MGP Database

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MGP003579

UniProt Annotations

Entry Information
Gene Nameinhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Protein EntryNEMO_HUMAN
UniProt IDQ9Y6K9
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q9Y6K9-1; Sequence=Displayed; Name=2; IsoId=Q9Y6K9-2; Sequence=VSP_041000; Name=3; IsoId=Q9Y6K9-3; Sequence=VSP_041001, VSP_041002;
DiseaseEctodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema (OLEDAID) [MIM:300301]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the association of anhidrotic ectodermal dysplasia with severe immunodeficiency, osteopetrosis and lymphedema. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseEctodermal dysplasia, anhidrotic, with immunodeficiency X-linked (EDAID) [MIM:300291]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. {ECO:0000269|PubMed:11047757, ECO:0000269|PubMed:11224521, ECO:0000269|PubMed:11242109, ECO:0000269|PubMed:12045264, ECO:0000269|PubMed:15100680}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseImmunodeficiency 33 (IMD33) [MIM:300636]: A X-linked recessive form of Mendelian susceptibility to mycobacterial disease, a rare condition characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non- tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. {ECO:0000269|PubMed:16818673}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DiseaseImmunodeficiency, NEMO-related, without anhidrotic ectodermal dysplasia (NEMOID) [MIM:300584]: Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased susceptibility to infections. Patients suffer from multiple episodes of infectious diseases. {ECO:0000269|PubMed:15100680, ECO:0000269|PubMed:15356572}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseIncontinentia pigmenti (IP) [MIM:308300]: 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. {ECO:0000269|PubMed:10839543, ECO:0000269|PubMed:11590134, ECO:0000269|PubMed:15229184, ECO:0000269|PubMed:17728323}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseRecurrent isolated invasive pneumococcal disease 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. {ECO:0000269|PubMed:16950813}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe leucine-zipper domain and the C2HC-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3. {ECO:0000269|PubMed:18313693, ECO:0000269|PubMed:19854139}.
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. {ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20724660}.
InteractionQ9NPF8:ADAP2; NbExp=2; IntAct=EBI-81279, EBI-718895; P04083:ANXA1; NbExp=6; IntAct=EBI-81279, EBI-354007; Q66PJ3:ARL6IP4; NbExp=2; IntAct=EBI-81279, EBI-2683099; Q13315:ATM; NbExp=4; IntAct=EBI-81279, EBI-495465; Q13535:ATR; NbExp=2; IntAct=EBI-81279, EBI-968983; P05937:CALB1; NbExp=3; IntAct=EBI-81279, EBI-4286943; Q16543:CDC37; NbExp=4; IntAct=EBI-81279, EBI-295634; P24941:CDK2; NbExp=4; IntAct=EBI-81279, EBI-375096; O15111:CHUK; NbExp=20; IntAct=EBI-81279, EBI-81249; Q9UNS2:COPS3; NbExp=2; IntAct=EBI-81279, EBI-350590; P36888:FLT3; NbExp=2; IntAct=EBI-81279, EBI-3946257; Q14161:GIT2; NbExp=6; IntAct=EBI-81279, EBI-1046878; P07900:HSP90AA1; NbExp=3; IntAct=EBI-81279, EBI-296047; P08238:HSP90AB1; NbExp=2; IntAct=EBI-81279, EBI-352572; O14920:IKBKB; NbExp=25; IntAct=EBI-81279, EBI-81266; Q8VSC3:ipaH9.8 (xeno); NbExp=8; IntAct=EBI-81279, EBI-6125799; P05783:KRT18; NbExp=3; IntAct=EBI-81279, EBI-297888; P05787:KRT8; NbExp=2; IntAct=EBI-81279, EBI-297852; Q9UDY8:MALT1; NbExp=2; IntAct=EBI-81279, EBI-1047372; P01106:MYC; NbExp=3; IntAct=EBI-81279, EBI-447544; P25963:NFKBIA; NbExp=5; IntAct=EBI-81279, EBI-307386; P67775:PPP2CA; NbExp=4; IntAct=EBI-81279, EBI-712311; Q9BYM8:RBCK1; NbExp=4; IntAct=EBI-81279, EBI-2340624; Q13546:RIPK1; NbExp=7; IntAct=EBI-81279, EBI-358507; Q9UBF6:RNF7; NbExp=3; IntAct=EBI-81279, EBI-398632; Q9BVN2-2:RUSC1; NbExp=4; IntAct=EBI-81279, EBI-6257338; Q9HC62:SENP2; NbExp=3; IntAct=EBI-81279, EBI-714881; Q9H0F6:SHARPIN; NbExp=4; IntAct=EBI-81279, EBI-3942966; Q13501:SQSTM1; NbExp=2; IntAct=EBI-81279, EBI-307104; P12931:SRC; NbExp=3; IntAct=EBI-81279, EBI-621482; P63165:SUMO1; NbExp=3; IntAct=EBI-81279, EBI-80140; P21579:SYT1; NbExp=3; IntAct=EBI-81279, EBI-524909; Q9UHD2:TBK1; NbExp=2; IntAct=EBI-81279, EBI-356402; P01375:TNF; NbExp=2; IntAct=EBI-81279, EBI-359977; P21580:TNFAIP3; NbExp=4; IntAct=EBI-81279, EBI-527670; Q15025:TNIP1; NbExp=4; IntAct=EBI-81279, EBI-357849; Q8NFZ5:TNIP2; NbExp=6; IntAct=EBI-81279, EBI-359372; P0CG48:UBC; NbExp=4; IntAct=EBI-81279, EBI-3390054; Q5D1E8:ZC3H12A; NbExp=2; IntAct=EBI-81279, EBI-747793;
PtmNeddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity. {ECO:0000269|PubMed:21474709}.
PtmPhosphorylation at Ser-68 attenuates aminoterminal homodimerization. {ECO:0000269|PubMed:17977820}.
PtmPolyubiquitinated 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. 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. Monoubiquitinated on Lys-277 and Lys-309; promotes nuclear export. Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral innate and inflammatory responses. Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-264, Lys-277, Lys-285, Lys-292, Lys-302, Lys-309 and Lys-326; the head- to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation. Polyubiquitinated on Lys-309 and Lys-321 via 'Lys-27'-linked ubiquitin by Shigella flexneri E3 ubiquitin-protein ligase ipah9.8, leading to its degradation by the proteasome. {ECO:0000269|PubMed:14651848, ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:15620648, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20010814, ECO:0000269|PubMed:21455181}.
PtmSumoylated on Lys-277 and Lys-309 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues. {ECO:0000269|PubMed:14651848, ECO:0000269|PubMed:16497931, ECO:0000269|PubMed:19136968, ECO:0000269|PubMed:20010814, ECO:0000269|PubMed:21455181}.
SimilarityContains 1 C2HC-type zinc finger. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:14651848}. Nucleus {ECO:0000269|PubMed:14651848}. Note=Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress.
SubunitHomodimer; 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. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. 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 IKBKE. Interacts with TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with ZFAND5. Interacts with RIPK2. Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG. Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin. Binds polyubiquitin; the interaction is mediated by two domains; reports about the binding to 'Lys-63'-linked and/or linear polyubiquitin, respective binding affinities and stoichiometry are conflicting. Interacts with Shigella flexneri ipah9.8; the interaction promotes TNIP1- dependent 'Lys-27'-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. Interacts with NLRP10. {ECO:0000269|PubMed:10364167, ECO:0000269|PubMed:11064457, ECO:0000269|PubMed:11080499, ECO:0000269|PubMed:11389905, ECO:0000269|PubMed:11418127, ECO:0000269|PubMed:11971985, ECO:0000269|PubMed:12133833, ECO:0000269|PubMed:12917691, ECO:0000269|PubMed:14754897, ECO:0000269|PubMed:15456791, ECO:0000269|PubMed:16360037, ECO:0000269|PubMed:16497931, ECO:0000269|PubMed:17728323, ECO:0000269|PubMed:17977820, ECO:0000269|PubMed:18079694, ECO:0000269|PubMed:18164680, ECO:0000269|PubMed:18462684, ECO:0000269|PubMed:20010814, ECO:0000269|PubMed:22099304, ECO:0000269|PubMed:22672233, ECO:0000269|PubMed:23453969}.
Tissue SpecificityHeart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
Web ResourceName=IKBKGbase; Note=IKBKG mutation db; URL="http://structure.bmc.lu.se/idbase/IKBKGbase/";
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