NF-kappa-B essential modulator

NameNF-kappa-B essential modulator
Synonyms
  • FIP-3
  • FIP3
  • I-kappa-B kinase subunit gamma
  • IkB kinase subunit gamma
  • IkB kinase-associated protein 1
  • IKK-gamma
  • IKKAP1
  • IKKG
  • Inhibitor of nuclear factor kappa-B kinase subunit gamma
  • NEMO
  • NF-kappa-B essential modifier
Gene NameIKBKG
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004702|NF-kappa-B essential modulator
MNRHLWKSQLCEMVQPSGGPAADQDVLGEESPLGKPAMLHLPSEQGAPETLQRCLEENQE
LRDAIRQSNQILRERCEELLHFQASQREEKEFLMCKFQEARKLVERLGLEKLDLKRQKEQ
ALREVEHLKRCQQQMAEDKASVKAQVTSLLGELQESQSRLEAATKECQALEGRARAASEQ
ARQLESEREALQQQHSVQVDQLRMQGQSVEAALRMERQAASEEKRKLAQLQVAYHQLFQE
YDNHIKSSVVGSERKRGMQLEDLKQQLQQAEEALVAKQEVIDKLKEEAEQHKIVMETVPV
LKAQADIYKADFQAERQAREKLAEKKELLQEQLEQLQREYSKLKASCQESARIEDMRKRH
VEVSQAPLPPAPAYLSSPLALPSQRRSPPEEPPDFCCPKCQYQAPDMDTLQIHVMECIE
Number of residues419
Molecular Weight48197.35
Theoretical pI5.46
GO Classification
Functions
  • protein heterodimerization activity
  • signal transducer activity
  • ubiquitin protein ligase binding
  • linear polyubiquitin binding
  • protein domain specific binding
  • metal ion binding
  • protein homodimerization activity
Processes
  • positive regulation of NF-kappaB transcription factor activity
  • Fc-epsilon receptor signaling pathway
  • negative regulation of neuron death
  • positive regulation of type I interferon production
  • apoptotic process
  • B cell homeostasis
  • MyD88-dependent toll-like receptor signaling pathway
  • positive regulation of transcription from RNA polymerase II promoter
  • MyD88-independent toll-like receptor signaling pathway
  • stimulatory C-type lectin receptor signaling pathway
  • nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
  • stress-activated MAPK cascade
  • cell surface receptor signaling pathway
  • nucleotide-binding oligomerization domain containing signaling pathway
  • toll-like receptor 10 signaling pathway
  • regulation of tumor necrosis factor-mediated signaling pathway
  • toll-like receptor 2 signaling pathway
  • transcription, DNA-templated
  • activation of NF-kappaB-inducing kinase activity
  • immune response
  • toll-like receptor 3 signaling pathway
  • activation of MAPK activity
  • inflammatory response
  • toll-like receptor 4 signaling pathway
  • JNK cascade
  • establishment of vesicle localization
  • toll-like receptor 5 signaling pathway
  • T cell receptor signaling pathway
  • toll-like receptor 9 signaling pathway
  • I-kappaB kinase/NF-kappaB signaling
  • toll-like receptor signaling pathway
  • response to virus
  • toll-like receptor TLR1
  • viral process
  • toll-like receptor TLR6
  • tumor necrosis factor-mediated signaling pathway
  • cellular response to DNA damage stimulus
  • TRIF-dependent toll-like receptor signaling pathway
  • positive regulation of I-kappaB kinase/NF-kappaB signaling
  • innate immune response
Components
  • mitotic spindle
  • IkappaB kinase complex
  • intracellular
  • cytoplasm
  • nucleus
  • ubiquitin ligase complex
  • cytosol
  • spindle pole
General FunctionUbiquitin protein ligase binding
Specific FunctionRegulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ9Y6K9
UniProtKB Entry NameNEMO_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019280|NF-kappa-B essential modulator (IKBKG)
ATGGCCCTTGTGATCCAGGTGGGGAAACTAAGGCCCAGAGAAGTGAGGACCCCGCAGACT
ATCAATCCCAGTCTCTTCCCCTCACTCCCTGTGAAGCTCTCCAGCATCATCGAGGTCCCA
TCAGGTGGGGAAAGATGCTGTTCCAGGCGCACACTAGTCTACAAGGCCAGAGCTTTCTGG
AAGGGGGCACCCTTGCCCTGTTGGATGAATAGGCACCTCTGGAAGAGCCAACTGTGTGAG
ATGGTGCAGCCCAGTGGTGGCCCGGCAGCAGATCAGGACGTACTGGGCGAAGAGTCTCCT
CTGGGGAAGCCAGCCATGCTGCACCTGCCTTCAGAACAGGGCGCTCCTGAGACCCTCCAG
CGCTGCCTGGAGGAGAATCAAGAGCTCCGAGATGCCATCCGGCAGAGCAACCAGATTCTG
CGGGAGCGCTGCGAGGAGCTTCTGCATTTCCAAGCCAGCCAGAGGGAGGAGAAGGAGTTC
CTCATGTGCAAGTTCCAGGAGGCCAGGAAACTGGTGGAGAGACTCGGCCTGGAGAAGCTC
GATCTGAAGAGGCAGAAGGAGCAGGCTCTGCGGGAGGTGGAGCACCTGAAGAGATGCCAG
CAGCAGATGGCTGAGGACAAGGCCTCTGTGAAAGCCCAGGTGACGTCCTTGCTCGGGGAG
CTGCAGGAGAGCCAGAGTCGCTTGGAGGCTGCCACTAAGGAATGCCAGGCTCTGGAGGGT
CGGGCCCGGGCGGCCAGCGAGCAGGCGCGGCAGCTGGAGAGTGAGCGCGAGGCGCTGCAG
CAGCAGCACAGCGTGCAGGTGGACCAGCTGCGCATGCAGGGCCAGAGCGTGGAGGCCGCG
CTCCGCATGGAGCGCCAGGCCGCCTCGGAGGAGAAGAGGAAGCTGGCCCAGTTGCAGGTG
GCCTATCACCAGCTCTTCCAAGAATACGACAACCACATCAAGAGCAGCGTGGTGGGCAGT
GAGCGGAAGCGAGGAATGCAGCTGGAAGATCTCAAACAGCAGCTCCAGCAGGCCGAGGAG
GCCCTGGTGGCCAAACAGGAGGTGATCGATAAGCTGAAGGAGGAGGCCGAGCAGCACAAG
ATTGTGATGGAGACCGTTCCGGTGCTGAAGGCCCAGGCGGATATCTACAAGGCGGACTTC
CAGGCTGAGAGGCAGGCCCGGGAGAAGCTGGCCGAGAAGAAGGAGCTCCTGCAGGAGCAG
CTGGAGCAGCTGCAGAGGGAGTACAGCAAACTGAAGGCCAGCTGTCAGGAGTCGGCCAGG
ATCGAGGACATGAGGAAGCGGCATGTCGAGGTCTCCCAGGCCCCCTTGCCCCCCGCCCCT
GCCTACCTCTCCTCTCCCCTGGCCCTGCCCAGCCAGAGGAGGAGCCCCCCCGAGGAGCCA
CCTGACTTCTGCTGTCCCAAGTGCCAGTATCAGGCCCCTGATATGGACACCCTGCAGATA
CATGTCATGGAGTGCATTGAGTAG
GenBank Gene IDAF062089
GeneCard IDNot Available
GenAtlas IDIKBKG
HGNC IDHGNC:5961
Chromosome LocationX
LocusXq28
References
  1. Li Y, Kang J, Friedman J, Tarassishin L, Ye J, Kovalenko A, Wallach D, Horwitz MS: Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1042-7. 9927690
  2. Jin DY, Jeang KT: Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28. J Biomed Sci. 1999 Mar-Apr;6(2):115-20. 10087442
  3. Rothwarf DM, Zandi E, Natoli G, Karin M: IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature. 1998 Sep 17;395(6699):297-300. 9751060
  4. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, Israel A, Heiss NS, Klauck SM, Kioschis P, Wiemann S, Poustka A, Esposito T, Bardaro T, Gianfrancesco F, Ciccodicola A, D'Urso M, Woffendin H, Jakins T, Donnai D, Stewart H, Kenwrick SJ, Aradhya S, Yamagata T, Levy M, Lewis RA, Nelson DL: Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium. Nature. 2000 May 25;405(6785):466-72. 10839543
  5. Ye Z, Connor JR: cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs. Biochem Biophys Res Commun. 2000 Aug 18;275(1):223-7. 10944468
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  7. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. 15772651
  8. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  9. Mercurio F, Murray BW, Shevchenko A, Bennett BL, Young DB, Li JW, Pascual G, Motiwala A, Zhu H, Mann M, Manning AM: IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex. Mol Cell Biol. 1999 Feb;19(2):1526-38. 9891086
  10. Jin DY, Giordano V, Kibler KV, Nakano H, Jeang KT: Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma. J Biol Chem. 1999 Jun 18;274(25):17402-5. 10364167
  11. Xiao G, Sun SC: Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein. Oncogene. 2000 Oct 26;19(45):5198-203. 11064457
  12. Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R: Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions. FEBS Lett. 2001 Jun 1;498(1):93-7. 11389905
  13. Hong X, Xu L, Li X, Zhai Z, Shu H: CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation. FEBS Lett. 2001 Jun 15;499(1-2):133-6. 11418127
  14. Li XH, Fang X, Gaynor RB: Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex. J Biol Chem. 2001 Feb 9;276(6):4494-500. Epub 2000 Nov 15. 11080499
  15. Chariot A, Leonardi A, Muller J, Bonif M, Brown K, Siebenlist U: Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases. J Biol Chem. 2002 Oct 4;277(40):37029-36. Epub 2002 Jul 19. 12133833
  16. Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY, Tsai MJ, O'Malley BW: Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase. Mol Cell Biol. 2002 May;22(10):3549-61. 11971985
  17. Huang TT, Wuerzberger-Davis SM, Wu ZH, Miyamoto S: Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress. Cell. 2003 Nov 26;115(5):565-76. 14651848
  18. Carter RS, Pennington KN, Ungurait BJ, Ballard DW: In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase. J Biol Chem. 2003 May 30;278(22):19642-8. Epub 2003 Mar 25. 12657630
  19. Tegethoff S, Behlke J, Scheidereit C: Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation. Mol Cell Biol. 2003 Mar;23(6):2029-41. 12612076
  20. Kovalenko A, Chable-Bessia C, Cantarella G, Israel A, Wallach D, Courtois G: The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature. 2003 Aug 14;424(6950):801-5. 12917691
  21. Abbott DW, Wilkins A, Asara JM, Cantley LC: The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO. Curr Biol. 2004 Dec 29;14(24):2217-27. 15620648
  22. Huang J, Teng L, Li L, Liu T, Li L, Chen D, Xu LG, Zhai Z, Shu HB: ZNF216 Is an A20-like and IkappaB kinase gamma-interacting inhibitor of NFkappaB activation. J Biol Chem. 2004 Apr 16;279(16):16847-53. Epub 2004 Jan 30. 14754897
  23. Bruey JM, Bruey-Sedano N, Newman R, Chandler S, Stehlik C, Reed JC: PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages. J Biol Chem. 2004 Dec 10;279(50):51897-907. Epub 2004 Sep 28. 15456791
  24. Sun L, Deng L, Ea CK, Xia ZP, Chen ZJ: The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004 May 7;14(3):289-301. 15125833
  25. Zhou H, Wertz I, O'Rourke K, Ultsch M, Seshagiri S, Eby M, Xiao W, Dixit VM: Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004 Jan 8;427(6970):167-71. Epub 2003 Dec 24. 14695475
  26. Janssens S, Tinel A, Lippens S, Tschopp J: PIDD mediates NF-kappaB activation in response to DNA damage. Cell. 2005 Dec 16;123(6):1079-92. 16360037
  27. Wu CJ, Conze DB, Li T, Srinivasula SM, Ashwell JD: Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat Cell Biol. 2006 Apr;8(4):398-406. Epub 2006 Mar 19. 16547522
  28. Wu ZH, Shi Y, Tibbetts RS, Miyamoto S: Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli. Science. 2006 Feb 24;311(5764):1141-6. 16497931
  29. Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG: Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem. 2007 Feb 9;282(6):4102-12. Epub 2006 Nov 29. 17135271
  30. Herscovitch M, Comb W, Ennis T, Coleman K, Yong S, Armstead B, Kalaitzidis D, Chandani S, Gilmore TD: Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347. Biochem Biophys Res Commun. 2008 Feb 29;367(1):103-8. doi: 10.1016/j.bbrc.2007.12.123. Epub 2007 Dec 28. 18164680
  31. Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Nunez G, Inohara N: A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 2008 Jan 23;27(2):373-83. Epub 2007 Dec 13. 18079694
  32. Palkowitsch L, Leidner J, Ghosh S, Marienfeld RB: Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity. J Biol Chem. 2008 Jan 4;283(1):76-86. Epub 2007 Oct 31. 17977820
  33. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. 18691976
  34. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  35. Cordier F, Grubisha O, Traincard F, Veron M, Delepierre M, Agou F: The zinc finger of NEMO is a functional ubiquitin-binding domain. J Biol Chem. 2009 Jan 30;284(5):2902-7. doi: 10.1074/jbc.M806655200. Epub 2008 Nov 25. 19033441
  36. Zeng W, Xu M, Liu S, Sun L, Chen ZJ: Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3. Mol Cell. 2009 Oct 23;36(2):315-25. doi: 10.1016/j.molcel.2009.09.037. 19854139
  37. Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, Yamamoto M, Akira S, Takao T, Tanaka K, Iwai K: Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009 Feb;11(2):123-32. doi: 10.1038/ncb1821. Epub 2009 Jan 11. 19136968
  38. Grubisha O, Kaminska M, Duquerroy S, Fontan E, Cordier F, Haouz A, Raynal B, Chiaravalli J, Delepierre M, Israel A, Veron M, Agou F: DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding. J Mol Biol. 2010 Jan 8;395(1):89-104. doi: 10.1016/j.jmb.2009.10.018. Epub 2009 Oct 23. 19854204
  39. Ashida H, Kim M, Schmidt-Supprian M, Ma A, Ogawa M, Sasakawa C: A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response. Nat Cell Biol. 2010 Jan;12(1):66-73; sup pp 1-9. doi: 10.1038/ncb2006. Epub 2009 Dec 13. 20010814
  40. Arimoto K, Funami K, Saeki Y, Tanaka K, Okawa K, Takeuchi O, Akira S, Murakami Y, Shimotohno K: Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15856-61. doi: 10.1073/pnas.1004621107. Epub 2010 Aug 19. 20724660
  41. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  42. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  43. Noguchi K, Okumura F, Takahashi N, Kataoka A, Kamiyama T, Todo S, Hatakeyama S: TRIM40 promotes neddylation of IKKgamma and is downregulated in gastrointestinal cancers. Carcinogenesis. 2011 Jul;32(7):995-1004. doi: 10.1093/carcin/bgr068. Epub 2011 Apr 7. 21474709
  44. Nanda SK, Venigalla RK, Ordureau A, Patterson-Kane JC, Powell DW, Toth R, Arthur JS, Cohen P: Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011 Jun 6;208(6):1215-28. doi: 10.1084/jem.20102177. Epub 2011 May 23. 21606507
  45. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ: Direct, noncatalytic mechanism of IKK inhibition by A20. Mol Cell. 2011 Nov 18;44(4):559-71. doi: 10.1016/j.molcel.2011.09.015. 22099304
  46. Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, Haas TL, Webb AI, Rickard JA, Anderton H, Wong WW, Nachbur U, Gangoda L, Warnken U, Purcell AW, Silke J, Walczak H: Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011 Mar 31;471(7340):591-6. doi: 10.1038/nature09816. 21455173
  47. Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, Tanaka K, Nakano H, Iwai K: SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. Nature. 2011 Mar 31;471(7340):633-6. doi: 10.1038/nature09815. 21455180
  48. Ikeda F, Deribe YL, Skanland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J, Tokunaga F, Androulidaki A, Nakagawa T, Pasparakis M, Iwai K, Sundberg JP, Schaefer L, Rittinger K, Macek B, Dikic I: SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature. 2011 Mar 31;471(7340):637-41. doi: 10.1038/nature09814. 21455181
  49. Lautz K, Damm A, Menning M, Wenger J, Adam AC, Zigrino P, Kremmer E, Kufer TA: NLRP10 enhances Shigella-induced pro-inflammatory responses. Cell Microbiol. 2012 Oct;14(10):1568-83. doi: 10.1111/j.1462-5822.2012.01822.x. Epub 2012 Jun 21. 22672233
  50. Zhou AY, Shen RR, Kim E, Lock YJ, Xu M, Chen ZJ, Hahn WC: IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex. Cell Rep. 2013 Mar 28;3(3):724-33. doi: 10.1016/j.celrep.2013.01.031. Epub 2013 Feb 28. 23453969
  51. Jackson SS, Coughlin EE, Coon JJ, Miyamoto S: Identifying post-translational modifications of NEMO by tandem mass spectrometry after high affinity purification. Protein Expr Purif. 2013 Nov;92(1):48-53. doi: 10.1016/j.pep.2013.08.020. Epub 2013 Sep 6. 24012789
  52. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. 24275569
  53. Cordier F, Vinolo E, Veron M, Delepierre M, Agou F: Solution structure of NEMO zinc finger and impact of an anhidrotic ectodermal dysplasia with immunodeficiency-related point mutation. J Mol Biol. 2008 Apr 11;377(5):1419-32. doi: 10.1016/j.jmb.2008.01.048. Epub 2008 Jan 30. 18313693
  54. Rushe M, Silvian L, Bixler S, Chen LL, Cheung A, Bowes S, Cuervo H, Berkowitz S, Zheng T, Guckian K, Pellegrini M, Lugovskoy A: Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site. Structure. 2008 May;16(5):798-808. doi: 10.1016/j.str.2008.02.012. 18462684
  55. Lo YC, Lin SC, Rospigliosi CC, Conze DB, Wu CJ, Ashwell JD, Eliezer D, Wu H: Structural basis for recognition of diubiquitins by NEMO. Mol Cell. 2009 Mar 13;33(5):602-15. doi: 10.1016/j.molcel.2009.01.012. Epub 2009 Jan 29. 19185524
  56. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM: A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000 Dec;67(6):1555-62. Epub 2000 Oct 24. 11047757
  57. Aradhya S, Woffendin H, Jakins T, Bardaro T, Esposito T, Smahi A, Shaw C, Levy M, Munnich A, D'Urso M, Lewis RA, Kenwrick S, Nelson DL: A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations. Hum Mol Genet. 2001 Sep 15;10(19):2171-9. 11590134
  58. Doffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, Bodemer C, Kenwrick S, Dupuis-Girod S, Blanche S, Wood P, Rabia SH, Headon DJ, Overbeek PA, Le Deist F, Holland SM, Belani K, Kumararatne DS, Fischer A, Shapiro R, Conley ME, Reimund E, Kalhoff H, Abinun M, Munnich A, Israel A, Courtois G, Casanova JL: X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001 Mar;27(3):277-85. 11242109
  59. Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W: Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001 Mar;2(3):223-8. 11224521
  60. Orange JS, Brodeur SR, Jain A, Bonilla FA, Schneider LC, Kretschmer R, Nurko S, Rasmussen WL, Kohler JR, Gellis SE, Ferguson BM, Strominger JL, Zonana J, Ramesh N, Ballas ZK, Geha RS: Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest. 2002 Jun;109(11):1501-9. 12045264
  61. Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, Israel A, Courtois G, D'Urso M, Ursini MV: Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation. Hum Mol Genet. 2004 Aug 15;13(16):1763-73. Epub 2004 Jun 30. 15229184
  62. Orange JS, Jain A, Ballas ZK, Schneider LC, Geha RS, Bonilla FA: The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation. J Allergy Clin Immunol. 2004 Apr;113(4):725-33. 15100680
  63. Orange JS, Levy O, Brodeur SR, Krzewski K, Roy RM, Niemela JE, Fleisher TA, Bonilla FA, Geha RS: Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia. J Allergy Clin Immunol. 2004 Sep;114(3):650-6. 15356572
  64. Filipe-Santos O, Bustamante J, Haverkamp MH, Vinolo E, Ku CL, Puel A, Frucht DM, Christel K, von Bernuth H, Jouanguy E, Feinberg J, Durandy A, Senechal B, Chapgier A, Vogt G, de Beaucoudrey L, Fieschi C, Picard C, Garfa M, Chemli J, Bejaoui M, Tsolia MN, Kutukculer N, Plebani A, Notarangelo L, Bodemer C, Geissmann F, Israel A, Veron M, Knackstedt M, Barbouche R, Abel L, Magdorf K, Gendrel D, Agou F, Holland SM, Casanova JL: X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production. J Exp Med. 2006 Jul 10;203(7):1745-59. Epub 2006 Jul 3. 16818673
  65. Sebban-Benin H, Pescatore A, Fusco F, Pascuale V, Gautheron J, Yamaoka S, Moncla A, Ursini MV, Courtois G: Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti. Hum Mol Genet. 2007 Dec 1;16(23):2805-15. Epub 2007 Aug 29. 17728323
  66. Hsiao PF, Lin SP, Chiang SS, Wu YH, Chen HC, Lin YC: NEMO gene mutations in Chinese patients with incontinentia pigmenti. J Formos Med Assoc. 2010 Mar;109(3):192-200. doi: 10.1016/S0929-6646(10)60042-3. 20434027
  67. Conte MI, Pescatore A, Paciolla M, Esposito E, Miano MG, Lioi MB, McAleer MA, Giardino G, Pignata C, Irvine AD, Scheuerle AE, Royer G, Hadj-Rabia S, Bodemer C, Bonnefont JP, Munnich A, Smahi A, Steffann J, Fusco F, Ursini MV: Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease. Hum Mutat. 2014 Feb;35(2):165-77. doi: 10.1002/humu.22483. Epub 2013 Dec 12. 24339369
  68. Ku CL, Picard C, Erdos M, Jeurissen A, Bustamante J, Puel A, von Bernuth H, Filipe-Santos O, Chang HH, Lawrence T, Raes M, Marodi L, Bossuyt X, Casanova JL: IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease. J Med Genet. 2007 Jan;44(1):16-23. Epub 2006 Sep 1. 16950813