TRADD

TRADD
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1F2H, 1F3V
Identifiers
Aliases	TRADD, Hs.89862, TNFRSF1A associated via death domain
External IDs	OMIM: 603500; MGI: 109200; HomoloGene: 2807; GeneCards: TRADD; OMA:TRADD - orthologs
Gene location (Human)
Chr.	Chromosome 16 (human)
End	67,159,909 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	105,991,241 bp
RNA expression pattern
	Top expressed in
	pancreatic ductal cell; ; granulocyte; ; right uterine tube; ; mucosa of transverse colon; ; amniotic fluid; ; parotid gland; ; blood; ; palpebral conjunctiva; ; epithelium of nasopharynx; ; gingival epithelium;
	Top expressed in
	intestinal villus; ; left colon; ; Ileal epithelium; ; lumbar spinal ganglion; ; jejunum; ; plantaris muscle; ; extensor digitorum longus muscle; ; duodenum; ; blood; ; epithelium of stomach;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	death domain binding; kinase binding; protein binding; identical protein binding; tumor necrosis factor receptor binding; protein-containing complex binding; molecular adaptor activity; transmembrane receptor protein tyrosine kinase adaptor activity;
Cellular component	cytoplasm; cytosol; receptor complex; plasma membrane; death-inducing signaling complex; membrane raft; cytoskeleton; nucleus; protein-containing complex;
Biological process	extrinsic apoptotic signaling pathway; positive regulation of hair follicle development; regulation of tumor necrosis factor-mediated signaling pathway; tumor necrosis factor-mediated signaling pathway; death-inducing signaling complex assembly; positive regulation of NF-kappaB transcription factor activity; positive regulation of apoptotic process; positive regulation of I-kappaB kinase/NF-kappaB signaling; regulation of extrinsic apoptotic signaling pathway via death domain receptors; I-kappaB kinase/NF-kappaB signaling; activation of cysteine-type endopeptidase activity involved in apoptotic process; extrinsic apoptotic signaling pathway via death domain receptors; signal transduction; apoptotic process; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; protein heterooligomerization; positive regulation of cell migration; positive regulation of inflammatory response; cellular response to tumor necrosis factor; positive regulation of NIK/NF-kappaB signaling; transmembrane receptor protein tyrosine kinase signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	8717
	71609
	ENSG00000102871
	ENSMUSG00000031887
	Q15628
	Q3U0V2
	NM_003789; NM_153425; NM_001323552
	NM_001033161
	NP_001310481; NP_003780
	NP_001028333
	Wikidata
View/Edit Human	View/Edit Mouse

Tumor necrosis factor receptor type 1-associated DEATH domain protein is a protein that in humans is encoded by the TRADD gene.^[5]^[6]

TRADD is an adaptor protein.

Function

The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-κB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor TNFRSF6/FAS and adaptor protein FADD/MORT1, and is involved in the Fas-induced cell death pathway.^[6]

Signaling pathway of TNF-R1. Dashed grey lines represent multiple steps

Interactions

TRADD has been shown to interact with:

FADD,^[7]^[8]^[9]
Keratin 18^[10]
RIPK1,^[11]
STAT1,^[12]
TNFRSF1A,^[7]^[11]^[13]^[14]^[15]^[16]^[17]
TNFRSF25,^[18] and
TRAF2.^[7]^[19]^[20]^[21]^[22]^[23]^[24]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000102871 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031887 – 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.
^ Hsu H, Xiong J, Goeddel DV (June 1995). "The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation". Cell. 81 (4): 495–504. doi:10.1016/0092-8674(95)90070-5. PMID 7758105. S2CID 14301562.
^ ^a ^b "Entrez Gene: TRADD TNFRSF1A-associated via death domain".
^ ^a ^b ^c Hsu H, Shu HB, Pan MG, Goeddel DV (January 1996). "TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways". Cell. 84 (2): 299–308. doi:10.1016/s0092-8674(00)80984-8. PMID 8565075. S2CID 13171355.
^ Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP (September 2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". J. Neurochem. 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633. S2CID 21971958.
^ Thomas LR, Stillman DJ, Thorburn A (September 2002). "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen". J. Biol. Chem. 277 (37): 34343–8. doi:10.1074/jbc.M204169200. PMID 12107169.
^ Inada H, Izawa I, Nishizawa M, Fujita E, Kiyono T, Takahashi T, Momoi T, Inagaki M (October 2001). "Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD". J. Cell Biol. 155 (3): 415–26. doi:10.1083/jcb.200103078. PMC 2150850. PMID 11684708.
^ ^a ^b Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (April 1996). "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex". Immunity. 4 (4): 387–96. doi:10.1016/s1074-7613(00)80252-6. PMID 8612133.
^ Wang Y, Wu TR, Cai S, Welte T, Chin YE (July 2000). "Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation". Mol. Cell. Biol. 20 (13): 4505–12. doi:10.1128/mcb.20.13.4505-4512.2000. PMC 85828. PMID 10848577.
^ Jiang Y, Woronicz JD, Liu W, Goeddel DV (January 1999). "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains". Science. 283 (5401): 543–6. doi:10.1126/science.283.5401.543. PMID 9915703.
^ Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke M (April 1999). "Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling". J. Biol. Chem. 274 (15): 10203–12. doi:10.1074/jbc.274.15.10203. PMID 10187805.
^ 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.
^ Shu HB, Takeuchi M, Goeddel DV (November 1996). "The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13973–8. Bibcode:1996PNAS...9313973S. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045.
^ Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D (January 2009). "Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)". Biochem. J. 417 (1): 149–60. doi:10.1042/BJ20081885. PMID 18939944.
^ Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham CJ, Brown R, Farrow SN (November 1996). "A death-domain-containing receptor that mediates apoptosis". Nature. 384 (6607): 372–5. doi:10.1038/384372a0. PMID 8934525. S2CID 4283742.
^ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
^ 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". J. Biol. Chem. 271 (33): 19935–42. doi:10.1074/jbc.271.33.19935. PMID 8702708.
^ Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H (June 2000). "A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction". Cell. 101 (7): 777–87. doi:10.1016/s0092-8674(00)80889-2. PMID 10892748. S2CID 5928713.
^ Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL (June 2000). "Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway". Mol. Cell. 5 (6): 1051–7. doi:10.1016/s1097-2765(00)80270-1. PMID 10911999.
^ Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (September 2001). "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. Biol. Chem. 276 (39): 36530–4. doi:10.1074/jbc.M104837200. PMID 11479302.
^ Malinin NL, Boldin MP, Kovalenko AV, Wallach D (February 1997). "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1". Nature. 385 (6616): 540–4. doi:10.1038/385540a0. PMID 9020361. S2CID 4366355.

External links

TRADD+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000102871 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000031887 – 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.

[pmid7758105-5] Hsu H, Xiong J, Goeddel DV (June 1995). "The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation". Cell. 81 (4): 495–504. doi:10.1016/0092-8674(95)90070-5. PMID 7758105. S2CID 14301562.

[entrez-6] "Entrez Gene: TRADD TNFRSF1A-associated via death domain".

[pmid8565075-7] Hsu H, Shu HB, Pan MG, Goeddel DV (January 1996). "TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways". Cell. 84 (2): 299–308. doi:10.1016/s0092-8674(00)80984-8. PMID 8565075. S2CID 13171355.

[pmid12911633-8] Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP (September 2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". J. Neurochem. 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633. S2CID 21971958.

[pmid12107169-9] Thomas LR, Stillman DJ, Thorburn A (September 2002). "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen". J. Biol. Chem. 277 (37): 34343–8. doi:10.1074/jbc.M204169200. PMID 12107169.

[pmid11684708-10] Inada H, Izawa I, Nishizawa M, Fujita E, Kiyono T, Takahashi T, Momoi T, Inagaki M (October 2001). "Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD". J. Cell Biol. 155 (3): 415–26. doi:10.1083/jcb.200103078. PMC 2150850. PMID 11684708.

[pmid8612133-11] Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (April 1996). "TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex". Immunity. 4 (4): 387–96. doi:10.1016/s1074-7613(00)80252-6. PMID 8612133.

[pmid10848577-12] Wang Y, Wu TR, Cai S, Welte T, Chin YE (July 2000). "Stat1 as a component of tumor necrosis factor alpha receptor 1-TRADD signaling complex to inhibit NF-kappaB activation". Mol. Cell. Biol. 20 (13): 4505–12. doi:10.1128/mcb.20.13.4505-4512.2000. PMC 85828. PMID 10848577.

[pmid9915703-13] Jiang Y, Woronicz JD, Liu W, Goeddel DV (January 1999). "Prevention of constitutive TNF receptor 1 signaling by silencer of death domains". Science. 283 (5401): 543–6. doi:10.1126/science.283.5401.543. PMID 9915703.

[pmid10187805-14] Schütze S, Machleidt T, Adam D, Schwandner R, Wiegmann K, Kruse ML, Heinrich M, Wickel M, Krönke M (April 1999). "Inhibition of receptor internalization by monodansylcadaverine selectively blocks p55 tumor necrosis factor receptor death domain signaling". J. Biol. Chem. 274 (15): 10203–12. doi:10.1074/jbc.274.15.10203. PMID 10187805.

[pmid9082980-15] 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.

[pmid8943045-16] Shu HB, Takeuchi M, Goeddel DV (November 1996). "The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13973–8. Bibcode:1996PNAS...9313973S. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045.

[pmid18939944-17] Blankenship JW, Varfolomeev E, Goncharov T, Fedorova AV, Kirkpatrick DS, Izrael-Tomasevic A, Phu L, Arnott D, Aghajan M, Zobel K, Bazan JF, Fairbrother WJ, Deshayes K, Vucic D (January 2009). "Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1)". Biochem. J. 417 (1): 149–60. doi:10.1042/BJ20081885. PMID 18939944.

[pmid8934525-18] Kitson J, Raven T, Jiang YP, Goeddel DV, Giles KM, Pun KT, Grinham CJ, Brown R, Farrow SN (November 1996). "A death-domain-containing receptor that mediates apoptosis". Nature. 384 (6607): 372–5. doi:10.1038/384372a0. PMID 8934525. S2CID 4283742.

[pmid14743216-19] Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.

[pmid8702708-20] 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". J. Biol. Chem. 271 (33): 19935–42. doi:10.1074/jbc.271.33.19935. PMID 8702708.

[pmid10892748-21] Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H (June 2000). "A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction". Cell. 101 (7): 777–87. doi:10.1016/s0092-8674(00)80889-2. PMID 10892748. S2CID 5928713.

[pmid10911999-22] Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL (June 2000). "Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway". Mol. Cell. 5 (6): 1051–7. doi:10.1016/s1097-2765(00)80270-1. PMID 10911999.

[pmid11479302-23] Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H (September 2001). "Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death". J. Biol. Chem. 276 (39): 36530–4. doi:10.1074/jbc.M104837200. PMID 11479302.

[pmid9020361-24] Malinin NL, Boldin MP, Kovalenko AV, Wallach D (February 1997). "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1". Nature. 385 (6616): 540–4. doi:10.1038/385540a0. PMID 9020361. S2CID 4366355.

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TRADD

Function

Interactions

See also

References

Further reading

External links