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Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Protein IKBKG PDB 2JVX.png
Rendering based on PDB 2JVX.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols IKBKG ; AMCBX1; FIP-3; FIP3; Fip3p; IKK-gamma; IP; IP1; IP2; IPD2; NEMO; ZC2HC9
External IDs OMIM300248 MGI1338074 HomoloGene2698 ChEMBL: 4967 GeneCards: IKBKG Gene
RNA expression pattern
PBB GE IKBKG 36004 at tn.png
PBB GE IKBKG 209929 s at tn.png
More reference expression data
Species Human Mouse
Entrez 8517 16151
Ensembl ENSG00000073009 ENSMUSG00000004221
UniProt Q9Y6K9 O88522
RefSeq (mRNA) NM_001099856 NM_001136067
RefSeq (protein) NP_001093326 NP_001129539
Location (UCSC) Chr HG1497_PATCH:
153.72 – 153.73 Mb
Chr X:
74.39 – 74.45 Mb
PubMed search [1] [2]

NF-kappa-B essential modulator (NEMO) also known as inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase complex that activates NF-κB.[1] The human gene for IKBKG is located on chromosome Xq28.[2] Multiple transcript variants encoding different isoforms have been found for this gene.


Main article: IκB kinase

NEMO (IKK-γ) is the regulatory subunit of the inhibitor of IκB kinase (IKK) complex, which activates NF-κB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways.

Clinical significance[edit]

Mutations in the IKBKG gene results in incontinentia pigmenti,[3] hypohidrotic ectodermal dysplasia,[4] and several other types of immunodeficiencies.

Incontinentia Pigmenti (IP) is an X-linked dominant disease caused by a mutation in the IKBKG gene. Since IKBKG helps activate NF-κB, which protects cells against TNF-alpha induced apoptosis, a lack of IKBKG (and hence a lack of active NF-κB) makes cells more prone to apoptosis.


IKBKG has been shown to interact with:


  1. ^ Rothwarf DM, Zandi E, Natoli G, Karin M (1998). "IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex". Nature 395 (6699): 297–300. doi:10.1038/26261. PMID 9751060. 
  2. ^ Jin DY, Jeang KT (1999). "Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28". J. Biomed. Sci. 6 (2): 115–20. doi:10.1159/000025378. PMID 10087442. 
  3. ^ 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 (September 2001). "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations". Hum. Mol. Genet. 10 (19): 2171–9. doi:10.1093/hmg/10.19.2171. PMID 11590134. 
  4. ^ Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, Shapira SK, Farndon PA, Wara DW, Emmal SA, Ferguson BM (December 2000). "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. 67 (6): 1555–62. doi:10.1086/316914. PMC 1287930. PMID 11047757. 
  5. ^ Wu, Chuan-Jin; Ashwell Jonathan D (February 2008). "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-κB activation". Proc. Natl. Acad. Sci. U.S.A. (United States) 105 (8): 3023–8. doi:10.1073/pnas.0712313105. PMC 2268578. PMID 18287044. 
  6. ^ Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216. 
  7. ^ a b c Chen, Guoqing; Cao Ping; Goeddel David V (February 2002). "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Mol. Cell (United States) 9 (2): 401–10. doi:10.1016/S1097-2765(02)00450-1. ISSN 1097-2765. PMID 11864612. 
  8. ^ Agou, Fabrice; Ye Fei; Goffinont Stéphane; Courtois Gilles; Yamaoka Shoji; Israël Alain; Véron Michel (May 2002). "NEMO trimerizes through its coiled-coil C-terminal domain". J. Biol. Chem. (United States) 277 (20): 17464–75. doi:10.1074/jbc.M201964200. ISSN 0021-9258. PMID 11877453. 
  9. ^ a b Deng, L; Wang C; Spencer E; Yang L; Braun A; You J; Slaughter C; Pickart C; Chen Z J (October 2000). "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain". Cell (UNITED STATES) 103 (2): 351–61. doi:10.1016/S0092-8674(00)00126-4. ISSN 0092-8674. PMID 11057907. 
  10. ^ a b Shifera, Amde Selassie; Horwitz Marshall S (March 2008). "Mutations in the zinc finger domain of IKK gamma block the activation of NF-kappa B and the induction of IL-2 in stimulated T lymphocytes". Mol. Immunol. (England) 45 (6): 1633–45. doi:10.1016/j.molimm.2007.09.036. ISSN 0161-5890. PMID 18207244. 
  11. ^ a b Chariot, Alain; Leonardi Antonio; Muller Jurgen; Bonif Marianne; Brown Keith; Siebenlist Ulrich (October 2002). "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. (United States) 277 (40): 37029–36. doi:10.1074/jbc.M205069200. ISSN 0021-9258. PMID 12133833. 
  12. ^ a b Wu, Ray-Chang; Qin Jun, Hashimoto Yoshihiro, Wong Jiemin, Xu Jianming, Tsai Sophia Y, Tsai Ming-Jer, O'Malley Bert W (May 2002). "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator Activity by IκB Kinase". Mol. Cell. Biol. (United States) 22 (10): 3549–61. doi:10.1128/MCB.22.10.3549-3561.2002. ISSN 0270-7306. PMC 133790. PMID 11971985. 
  13. ^ Conze, Dietrich B; Wu Chuan-Jin; Thomas James A; Landstrom Allison; Ashwell Jonathan D (May 2008). "Lys63-Linked Polyubiquitination of IRAK-1 Is Required for Interleukin-1 Receptor- and Toll-Like Receptor-Mediated NF-κB Activation". Mol. Cell. Biol. (United States) 28 (10): 3538–47. doi:10.1128/MCB.02098-07. PMC 2423148. PMID 18347055. 
  14. ^ a b Windheim, Mark; Stafford Margaret; Peggie Mark; Cohen Philip (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 IκBα Kinase". Mol. Cell. Biol. (United States) 28 (5): 1783–91. doi:10.1128/MCB.02380-06. PMC 2258775. PMID 18180283. 
  15. ^ Prajapati, Shashi; Verma Udit; Yamamoto Yumi; Kwak Youn Tae; Gaynor Richard B (January 2004). "Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity". J. Biol. Chem. (United States) 279 (3): 1739–46. doi:10.1074/jbc.M306273200. ISSN 0021-9258. PMID 14585847. 
  16. ^ Zhang, S Q; Kovalenko A; Cantarella G; Wallach D (March 2000). "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity (UNITED STATES) 12 (3): 301–11. doi:10.1016/S1074-7613(00)80183-1. ISSN 1074-7613. PMID 10755617. 
  17. ^ Leonardi, A; Chariot A; Claudio E; Cunningham K; Siebenlist U (September 2000). "CIKS, a connection to IκB kinase and stress-activated protein kinase". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10494–9. doi:10.1073/pnas.190245697. ISSN 0027-8424. PMC 27052. PMID 10962033. 
  18. ^ Li, X; Commane M; Nie H; Hua X; Chatterjee-Kishore M; Wald D; Haag M; Stark G R (September 2000). "Act1, an NF-κB-activating protein". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10489–93. doi:10.1073/pnas.160265197. ISSN 0027-8424. PMC 27051. PMID 10962024. 
  19. ^ Lamothe, Betty; Campos Alejandro D; Webster William K; Gopinathan Ambily; Hur Lana; Darnay Bryant G (September 2008). "The RING Domain and First Zinc Finger of TRAF6 Coordinate Signaling by Interleukin-1, Lipopolysaccharide, and RANKL". J. Biol. Chem. (United States) 283 (36): 24871–80. doi:10.1074/jbc.M802749200. ISSN 0021-9258. PMC 2529010. PMID 18617513. 

Further reading[edit]

External links[edit]