Death receptor 5

Tumor necrosis factor receptor superfamily, member 10b
PDB rendering based on 1d0g.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1D0G​, 1D4V​, 1DU3​, 1ZA3​, 2H9G​, 4I9X​, 4N90​, 4OD2​
Identifiers
Symbols	TNFRSF10B ; CD262; DR5; KILLER; KILLER/DR5; TRAIL-R2; TRAILR2; TRICK2; TRICK2A; TRICK2B; TRICKB; ZTNFR9
External IDs	OMIM: 603612 HomoloGene: 117702 ChEMBL: 1075153 GeneCards: TNFRSF10B Gene
Gene ontology Molecular function • receptor activity • protein binding • TRAIL binding Cellular component • intracellular • plasma membrane • cell surface • integral component of membrane Biological process • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • cell surface receptor signaling pathway • activation of NF-kappaB-inducing kinase activity • extrinsic apoptotic signaling pathway via death domain receptors • regulation of necrotic cell death • programmed cell death • response to endoplasmic reticulum stress • regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • necroptotic process • cellular response to mechanical stimulus • extrinsic apoptotic signaling pathway • activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway • programmed necrotic cell death • regulation of extrinsic apoptotic signaling pathway via death domain receptors Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8795	n/a
Ensembl	ENSG00000120889	n/a
UniProt	O14763	n/a
RefSeq (mRNA)	NM_003842	n/a
RefSeq (protein)	NP_003833	n/a
Location (UCSC)	Chr 8: 23.02 – 23.07 Mb	n/a
PubMed search		n/a

Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAILR2) and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces apoptosis signal. Mice have a homologous gene, tnfrsf10b, that has been essential in the elucidation of the function of this gene in humans. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein.^[1]

Interactions

DR5 has been shown to interact with:

• Caspase 8,^[2][3]
• Caspase 10,^[2][3]
• FADD,^[2][4] and
• TRAIL.^[5][6][7]

Cancer therapy

Monoclonal antibodies targeting DR5 have been developed and are currently under clinical trials for patients suffer from a variety of cancer types, see Tigatuzumab (CS-1008).

See also

• Cluster of differentiation
• Tumor necrosis factor receptor
• Tigatuzumab

References

1. "Entrez Gene: TNFRSF10B tumor necrosis factor receptor superfamily, member 10b".
2. Gajate C, Mollinedo F (Mar 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMID 15659383.
3. MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES (Oct 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.
4. Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L (Dec 1997). "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.
5. Kaptein A, Jansen M, Dilaver G, Kitson J, Dash L, Wang E, Owen MJ, Bodmer JL, Tschopp J, Farrow SN (Nov 2000). "Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3)". FEBS Lett. 485 (2-3): 135–41. doi:10.1016/s0014-5793(00)02219-5. PMID 11094155.
6. 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 (Sep 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.
7. Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM (Oct 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.

Further reading

• Abe K, Kurakin A, Mohseni-Maybodi M, Kay B, Khosravi-Far R (2001). "The complexity of TNF-related apoptosis-inducing ligand". Annals of the New York Academy of Sciences 926 (1): 52–63. doi:10.1111/j.1749-6632.2000.tb05598.x. PMID 11193041.
• Cha SS, Song YL, Oh BH (2004). "Specificity of molecular recognition learned from the crystal structures of TRAIL and the TRAIL:sDR5 complex". Vitamins and Hormones 67: 1–17. doi:10.1016/S0083-6729(04)67001-4. PMID 15110168.
• Kimberley FC, Screaton GR (Oct 2004). "Following a TRAIL: update on a ligand and its five receptors". Cell Research 14 (5): 359–72. doi:10.1038/sj.cr.7290236. PMID 15538968.
• Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (Aug 1997). "An antagonist decoy receptor and a death domain-containing receptor for TRAIL". Science 277 (5327): 815–8. doi:10.1126/science.277.5327.815. PMID 9242610.
• Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (Aug 1997). "Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors". Science 277 (5327): 818–21. doi:10.1126/science.277.5327.818. PMID 9242611.
• Screaton GR, Mongkolsapaya J, Xu XN, Cowper AE, McMichael AJ, Bell JI (Sep 1997). "TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL". Current Biology 7 (9): 693–6. doi:10.1016/S0960-9822(06)00297-1. PMID 9285725.
• 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 (Sep 1997). "TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL". The EMBO Journal 16 (17): 5386–97. doi:10.1093/emboj/16.17.5386. PMC 1170170. PMID 9311998.
• MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES (Oct 1997). "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". The Journal of Biological Chemistry 272 (41): 25417–20. doi:10.1074/jbc.272.41.25417. PMID 9325248.
• Wu GS, Burns TF, McDonald ER, Jiang W, Meng R, Krantz ID, Kao G, Gan DD, Zhou JY, Muschel R, Hamilton SR, Spinner NB, Markowitz S, Wu G, el-Deiry WS (Oct 1997). "KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene". Nature Genetics 17 (2): 141–3. doi:10.1038/ng1097-141. PMID 9326928.
• Schneider P, Bodmer JL, Thome M, Hofmann K, Holler N, Tschopp J (Oct 1997). "Characterization of two receptors for TRAIL". FEBS Letters 416 (3): 329–34. doi:10.1016/S0014-5793(97)01231-3. PMID 9373179.
• Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, Ashkenazi A (Dec 1997). "A novel receptor for Apo2L/TRAIL contains a truncated death domain". Current Biology 7 (12): 1003–6. doi:10.1016/S0960-9822(06)00422-2. PMID 9382840.
• Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L (Dec 1997). "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, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J (Dec 1997). "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.
• Pai SI, Wu GS, Ozören N, Wu L, Jen J, Sidransky D, El-Deiry WS (Aug 1998). "Rare loss-of-function mutation of a death receptor gene in head and neck cancer". Cancer Research 58 (16): 3513–8. PMID 9721851.
• Arai T, Akiyama Y, Okabe S, Saito K, Iwai T, Yuasa Y (Nov 1998). "Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas". Cancer Letters 133 (2): 197–204. doi:10.1016/S0304-3835(98)00230-4. PMID 10072170.
• Mongkolsapaya J, Grimes JM, Chen N, Xu XN, Stuart DI, Jones EY, Screaton GR (Nov 1999). "Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation". Nature Structural Biology 6 (11): 1048–53. doi:10.1038/14935. PMID 10542098.
• Hymowitz SG, Christinger HW, Fuh G, Ultsch M, O'Connell M, Kelley RF, Ashkenazi A, de Vos AM (Oct 1999). "Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5". Molecular Cell 4 (4): 563–71. doi:10.1016/S1097-2765(00)80207-5. PMID 10549288.
• Kuang AA, Diehl GE, Zhang J, Winoto A (Aug 2000). "FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts". The Journal of Biological Chemistry 275 (33): 25065–8. doi:10.1074/jbc.C000284200. PMID 10862756.
• Trauzold A, Wermann H, Arlt A, Schütze S, Schäfer H, Oestern S, Röder C, Ungefroren H, Lampe E, Heinrich M, Walczak H, Kalthoff H (Jul 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.

External links

• TNFRSF10B protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.