TRAF6: Difference between revisions

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{{Infobox_gene}}
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'''TRAF6''' is a [[TRAF]] human protein.
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== Function ==
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The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including [[IRAK1|IRAK1/IRAK]], [[proto-oncogene tyrosine-protein kinase Src|SRC]] and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.<ref>{{cite web | title = Entrez Gene: TRAF6 TNF receptor-associated factor 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7189| accessdate = }}</ref>
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[[Image:Toll-like receptor pathways revised.jpg|thumbnail|center|500px|Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations]]{{clear|left}}
 
== Interactions ==
 
TRAF6 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 = pmid10921914>{{cite journal | vauthors = Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, Matsumoto K, Ichijo H | title = ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction | journal = J. Biol. Chem. | volume = 275 | issue = 42 | pages = 32747–52 | date = October 2000 | pmid = 10921914 | doi = 10.1074/jbc.M003042200 }}</ref>
* [[CD40 (protein)|CD40]],<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 = 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>
* [[FHL2]],<ref name = pmid18768464>{{cite journal | vauthors = Bai S, Zha J, Zhao H, Ross FP, Teitelbaum SL | title = Tumor necrosis factor receptor-associated factor 6 is an intranuclear transcriptional coactivator in osteoclasts | journal = J. Biol. Chem. | volume = 283 | issue = 45 | pages = 30861–7 | date = November 2008 | pmid = 18768464 | pmc = 2662164 | doi = 10.1074/jbc.M802525200 }}</ref>
* [[HSPB2]],<ref name = pmid18950704>{{cite journal | vauthors = Wu Y, Liu J, Zhang Z, Huang H, Shen J, Zhang S, Jiang Y, Luo L, Yin Z | title = HSP27 regulates IL-1 stimulated IKK activation through interacting with TRAF6 and affecting its ubiquitination | journal = Cell. Signal. | volume = 21 | issue = 1 | pages = 143–50 | date = January 2009 | pmid = 18950704 | doi = 10.1016/j.cellsig.2008.10.001 }}</ref>
* [[IKBKG]],<ref name = pmid18180283/><ref name = pmid18617513>{{cite journal | vauthors = Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG | title = The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL | journal = J. Biol. Chem. | volume = 283 | issue = 36 | pages = 24871–80 | date = September 2008 | pmid = 18617513 | pmc = 2529010 | doi = 10.1074/jbc.M802749200 }}</ref>
* [[IRAK1]],<ref name = pmid18234474/><ref name = pmid10383454/><ref name = pmid9374458/><ref name = pmid11518704>{{cite journal | vauthors = Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X | title = IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B | journal = J. Biol. Chem. | volume = 276 | issue = 45 | pages = 41661–7 | date = November 2001 | pmid = 11518704 | doi = 10.1074/jbc.M102262200 }}</ref><ref name = pmid8837778>{{cite journal | vauthors = Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV | title = TRAF6 is a signal transducer for interleukin-1 | journal = Nature | volume = 383 | issue = 6599 | pages = 443–6 | date = October 1996 | pmid = 8837778 | doi = 10.1038/383443a0 }}</ref><ref name = pmid12566447>{{cite journal | vauthors = Takatsuna H, Kato H, Gohda J, Akiyama T, Moriya A, Okamoto Y, Yamagata Y, Otsuka M, Umezawa K, Semba K, Inoue J | title = Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling | journal = J. Biol. Chem. | volume = 278 | issue = 14 | pages = 12144–50 | date = April 2003 | pmid = 12566447 | doi = 10.1074/jbc.M300720200 }}</ref><ref name = pmid11960013>{{cite journal | vauthors = Li S, Strelow A, Fontana EJ, Wesche H | title = IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 8 | pages = 5567–72 | date = April 2002 | pmid = 11960013 | pmc = 122810 | doi = 10.1073/pnas.082100399 }}</ref><ref name = pmid10920205>{{cite journal | vauthors = Ling L, Goeddel DV | title = T6BP, a TRAF6-interacting protein involved in IL-1 signaling | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 17 | pages = 9567–72 | date = August 2000 | pmid = 10920205 | pmc = 16905 | doi = 10.1073/pnas.170279097 }}</ref><ref name = pmid11259596>{{cite journal | vauthors = Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K | title = Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway | journal = Mol. Cell. Biol. | volume = 21 | issue = 7 | pages = 2475–84 | date = April 2001 | pmid = 11259596 | pmc = 86880 | doi = 10.1128/MCB.21.7.2475-2484.2001 }}</ref>
* [[IRAK2]],<ref name = pmid10383454>{{cite journal | vauthors = Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z | title = IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family | journal = J. Biol. Chem. | volume = 274 | issue = 27 | pages = 19403–10 | date = July 1999 | pmid = 10383454 | doi =  10.1074/jbc.274.27.19403}}</ref><ref name = pmid9374458>{{cite journal | vauthors = Muzio M, Ni J, Feng P, Dixit VM | title = IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling | journal = Science | volume = 278 | issue = 5343 | pages = 1612–5 | date = November 1997 | pmid = 9374458 | doi =  10.1126/science.278.5343.1612}}</ref>
* [[MAP3K7IP1]],<ref name = pmid10882101/><ref name = pmid19112497/><ref name = pmid10094049>{{cite journal | vauthors = Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K | title = The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway | journal = Nature | volume = 398 | issue = 6724 | pages = 252–6 | date = March 1999 | pmid = 10094049 | doi = 10.1038/18465 }}</ref>
* [[MAP3K7IP2]],<ref name = pmid18180283>{{cite journal | vauthors = Windheim M, Stafford M, Peggie M, Cohen P | title = Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase | journal = Mol. Cell. Biol. | volume = 28 | issue = 5 | pages = 1783–91 | date = March 2008 | pmid = 18180283 | pmc = 2258775 | doi = 10.1128/MCB.02380-06 }}</ref><ref name = pmid11259596/><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><ref name = pmid19112497>{{cite journal | vauthors = Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y | title = TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL | journal = PLoS ONE | volume = 3 | issue = 12 | pages = e4064 | pmid = 19112497 | pmc = 2603309 | doi = 10.1371/journal.pone.0004064 | editor1-last = Unutmaz | editor1-first = Derya | year=2008}}</ref><ref name = pmid14633987>{{cite journal | vauthors = Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K | title = Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling | journal = EMBO J. | volume = 22 | issue = 23 | pages = 6277–88 | date = Dec 2003 | pmid = 14633987 | pmc = 291846 | doi = 10.1093/emboj/cdg605 }}</ref><ref name = pmid18299187>{{cite journal | vauthors = Ma Q, Zhou L, Shi H, Huo K | title = NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation | journal = Cell. Signal. | volume = 20 | issue = 6 | pages = 1044–51 | date = June 2008 | pmid = 18299187 | doi = 10.1016/j.cellsig.2008.01.015 }}</ref>
* [[MAP3K7]]<ref name = pmid10921914/><ref name = pmid11259596/><ref name = pmid10882101/><ref name = pmid19112497/><ref name = pmid10094049/><ref name = pmid14633987/><ref name = pmid18758450>{{cite journal | vauthors = Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landström M | title = The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner | journal = Nat. Cell Biol. | volume = 10 | issue = 10 | pages = 1199–207 | date = October 2008 | pmid = 18758450 | doi = 10.1038/ncb1780 }}</ref>
* [[PPP4C]],<ref name = pmid18634786>{{cite journal | vauthors = Chen L, Dong W, Zou T, Ouyang L, He G, Liu Y, Qi Y | title = Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6 | journal = FEBS Lett. | volume = 582 | issue = 19 | pages = 2843–9 | date = August 2008 | pmid = 18634786 | doi = 10.1016/j.febslet.2008.07.014 }}</ref>
* [[RANK]],<ref name = pmid11809792>{{cite journal | vauthors = Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N | title = Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6 | journal = Mol. Cell. Biol. | volume = 22 | issue = 4 | pages = 992–1000 | date = February 2002 | pmid = 11809792 | pmc = 134634 | doi =  10.1128/mcb.22.4.992-1000.2002}}</ref><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>  
* [[SDCBP]],<ref name = pmid18234474>{{cite journal | vauthors = Chen F, Du Y, Zhang Z, Chen G, Zhang M, Shu HB, Zhai Z, Chen D | title = Syntenin negatively regulates TRAF6-mediated IL-1R/TLR4 signaling | journal = Cell. Signal. | volume = 20 | issue = 4 | pages = 666–74 | date = April 2008 | pmid = 18234474 | doi = 10.1016/j.cellsig.2007.12.002 }}</ref>
* [[SIGIRR]],<ref name = pmid12925853>{{cite journal | vauthors = Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X | title = SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling | journal = Nat. Immunol. | volume = 4 | issue = 9 | pages = 920–7 | date = September 2003 | pmid = 12925853 | doi = 10.1038/ni968 }}</ref>
* [[Sequestosome 1]],<ref name = pmid10747026>{{cite journal | vauthors = Sanz L, Diaz-Meco MT, Nakano H, Moscat J | title = The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway | journal = EMBO J. | volume = 19 | issue = 7 | pages = 1576–86 | date = April 2000 | pmid = 10747026 | pmc = 310227 | doi = 10.1093/emboj/19.7.1576 }}</ref>
* [[TAX1BP1]],<ref name = pmid10920205/>
* [[TNFAIP3]],<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}}</ref><ref name = pmid11463333>{{cite journal | vauthors = Evans PC, Taylor ER, Coadwell J, Heyninck K, Beyaert R, Kilshaw PJ | title = Isolation and characterization of two novel A20-like proteins | journal = Biochem. J. | volume = 357 | issue = Pt 3 | pages = 617–23 | date = August 2001 | pmid = 11463333 | pmc = 1221992 | doi =  10.1042/0264-6021:3570617}}</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>
* [[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>  and
* [[Ubiquitin C]].<ref name = pmid18617513/><ref name = pmid18299187/><ref name = pmid18634786/><ref name = pmid18724939>{{cite journal | vauthors = Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM | title = Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies | journal = Cell | volume = 134 | issue = 4 | pages = 668–78 | date = August 2008 | pmid = 18724939 | doi = 10.1016/j.cell.2008.07.039 }}</ref><ref name = pmid18347055>{{cite journal | vauthors = Conze DB, Wu CJ, Thomas JA, Landstrom A, Ashwell JD | title = Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation | journal = Mol. Cell. Biol. | volume = 28 | issue = 10 | pages = 3538–47 | date = May 2008 | pmid = 18347055 | pmc = 2423148 | doi = 10.1128/MCB.02098-07 }}</ref>
{{Div col end}}
 
==Model organisms==
[[Model organism]]s have been used in the study of TRAF6 function. A conditional [[knockout mouse]] line called ''Traf6<sup>tm2a(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=Traf6#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=Traf6&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;" |
|+ ''Traf6'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
|-
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
|-
{{GNF_Protein_box
| Insulin || bgcolor="#488ED3"|Normal
| image = PBB_Protein_TRAF6_image.jpg
 
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1lb4.
|-
| PDB = {{PDB2|1lb4}}, {{PDB2|1lb5}}, {{PDB2|1lb6}}, {{PDB2|2jmd}}
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
| Name = TNF receptor-associated factor 6
 
| HGNCid = 12036
|-
| Symbol = TRAF6
| Homozygous viability at P14 || bgcolor="#C40000"|Abnormal
| AltSymbols =; MGC:3310; RNF85
 
| OMIM = 602355
|-
| ECnumber =
| [[Recessive]] lethal study || bgcolor="#C40000"|Abnormal
| Homologene = 3395
 
| MGIid = 108072
|-
| GeneAtlas_image1 = PBB_GE_TRAF6_205558_at_tn.png
| Body weight || bgcolor="#488ED3"|Normal
| Function = {{GNF_GO|id=GO:0004842 |text = ubiquitin-protein ligase activity}} {{GNF_GO|id=GO:0004871 |text = signal transducer 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:0000209 |text = protein polyubiquitination}} {{GNF_GO|id=GO:0002726 |text = positive regulation of T cell cytokine production}} {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}} {{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:0043123 |text = positive regulation of I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0050852 |text = T cell receptor signaling pathway}} {{GNF_GO|id=GO:0050870 |text = positive regulation of T cell activation}}
| Neurological assessment || bgcolor="#488ED3"|Normal
| Orthologs = {{GNF_Ortholog_box
 
    | Hs_EntrezGene = 7189
|-
    | Hs_Ensembl = ENSG00000175104
| Grip strength || bgcolor="#488ED3"|Normal
    | Hs_RefseqProtein = NP_004611
 
    | Hs_RefseqmRNA = NM_004620
|-
    | Hs_GenLoc_db =
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
    | Hs_GenLoc_chr = 11
 
    | Hs_GenLoc_start = 36467299
|-
    | Hs_GenLoc_end = 36488398
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
    | Hs_Uniprot = Q9Y4K3
 
    | Mm_EntrezGene = 22034
|-
    | Mm_Ensembl = ENSMUSG00000027164
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
    | Mm_RefseqmRNA = NM_009424
 
    | Mm_RefseqProtein = NP_033450
|-
    | Mm_GenLoc_db = 
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
    | Mm_GenLoc_chr = 2
 
    | Mm_GenLoc_start = 101479279
|-
    | Mm_GenLoc_end = 101501817
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
    | Mm_Uniprot = Q6P9M0
 
  }}
|-
}}
| [[Radiography]] || bgcolor="#488ED3"|Normal
'''TRAF6''' is a [[TRAF]] human protein.
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
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| section_title =
| summary_text = The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/RANCE and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including [[IRAK1|IRAK1/IRAK]], SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.<ref>{{cite web | title = Entrez Gene: TRAF6 TNF receptor-associated factor 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7189| accessdate = }}</ref>
}}


[[Image:Toll-like receptor pathways revised.jpg|thumbnail|center|500px|Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations]]
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==References==
==References==
{{reflist|2}}
{{Reflist|colwidth=35em}}
==Further reading==
{{refbegin}}
{{PBB_Further_reading
| 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 }}
*{{cite journal  | author=Tanaka S, Nakamura K, Takahasi N, Suda T |title=Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. |journal=Immunol. Rev. |volume=208 |issue=  |pages= 30-49 |year= 2006 |pmid= 16313339 |doi= 10.1111/j.0105-2896.2005.00327.x }}
}}
{{refend}}


== 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 = Vlantis K, Polykratis A, Welz PS, van Loo G, Pasparakis M, Wullaert A | title = TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice| journal = Gut | volume = 65 | issue = 6 | pages = 935-43 | year = 2016 | pmid = 25761602 | doi = 10.1136/gutjnl-2014-308323 | pmc=4893119}}
* {{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 }}
* {{cite journal | vauthors = Tanaka S, Nakamura K, Takahasi N, Suda T | title = Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system | journal = Immunol. Rev. | volume = 208 | issue =  | pages = 30–49 | year = 2006 | pmid = 16313339 | doi = 10.1111/j.0105-2896.2005.00327.x }}
{{Refend}}


==External links==
== External links ==
* {{MeshName|TRAF6}}
* {{MeshName|TRAF6}}


{{biochem-stub}}
{{PDB Gallery|geneid=7189}}
{{WikiDoc Sources}}
{{Adaptor proteins}}
{{TLR signaling pathway}}
{{Cytokine receptor modulators}}

Latest revision as of 20:44, 12 April 2018

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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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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

TRAF6 is a TRAF human protein.

Function

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.[1]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

TRAF6 has been shown to interact with:

Model organisms

Model organisms have been used in the study of TRAF6 function. A conditional knockout mouse line called Traf6tm2a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[40] Male and female animals underwent a standardized phenotypic screen[41] to determine the effects of deletion.[42][43][44][45] Additional screens performed: - In-depth immunological phenotyping[46]

References

  1. ↑ "Entrez Gene: TRAF6 TNF receptor-associated factor 6".
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 4.0 4.1 Mochida Y, Takeda K, Saitoh M, Nishitoh H, Amagasa T, Ninomiya-Tsuji J, Matsumoto K, Ichijo H (October 2000). "ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction". J. Biol. Chem. 275 (42): 32747–52. doi:10.1074/jbc.M003042200. PMID 10921914.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Bai S, Zha J, Zhao H, Ross FP, Teitelbaum SL (November 2008). "Tumor necrosis factor receptor-associated factor 6 is an intranuclear transcriptional coactivator in osteoclasts". J. Biol. Chem. 283 (45): 30861–7. doi:10.1074/jbc.M802525200. PMC 2662164. PMID 18768464.
  8. ↑ Wu Y, Liu J, Zhang Z, Huang H, Shen J, Zhang S, Jiang Y, Luo L, Yin Z (January 2009). "HSP27 regulates IL-1 stimulated IKK activation through interacting with TRAF6 and affecting its ubiquitination". Cell. Signal. 21 (1): 143–50. doi:10.1016/j.cellsig.2008.10.001. PMID 18950704.
  9. ↑ 9.0 9.1 Windheim M, Stafford M, Peggie M, Cohen P (March 2008). "Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase". Mol. Cell. Biol. 28 (5): 1783–91. doi:10.1128/MCB.02380-06. PMC 2258775. PMID 18180283.
  10. ↑ 10.0 10.1 Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG (September 2008). "The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL". J. Biol. Chem. 283 (36): 24871–80. doi:10.1074/jbc.M802749200. PMC 2529010. PMID 18617513.
  11. ↑ 11.0 11.1 Chen F, Du Y, Zhang Z, Chen G, Zhang M, Shu HB, Zhai Z, Chen D (April 2008). "Syntenin negatively regulates TRAF6-mediated IL-1R/TLR4 signaling". Cell. Signal. 20 (4): 666–74. doi:10.1016/j.cellsig.2007.12.002. PMID 18234474.
  12. ↑ 12.0 12.1 Wesche H, Gao X, Li X, Kirschning CJ, Stark GR, Cao Z (July 1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". J. Biol. Chem. 274 (27): 19403–10. doi:10.1074/jbc.274.27.19403. PMID 10383454.
  13. ↑ 13.0 13.1 Muzio M, Ni J, Feng P, Dixit VM (November 1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science. 278 (5343): 1612–5. doi:10.1126/science.278.5343.1612. PMID 9374458.
  14. ↑ Qian Y, Commane M, Ninomiya-Tsuji J, Matsumoto K, Li X (November 2001). "IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B". J. Biol. Chem. 276 (45): 41661–7. doi:10.1074/jbc.M102262200. PMID 11518704.
  15. ↑ Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (October 1996). "TRAF6 is a signal transducer for interleukin-1". Nature. 383 (6599): 443–6. doi:10.1038/383443a0. PMID 8837778.
  16. ↑ Takatsuna H, Kato H, Gohda J, Akiyama T, Moriya A, Okamoto Y, Yamagata Y, Otsuka M, Umezawa K, Semba K, Inoue J (April 2003). "Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling". J. Biol. Chem. 278 (14): 12144–50. doi:10.1074/jbc.M300720200. PMID 12566447.
  17. ↑ Li S, Strelow A, Fontana EJ, Wesche H (April 2002). "IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5567–72. doi:10.1073/pnas.082100399. PMC 122810. PMID 11960013.
  18. ↑ 18.0 18.1 Ling L, Goeddel DV (August 2000). "T6BP, a TRAF6-interacting protein involved in IL-1 signaling". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9567–72. doi:10.1073/pnas.170279097. PMC 16905. PMID 10920205.
  19. ↑ 19.0 19.1 19.2 Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (April 2001). "Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway". Mol. Cell. Biol. 21 (7): 2475–84. doi:10.1128/MCB.21.7.2475-2484.2001. PMC 86880. PMID 11259596.
  20. ↑ 20.0 20.1 20.2 Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (April 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Mol. Cell. 5 (4): 649–58. doi:10.1016/s1097-2765(00)80244-0. PMID 10882101.
  21. ↑ 21.0 21.1 21.2 Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y (2008). Unutmaz D, ed. "TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL". PLoS ONE. 3 (12): e4064. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497.
  22. ↑ 22.0 22.1 Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (March 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature. 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049.
  23. ↑ 23.0 23.1 Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (Dec 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". EMBO J. 22 (23): 6277–88. doi:10.1093/emboj/cdg605. PMC 291846. PMID 14633987.
  24. ↑ 24.0 24.1 Ma Q, Zhou L, Shi H, Huo K (June 2008). "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation". Cell. Signal. 20 (6): 1044–51. doi:10.1016/j.cellsig.2008.01.015. PMID 18299187.
  25. ↑ Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landström M (October 2008). "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner". Nat. Cell Biol. 10 (10): 1199–207. doi:10.1038/ncb1780. PMID 18758450.
  26. ↑ 26.0 26.1 Chen L, Dong W, Zou T, Ouyang L, He G, Liu Y, Qi Y (August 2008). "Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6". FEBS Lett. 582 (19): 2843–9. doi:10.1016/j.febslet.2008.07.014. PMID 18634786.
  27. ↑ Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N (February 2002). "Receptor activator of NF-kappaB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containing RANK, TAB2, and TRAF6". Mol. Cell. Biol. 22 (4): 992–1000. doi:10.1128/mcb.22.4.992-1000.2002. PMC 134634. PMID 11809792.
  28. ↑ Darnay BG, Haridas V, Ni J, Moore PA, Aggarwal BB (August 1998). "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". J. Biol. Chem. 273 (32): 20551–5. doi:10.1074/jbc.273.32.20551. PMID 9685412.
  29. ↑ Darnay BG, Ni J, Moore PA, Aggarwal BB (March 1999). "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". J. Biol. Chem. 274 (12): 7724–31. doi:10.1074/jbc.274.12.7724. PMID 10075662.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L, Towne J, Sims JE, Stark GR, Li X (September 2003). "SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling". Nat. Immunol. 4 (9): 920–7. doi:10.1038/ni968. PMID 12925853.
  33. ↑ Sanz L, Diaz-Meco MT, Nakano H, Moscat J (April 2000). "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway". EMBO J. 19 (7): 1576–86. doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026.
  34. ↑ 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.
  35. ↑ Evans PC, Taylor ER, Coadwell J, Heyninck K, Beyaert R, Kilshaw PJ (August 2001). "Isolation and characterization of two novel A20-like proteins". Biochem. J. 357 (Pt 3): 617–23. doi:10.1042/0264-6021:3570617. PMC 1221992. PMID 11463333.
  36. ↑ 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 (July 2000). "TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation". J. Exp. Med. 192 (1): 137–43. doi:10.1084/jem.192.1.137. PMC 1887716. PMID 10880535.
  37. ↑ Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ (October 2000). "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain". Cell. 103 (2): 351–61. doi:10.1016/s0092-8674(00)00126-4. PMID 11057907.
  38. ↑ Newton K, Matsumoto ML, Wertz IE, Kirkpatrick DS, Lill JR, Tan J, Dugger D, Gordon N, Sidhu SS, Fellouse FA, Komuves L, French DM, Ferrando RE, Lam C, Compaan D, Yu C, Bosanac I, Hymowitz SG, Kelley RF, Dixit VM (August 2008). "Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies". Cell. 134 (4): 668–78. doi:10.1016/j.cell.2008.07.039. PMID 18724939.
  39. ↑ Conze DB, Wu CJ, Thomas JA, Landstrom A, Ashwell JD (May 2008). "Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation". Mol. Cell. Biol. 28 (10): 3538–47. doi:10.1128/MCB.02098-07. PMC 2423148. PMID 18347055.
  40. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  41. ↑ 41.0 41.1 "International Mouse Phenotyping Consortium".
  42. ↑ 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.
  43. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  44. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  45. ↑ 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.
  46. ↑ 46.0 46.1 "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

External links

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