Death receptor 4

TNFRSF10A
Identifiers
Aliases	TNFRSF10A, APO2, CD261, DR4, TRAILR-1, TRAILR1, tumor necrosis factor receptor superfamily member 10a, TNF receptor superfamily member 10a
External IDs	OMIM: 603611; MGI: 1341090; HomoloGene: 129806; GeneCards: TNFRSF10A; OMA:TNFRSF10A - orthologs
Gene location (Human)
Chr.	Chromosome 8 (human)
End	23,225,102 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	70,021,860 bp
RNA expression pattern
	Top expressed in
	buccal mucosa cell; ; nipple; ; pancreatic ductal cell; ; tendon of biceps brachii; ; pylorus; ; lymph node; ; superficial temporal artery; ; epithelium of colon; ; mucosa of pharynx; ; nasal epithelium;
	Top expressed in
	urethra; ; female urethra; ; male urethra; ; genital tubercle; ; morula; ; endothelial cell of lymphatic vessel; ; tail of embryo; ; lens; ; embryo; ; embryo;
	More reference expression data
	n/a
Gene ontology
Molecular function	TRAIL binding; transcription factor binding; protease binding; protein binding; tumor necrosis factor-activated receptor activity; death receptor activity; signaling receptor activity;
Cellular component	membrane; plasma membrane; integral component of plasma membrane; cell surface; intracellular anatomical structure; integral component of membrane;
Biological process	activation of NF-kappaB-inducing kinase activity; TRAIL-activated apoptotic signaling pathway; multicellular organism development; cell surface receptor signaling pathway; response to lipopolysaccharide; cellular response to mechanical stimulus; regulation of cell population proliferation; immune response; regulation of extrinsic apoptotic signaling pathway via death domain receptors; inflammatory response; activation of cysteine-type endopeptidase activity involved in apoptotic process; extrinsic apoptotic signaling pathway via death domain receptors; signal transduction; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; extrinsic apoptotic signaling pathway; tumor necrosis factor-mediated signaling pathway; apoptotic process; leukocyte migration; regulation of apoptotic process; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of apoptotic process;
	Sources:Amigo / QuickGO
Orthologs
	8797
	21933
	ENSG00000104689
	ENSMUSG00000022074
	O00220
	Q9QZM4
	NM_003844
	NM_020275
	NP_003835
	NP_064671
	Wikidata
View/Edit Human	View/Edit Mouse

Death receptor 4 (DR4), also known as TRAIL receptor 1 (TRAILR1) and tumor necrosis factor receptor superfamily member 10A (TNFRSF10A), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.^[5]^[6]

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL), and thus transduces cell death signal and induces cell apoptosis.^[7]

Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.^[8]

Interactions

TNFRSF10A has been shown to interact with DAP3.^[9]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000104689 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022074 – 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.
^ Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (Dec 1997). "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". EMBO J. 16 (17): 5386–97. doi:10.1093/emboj/16.17.5386. PMC 1170170. PMID 9311998.
^ Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (April 1997). "The receptor for the cytotoxic ligand TRAIL". Science. 276 (5309): 111–3. doi:10.1126/science.276.5309.111. PMID 9082980. S2CID 19984057.
^ "Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a".
^ Kuang AA, Diehl GE, Zhang J, Winoto A (2000). "FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts". J. Biol. Chem. 275 (33): 25065–8. doi:10.1074/jbc.C000284200. PMID 10862756.
^ Miyazaki T, Reed J C (June 2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins". Nat. Immunol. 2 (6): 493–500. doi:10.1038/88684. ISSN 1529-2908. PMID 11376335. S2CID 6923467.

Kimberley FC, Screaton GR (2005). "Following a TRAIL: update on a ligand and its five receptors". Cell Res. 14 (5): 359–72. doi:10.1038/sj.cr.7290236. PMID 15538968.
Fleury S, Thibodeau J, Croteau G, et al. (1995). "HLA-DR polymorphism affects the interaction with CD4". J. Exp. Med. 182 (3): 733–41. doi:10.1084/jem.182.3.733. PMC 2192178. PMID 7650480.
MacFarlane M, Ahmad M, Srinivasula SM, et al. (1997). "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". J. Biol. Chem. 272 (41): 25417–20. doi:10.1074/jbc.272.41.25417. PMID 9325248.
Schneider P, Bodmer JL, Thome M, et al. (1997). "Characterization of two receptors for TRAIL" (PDF). FEBS Lett. 416 (3): 329–34. doi:10.1016/S0014-5793(97)01231-3. PMID 9373179. S2CID 83145771.
Marsters SA, Sheridan JP, Pitti RM, et al. (1998). "A novel receptor for Apo2L/TRAIL contains a truncated death domain". Curr. Biol. 7 (12): 1003–6. Bibcode:1997CBio....7.1003M. doi:10.1016/S0960-9822(06)00422-2. PMID 9382840. S2CID 21645158.
Chaudhary PM, Eby M, Jasmin A, et al. (1998). "Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway". Immunity. 7 (6): 821–30. doi:10.1016/S1074-7613(00)80400-8. PMID 9430227.
Schneider P, Thome M, Burns K, et al. (1998). "TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB". Immunity. 7 (6): 831–6. doi:10.1016/S1074-7613(00)80401-X. PMID 9430228.
Diab BY, Lambert NC, L'Faqihi FE, et al. (1999). "Human collagen II peptide 256-271 preferentially binds to HLA-DR molecules associated with susceptibility to rheumatoid arthritis". Immunogenetics. 49 (1): 36–44. doi:10.1007/s002510050461. PMID 9811967. S2CID 22393348.
Costanzo A, Guiet C, Vito P (1999). "c-E10 is a caspase-recruiting domain-containing protein that interacts with components of death receptors signaling pathway and activates nuclear factor-kappaB". J. Biol. Chem. 274 (29): 20127–32. doi:10.1074/jbc.274.29.20127. PMID 10400625.
Hymowitz SG, Christinger HW, Fuh G, et al. (1999). "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5". Mol. Cell. 4 (4): 563–71. doi:10.1016/S1097-2765(00)80207-5. PMID 10549288.
Gibson SB, Oyer R, Spalding AC, et al. (2000). "Increased expression of death receptors 4 and 5 synergizes the apoptosis response to combined treatment with etoposide and TRAIL". Mol. Cell. Biol. 20 (1): 205–12. doi:10.1128/MCB.20.1.205-212.2000. PMC 85076. PMID 10594023.
Miyazaki T, Reed JC (2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins". Nat. Immunol. 2 (6): 493–500. doi:10.1038/88684. PMID 11376335. S2CID 6923467.
Trauzold A, Wermann H, Arlt A, et al. (2001). "CD95 and TRAIL receptor-mediated activation of protein kinase C and NF-kappaB contributes to apoptosis resistance in ductal pancreatic adenocarcinoma cells". Oncogene. 20 (31): 4258–69. doi:10.1038/sj.onc.1204559. PMID 11464292.
Dörr J, Bechmann I, Waiczies S, et al. (2002). "Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain". J. Neurosci. 22 (4): RC209. doi:10.1523/JNEUROSCI.22-04-j0001.2002. PMC 6757573. PMID 11844843.
Koyama S, Koike N, Adachi S (2002). "Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor". J. Cancer Res. Clin. Oncol. 128 (2): 73–9. doi:10.1007/s004320100292. PMID 11862476. S2CID 19509629.
Guan B, Yue P, Lotan R, Sun SY (2002). "Evidence that the human death receptor 4 is regulated by activator protein 1". Oncogene. 21 (20): 3121–9. doi:10.1038/sj.onc.1205430. PMID 12082627. S2CID 6726601.
Söderström TS, Poukkula M, Holmström TH, et al. (2002). "Mitogen-activated protein kinase/extracellular signal-regulated kinase signaling in activated T cells abrogates TRAIL-induced apoptosis upstream of the mitochondrial amplification loop and caspase-8". J. Immunol. 169 (6): 2851–60. doi:10.4049/jimmunol.169.6.2851. PMID 12218097.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000104689 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000022074 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9311998-5] Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (Dec 1997). "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". EMBO J. 16 (17): 5386–97. doi:10.1093/emboj/16.17.5386. PMC 1170170. PMID 9311998.

[pmid9082980-6] Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (April 1997). "The receptor for the cytotoxic ligand TRAIL". Science. 276 (5309): 111–3. doi:10.1126/science.276.5309.111. PMID 9082980. S2CID 19984057.

[entrez-7] "Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a".

[Kuang2000-8] Kuang AA, Diehl GE, Zhang J, Winoto A (2000). "FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts". J. Biol. Chem. 275 (33): 25065–8. doi:10.1074/jbc.C000284200. PMID 10862756.

[pmid11376335-9] Miyazaki T, Reed J C (June 2001). "A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins". Nat. Immunol. 2 (6): 493–500. doi:10.1038/88684. ISSN 1529-2908. PMID 11376335. S2CID 6923467.

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[4]

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[9]

v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD327 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Function

Interactions

References

Further reading