IKBKG

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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
Identifiers
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
Orthologs
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.

Function[edit]

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.

Interactions[edit]

IKBKG has been shown to interact with:

References[edit]

  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 et al. (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 et al. (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 CJ, Ashwell JD. "NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation". Proc. Natl. Acad. Sci. U.S.A. 105 (8): 3023–8. doi:10.1073/pnas.0712313105. PMC 2268578. PMID 18287044. 
  6. ^ Hayden MS, Ghosh S. "Keeping cartographers busy". Nat. Cell Biol. 6 (2): 87–9. doi:10.1038/ncb0204-87. 
  7. ^ a b c Chen G, Cao P, Goeddel DV. "TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90". Mol. Cell 9 (2): 401–10. PMID 11864612. 
  8. ^ Agou F, Ye F, Goffinont S, Courtois G, Yamaoka S, Israël A et al. "NEMO trimerizes through its coiled-coil C-terminal domain". J. Biol. Chem. 277 (20): 17464–75. doi:10.1074/jbc.M201964200. PMID 11877453. 
  9. ^ a b Deng L, Wang C, Spencer E, Yang L, Braun A, You J et al. "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. PMID 11057907. 
  10. ^ a b Shifera AS, Horwitz MS. "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. 45 (6): 1633–45. doi:10.1016/j.molimm.2007.09.036. PMID 18207244. 
  11. ^ a b 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. 277 (40): 37029–36. doi:10.1074/jbc.M205069200. PMID 12133833. 
  12. ^ a b Wu RC, Qin J, Hashimoto Y, Wong J, Xu J, Tsai SY et al. "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase". Mol. Cell. Biol. 22 (10): 3549–61. PMC 133790. PMID 11971985. 
  13. ^ Conze DB, Wu CJ, Thomas JA, Landstrom A, Ashwell JD. "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. 
  14. ^ a b Windheim M, Stafford M, Peggie M, Cohen P. "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. 
  15. ^ Prajapati S, Verma U, Yamamoto Y, Kwak YT, Gaynor RB. "Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity". J. Biol. Chem. 279 (3): 1739–46. doi:10.1074/jbc.M306273200. PMID 14585847. 
  16. ^ Zhang SQ, Kovalenko A, Cantarella G, Wallach D. "Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation". Immunity 12 (3): 301–11. PMID 10755617. 
  17. ^ Leonardi A, Chariot A, Claudio E, Cunningham K, Siebenlist U. "CIKS, a connection to Ikappa B kinase and stress-activated protein kinase". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10494–9. doi:10.1073/pnas.190245697. PMC 27052. PMID 10962033. 
  18. ^ Li X, Commane M, Nie H, Hua X, Chatterjee-Kishore M, Wald D et al. "Act1, an NF-kappa B-activating protein". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10489–93. doi:10.1073/pnas.160265197. PMC 27051. PMID 10962024. 
  19. ^ Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG. "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. 

Further reading[edit]

External links[edit]