NEMO
NF-kappa-B essential modifier
Inhibitor of nuclear factor kappa-B kinase subunit gamma
IkB kinase subunit gamma
I-kappa-B kinase gamma
IKK-gamma
IKKG
IkB kinase-associated protein 1
IKKAP1
FIP-3

Gene name

	Name:	IKBKG
	Synonyms:	FIP3, NEMO

From

Homo sapiens (Human)

[TaxID: 9606]

Taxonomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1073/pnas.96.3.1042; PubMed=9927690 [NCBI, ExPASy, EBI, Israel, Japan] Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., Wallach D., Horwitz M.S.; "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. 96:1042-1047(1999).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Mammary cancer; DOI=10.1159/000025378; PubMed=10087442 [NCBI, ExPASy, EBI, Israel, Japan] Jin D.-Y., Jeang K.-T.; "Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28."; J. Biomed. Sci. 6:115-120(1999).
[3]	NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. TISSUE=Cervix carcinoma; DOI=10.1038/26261; PubMed=9751060 [NCBI, ExPASy, EBI, Israel, Japan] Rothwarf D.M., Zandi E., Natoli G., Karin M.; "IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex."; Nature 395:297-300(1998).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT IP VAL-407. DOI=10.1038/35013114; PubMed=10839543 [NCBI, ExPASy, EBI, Israel, Japan] Smahi A., Courtois G., Vabres P., Yamaoka S., Heuertz S., Munnich A., Israel A., Heiss N.S., Klauck S.M., 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 S.J., Aradhya S., Yamagata T., Levy M., Lewis R.A., Nelson D.L.; "Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti."; Nature 405:466-472(2000).
[5]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Astrocytoma; DOI=10.1006/bbrc.2000.3282; PubMed=10944468 [NCBI, ExPASy, EBI, Israel, Japan] Ye Z., Connor J.R.; "cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs."; Biochem. Biophys. Res. Commun. 275:223-227(2000).
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.; "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
[7]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Lung, Placenta, and Skin; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[8]	NUCLEOTIDE SEQUENCE [MRNA] OF 51-419, AND PROTEIN SEQUENCE OF 144-159. TISSUE=Cervix carcinoma; PubMed=9891086 [NCBI, ExPASy, EBI, Israel, Japan] Mercurio F., Murray B.W., Shevchenko A., Bennett B.L., Young D.B., Li J.W., Pascual G., Motiwala A., Zhu H., Mann M., Manning A.M.; "IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex."; Mol. Cell. Biol. 19:1526-1538(1999).
[9]	INTERACTION WITH HTLV-1 TAX-1. DOI=10.1074/jbc.274.25.17402; PubMed=10364167 [NCBI, ExPASy, EBI, Israel, Japan] Jin D.-Y., Giordano V., Kibler K.V., Nakano H., Jeang K.-T.; "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. 274:17402-17405(1999).
[10]	INTERACTION WITH HTLV-1 TAX-1. DOI=10.1038/sj.onc.1203894; PubMed=11064457 [NCBI, ExPASy, EBI, Israel, Japan] Xiao G., Sun S.C.; "Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein."; Oncogene 19:5198-5203(2000).
[11]	INTERACTION WITH COPS3. DOI=10.1016/S0014-5793(01)02535-2; PubMed=11418127 [NCBI, ExPASy, EBI, Israel, Japan] Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B.; "CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation."; FEBS Lett. 499:133-136(2001).
[12]	SUBUNIT OF THE IKK COMPLEX. DOI=10.1074/jbc.M008353200; PubMed=11080499 [NCBI, ExPASy, EBI, Israel, Japan] Li X.-H., Fang X., Gaynor R.B.; "Role of ikkgamma/nemo in assembly of the IkappaB kinase complex."; J. Biol. Chem. 276:4494-4500(2001).
[13]	INTERACTION WITH TANK AND IKBKB. DOI=10.1074/jbc.M205069200; PubMed=12133833 [NCBI, ExPASy, EBI, Israel, Japan] 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. 277:37029-37036(2002).
[14]	SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKA AND IKKB. DOI=10.1128/MCB.22.10.3549-3561.2002; PubMed=11971985 [NCBI, ExPASy, EBI, Israel, Japan] Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W.; "Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase."; Mol. Cell. Biol. 22:3549-3561(2002).
[15]	SUMOYLATION AT LYS-277 AND LYS-309, UBIQUITINATION AT LYS-277 AND LYS-309, AND MUTAGENESIS OF LYS-277 AND LYS-309. DOI=10.1016/S0092-8674(03)00895-X; PubMed=14651848 [NCBI, ExPASy, EBI, Israel, Japan] Huang T.T., Wuerzberger-Davis S.M., Wu Z.H., Miyamoto S.; "Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress."; Cell 115:565-576(2003).
[16]	PHOSPHORYLATION AT SER-31; SER-43 AND SER-376. DOI=10.1074/jbc.M301705200; PubMed=12657630 [NCBI, ExPASy, EBI, Israel, Japan] Carter R.S., Pennington K.N., Ungurait B.J., Ballard D.W.; "In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase."; J. Biol. Chem. 278:19642-19648(2003).
[17]	SELF-ASSOCIATION, AND COMPOSITION OF THE IKK COMPLEX. DOI=10.1128/MCB.23.6.2029-2041.2003; PubMed=12612076 [NCBI, ExPASy, EBI, Israel, Japan] 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. 23:2029-2041(2003).
[18]	INTERACTION WITH CYLD. DOI=10.1038/nature01802; PubMed=12917691 [NCBI, ExPASy, EBI, Israel, Japan] Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., Courtois G.; "The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."; Nature 424:801-805(2003).
[19]	UBIQUITINATION AT LYS-285. DOI=10.1016/j.cub.2004.12.032; PubMed=15620648 [NCBI, ExPASy, EBI, Israel, Japan] Abbott D.W., Wilkins A., Asara J.M., Cantley L.C.; "The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO."; Curr. Biol. 14:2217-2227(2004).
[20]	INTERACTION WITH NALP2. DOI=10.1074/jbc.M406741200; PubMed=15456791 [NCBI, ExPASy, EBI, Israel, Japan] Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C.; "PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages."; J. Biol. Chem. 279:51897-51907(2004).
[21]	UBIQUITINATION. DOI=10.1016/S1097-2765(04)00236-9; PubMed=15125833 [NCBI, ExPASy, EBI, Israel, Japan] Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.; "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."; Mol. Cell 14:289-301(2004).
[22]	UBIQUITINATION AT LYS-399, AND MUTAGENESIS OF LYS-399. DOI=10.1038/nature02273; PubMed=14695475 [NCBI, ExPASy, EBI, Israel, Japan] Zhou H., Wertz I., O'Rourke K., Ultsch M., Seshagiri S., Eby M., Xiao W., Dixit V.M.; "Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO."; Nature 427:167-171(2004).
[23]	INTERACTION WITH LRDD. DOI=10.1016/j.cell.2005.09.036; PubMed=16360037 [NCBI, ExPASy, EBI, Israel, Japan] Janssens S., Tinel A., Lippens S., Tschopp J.; "PIDD mediates NF-kappaB activation in response to DNA damage."; Cell 123:1079-1092(2005).
[24]	INTERACTION WITH ATM, PHOSPHORYLATION AT SER-85, AND MUTAGENESIS OF SER-85. DOI=10.1126/science.1121513; PubMed=16497931 [NCBI, ExPASy, EBI, Israel, Japan] Wu Z.H., Shi Y., Tibbetts R.S., Miyamoto S.; "Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli."; Science 311:1141-1146(2006).
[25]	SUBUNIT, AND DISULFIDE BONDS. DOI=10.1016/j.bbrc.2007.12.123; PubMed=18164680 [NCBI, ExPASy, EBI, Israel, Japan] Herscovitch M., Comb W., Ennis T., Coleman K., Yong S., Armstead B., Kalaitzidis D., Chandani S., Gilmore T.D.; "Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347."; Biochem. Biophys. Res. Commun. 367:103-108(2008).
[26]	INTERACTION WITH IKBKB, PHOSPHORYLATION AT SER-68, AND MUTAGENESIS OF SER-68. DOI=10.1074/jbc.M708856200; PubMed=17977820 [NCBI, ExPASy, EBI, Israel, Japan] Palkowitsch L., Leidner J., Ghosh S., Marienfeld R.B.; "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. 283:76-86(2008).
[27]	PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377 AND SER-387, AND MASS SPECTROMETRY. DOI=10.1073/pnas.0805139105; PubMed=18669648 [NCBI, ExPASy, EBI, Israel, Japan] Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.; "A quantitative atlas of mitotic phosphorylation."; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[28]	STRUCTURE BY NMR OF 394-419 OF WILD-TYPE AND MUTANT PHE-417, AND ZINC-FINGER. DOI=10.1016/j.jmb.2008.01.048; PubMed=18313693 [NCBI, ExPASy, EBI, Israel, Japan] 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. 377:1419-1432(2008).
[29]	X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 44-111 IN COMPLEX WITH CHUK AND IKBKB, AND SUBUNIT. DOI=10.1016/j.str.2008.02.012; PubMed=18462684 [NCBI, ExPASy, EBI, Israel, Japan] Rushe M., Silvian L., Bixler S., Chen L.L., 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 16:798-808(2008).
[30]	VARIANTS EDAXID ARG-417 AND PHE-417. DOI=10.1086/316914; PubMed=11047757 [NCBI, ExPASy, EBI, Israel, Japan] Zonana J., Elder M.E., Schneider L.C., Orlow S.J., Moss C., Golabi M., Shapira S.K., Farndon P.A., Wara D.W., Emmal S.A., Ferguson B.M.; "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. 67:1555-1562(2000).
[31]	VARIANTS IP LYS-57 AND VAL-407. DOI=10.1093/hmg/10.19.2171; PubMed=11590134 [NCBI, ExPASy, EBI, Israel, Japan] Aradhya S., Woffendin H., Jakins T., Bardaro T., Esposito T., Smahi A., Shaw C., Levy M., Munnich A., D'Urso M., Lewis R.A., Kenwrick S., Nelson D.L.; "A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations."; Hum. Mol. Genet. 10:2171-2179(2001).
[32]	VARIANTS EDAXID PRO-175; PRO-227; GLY-288; ASN-311; ARG-417 AND PHE-417. DOI=10.1038/85837; PubMed=11242109 [NCBI, ExPASy, EBI, Israel, Japan] Doeffinger R., Smahi A., Bessia C., Geissmann F., Feinberg J., Durandy A., Bodemer C., Kenwrick S.J., Dupuis-Girod S., Blanche S., Wood P., Rabia S.H., Headon D.J., Overbeek P.A., Le Deist F., Holland S.M., Belani K., Kumararatne D.S., Fischer A., Shapiro R., Conley M.E., Reimund E., Kalhoff H., Abinun M., Munnich A., Israael A., Courtois G., Casanova J.-L.; "X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa B signaling."; Nat. Genet. 27:277-285(2001).
[33]	VARIANTS EDAXID VAL-406 AND ARG-417. DOI=10.1038/85277; PubMed=11224521 [NCBI, ExPASy, EBI, Israel, Japan] Jain A., Ma C.A., Liu S., Brown M., Cohen J., Strober W.; "Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia."; Nat. Immunol. 2:223-228(2001).
[34]	VARIANTS EDAXID ARG-153 AND ARG-417. PubMed=12045264 [NCBI, ExPASy, EBI, Israel, Japan] Orange J.S., Brodeur S.R., Jain A., Bonilla F.A., Schneider L.C., Kretschmer R., Nurko S., Rasmussen W.L., Koehler J.R., Gellis S.E., Ferguson B.M., Strominger J.L., Zonana J., Ramesh N., Ballas Z.K., Geha R.S.; "Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations."; J. Clin. Invest. 109:1501-1509(2002).
[35]	VARIANTS IP LYS-57; LYS-90 DEL; ASN-113 AND TRP-123, AND CHARACTERIZATION OF VARIANTS IP LYS-57; LYS-90 DEL; ASN-113 AND TRP-123. DOI=10.1093/hmg/ddh192; PubMed=15229184 [NCBI, ExPASy, EBI, Israel, Japan] Fusco F., Bardaro T., Fimiani G., Mercadante V., Miano M.G., Falco G., Israeel A., Courtois G., D'Urso M., Ursini M.V.; "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. 13:1763-1773(2004).
[36]	VARIANTS EDAXID ARG-153; ARG-417 AND TYR-417. DOI=10.1016/j.jaci.2004.01.762; PubMed=15100680 [NCBI, ExPASy, EBI, Israel, Japan] Orange J.S., Jain A., Ballas Z.K., Schneider L.C., Geha R.S., Bonilla F.A.; "The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation."; J. Allergy Clin. Immunol. 113:725-733(2004).
[37]	INVOLVEMENT IN IMMUNODEFICIENCY WITHOUT ANHIDROTIC ECTODERMAL DYSPLASIA. DOI=10.1016/j.jaci.2004.06.052; PubMed=15356572 [NCBI, ExPASy, EBI, Israel, Japan] Orange J.S., Levy O., Brodeur S.R., Krzewski K., Roy R.M., Niemela J.E., Fleisher T.A., Bonilla F.A., Geha R.S.; "Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia."; J. Allergy Clin. Immunol. 114:650-656(2004).
[38]	VARIANTS AMCBX1 ALA-315 AND GLN-319. DOI=10.1084/jem.20060085; PubMed=16818673 [NCBI, ExPASy, EBI, Israel, Japan] Filipe-Santos O., Bustamante J., Haverkamp M.H., Vinolo E., Ku C.-L., Puel A., Frucht D.M., 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 M.N., Kutukculer N., Plebani A., Notarangelo L., Bodemer C., Geissmann F., Israeel A., Veron M., Knackstedt M., Barbouche R., Abel L., Magdorf K., Gendrel D., Agou F., Holland S.M., Casanova J.-L.; "X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production."; J. Exp. Med. 203:1745-1759(2006).
[39]	VARIANT IP PRO-323, AND INTERACTION WITH TRAF6. DOI=10.1093/hmg/ddm237; PubMed=17728323 [NCBI, ExPASy, EBI, Israel, Japan] Sebban-Benin H., Pescatore A., Fusco F., Pascuale V., Gautheron J., Yamaoka S., Moncla A., Ursini M.V., Courtois G.; "Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti."; Hum. Mol. Genet. 16:2805-2815(2007).
[40]	VARIANT IPD2 GLY-173. DOI=10.1136/jmg.2006.044446; PubMed=16950813 [NCBI, ExPASy, EBI, Israel, Japan] Ku C.-L., Picard C., Erdos M., Jeurissen A., Bustamante J., Puel A., von Bernuth H., Filipe-Santos O., Chang H.-H., Lawrence T., Raes M., Marodi L., Bossuyt X., Casanova J.-L.; "IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease."; J. Med. Genet. 44:16-23(2007).

Comments

FUNCTION: Regulatory 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. 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 (By similarity).
SUBUNIT: Homodimer; disulfide-linked. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Interacts with COPS3, CYLD, NALP2, TRPC4AP and LRDD. Interacts with ATM; the complex is exported from the nucleus. Interacts with TRAF6. Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG. Interacts with TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG.
INTERACTION:
O15111:CHUK; NbExp=3; IntAct=EBI-81279, EBI-81249;
Q9UNS2:COPS3; NbExp=1; IntAct=EBI-81279, EBI-350590;
O14920:IKBKB; NbExp=3; IntAct=EBI-81279, EBI-81266;
Q9Y6Q9:NCOA3; NbExp=1; IntAct=EBI-81279, EBI-81196;
Q13546:RIPK1; NbExp=1; IntAct=EBI-81279, EBI-358507;
P12931:SRC; NbExp=1; IntAct=EBI-81279, EBI-621482;
Q8NFZ5:TNIP2; NbExp=2; IntAct=EBI-81279, EBI-359372;
SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
PTM: Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.
PTM: Polyubiquitinated on Lys-285 through 'Lys-63'; the ubiquitination is mediated by NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.
PTM: Polyubiquitinated on Lys-399 through 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway.
PTM: Sumoylated on Lys-277 and Lys-309 by SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.
PTM: Mono-ubiquitinated on Lys-277 and Lys-309; promotes nuclear export.
DISEASE: Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency X-linked (EDAXID) [MIM:300291]; also known as hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDAXID is characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.
DISEASE: Defects in IKBKG are the cause of ectodermal dysplasia anhidrotic with immunodeficiency-osteopetrosis-lymphedema (OLEDAID) [MIM:300301].
DISEASE: Defects in IKBKG are a cause of immunodeficiency without anhidrotic ectodermal dysplasia [MIM:300584]; also called isolated immunodeficiency or pure immunodeficiency. Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased infection susceptibility. Patients suffer from multiple episodes of infectious diseases.
DISEASE: Defects in IKBKG are the cause of susceptibility to X-linked familial atypical micobacteriosis type 1 (AMCBX1) [MIM:300636]; also known as X-linked disseminated atypical mycobacterial infection type 1 or X-linked susceptibility to mycobacterial disease type 1. AMCBX1 is the X-linked recessive form of mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.
DISEASE: Defects in IKBKG are the cause of recurrent isolated invasive pneumococcal disease type 2 (IPD2) [MIM:300640]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.
DISEASE: Defects in IKBKG are the cause of incontinentia pigmenti (IP) [MIM:308300]; formerly designed familial incontinentia pigmenti type II (IP2). IP is a genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.
SIMILARITY: Contains 1 C2HC-type zinc finger.
WEB RESOURCE: Name=IKBKGbase; Note=IKBKG mutation db; URL="http://bioinf.uta.fi/IKBKGbase/";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=IKBKG";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF062089; AAD12183.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF091453; AAD38081.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF074382; AAC36330.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ271718; CAB93146.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF261086; AAF99679.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019621; AAV38427.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000299; AAH00299.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC012114; AAH12114.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC050612; AAH50612.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00002411; -.

RefSeq

NP_001093327.1; -.
NP_001138727.1; -.
NP_003630.1; -.

UniGene

Hs.43505

3D structure databases

PDB

2JVX; NMR; -; A=394-419.	[ExPASy / RCSB / EBI]
2JVY; NMR; -; A=394-419.	[ExPASy / RCSB / EBI]
3BRT; X-ray; 2.25 A; B/D=46-111.	[ExPASy / RCSB / EBI]
3BRV; X-ray; 2.20 A; B/D=44-111.	[ExPASy / RCSB / EBI]
3CL3; X-ray; 3.20 A; D/E=150-272.	[ExPASy / RCSB / EBI]
3FX0; X-ray; 3.20 A; A/B=246-337.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

2JVX; -.
2JVY; -.
3BRT; -.
3BRV; -.
3CL3; -.
3FX0; -.

ModBase

Q9Y6K9.

Protein-protein interaction databases

DIP

DIP:27528N; -.

IntAct

Q9Y6K9; 130.

PTM databases

PhosphoSite

Q9Y6K9; -.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway; BCR signaling pathway.
nfkappabcanonicalpathway; Canonical NF-kappaB pathway.
fcer1pathway; Fc-epsilon receptor I signaling in mast cells.
il1pathway; IL1-mediated signaling events.
p75ntrpathway; p75(NTR)-mediated signaling.
tcrpathway; TCR signaling in naive CD4+ T cells.
cd8tcrpathway; TCR signaling in naive CD8+ T cells.
tnfpathway; TNF receptor signaling pathway.
trail_pathway; TRAIL signaling pathway.

Reactome

REACT_6900; Signaling in Immune system.

Organism-specific databases

GeneCards

GC0XP153423; -.

H-InvDB

HIX0017162; -.
HIX0077206; -.

HGNC:5961; IKBKG.

CAB010373; -.
HPA000426; -.

MIM

300248; gene. [NCBI / EBI]
300291; phenotype. [NCBI / EBI]
300301; phenotype. [NCBI / EBI]
300584; phenotype. [NCBI / EBI]
300636; phenotype. [NCBI / EBI]
300640; phenotype. [NCBI / EBI]
308300; phenotype. [NCBI / EBI]

Orphanet

69088; Ectodermal dysplasia - anhidrotic, with immunodeficiency - osteopetrosis - lymphedema.
69712; Hyper-IgM syndrome.
464; Incontinentia pigmenti.

PharmGKB

PA29777; -.

Gene expression databases

Q9Y6K9; -.

Q9Y6K9; -.

HS_IKBKG; -.

ENSG00000073009; Homo sapiens.

Ontologies

GO:0005829;	Cellular component: cytosol (inferred from experiment from Reactome).
GO:0005634;	Cellular component: nucleus (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0004871;	Molecular function: signal transducer activity (traceable author statement from ProtInc).
GO:0008270;	Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0007249;	Biological process: I-kappaB kinase/NF-kappaB cascade (traceable author statement from ProtInc).
GO:0006955;	Biological process: immune response (traceable author statement from ProtInc).
GO:0006917;	Biological process: induction of apoptosis (traceable author statement from ProtInc).
GO:0044419;	Biological process: interspecies interaction between organisms (inferred from electronic annotation from UniProtKB-KW).
GO:0006355;	Biological process: regulation of transcription, DNA-dependent (inferred from electronic annotation from UniProtKB-KW).
GO:0050852;	Biological process: T cell receptor signaling pathway (traceable author statement from UniProtKB).
GO:0006350;	Biological process: transcription (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Proteomic databases

PRIDE

Q9Y6K9; -.

Genome annotation databases

Ensembl

ENSG00000073009; Homo sapiens. [Contig view]

GeneID

8517; -.

KEGG

hsa:8517; -.

Phylogenomic databases

HOVERGEN

Q9Y6K9; -.

Other

31882; -.

IKBKG; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Coiled coil; Cytoplasm; Direct protein sequencing; Disease mutation; Disulfide bond; Ectodermal dysplasia; Host-virus interaction; Isopeptide bond; Metal-binding; Nucleus; Osteopetrosis; Phosphoprotein; Transcription; Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 419`	`419`	`NF-kappa-B essential modulator.`	`PRO_0000096782`
`DOMAIN`	`322 343`	`22`	`Leucine-zipper (Potential).`
`ZN_FING`	`396 417`	`22`	`C2HC-type.`
`REGION`	`44 111`	`68`	`Interaction with CHUK/IKBKB.`
`REGION`	`246 365`	`120`	`Self-association.`
`REGION`	`382 419`	`38`	`Interaction with CYLD.`
`COILED`	`49 356`	`308`	`Potential.`
`MOD_RES`	`31 31`		`Phosphoserine; by IKKB.`
`MOD_RES`	`43 43`		`Phosphoserine; by IKKB.`
`MOD_RES`	`68 68`		`Phosphoserine.`
`MOD_RES`	`85 85`		`Phosphoserine; by ATM.`
`MOD_RES`	`376 376`		`Phosphoserine; by IKKB.`
`MOD_RES`	`377 377`		`Phosphoserine.`
`MOD_RES`	`387 387`		`Phosphoserine.`
`DISULFID`	`54 54`		`Interchain.`
`DISULFID`	`347 347`		`Interchain.`
`CROSSLNK`	`277 277`		`Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO).`
`CROSSLNK`	`283 283`		`Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).`
`CROSSLNK`	`309 309`		`Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO).`
`CROSSLNK`	`399 399`		`Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).`
`VARIANT`	`57 57`	`1`	`E -> K (in IP; shows the same luciferase activity as the control).`	`VAR_026491`
`VARIANT`	`90 90`	`1`	`Missing (in IP; only 46.3% of the activation obtained with the wild-type protein).`	`VAR_026492`
`VARIANT`	`113 113`	`1`	`D -> N (in IP; shows the same luciferase activity as the control).`	`VAR_026493`
`VARIANT`	`123 123`	`1`	`R -> W (in IP; shows the same luciferase activity as the control).`	`VAR_026494`
`VARIANT`	`153 153`	`1`	`L -> R (in EDAXID).`	`VAR_026495`
`VARIANT`	`173 173`	`1`	`R -> G (in IPD2).`	`VAR_031958`
`VARIANT`	`175 175`	`1`	`R -> P (in EDAXID).`	`VAR_011320`
`VARIANT`	`227 227`	`1`	`L -> P (in EDAXID).`	`VAR_011321`
`VARIANT`	`288 288`	`1`	`A -> G (in EDAXID).`	`VAR_011322`
`VARIANT`	`311 311`	`1`	`D -> N (in EDAXID).`	`VAR_011323`
`VARIANT`	`315 315`	`1`	`E -> A (in AMCBX1).`	`VAR_031959`
`VARIANT`	`319 319`	`1`	`R -> Q (in AMCBX1).`	`VAR_031960`
`VARIANT`	`323 323`	`1`	`A -> P (in IP; diminishes interaction with TRAF6 and polyubiquitination).`	`VAR_042666`
`VARIANT`	`406 406`	`1`	`D -> V (in EDAXID).`	`VAR_011324`
`VARIANT`	`407 407`	`1`	`M -> V (in IP).`	`VAR_009182`
`VARIANT`	`417 417`	`1`	`C -> F (in EDAXID).`	`VAR_011325`
`VARIANT`	`417 417`	`1`	`C -> R (in EDAXID).`	`VAR_011326`
`VARIANT`	`417 417`	`1`	`C -> Y (in EDAXID).`	`VAR_026496`
`MUTAGEN`	`68 68`		`S->A: Increases formation of homodimers.`
`MUTAGEN`	`68 68`		`S->E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity.`
`MUTAGEN`	`85 85`		`S->A: Decreases ubiquitination and abolishes nuclear export.`
`MUTAGEN`	`277 277`		`K->A: Abolishes sumoylation and IKK activation; when associated with A-309.`
`MUTAGEN`	`309 309`		`K->A: Abolishes sumoylation and IKK activation; when associated with A-277.`
`MUTAGEN`	`399 399`		`K->R: Abolishes ubiquitination mediated by BCL10.`
`CONFLICT`	`341 341`		`S -> R (in Ref. 1; AAD12183).`
`CONFLICT`	`387 387`		`S -> R (in Ref. 1; AAD12183).`
`HELIX`	`50 108`	`59`
`TURN`	`194 196`	`3`
`HELIX`	`197 249`	`53`

Sequence information

Length: 419 AA [This is the length of the unprocessed precursor]

Molecular weight: 48198 Da [This is the MW of the unprocessed precursor]

CRC64: 322D1037881447FF [This is a checksum on the sequence]

        10         20         30         40         50         60 
MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET LQRCLEENQE 

        70         80         90        100        110        120 
LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA RKLVERLGLE KLDLKRQKEQ 

       130        140        150        160        170        180 
ALREVEHLKR CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKECQAL EGRARAASEQ 

       190        200        210        220        230        240 
ARQLESEREA LQQQHSVQVD QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE 

       250        260        270        280        290        300 
YDNHIKSSVV GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV 

       310        320        330        340        350        360 
LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES ARIEDMRKRH 

       370        380        390        400        410 
VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC QYQAPDMDTL QIHVMECIE

Q9Y6K9 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools