IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)

Hoesel B, Schmid JA. The complexity of NF-?B signaling in inflammation and cancer. Molecular Cancer. 2013 Aug 02;12(1):86. doi: 10.1186/1476-4598-12-86.; Shifera AS. The zinc finger domain of IKK? (NEMO) protein in health and disease. J Cellular Molecular Medi. 2010 Mar 15;14(10):2404–14. doi: 10.1111/j.1582-4934.2010.01054.x.; Lawrence T. The Nuclear Factor NF- B Pathway in Inflammation. Cold Spring Harbor Perspectives in Biology. 2009 Oct 07;1(6):a001651. doi: 10.1101/cshperspect.a001651.; Oeckinghaus A, Ghosh S. The NF- B Family of Transcription Factors and Its Regulation. Cold Spring Harbor Perspectives in Biology. 2009 Sep 02;1(4):a000034. doi: 10.1101/cshperspect.a000034.; Hanson EP, Monaco-Shawver L, Solt LA, Madge LA, Banerjee PP, May MJ, Orange JS. Hypomorphic nuclear factor-?B essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. Journal of Allergy and Clinical Immunology. 2008 Dec;122(6):1169–1177.e16. doi: 10.1016/j.jaci.2008.08.018.; Fusco F, Pescatore A, Bal E, Ghoul A, Paciolla M, Lioi MB, D'Urso M, Rabia SH, Bodemer C, Bonnefont JP, Munnich A, Miano MG, Smahi A, Ursini MV. Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations. Hum Mutat. 2008 May;29(5):595–604. doi: 10.1002/humu.20739. PMID: 18350553.; Vinolo E, Sebban H, Chaffotte A, Israël A, Courtois G, Véron M, Agou F. A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide- and tumor necrosis factor-mediated NF-kappa B activation. J Biol Chem. 2006 Mar 10;281(10):6334–48. doi: 10.1074/jbc.m510118200. PMID: 16379012.; 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. doi: 10.1016/j.jaci.2004.06.052. PMID: 15356572.; Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, Israël 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. doi: 10.1093/hmg/ddh192. PMID: 15229184.; 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. doi: 10.1093/hmg/10.19.2171. PMID: 11590134.; 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. doi: 10.1038/85277. PMID: 11224521.; Döffinger 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, Israël 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. doi: 10.1038/85837. PMID: 11242109.; Kaltschmidt B, Kaltschmidt C, Hofmann TG, Hehner SP, Dröge W, Schmitz ML. The pro- or anti-apoptotic function of NF-kappaB is determined by the nature of the apoptotic stimulus. Eur J Biochem. 2000 Jun;267(12):3828–35. doi: 10.1046/j.1432-1327.2000.01421.x. PMID: 10849002.; 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. doi: 10.1038/26261. PMID: 9751060.; Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-?B and cytokine-inducible enhancers. The FASEB Journal. 1995 Jul;9(10):899–909. doi: 10.1096/fasebj.9.10.7542214.

Metabolites



Enzyme

EC Number name full name note
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)
2.7.11.10 IkappaB kinase ATP:[IkappaB protein] phosphotransferase


Proteins

Protein ID name full name