Death receptor 4

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]

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
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p21.3 Start 23,190,452 bp[1] End 23,225,102 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 D2 Start 69,767,472 bp[2] End 69,784,411 bp[2]
Gene ontology Molecular function • TRAIL binding • transcription factor binding • protease binding • GO:0001948 protein binding • tumor necrosis factor-activated receptor activity • death receptor activity • signaling receptor activity Cellular component • membrane • cell membrane • integral component of plasma membrane • cell surface • intracellular • 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 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
Species	Human	Mouse
Entrez	8797	21933
Ensembl	ENSG00000104689	ENSMUSG00000022074
UniProt	O00220	Q9QZM4
RefSeq (mRNA)	NM_003844	NM_020275
RefSeq (protein)	NP_003835	NP_064671
Location (UCSC)	Chr 8: 23.19 – 23.23 Mb	Chr 14: 69.77 – 69.78 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000104689 - Ensembl, May 2017
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.
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.
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.
7. "Entrez Gene: TNFRSF10A tumor necrosis factor receptor superfamily, member 10a".
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.
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.

Further reading

• 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.
• 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. doi:10.1016/S0960-9822(06)00422-2. PMID 9382840.
• 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.
• 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.
• 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. 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.
• 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.
• 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.