Editing TRAF1

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''TNF receptor-associated factor 1''' is a [[protein]] that in humans is encoded by the ''TRAF1'' [[gene]].<ref name="pmid8069916">{{cite journal | vauthors = Rothe M, Wong SC, Henzel WJ, Goeddel DV | title = A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor | journal = Cell | volume = 78 | issue = 4 | pages = 681–92 | date = September 1994 | pmid = 8069916 | doi = 10.1016/0092-8674(94)90532-0 | s2cid = 28055231 }}</ref>

== 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 [[inhibitor of apoptosis protein|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.<ref name="entrez">{{cite web | title = Entrez Gene: TRAF1 TNF receptor-associated factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7185}}</ref> TRAF1 also functions as a negative regulator of inflammation by interfering with the linear ubiquitination of NEMO downstream of TLR signaling.<ref>{{Cite journal|last1=Abdul-Sater|first1=Ali A|last2=Edilova|first2=Maria I|last3=Clouthier|first3=Derek L|last4=Mbanwi|first4=Achire|last5=Kremmer|first5=Elisabeth|last6=Watts|first6=Tania H|title=The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease|journal=Nature Immunology|volume=18|issue=1|pages=26–35|doi=10.1038/ni.3618|pmid=27893701|year=2017|s2cid=19487408}}</ref> This explains why TRAF1 polymorphisms cause an increased risk for rheumatic diseases.<ref>{{Cite journal|last1=Plenge|first1=Robert M.|last2=Seielstad|first2=Mark|last3=Padyukov|first3=Leonid|last4=Lee|first4=Annette T.|last5=Remmers|first5=Elaine F.|last6=Ding|first6=Bo|last7=Liew|first7=Anthony|last8=Khalili|first8=Houman|last9=Chandrasekaran|first9=Alamelu|date=2007-09-20|title=TRAF1–C5 as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study|journal=New England Journal of Medicine|volume=357|issue=12|pages=1199–1209|doi=10.1056/NEJMoa073491|issn=0028-4793|pmc=2636867|pmid=17804836}}</ref>

== Interactions ==

TRAF1 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[BIRC2]],<ref name = pmid9384571/><ref name = pmid11907583/><ref name = pmid8943045>{{cite journal | vauthors = Shu HB, Takeuchi M, Goeddel DV | title = The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 24 | pages = 13973–8 | date = November 1996 | pmid = 8943045 | pmc = 19479 | doi =  10.1073/pnas.93.24.13973| bibcode = 1996PNAS...9313973S | doi-access = free }}</ref> 
* [[Baculoviral IAP repeat-containing protein 3]],<ref name = pmid9384571>{{cite journal | vauthors = Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC | title = The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases | journal = EMBO J. | volume = 16 | issue = 23 | pages = 6914–25 | date = Dec 1997 | pmid = 9384571 | pmc = 1170295 | doi = 10.1093/emboj/16.23.6914 }}</ref><ref name = pmid11907583>{{cite journal | vauthors = Li X, Yang Y, Ashwell JD | title = TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2 | journal = Nature | volume = 416 | issue = 6878 | pages = 345–7 | date = March 2002 | pmid = 11907583 | doi = 10.1038/416345a | bibcode = 2002Natur.416..345L | s2cid = 4325926 | url = https://zenodo.org/record/1233217 }}</ref> 
* [[CFLAR]],<ref name = pmid9208847>{{cite journal | vauthors = Shu HB, Halpin DR, Goeddel DV | title = Casper is a FADD- and caspase-related inducer of apoptosis | journal = Immunity | volume = 6 | issue = 6 | pages = 751–63 | date = June 1997 | pmid = 9208847 | doi =  10.1016/s1074-7613(00)80450-1| doi-access = free }}</ref><ref name = pmid10837247>{{cite journal | vauthors = Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, Burns K, Hahne M, Kennedy N, Kovacsovics M, Tschopp J | title = The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways | journal = Curr. Biol. | volume = 10 | issue = 11 | pages = 640–8 | date = June 2000 | pmid = 10837247 | doi =  10.1016/s0960-9822(00)00512-1| s2cid = 14819939 | doi-access = free }}</ref> 
* [[Caspase 8]],<ref name = pmid12887920>{{cite journal | vauthors = Micheau O, Tschopp J | title = Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes | journal = Cell | volume = 114 | issue = 2 | pages = 181–90 | date = July 2003 | pmid = 12887920 | doi =  10.1016/s0092-8674(03)00521-x| s2cid = 17145731 | url = https://www.hal.inserm.fr/inserm-00527105/file/Figures_Cell_OM.pdf }}</ref><ref name = pmid11098060>{{cite journal | vauthors = Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC | title = TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis | journal = J. Biol. Chem. | volume = 276 | issue = 11 | pages = 8087–93 | date = March 2001 | pmid = 11098060 | doi = 10.1074/jbc.M009450200 | doi-access = free }}</ref> 
* [[HIVEP3]],<ref name = pmid11804591>{{cite journal | vauthors = Oukka M, Kim ST, Lugo G, Sun J, Wu LC, Glimcher LH | title = A mammalian homolog of Drosophila schnurri, KRC, regulates TNF receptor-driven responses and interacts with TRAF2 | journal = Mol. Cell | volume = 9 | issue = 1 | pages = 121–31 | date = January 2002 | pmid = 11804591 | doi =  10.1016/s1097-2765(01)00434-8| doi-access = free }}</ref> 
* [[RANK]]<ref name = pmid9852070>{{cite journal | vauthors = Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC | title = 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 | journal = J. Biol. Chem. | volume = 273 | issue = 51 | pages = 34120–7 | date = Dec 1998 | pmid = 9852070 | doi =  10.1074/jbc.273.51.34120| doi-access = free }}</ref><ref name = pmid10025951>{{cite journal | vauthors = Kim HH, Lee DE, Shin JN, Lee YS, Jeon YM, Chung CH, Ni J, Kwon BS, Lee ZH | title = Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase | journal = FEBS Lett. | volume = 443 | issue = 3 | pages = 297–302 | date = January 1999 | pmid = 10025951 | doi =  10.1016/s0014-5793(98)01731-1| s2cid = 46210019 | doi-access = free }}</ref> 
* [[TNFAIP3]],<ref name = pmid8692885>{{cite journal | vauthors = Song HY, Rothe M, Goeddel DV | title = The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 13 | pages = 6721–5 | date = June 1996 | pmid = 8692885 | pmc = 39093 | doi =  10.1073/pnas.93.13.6721| bibcode = 1996PNAS...93.6721S | doi-access = free }}</ref><ref name = pmid9928991>{{cite journal | vauthors = Heyninck K, Beyaert R | title = The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6 | journal = FEBS Lett. | volume = 442 | issue = 2–3 | pages = 147–50 | date = January 1999 | pmid = 9928991 | doi =  10.1016/s0014-5793(98)01645-7| s2cid = 19072203 | doi-access = free }}</ref> 
* [[TRAF interacting protein]],<ref name = pmid9104814>{{cite journal | vauthors = Lee SY, Lee SY, Choi Y | title = 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 | journal = J. Exp. Med. | volume = 185 | issue = 7 | pages = 1275–85 | date = April 1997 | pmid = 9104814 | pmc = 2196258 | doi =  10.1084/jem.185.7.1275}}</ref> and
* [[TRAF2]].<ref name = pmid14743216>{{cite journal | vauthors = 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 | title = A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway | journal = Nat. Cell Biol. | volume = 6 | issue = 2 | pages = 97–105 | date = February 2004 | pmid = 14743216 | doi = 10.1038/ncb1086 | s2cid = 11683986 }}</ref><ref name = pmid8702708>{{cite journal | vauthors = Takeuchi M, Rothe M, Goeddel DV | title = Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 19935–42 | date = August 1996 | pmid = 8702708 | doi =  10.1074/jbc.271.33.19935| doi-access = free }}</ref> 
* [[RNF31]].<ref name = pmid27893701>{{cite journal | vauthors = Abdul-Sater AA, Edilova MI, Clouthier DL, Mbanwi A, Kremmer E, Watts TH | title = The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease | journal = Nat. Immunol. | volume = 18 | issue = 1 | pages = 26–35 | date = November 2016 | pmid = 27893701 | doi = 10.1038/ni.3618 | s2cid = 19487408 }}</ref>
* [[RBCK1]].<ref name = pmid27893701>{{cite journal | vauthors = Abdul-Sater AA, Edilova MI, Clouthier DL, Mbanwi A, Kremmer E, Watts TH | title = The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease | journal = Nat. Immunol. | volume = 18 | issue = 1 | pages = 26–35 | date = November 2016 | pmid = 27893701 | doi = 10.1038/ni.3618 | s2cid = 19487408 }}</ref>
* [[SHARPIN]].<ref name = pmid27893701>{{cite journal | vauthors = Abdul-Sater AA, Edilova MI, Clouthier DL, Mbanwi A, Kremmer E, Watts TH | title = The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and this underlies its role in rheumatic disease | journal = Nat. Immunol. | volume = 18 | issue = 1 | pages = 26–35 | date = November 2016 | pmid = 27893701 | doi = 10.1038/ni.3618 | s2cid = 19487408 }}</ref>{{Div col end}}

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Wajant H, Henkler F, Scheurich P | title = The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators. | journal = Cell. Signal. | volume = 13 | issue = 6 | pages = 389–400 | year = 2001 | pmid = 11384837 | doi = 10.1016/S0898-6568(01)00160-7 }}
* {{cite journal | vauthors = Bradley JR, Pober JS | title = Tumor necrosis factor receptor-associated factors (TRAFs). | journal = Oncogene | volume = 20 | issue = 44 | pages = 6482–91 | year = 2001 | pmid = 11607847 | doi = 10.1038/sj.onc.1204788 | doi-access = free }}
* {{cite journal | vauthors = Hu HM, O'Rourke K, Boguski MS, Dixit VM | title = A novel RING finger protein interacts with the cytoplasmic domain of CD40. | journal = J. Biol. Chem. | volume = 269 | issue = 48 | pages = 30069–72 | year = 1994 | doi = 10.1016/S0021-9258(18)43772-6 | pmid = 7527023 | doi-access = free }}
* {{cite journal | vauthors = Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E | title = The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family. | journal = Cell | volume = 80 | issue = 3 | pages = 389–99 | year = 1995 | pmid = 7859281 | doi = 10.1016/0092-8674(95)90489-1 | s2cid = 17984027 | doi-access = free }}
* {{cite journal | vauthors = Hsu H, Shu HB, Pan MG, Goeddel DV | title = TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. | journal = Cell | volume = 84 | issue = 2 | pages = 299–308 | year = 1996 | pmid = 8565075 | doi = 10.1016/S0092-8674(00)80984-8 | s2cid = 13171355 | doi-access = free }}
* {{cite journal | vauthors = Hsu H, Huang J, Shu HB, Baichwal V, Goeddel DV | title = TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. | journal = Immunity | volume = 4 | issue = 4 | pages = 387–96 | year = 1996 | pmid = 8612133 | doi = 10.1016/S1074-7613(00)80252-6 | doi-access = free }}
* {{cite journal | vauthors = Lee SY, Park CG, Choi Y | title = 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. | journal = J. Exp. Med. | volume = 183 | issue = 2 | pages = 669–74 | year = 1996 | pmid = 8627180 | pmc = 2192463 | doi = 10.1084/jem.183.2.669 }}
* {{cite journal | vauthors = Gedrich RW, Gilfillan MC, Duckett CS, Van Dongen JL, Thompson CB | title = CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins. | journal = J. Biol. Chem. | volume = 271 | issue = 22 | pages = 12852–8 | year = 1996 | pmid = 8662842 | doi = 10.1074/jbc.271.22.12852 | doi-access = free }}
* {{cite journal | vauthors = Song HY, Rothe M, Goeddel DV | title = The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 13 | pages = 6721–5 | year = 1996 | pmid = 8692885 | pmc = 39093 | doi = 10.1073/pnas.93.13.6721 | bibcode = 1996PNAS...93.6721S | doi-access = free }}
* {{cite journal | vauthors = Takeuchi M, Rothe M, Goeddel DV | title = Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins. | journal = J. Biol. Chem. | volume = 271 | issue = 33 | pages = 19935–42 | year = 1996 | pmid = 8702708 | doi = 10.1074/jbc.271.33.19935 | doi-access = free }}
* {{cite journal | vauthors = Rothe M, Xiong J, Shu HB, Williamson K, Goddard A, Goeddel DV | title = I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 16 | pages = 8241–6 | year = 1996 | pmid = 8710854 | pmc = 38654 | doi = 10.1073/pnas.93.16.8241 | bibcode = 1996PNAS...93.8241R | doi-access = free }}
* {{cite journal | vauthors = Shu HB, Takeuchi M, Goeddel DV | title = The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 24 | pages = 13973–8 | year = 1997 | pmid = 8943045 | pmc = 19479 | doi = 10.1073/pnas.93.24.13973 | doi-access = free }}
* {{cite journal | vauthors = Lee SY, Lee SY, Choi Y | title = 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. | journal = J. Exp. Med. | volume = 185 | issue = 7 | pages = 1275–85 | year = 1997 | pmid = 9104814 | pmc = 2196258 | doi = 10.1084/jem.185.7.1275 }}
* {{cite journal | vauthors = Marsters SA, Ayres TM, Skubatch M, Gray CL, Rothe M, Ashkenazi A | title = 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. | journal = J. Biol. Chem. | volume = 272 | issue = 22 | pages = 14029–32 | year = 1997 | pmid = 9162022 | doi = 10.1074/jbc.272.22.14029 | doi-access = free }}
* {{cite journal | vauthors = Boucher LM, Marengère LE, Lu Y, Thukral S, Mak TW | title = Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily. | journal = Biochem. Biophys. Res. Commun. | volume = 233 | issue = 3 | pages = 592–600 | year = 1997 | pmid = 9168896 | doi = 10.1006/bbrc.1997.6509 }}
* {{cite journal | vauthors = Shu HB, Halpin DR, Goeddel DV | title = Casper is an FADD- and caspase-related inducer of apoptosis. | journal = Immunity | volume = 6 | issue = 6 | pages = 751–63 | year = 1997 | pmid = 9208847 | doi = 10.1016/S1074-7613(00)80450-1 | doi-access = free }}
* {{cite journal | vauthors = Song HY, Régnier CH, Kirschning CJ, Goeddel DV, Rothe M | title = 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. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 94 | issue = 18 | pages = 9792–6 | year = 1997 | pmid = 9275204 | pmc = 23270 | doi = 10.1073/pnas.94.18.9792 | bibcode = 1997PNAS...94.9792S | doi-access = free }}
* {{cite journal | vauthors = Siemienski K, Peters N, Scheurich P, Wajant H | title = Organization of the human tumour necrosis factor receptor-associated factor 1 (TRAF1) gene and mapping to chromosome 9q33-34. | journal = Gene | volume = 195 | issue = 1 | pages = 35–9 | year = 1997 | pmid = 9300817 | doi = 10.1016/S0378-1119(97)00147-9 }}
{{Refend}}{{Adaptor proteins}}
{{Cytokine receptor modulators}}