necrosis factor mediated signaling pathway negative regulation of dna binding transcription factor activity multicellular organism development t cell proliferation response to lipopolysaccharide regulation of cell population proliferation positive regulation of b cell proliferation immune response apoptotic signaling pathway viral entry into host cell inflammatory response negative regulation of transcription dna templated viral process cellular defense response regulation of protein kinase activity negative regulation of activation induced cell death of t cells negative regulation of extrinsic apoptotic signaling pathway sources amigo quickgo orthologs databases ncbi entry oma entry species human mouse entrez 7293 22163 ensembl ensg00000186827 n a uniprot p43489 p47741 refseq mrna nm_003327 nm_011659 refseq protein np_003318 np_035789 location ucsc chr 1 1 21 1 21 mb n a pubmed search 2 3 wikidata view edit human view edit mouse tumor necrosis factor receptor superfamily member 4 tnfrsf4 also known as cd134 and ox40 receptor is a member of the tnfr superfamily of receptors which is not constitutively expressed on resting naïve t cells unlike cd28 ox40 is a secondary co stimulatory immune checkpoint molecule expressed after 24 to 72 hours following activation its ligand ox40l is also not expressed on resting antigen presenting cells but is following their activation expression of ox40 is dependent on full activation of the t cell without cd28 expression of ox40 is delayed and of fourfold lower levels function edit ox40 has no effect on the proliferative abilities of cd4 cells for the first three days however after this time proliferation begins to slow and cells die at a greater rate due to an inability to maintain a high level of pkb activity and expression of bcl 2 bcl xl and survivin ox40l binds to ox40 receptors on t cells preventing them from dying and subsequently increasing cytokine production ox40 has a critical role in the maintenance of an immune response beyond the first few days and onwards to a memory response due to its ability to enhance survival ox40 also plays a crucial role in both th1 and th2 mediated reactions in vivo ox40 binds traf2 3 and 5 as well as pi3k by an unknown mechanism traf2 is required for survival via nf κb and memory cell generation whereas traf5 seems to have a more negative or modulatory role as knockouts have higher levels of cytokines and are more susceptible to th2 mediated inflammation traf3 may play a critical role in ox40 mediated signal transduction ctla 4 is down regulated following ox40 engagement in vivo and the ox40 specific traf3 dn defect was partially overcome by ctla 4 blockade in vivo traf3 may be linked to ox40 mediated memory t cell expansion and survival and point to the down regulation of ctla 4 as a possible control element to enhance early t cell expansion through ox40 signaling clinical significance edit ox40 has been implicated in the pathologic cytokine storm associated with certain viral infections including the h5n1 bird flu citation needed as a drug or drug target edit an artificially created biologic fusion protein ox40 immunoglobulin ox40 ig prevents ox40 from reaching the t cell receptors thus reducing the t cell response experiments in mice have demonstrated that ox40 ig can reduce the symptoms associated with the cytokine storm an immune overreaction while allowing the immune system to fight off the virus successfully citation needed an anti ox40 antibody gsk3174998 has started clinical trials as a cancer treatment 4 research in mice has included the combination of an agonistic ox40 antibody clone ox86 injected directly into a tumor in combination with an unmethylated cpg oligonucleotide which as a tlr9 ligand activates expression of ox40 so that it can be affected 5 interactions edit cd134 has been shown to interact with traf5 6 and traf2 7 references edit 1 2 3 grch38 ensembl release 89 ensg00000186827 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine mouse pubmed reference national center for biotechnology information u s national library of medicine gsk and merck to study immunotherapy combination as potential cancer treatment nov 2015 archived from the original on 4 february 2017 retrieved 6 april 2016 sagiv barfi i czerwinski dk levy s alam is mayer at gambhir ss levy r 2018 eradication of spontaneous malignancy by local immunotherapy science translational medicine 10 426 eaan4488 doi 10 1126 scitranslmed aan4488 issn 1946 6234 pmc 5997264 pmid 29386357 kawamata s hori t imura a takaori kondo a uchiyama t march 1998 activation of ox40 signal transduction pathways leads to tumor necrosis factor receptor associated factor traf 2 and traf5 mediated nf kappab activation the journal of biological chemistry 273 10 5808 14 doi 10 1074 jbc 273 10 5808 pmid 9488716 arch rh thompson cb january 1998 4 1bb and ox40 are members of a tumor necrosis factor tnf nerve growth factor receptor subfamily that bind tnf receptor associated factors and activate nuclear factor kappab molecular and cellular biology 18 1 558 65 doi 10 1128 mcb 18 1 558 pmc 121523 pmid 9418902 external links edit human tnfrsf4 genome location and tnfrsf4 gene details page in the ucsc genome browser further reading edit so t salek ardakani s nakano h ware cf croft m april 2004 tnf receptor associated factor 5 limits the induction of th2 immune responses journal of immunology 172 7 4292 7 doi 10 4049 jimmunol 172 7 4292 pmid 15034043 song j salek ardakani s rogers pr cheng m van parijs l croft m february 2004 the costimulation regulated duration of pkb activation controls t cell longevity nature immunology 5 2 150 8 doi 10 1038 ni1030 pmid 14730361 s2cid 10102422 song j so t cheng m tang x croft m may 2005 sustained survivin expression from ox40 costimulatory signals drives t cell clonal expansion immunity 22 5 621 31 doi 10 1016 j immuni 2005 03 012 pmid 15894279 croft m august 2003 co stimulatory members of the tnfr family keys to effective t cell immunity nature reviews immunology 3 8 609 20 doi 10 1038 nri1148 pmid 12974476 s2cid 10503208 rogers pr song j gramaglia i killeen n croft m september 2001 ox40 promotes bcl xl and bcl 2 expression and is essential for long term survival of cd4 t cells immunity 15 3 445 55 doi 10 1016 s1074 7613 01 00191 1 pmid 11567634 watts th 2005 tnf tnfr family members in costimulation of t cell responses annual review of immunology 23 23 68 doi 10 1146 annurev immunol 23 021704 115839 pmid 15771565 v t e proteins clusters of differentiation see also list of human clusters of differentiation 1 50 1 a c 1a 1b 1d 1e 2 3 γ δ ε 4 5 6 7 8 a 9 10 11 a b c d 13 14 15 16 a b 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 a b 33 34 35 36 37 38 39 40 41 42 a b c d 43 44 45 46 47 48 49 a b c d e f 50 51 100 51 52 53 54 55 56 57 58 59 61 62 e l p 63 64 a b c 66 a b c d e f 68 69 70 71 72 73 74 78 79 a b 80 81 82 83 84 85 a d e h j k 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 150 101 102 103 104 105 106 107 a b 108 109 110 111 112 113 114 115 116 117 118 119 120 a b 121 a b 122 123 124 125 126 127 129 130 131 132 133 134 135 136 137 138 140b 141 142 143 144 146 147 148 150 151 200 151 152 153 154 155 156 a b c 157 158 a d e i k 159 a c 160 161 162 163 164 166 167 a b 168 169 170 171 172 a b g 174 177 178 179 a b 180 181 182 183 184 185 186 191 192 193 194 195 196 197 w198 w199 200 201 250 201 202b 204 205 206 207 208 209 w210 a b 212 213a 1 2 217 218 a b 220 221 222 223 224 225 226 227 228 229 230 233 234 235 a b 236 238 239 240ce 240d 241 243 244 246 247 248 249 251 300 252 253 254 256 257 258 261 262 263 264 265 266 267 268 269 271 272 273 274 275 276 278 279 280 281 282 283 284 286 288 289 290 292 w293 294 295 297 298 299 301 350 300a 301 302 303 304 305 306 307 309 312 314 315 316 317 318 320 321 322 324 325 326 327 328 329 331 332 333 334 335 336 337 338 339 340 344 349 350 351 371 351 352 353 354 355 357 358 360 361 362 363 364 365 366 367 368 369 370 371 category commons v t e cytokine receptors chemokine receptor gpcrs cc ccr1 ccr2 ccrl2 ccr3 ccr4 ccr5 ccr6 ccr7 ccr8 ccr9 ccr10 cxc cxcr1 cxcr2 cxcr3 cxcr4 cxcr5 cxcr6 other cx3c cx3cr1 xc xcr1 ackr 1 2 3 4 5 cmklr1 tnf receptor 1 10 tnfr1 tnfrsf1a tnfr2 tnfrsf1b ltbr tnfrsf3 tnfrsf4 cd40 tnfrsf5 fas receptor tnfrsf6 dcr3 tnfrsf6b cd27 tnfrsf7 cd30 tnfrsf8 tnfrsf9 11 20 dr4 tnfrsf10a dr5 tnfrsf10b dcr1 tnfrsf10c dcr2 tnfrsf10d rank tnfrsf11a osteoprotegerin tnfrsf11b tweakr tnfrsf12a taci tnfrsf13b baffr tnfrsf13c hvem tnfrsf14 ngfr tnfrsf16 bcma tnfrsf17 gitr tnfrsf18 taj troy tnfrsf19 21 27 dr6 tnfrsf21 dr3 tnfrsf25 eda2r tnfrsf27 jak stat type i γ chain interleukin receptors il2r il2ra il2rb il15r il4r il13r il13ra1 il13ra2 il7r il7ra il9r il21r β chain interleukin receptors il3r il3ra il5r il5ra gm csf gp130 interleukin receptors il6ra 11 il11ra 27 il27ra osmr lifr cntfr il12rb1 interleukin receptors il12r il12rb1 il12rb2 il23r other other csf receptors epo g csf thrombopoietin hormone receptor gh prolactin type ii interleukin receptors il10r il10ra il10rb il22r il22ra1 il22ra2 il20r il20ra il20rb il28r interferon receptors α β ifnar1 ifnar2 γ ifngr1 ifngr2 ig superfamily il1 il1r1 il1r2 il18r il18r1 il 17 family il17 il17ra il17rb il17rc il17rd il17re enzyme linked receptor tyr csf1r kit ser thr tgf beta tgfbr1 tgfbr2 family category commons v t e cytokine receptor modulators chemokine see here instead csf erythropoietin agonists ara 290 asialo erythropoietin carbamylated erythropoietin cnto 530 darbepoetin alfa epoetin alfa epoetin beta epoetin delta epoetin epsilon epoetin gamma epoetin kappa epoetin omega epoetin theta epoetin zeta erythropoietin epo erythropoietin fc methoxy polyethylene glycol epoetin beta cera mircera peginesatide pegol sihematide epo 018b g csf csf3 agonists filgrastim granulocyte colony stimulating factor lenograstim leridistim lipegfilgrastim nartograstim pegfilgrastim pegnartograstim gm csf csf2 agonists ecogramostim granulocyte macrophage colony stimulating factor milodistim molgramostim regramostim sargramostim antibodies mavrilimumab namilumab otilimab m csf csf1 agonists cilmostim interleukin 34 lanimostim macrophage colony stimulating factor mirimostim kinase inhibitors agerafenib scf c kit see here instead thrombopoietin agonists eltrombopag pegacaristim promegapoietin romiplostim avatrombopag lusutrombopag thrombopoietin thpo mgdf interferon ifnar α β i agonists albinterferon interferon alpha interferon alfa ifn α interferon alfa ifna1 ifna2 ifna4 ifna5 ifna6 ifna7 ifna8 ifna10 ifna13 ifna14 ifna16 ifna17 ifna21 interferon alfa 2a interferon alfa 2b interferon alfa n1 interferon alfacon 1 interferon alpha n3 interferon beta ifn β ifnb1 ifnb3 interferon beta 1a interferon beta 1b interferon kappa ifn ε κ τ ζ ifnk interferon omega ifn ω ifnw1 peginterferon alfa 2a peginterferon alfa 2b antibodies anifrolumab faralimomab medi 545 rontalizumab sifalimumab decoy receptors bifarcept ifngr γ ii agonists interferon gamma ifn γ interferon gamma 1b antibodies emapalumab fontolizumab ifnlr λ iii see il 28r ifnlr here instead interleukin see here instead tgfβ see here instead tnf see here instead others jak inhibitors jak1 abrocitinib baricitinib deuruxolitinib filgotinib momelotinib oclacitinib peficitinib ruxolitinib tofacitinib tasocitinib upadacitinib jak2 atiprimod azd 1480 baricitinib chz868 cucurbitacin i elatericin b jsi 124 cyt387 deuruxolitinib lestaurtinib nsc 7908 nsc 33994 pacritinib peficitinib ruxolitinib sd 1008 tofacitinib tasocitinib jak3 cercosporamide decernotinib vx 509 peficitinib ritlecitinib tcs 21311 tofacitinib tasocitinib whi p 154 zm 39923 zm 449829 tyk2 deucravacitinib others additional cytokines cardiotrophin 1 ct 1 fms like tyrosine kinase 3 ligand flt3l leukemia leukocyte inhibitory factor lif oncostatin m osm thymic stromal lymphopoietin tslp additional cytokine receptor modulators emfilermin lestaurtinib midostaurin quizartinib sorafenib sunitinib retrieved from https en wikipedia org w index php title tnfrsf4 oldid 1360484522 categories genes on human chromosome 1 t cells clusters of differentiation hidden categories articles with short description short description is different from wikidata all articles with unsourced statements articles with unsourced statements from april 2016 use dmy dates from april 2017 this page was last edited on 21 june 2026 at 19 23 utc page was rendered with parsoid text is available under the creative commons attribution sharealike 4 0 license additional terms may apply by using this site you agree to the terms of use and privacy policy wikipedia is a registered trademark of the wikimedia foundation inc a non profit organization privacy policy about wikipedia disclaimers contact wikipedia legal safety contacts code of conduct developers statistics cookie statement mobile view search search 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