TRAF2: Difference between revisions

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{{Infobox_gene}}
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| require_manual_inspection = no
| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
'''TNF receptor-associated factor 2''' is a [[protein]] that in humans is encoded by the ''TRAF2'' [[gene]].<ref name="pmid7639698">{{cite journal | vauthors = Song HY, Donner DB | title = Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor | journal = Biochem J | volume = 309 | issue = Pt 3 | pages = 825–9 | date = September 1995 | pmid = 7639698 | pmc = 1135706 | doi =  }}</ref>
{{GNF_Protein_box
| image = PBB_Protein_TRAF2_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1ca4.
| PDB = {{PDB2|1ca4}}, {{PDB2|1ca9}}, {{PDB2|1czy}}, {{PDB2|1czz}}, {{PDB2|1d00}}, {{PDB2|1d01}}, {{PDB2|1d0a}}, {{PDB2|1d0j}}, {{PDB2|1f3v}}, {{PDB2|1qsc}}
| Name = TNF receptor-associated factor 2
| HGNCid = 12032
| Symbol = TRAF2
| AltSymbols =; TRAP; MGC:45012; TRAP3
| OMIM = 601895
| ECnumber = 
| Homologene = 22520
| MGIid = 101835
| GeneAtlas_image1 = PBB_GE_TRAF2_204413_at_tn.png
| Function = {{GNF_GO|id=GO:0004871 |text = signal transducer activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component =
| Process = {{GNF_GO|id=GO:0002726 |text = positive regulation of T cell cytokine production}} {{GNF_GO|id=GO:0006461 |text = protein complex assembly}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007250 |text = activation of NF-kappaB-inducing kinase}} {{GNF_GO|id=GO:0042981 |text = regulation of apoptosis}} {{GNF_GO|id=GO:0050870 |text = positive regulation of T cell activation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7186
    | Hs_Ensembl = ENSG00000127191
    | Hs_RefseqProtein = NP_066961
    | Hs_RefseqmRNA = NM_021138
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 9
    | Hs_GenLoc_start = 138900786
    | Hs_GenLoc_end = 138940887
    | Hs_Uniprot = Q12933
    | Mm_EntrezGene = 22030
    | Mm_Ensembl = ENSMUSG00000026942
    | Mm_RefseqmRNA = NM_009422
    | Mm_RefseqProtein = NP_033448
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 25339991
    | Mm_GenLoc_end = 25368903
    | Mm_Uniprot = Q3TWR1
  }}
}}


'''TNF receptor-associated factor 2''', also known as '''TRAF2''', is a human [[gene]].
== Function ==


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and [[TRAF1]] interacts with the [[Inhibitor of apoptosis|IAP]] family members [[BIRC2|cIAP1]] and [[BIRC3|cIAP2]], and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of [[caspase]] activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.<ref>{{cite web | title = Entrez Gene: TRAF2 TNF receptor-associated factor 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7186| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this protein and TRAF1 interacts with the inhibitor-of-apoptosis proteins (IAPs), and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. BIRC2/c-IAP1, an apoptosis inhibitor possessing ubiquitin ligase activity, can unbiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.<ref>{{cite web | title = Entrez Gene: TRAF2 TNF receptor-associated factor 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7186| accessdate = }}</ref>
}}


[[Image:TNF signaling.jpg|thumbnail|left|400px|Signaling pathway of [[Tumor necrosis factor-alpha|TNF]]-R1. Dashed grey lines represent multiple steps]]
[[Image:TNF signaling.jpg|thumbnail|left|400px|Signaling pathway of [[Tumor necrosis factor-alpha|TNF]]-R1. Dashed grey lines represent multiple steps]]
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==References==
== Interactions ==
{{reflist|2}}
TRAF2 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[ASK1]],<ref name = pmid9774977>{{cite journal | vauthors = Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H | title = ASK1 is essential for JNK/SAPK activation by TRAF2 | journal = Mol. Cell | volume = 2 | issue = 3 | pages = 389–95 | date = September 1998 | pmid = 9774977 | doi =  10.1016/s1097-2765(00)80283-x}}</ref><ref name = pmid10523862>{{cite journal | vauthors = Hoeflich KP, Yeh WC, Yao Z, Mak TW, Woodgett JR | title = Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1) | journal = Oncogene | volume = 18 | issue = 42 | pages = 5814–20 | date = October 1999 | pmid = 10523862 | doi = 10.1038/sj.onc.1202975 }}</ref><ref name = pmid17015619>{{cite journal | vauthors = Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL | title = Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways | journal = J. Cell Biol. | volume = 175 | issue = 1 | pages = 121–33 | date = October 2006 | pmid = 17015619 | pmc = 2064504 | doi = 10.1083/jcb.200604129 }}</ref>
* [[BCL10]],<ref name = pmid10753917>{{cite journal | vauthors = Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M | title = Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein | journal = J. Biol. Chem. | volume = 275 | issue = 15 | pages = 11114–20 | date = April 2000 | pmid = 10753917 | doi =  10.1074/jbc.275.15.11114}}</ref>
* [[BIRC2]],<ref name = pmid10753917/><ref name = pmid8943045/><ref name = pmid8643514/><ref name = pmid9384571/><ref name = pmid11907583/><ref name = pmid16189514>{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}</ref>
* [[Baculoviral IAP repeat-containing protein 3]],<ref name = pmid10753917/><ref name = pmid8643514>{{cite journal | vauthors = Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL | title = Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 10 | pages = 4974–8 | date = May 1996 | pmid = 8643514 | pmc = 39390 | doi =  10.1073/pnas.93.10.4974}}</ref><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 }}</ref>
* [[CASP8AP2]],<ref name = pmid11340079>{{cite journal | vauthors = Choi YH, Kim KB, Kim HH, Hong GS, Kwon YK, Chung CW, Park YM, Shen ZJ, Kim BJ, Lee SY, Jung YK | title = FLASH coordinates NF-kappa B activity via TRAF2 | journal = J. Biol. Chem. | volume = 276 | issue = 27 | pages = 25073–7 | date = July 2001 | pmid = 11340079 | doi = 10.1074/jbc.M102941200 }}</ref>
* [[CD134]],<ref name = pmid9418902/>
* [[CD137]],<ref name = pmid9418902>{{cite journal | vauthors = Arch RH, Thompson CB | title = 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 558–65 | date = January 1998 | pmid = 9418902 | pmc = 121523 | doi =  }}</ref><ref name = pmid9464265>{{cite journal | vauthors = Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS | title = Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B | journal = Biochem. Biophys. Res. Commun. | volume = 242 | issue = 3 | pages = 613–20 | date = January 1998 | pmid = 9464265 | doi = 10.1006/bbrc.1997.8016 }}</ref>
* [[CD27]],<ref name = pmid9794406>{{cite journal | vauthors = Yamamoto H, Kishimoto T, Minamoto S | title = NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27 | journal = J. Immunol. | volume = 161 | issue = 9 | pages = 4753–9 | date = November 1998 | pmid = 9794406 | doi =  }}</ref><ref name = pmid9582383>{{cite journal | vauthors = Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware CF, Malinin NL, Wallach D, Yagita H, Okumura K | title = CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase | journal = J. Biol. Chem. | volume = 273 | issue = 21 | pages = 13353–8 | date = May 1998 | pmid = 9582383 | doi =  10.1074/jbc.273.21.13353}}</ref>
* [[CD40 (protein)|CD40]],<ref name = pmid10411888>{{cite journal | vauthors = McWhirter SM, Pullen SS, Holton JM, Crute JJ, Kehry MR, Alber T | title = Crystallographic analysis of CD40 recognition and signaling by human TRAF2 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 15 | pages = 8408–13 | date = July 1999 | pmid = 10411888 | pmc = 17529 | doi =  10.1073/pnas.96.15.8408}}</ref><ref name = pmid9990007>{{cite journal | vauthors = Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T, Inoue J | title = Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 4 | pages = 1234–9 | date = February 1999 | pmid = 9990007 | pmc = 15446 | doi =  10.1073/pnas.96.4.1234}}</ref><ref name = pmid9020361>{{cite journal | vauthors = Malinin NL, Boldin MP, Kovalenko AV, Wallach D | title = MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1 | journal = Nature | volume = 385 | issue = 6616 | pages = 540–4 | date = February 1997 | pmid = 9020361 | doi = 10.1038/385540a0 }}</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}}</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}}</ref>
* [[CHUK]],<ref name = pmid11359906/><ref name = pmid19150425/><ref name = pmid9244310>{{cite journal | vauthors = Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M | title = Identification and characterization of an IkappaB kinase | journal = Cell | volume = 90 | issue = 2 | pages = 373–83 | date = July 1997 | pmid = 9244310 | doi =  10.1016/S0092-8674(00)80344-X}}</ref>
* [[Caveolin 1]],<ref name = pmid11112773>{{cite journal | vauthors = Feng X, Gaeta ML, Madge LA, Yang JH, Bradley JR, Pober JS | title = Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors | journal = J. Biol. Chem. | volume = 276 | issue = 11 | pages = 8341–9 | date = March 2001 | pmid = 11112773 | doi = 10.1074/jbc.M007116200 }}</ref><ref name = pmid11805080>{{cite journal | vauthors = Cao H, Courchesne WE, Mastick CC | title = A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase | journal = J. Biol. Chem. | volume = 277 | issue = 11 | pages = 8771–4 | date = March 2002 | pmid = 11805080 | doi = 10.1074/jbc.C100661200 }}</ref>
* [[EDARADD]],<ref name = pmid11882293>{{cite journal | vauthors = Yan M, Zhang Z, Brady JR, Schilbach S, Fairbrother WJ, Dixit VM | title = Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice | journal = Curr. Biol. | volume = 12 | issue = 5 | pages = 409–13 | date = March 2002 | pmid = 11882293 | doi =  10.1016/s0960-9822(02)00687-5}}</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}}</ref>
* [[IKK2]],<ref name = pmid11359906>{{cite journal | vauthors = Devin A, Lin Y, Yamaoka S, Li Z, Karin M | title = The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF | journal = Mol. Cell. Biol. | volume = 21 | issue = 12 | pages = 3986–94 | date = June 2001 | pmid = 11359906 | pmc = 87061 | doi = 10.1128/MCB.21.12.3986-3994.2001 }}</ref><ref name = pmid19150425>{{cite journal | vauthors = Li S, Wang L, Dorf ME | title = PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination | journal = Mol. Cell | volume = 33 | issue = 1 | pages = 30–42 | date = January 2009 | pmid = 19150425 | pmc = 2643372 | doi = 10.1016/j.molcel.2008.11.023 }}</ref>
* [[Low affinity nerve growth factor receptor]],<ref name = pmid10514511>{{cite journal | vauthors = Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE | title = TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction | journal = J. Biol. Chem. | volume = 274 | issue = 42 | pages = 30202–8 | date = October 1999 | pmid = 10514511 | doi =  10.1074/jbc.274.42.30202}}</ref>
* [[MAP3K14]],<ref name = pmid9020361/><ref name = pmid11278268>{{cite journal | vauthors = Luftig MA, Cahir-McFarland E, Mosialos G, Kieff E|authorlink4= Elliott D. Kieff | title = Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40 | journal = J. Biol. Chem. | volume = 276 | issue = 18 | pages = 14602–6 | date = May 2001 | pmid = 11278268 | doi = 10.1074/jbc.C100103200 }}</ref>
* [[MAP3K1]]<ref name = pmid10346818>{{cite journal | vauthors = Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M | title = Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain | journal = Genes Dev. | volume = 13 | issue = 10 | pages = 1297–308 | date = May 1999 | pmid = 10346818 | pmc = 316725 | doi =  10.1101/gad.13.10.1297}}</ref>
* [[MAP3K7IP2]],<ref name = pmid19150425/><ref name = pmid10882101>{{cite journal | vauthors = Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K | title = TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway | journal = Mol. Cell | volume = 5 | issue = 4 | pages = 649–58 | date = April 2000 | pmid = 10882101 | doi =  10.1016/s1097-2765(00)80244-0}}</ref>
* [[MAP4K2]],<ref name = pmid9712898>{{cite journal | vauthors = Yuasa T, Ohno S, Kehrl JH, Kyriakis JM | title = Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38 | journal = J. Biol. Chem. | volume = 273 | issue = 35 | pages = 22681–92 | date = August 1998 | pmid = 9712898 | doi =  10.1074/jbc.273.35.22681}}</ref>
* [[MAP4K5]],<ref name = pmid10477597>{{cite journal | vauthors = Shi CS, Leonardi A, Kyriakis J, Siebenlist U, Kehrl JH | title = TNF-mediated activation of the stress-activated protein kinase pathway: TNF receptor-associated factor 2 recruits and activates germinal center kinase related | journal = J. Immunol. | volume = 163 | issue = 6 | pages = 3279–85 | date = September 1999 | pmid = 10477597 | doi =  }}</ref>
* [[RANK]],<ref name = pmid9685412>{{cite journal | vauthors = Darnay BG, Haridas V, Ni J, Moore PA, Aggarwal BB | title = Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase | journal = J. Biol. Chem. | volume = 273 | issue = 32 | pages = 20551–5 | date = August 1998 | pmid = 9685412 | doi =  10.1074/jbc.273.32.20551}}</ref><ref name = pmid10075662>{{cite journal | vauthors = Darnay BG, Ni J, Moore PA, Aggarwal BB | title = Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif | journal = J. Biol. Chem. | volume = 274 | issue = 12 | pages = 7724–31 | date = March 1999 | pmid = 10075662 | doi =  10.1074/jbc.274.12.7724}}</ref><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}}</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}}</ref>
* [[RIPK1]],<ref name = pmid9020361/><ref name = pmid8702708/><ref name = pmid8612133/><ref name = pmid11479302>{{cite journal | vauthors = Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, Hashimoto H, Mak TW, Yagita H, Okumura K, Yeh WC, Nakano H | title = Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death | journal = J. Biol. Chem. | volume = 276 | issue = 39 | pages = 36530–4 | date = September 2001 | pmid = 11479302 | doi = 10.1074/jbc.M104837200 }}</ref>
* [[Sphingosine kinase 1|SPHK1]],<ref name = pmid11777919>{{cite journal | vauthors = Xia P, Wang L, Moretti PA, Albanese N, Chai F, Pitson SM, D'Andrea RJ, Gamble JR, Vadas MA | title = Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling | journal = J. Biol. Chem. | volume = 277 | issue = 10 | pages = 7996–8003 | date = March 2002 | pmid = 11777919 | doi = 10.1074/jbc.M111423200 | pmc = 3234989 }}</ref>
* [[TANK (gene)|TANK]],<ref name = pmid14743216/><ref name = pmid8710854/><ref name = pmid10759890>{{cite journal | vauthors = Nomura F, Kawai T, Nakanishi K, Akira S | title = NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation | journal = Genes Cells | volume = 5 | issue = 3 | pages = 191–202 | date = March 2000 | pmid = 10759890 | doi =  10.1046/j.1365-2443.2000.00315.x}}</ref><ref name = pmid10581243>{{cite journal | vauthors = Pomerantz JL, Baltimore D | title = NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase | journal = EMBO J. | volume = 18 | issue = 23 | pages = 6694–704 | date = Dec 1999 | pmid = 10581243 | pmc = 1171732 | doi = 10.1093/emboj/18.23.6694 }}</ref>
* [[TANK-binding kinase 1]],<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 }}</ref><ref name = pmid10990461>{{cite journal | vauthors = Bonnard M, Mirtsos C, Suzuki S, Graham K, Huang J, Ng M, Itié A, Wakeham A, Shahinian A, Henzel WJ, Elia AJ, Shillinglaw W, Mak TW, Cao Z, Yeh WC | title = Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription | journal = EMBO J. | volume = 19 | issue = 18 | pages = 4976–85 | date = September 2000 | pmid = 10990461 | pmc = 314216 | doi = 10.1093/emboj/19.18.4976 }}</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}}</ref>
* [[TNFRSF13B]],<ref name = pmid10880535>{{cite journal | vauthors = Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H | title = TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation | journal = J. Exp. Med. | volume = 192 | issue = 1 | pages = 137–43 | date = July 2000 | pmid = 10880535 | pmc = 1887716 | doi =  10.1084/jem.192.1.137}}</ref>
* [[TNFRSF14]],<ref name = pmid9162022/><ref name = pmid9153189>{{cite journal | vauthors = Hsu H, Solovyev I, Colombero A, Elliott R, Kelley M, Boyle WJ | title = ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5 | journal = J. Biol. Chem. | volume = 272 | issue = 21 | pages = 13471–4 | date = May 1997 | pmid = 9153189 | doi =  10.1074/jbc.272.21.13471}}</ref>
* [[TNFRSF1A]],<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}}</ref><ref name = pmid8612133>{{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 | date = April 1996 | pmid = 8612133 | doi =  10.1016/S1074-7613(00)80252-6}}</ref><ref name = pmid8565075>{{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 | date = January 1996 | pmid = 8565075 | doi =  10.1016/S0092-8674(00)80984-8}}</ref>
* [[TNFRSF1B]],<ref name = pmid7639698 /><ref name = pmid8702708/><ref name = pmid14743216/><ref name = pmid8710854>{{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 | date = August 1996 | pmid = 8710854 | pmc = 38654 | doi =  10.1073/pnas.93.16.8241}}</ref><ref name = pmid9162022>{{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 | date = May 1997 | pmid = 9162022 | doi =  10.1074/jbc.272.22.14029}}</ref><ref name = pmid11907088>{{cite journal | vauthors = Hostager BS, Bishop GA | title = Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b | journal = J. Immunol. | volume = 168 | issue = 7 | pages = 3318–22 | date = April 2002 | pmid = 11907088 | doi =  10.4049/jimmunol.168.7.3318}}</ref><ref name = pmid18671942>{{cite journal | vauthors = Carpentier I, Coornaert B, Beyaert R | title = Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation | journal = Biochem. Biophys. Res. Commun. | volume = 374 | issue = 4 | pages = 752–7 | date = October 2008 | pmid = 18671942 | doi = 10.1016/j.bbrc.2008.07.103 }}</ref>
* [[TNFSF14]],<ref name = pmid12571250>{{cite journal | vauthors = Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin LL | title = Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis | journal = J. Biol. Chem. | volume = 278 | issue = 16 | pages = 14363–9 | date = April 2003 | pmid = 12571250 | doi = 10.1074/jbc.M208672200 }}</ref>
* [[TRADD]],<ref name = pmid9020361/><ref name = pmid8702708/><ref name = pmid11479302/><ref name = pmid14743216/><ref name = pmid8565075/><ref name = pmid10892748>{{cite journal | vauthors = Park YC, Ye H, Hsia C, Segal D, Rich RL, Liou HC, Myszka DG, Wu H | title = A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction | journal = Cell | volume = 101 | issue = 7 | pages = 777–87 | date = June 2000 | pmid = 10892748 | doi =  10.1016/S0092-8674(00)80889-2}}</ref><ref name = pmid10911999>{{cite journal | vauthors = Tsao DH, McDonagh T, Telliez JB, Hsu S, Malakian K, Xu GY, Lin LL | title = Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway | journal = Mol. Cell | volume = 5 | issue = 6 | pages = 1051–7 | date = June 2000 | pmid = 10911999 | doi =  10.1016/S1097-2765(00)80270-1}}</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>
* [[TRAF1]],<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}}</ref><ref name = pmid14743216/>  and
* [[UBE2N]].<ref name = pmid11057907>{{cite journal | vauthors = Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ | title = Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain | journal = Cell | volume = 103 | issue = 2 | pages = 351–61 | date = October 2000 | pmid = 11057907 | doi =  10.1016/S0092-8674(00)00126-4}}</ref>
{{Div col end}}
{{Clear}}
 
==Model organisms==
[[Model organism]]s have been used in the study of TRAF2 function. A conditional [[knockout mouse]] line called ''Traf2<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Traf2#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, ((Sanger Institute Mouse Genetics Project)), Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Traf2&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Traf2'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
|-
| Insulin || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#C40000"|Abnormal
 
|-
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Influenza Challenge || bgcolor="#488ED3"|Normal


==Further reading==
|-
{{refbegin | 2}}
|}
{{PBB_Further_reading
{{clear}}
| citations =
*{{cite journal  | author=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=  }}
*{{cite journal  | author=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 }}
}}
{{refend}}


==References==
{{Reflist|33em}}


{{protein-stub}}
== Further reading ==
{{Refbegin}}
* {{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 }}
{{Refend}}


{{biochem-stub}}
{{PDB Gallery|geneid=7186}}
{{WikiDoc Sources}}
{{Adaptor proteins}}
{{Apoptosis signaling pathway}}
{{Cytokine receptor modulators}}

Latest revision as of 07:31, 10 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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View/Edit Human

TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.[1]

Function

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms complexes with other TRAF proteins. TRAF2 is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-κB. The protein complex formed by TRAF2 and TRAF1 interacts with the IAP family members cIAP1 and cIAP2, and functions as a mediator of the anti-apoptotic signals from TNF receptors. The interaction of this protein with TRADD, a TNF receptor associated apoptotic signal transducer, ensures the recruitment of IAPs for the direct inhibition of caspase activation. cIAP1 can ubiquitinate and induce the degradation of this protein, and thus potentiate TNF-induced apoptosis. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of only one transcript has been determined.[2]

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

Interactions

TRAF2 has been shown to interact with:

Model organisms

Model organisms have been used in the study of TRAF2 function. A conditional knockout mouse line called Traf2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[60] Male and female animals underwent a standardized phenotypic screen[61] to determine the effects of deletion.[62][63][64][65] Additional screens performed: - In-depth immunological phenotyping[66]

References

  1. ↑ 1.0 1.1 Song HY, Donner DB (September 1995). "Association of a RING finger protein with the cytoplasmic domain of the human type-2 tumour necrosis factor receptor". Biochem J. 309 (Pt 3): 825–9. PMC 1135706. PMID 7639698.
  2. ↑ "Entrez Gene: TRAF2 TNF receptor-associated factor 2".
  3. ↑ Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H (September 1998). "ASK1 is essential for JNK/SAPK activation by TRAF2". Mol. Cell. 2 (3): 389–95. doi:10.1016/s1097-2765(00)80283-x. PMID 9774977.
  4. ↑ Hoeflich KP, Yeh WC, Yao Z, Mak TW, Woodgett JR (October 1999). "Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)". Oncogene. 18 (42): 5814–20. doi:10.1038/sj.onc.1202975. PMID 10523862.
  5. ↑ Gan B, Peng X, Nagy T, Alcaraz A, Gu H, Guan JL (October 2006). "Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways". J. Cell Biol. 175 (1): 121–33. doi:10.1083/jcb.200604129. PMC 2064504. PMID 17015619.
  6. ↑ 6.0 6.1 6.2 Yoneda T, Imaizumi K, Maeda M, Yui D, Manabe T, Katayama T, Sato N, Gomi F, Morihara T, Mori Y, Miyoshi K, Hitomi J, Ugawa S, Yamada S, Okabe M, Tohyama M (April 2000). "Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein". J. Biol. Chem. 275 (15): 11114–20. doi:10.1074/jbc.275.15.11114. PMID 10753917.
  7. ↑ 7.0 7.1 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.
  8. ↑ 8.0 8.1 Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL (May 1996). "Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors". Proc. Natl. Acad. Sci. U.S.A. 93 (10): 4974–8. doi:10.1073/pnas.93.10.4974. PMC 39390. PMID 8643514.
  9. ↑ 9.0 9.1 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. ↑ 10.0 10.1 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.
  11. ↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  12. ↑ Choi YH, Kim KB, Kim HH, Hong GS, Kwon YK, Chung CW, Park YM, Shen ZJ, Kim BJ, Lee SY, Jung YK (July 2001). "FLASH coordinates NF-kappa B activity via TRAF2". J. Biol. Chem. 276 (27): 25073–7. doi:10.1074/jbc.M102941200. PMID 11340079.
  13. ↑ 13.0 13.1 Arch RH, Thompson CB (January 1998). "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB". Mol. Cell. Biol. 18 (1): 558–65. PMC 121523. PMID 9418902.
  14. ↑ Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS (January 1998). "Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B". Biochem. Biophys. Res. Commun. 242 (3): 613–20. doi:10.1006/bbrc.1997.8016. PMID 9464265.
  15. ↑ Yamamoto H, Kishimoto T, Minamoto S (November 1998). "NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27". J. Immunol. 161 (9): 4753–9. PMID 9794406.
  16. ↑ Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware CF, Malinin NL, Wallach D, Yagita H, Okumura K (May 1998). "CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase". J. Biol. Chem. 273 (21): 13353–8. doi:10.1074/jbc.273.21.13353. PMID 9582383.
  17. ↑ McWhirter SM, Pullen SS, Holton JM, Crute JJ, Kehry MR, Alber T (July 1999). "Crystallographic analysis of CD40 recognition and signaling by human TRAF2". Proc. Natl. Acad. Sci. U.S.A. 96 (15): 8408–13. doi:10.1073/pnas.96.15.8408. PMC 17529. PMID 10411888.
  18. ↑ Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T, Inoue J (February 1999). "Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1234–9. doi:10.1073/pnas.96.4.1234. PMC 15446. PMID 9990007.
  19. ↑ 19.0 19.1 19.2 19.3 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 22.0 22.1 Devin A, Lin Y, Yamaoka S, Li Z, Karin M (June 2001). "The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF". Mol. Cell. Biol. 21 (12): 3986–94. doi:10.1128/MCB.21.12.3986-3994.2001. PMC 87061. PMID 11359906.
  23. ↑ 23.0 23.1 23.2 Li S, Wang L, Dorf ME (January 2009). "PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination". Mol. Cell. 33 (1): 30–42. doi:10.1016/j.molcel.2008.11.023. PMC 2643372. PMID 19150425.
  24. ↑ Régnier CH, Song HY, Gao X, Goeddel DV, Cao Z, Rothe M (July 1997). "Identification and characterization of an IkappaB kinase". Cell. 90 (2): 373–83. doi:10.1016/S0092-8674(00)80344-X. PMID 9244310.
  25. ↑ Feng X, Gaeta ML, Madge LA, Yang JH, Bradley JR, Pober JS (March 2001). "Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors". J. Biol. Chem. 276 (11): 8341–9. doi:10.1074/jbc.M007116200. PMID 11112773.
  26. ↑ Cao H, Courchesne WE, Mastick CC (March 2002). "A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase". J. Biol. Chem. 277 (11): 8771–4. doi:10.1074/jbc.C100661200. PMID 11805080.
  27. ↑ Yan M, Zhang Z, Brady JR, Schilbach S, Fairbrother WJ, Dixit VM (March 2002). "Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice". Curr. Biol. 12 (5): 409–13. doi:10.1016/s0960-9822(02)00687-5. PMID 11882293.
  28. ↑ 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.
  29. ↑ Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE (October 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". J. Biol. Chem. 274 (42): 30202–8. doi:10.1074/jbc.274.42.30202. PMID 10514511.
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  39. ↑ 39.0 39.1 39.2 39.3 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.
  40. ↑ 40.0 40.1 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.
  41. ↑ 41.0 41.1 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.
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  43. ↑ 43.0 43.1 43.2 43.3 43.4 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.
  44. ↑ 44.0 44.1 Rothe M, Xiong J, Shu HB, Williamson K, Goddard A, Goeddel DV (August 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.
  45. ↑ Nomura F, Kawai T, Nakanishi K, Akira S (March 2000). "NF-kappaB activation through IKK-i-dependent I-TRAF/TANK phosphorylation". Genes Cells. 5 (3): 191–202. doi:10.1046/j.1365-2443.2000.00315.x. PMID 10759890.
  46. ↑ Pomerantz JL, Baltimore D (Dec 1999). "NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase". EMBO J. 18 (23): 6694–704. doi:10.1093/emboj/18.23.6694. PMC 1171732. PMID 10581243.
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  52. ↑ 52.0 52.1 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.
  53. ↑ Hostager BS, Bishop GA (April 2002). "Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b". J. Immunol. 168 (7): 3318–22. doi:10.4049/jimmunol.168.7.3318. PMID 11907088.
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  57. ↑ 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.
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  62. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
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  65. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  66. ↑ 66.0 66.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

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.
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