TRAF1

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.[5]

TRAF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3M0D
Identifiers
Aliases	TRAF1, EBI6, MGC:10353, TNF receptor associated factor 1
External IDs	OMIM: 601711 MGI: 101836 HomoloGene: 4138 GeneCards: TRAF1
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q33.2 Start 120,902,393 bp[1] End 120,929,173 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 B Start 34,941,750 bp[2] End 34,961,772 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • thioesterase binding • zinc ion binding • GO:0001948 protein binding • ubiquitin protein ligase binding • identical protein binding • tumor necrosis factor receptor binding Cellular component • cytoplasm • cytosol • macromolecular complex Biological process • regulation of apoptotic process • regulation of tumor necrosis factor-mediated signaling pathway • regulation of extrinsic apoptotic signaling pathway • signal transduction • apoptotic process • positive regulation of NF-kappaB transcription factor activity • macromolecular complex assembly Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	7185	22029
Ensembl	ENSG00000056558	ENSMUSG00000026875
UniProt	Q13077	P39428
RefSeq (mRNA)	NM_005658 NM_001190945 NM_001190947	NM_009421 NM_001326601
RefSeq (protein)	NP_001177874 NP_001177876 NP_005649	NP_001313530 NP_033447
Location (UCSC)	Chr 9: 120.9 – 120.93 Mb	Chr 2: 34.94 – 34.96 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 (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF2 also interacts with IAP, and thus mediates the anti-apoptotic signals from TNF receptors. The expression of this protein can be induced by Epstein-Barr virus (EBV). EBV infection membrane protein 1 (LMP1) is found to interact with this and other TRAF proteins; this interaction is thought to link LMP1-mediated B lymphocyte transformation to the signal transduction from TNFR family receptors.[6] TRAF1 also functions as a negative regulator of inflammation by interfering with the linear ubiquitination of NEMO downstream of TLR signaling.[7] This explains why TRAF1 polymorphisms cause an increased risk for rheumatic diseases.[8]

Interactions

TRAF1 has been shown to interact with:

• BIRC2,[9][10][11]
• Baculoviral IAP repeat-containing protein 3,[9][10]
• CFLAR,[12][13]
• Caspase 8,[14][15]
• HIVEP3,[16]
• RANK[17][18]
• TNFAIP3,[19][20]
• TRAF interacting protein,[21] and
• TRAF2.[22][23]
• RNF31.[24]
• RBCK1.[24]
• SHARPIN.[24]

References

1. GRCh38: Ensembl release 89: ENSG00000056558 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026875 - 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. Rothe M, Wong SC, Henzel WJ, Goeddel DV (September 1994). "A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor". Cell. 78 (4): 681–92. doi:10.1016/0092-8674(94)90532-0. PMID 8069916. S2CID 28055231.
6. "Entrez Gene: TRAF1 TNF receptor-associated factor 1".
7. Abdul-Sater, Ali A; Edilova, Maria I; Clouthier, Derek L; Mbanwi, Achire; Kremmer, Elisabeth; Watts, Tania H (2017). "The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease". Nature Immunology. 18 (1): 26–35. doi:10.1038/ni.3618. PMID 27893701. S2CID 19487408.
8. Plenge, Robert M.; Seielstad, Mark; Padyukov, Leonid; Lee, Annette T.; Remmers, Elaine F.; Ding, Bo; Liew, Anthony; Khalili, Houman; Chandrasekaran, Alamelu (2007-09-20). "TRAF1–C5 as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study". New England Journal of Medicine. 357 (12): 1199–1209. doi:10.1056/NEJMoa073491. ISSN 0028-4793. PMC 2636867. PMID 17804836.
9. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (Dec 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. 16 (23): 6914–25. doi:10.1093/emboj/16.23.6914. PMC 1170295. PMID 9384571.
10. Li X, Yang Y, Ashwell JD (March 2002). "TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2". Nature. 416 (6878): 345–7. doi:10.1038/416345a. PMID 11907583. S2CID 4325926.
11. 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. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045.
12. Shu HB, Halpin DR, Goeddel DV (June 1997). "Casper is a FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751–63. doi:10.1016/s1074-7613(00)80450-1. PMID 9208847.
13. Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, Burns K, Hahne M, Kennedy N, Kovacsovics M, Tschopp J (June 2000). "The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways". Curr. Biol. 10 (11): 640–8. doi:10.1016/s0960-9822(00)00512-1. PMID 10837247. S2CID 14819939.
14. Micheau O, Tschopp J (July 2003). "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes" (PDF). Cell. 114 (2): 181–90. doi:10.1016/s0092-8674(03)00521-x. PMID 12887920. S2CID 17145731.
15. Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC (March 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 (11): 8087–93. doi:10.1074/jbc.M009450200. PMID 11098060.
16. Oukka M, Kim ST, Lugo G, Sun J, Wu LC, Glimcher LH (January 2002). "A mammalian homolog of Drosophila schnurri, KRC, regulates TNF receptor-driven responses and interacts with TRAF2". Mol. Cell. 9 (1): 121–31. doi:10.1016/s1097-2765(01)00434-8. PMID 11804591.
17. Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC (Dec 1998). "The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily". J. Biol. Chem. 273 (51): 34120–7. doi:10.1074/jbc.273.51.34120. PMID 9852070.
18. Kim HH, Lee DE, Shin JN, Lee YS, Jeon YM, Chung CH, Ni J, Kwon BS, Lee ZH (January 1999). "Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase". FEBS Lett. 443 (3): 297–302. doi:10.1016/s0014-5793(98)01731-1. PMID 10025951. S2CID 46210019.
19. Song HY, Rothe M, Goeddel DV (June 1996). "The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation". Proc. Natl. Acad. Sci. U.S.A. 93 (13): 6721–5. doi:10.1073/pnas.93.13.6721. PMC 39093. PMID 8692885.
20. Heyninck K, Beyaert R (January 1999). "The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6". FEBS Lett. 442 (2–3): 147–50. doi:10.1016/s0014-5793(98)01645-7. PMID 9928991. S2CID 19072203.
21. Lee SY, Lee SY, Choi Y (April 1997). "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation". J. Exp. Med. 185 (7): 1275–85. doi:10.1084/jem.185.7.1275. PMC 2196258. PMID 9104814.
22. 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.
23. 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.
24. Abdul-Sater AA, Edilova MI, Clouthier DL, Mbanwi A, Kremmer E, Watts TH (November 2016). "The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease". Nat. Immunol. 18 (1): 26–35. doi:10.1038/ni.3618. PMID 27893701. S2CID 19487408.

Further reading

• Wajant H, Henkler F, Scheurich P (2001). "The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators". Cell. Signal. 13 (6): 389–400. doi:10.1016/S0898-6568(01)00160-7. PMID 11384837.
• Bradley JR, Pober JS (2001). "Tumor necrosis factor receptor-associated factors (TRAFs)". Oncogene. 20 (44): 6482–91. doi:10.1038/sj.onc.1204788. PMID 11607847.
• Hu HM, O'Rourke K, Boguski MS, Dixit VM (1994). "A novel RING finger protein interacts with the cytoplasmic domain of CD40". J. Biol. Chem. 269 (48): 30069–72. PMID 7527023.
• Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E (1995). "The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family". Cell. 80 (3): 389–99. doi:10.1016/0092-8674(95)90489-1. PMID 7859281. S2CID 17984027.
• Hsu H, Shu HB, Pan MG, Goeddel DV (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.
• Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV (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.
• Lee SY, Park CG, Choi Y (1996). "T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors". J. Exp. Med. 183 (2): 669–74. doi:10.1084/jem.183.2.669. PMC 2192463. PMID 8627180.
• Gedrich RW, Gilfillan MC, Duckett CS, Van Dongen JL, Thompson CB (1996). "CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins". J. Biol. Chem. 271 (22): 12852–8. doi:10.1074/jbc.271.22.12852. PMID 8662842.
• Song HY, Rothe M, Goeddel DV (1996). "The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation". Proc. Natl. Acad. Sci. U.S.A. 93 (13): 6721–5. doi:10.1073/pnas.93.13.6721. PMC 39093. PMID 8692885.
• Takeuchi M, Rothe M, Goeddel DV (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.
• Rothe M, Xiong J, Shu HB, Williamson K, Goddard A, Goeddel DV (1996). "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8241–6. doi:10.1073/pnas.93.16.8241. PMC 38654. PMID 8710854.
• Shu HB, Takeuchi M, Goeddel DV (1997). "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. doi:10.1073/pnas.93.24.13973. PMC 19479. PMID 8943045.
• Lee SY, Lee SY, Choi Y (1997). "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation". J. Exp. Med. 185 (7): 1275–85. doi:10.1084/jem.185.7.1275. PMC 2196258. PMID 9104814.
• Marsters SA, Ayres TM, Skubatch M, Gray CL, Rothe M, Ashkenazi A (1997). "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1". J. Biol. Chem. 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. PMID 9162022.
• Boucher LM, Marengère LE, Lu Y, Thukral S, Mak TW (1997). "Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily". Biochem. Biophys. Res. Commun. 233 (3): 592–600. doi:10.1006/bbrc.1997.6509. PMID 9168896.
• Shu HB, Halpin DR, Goeddel DV (1997). "Casper is an FADD- and caspase-related inducer of apoptosis". Immunity. 6 (6): 751–63. doi:10.1016/S1074-7613(00)80450-1. PMID 9208847.
• Song HY, Régnier CH, Kirschning CJ, Goeddel DV, Rothe M (1997). "Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2". Proc. Natl. Acad. Sci. U.S.A. 94 (18): 9792–6. doi:10.1073/pnas.94.18.9792. PMC 23270. PMID 9275204.
• Siemienski K, Peters N, Scheurich P, Wajant H (1997). "Organization of the human tumour necrosis factor receptor-associated factor 1 (TRAF1) gene and mapping to chromosome 9q33-34". Gene. 195 (1): 35–9. doi:10.1016/S0378-1119(97)00147-9. PMID 9300817.