UniProtKB - Q9Y6K9 (NEMO_HUMAN)
NF-kappa-B essential modulator
IKBKG
Functioni
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 389 – 419 | CCHC NOA-typePROSITE-ProRule annotationAdd BLAST | 31 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- K63-linked polyubiquitin modification-dependent protein binding Source: GO_Central
- linear polyubiquitin binding Source: ParkinsonsUK-UCL
- metal ion binding Source: UniProtKB-KW
- peroxisome proliferator activated receptor binding Source: Ensembl
- protein-containing complex binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- transferrin receptor binding Source: ARUK-UCL
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
GO - Biological processi
- activation of MAPK activity Source: Reactome
- anoikis Source: BHF-UCL
- antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent Source: Reactome
- apoptotic process Source: ProtInc
- cellular response to DNA damage stimulus Source: UniProtKB
- establishment of vesicle localization Source: UniProtKB
- Fc-epsilon receptor signaling pathway Source: Reactome
- I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- immune response Source: ProtInc
- inflammatory response Source: UniProtKB
- innate immune response Source: UniProtKB
- interleukin-1-mediated signaling pathway Source: Reactome
- JNK cascade Source: Reactome
- MyD88-independent toll-like receptor signaling pathway Source: Reactome
- negative regulation of neuron death Source: ParkinsonsUK-UCL
- nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
- positive regulation of macroautophagy Source: BHF-UCL
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- protein-containing complex assembly Source: UniProtKB
- protein deubiquitination Source: Reactome
- regulation of I-kappaB kinase/NF-kappaB signaling Source: GO_Central
- regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
- response to virus Source: UniProtKB
- stimulatory C-type lectin receptor signaling pathway Source: Reactome
- stress-activated MAPK cascade Source: Reactome
- T cell receptor signaling pathway Source: Reactome
- TRIF-dependent toll-like receptor signaling pathway Source: Reactome
- viral process Source: UniProtKB-KW
Keywordsi
Biological process | DNA damage, Host-virus interaction, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6K9 |
Reactomei | R-HSA-1169091, Activation of NF-kappaB in B cells R-HSA-1236974, ER-Phagosome pathway R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment R-HSA-1810476, RIP-mediated NFkB activation via ZBP1 R-HSA-202424, Downstream TCR signaling R-HSA-2871837, FCERI mediated NF-kB activation R-HSA-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-450302, activated TAK1 mediates p38 MAPK activation R-HSA-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-HSA-4755510, SUMOylation of immune response proteins R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5602636, IKBKB deficiency causes SCID R-HSA-5603027, IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) R-HSA-5603029, IkBA variant leads to EDA-ID R-HSA-5607764, CLEC7A (Dectin-1) signaling R-HSA-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-9020702, Interleukin-1 signaling R-HSA-933542, TRAF6 mediated NF-kB activation R-HSA-933543, NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-937039, IRAK1 recruits IKK complex R-HSA-937041, IKK complex recruitment mediated by RIP1 R-HSA-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
SABIO-RKi | Q9Y6K9 |
SIGNORi | Q9Y6K9 |
Protein family/group databases
MoonDBi | Q9Y6K9, Predicted |
Names & Taxonomyi
Protein namesi | Recommended name: NF-kappa-B essential modulatorShort name: NEMO Alternative name(s): FIP-3 IkB kinase-associated protein 1 Short name: IKKAP1 Inhibitor of nuclear factor kappa-B kinase subunit gamma Short name: I-kappa-B kinase subunit gamma Short name: IKK-gamma Short name: IKKG Short name: IkB kinase subunit gamma NF-kappa-B essential modifier |
Gene namesi | Name:IKBKG Synonyms:FIP3, NEMO |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5961, IKBKG |
MIMi | 300248, gene |
neXtProti | NX_Q9Y6K9 |
VEuPathDBi | HostDB:ENSG00000269335.5 |
Subcellular locationi
Cytoskeleton
- mitotic spindle Source: UniProtKB
- spindle pole Source: UniProtKB
Cytosol
- cytosol Source: HPA
- IkappaB kinase complex Source: MGI
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
- ubiquitin ligase complex Source: ParkinsonsUK-UCL
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Ectodermal dysplasia and immunodeficiency 1 (EDAID1)9 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026495 | 153 | L → R in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar. | 1 | |
Natural variantiVAR_011320 | 175 | R → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar. | 1 | |
Natural variantiVAR_011321 | 227 | L → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar. | 1 | |
Natural variantiVAR_011322 | 288 | A → G in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar. | 1 | |
Natural variantiVAR_011323 | 311 | D → N in EDAID1; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar. | 1 | |
Natural variantiVAR_011324 | 406 | D → V in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar. | 1 | |
Natural variantiVAR_011325 | 417 | C → F in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar. | 1 | |
Natural variantiVAR_011326 | 417 | C → R in EDAID1; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar. | 1 |
Immunodeficiency 33 (IMD33)6 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031958 | 173 | R → G in IMD33. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar. | 1 | |
Natural variantiVAR_031959 | 315 | E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs137853331EnsemblClinVar. | 1 | |
Natural variantiVAR_031960 | 319 | R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar. | 1 | |
Natural variantiVAR_026496 | 417 | C → Y in IMD33. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar. | 1 |
Incontinentia pigmenti (IP)7 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026491 | 57 | E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar. | 1 | |
Natural variantiVAR_026492 | 90 | Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication | 1 | |
Natural variantiVAR_026494 | 123 | R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar. | 1 | |
Natural variantiVAR_072603 | 170 | L → P in IP. 1 Publication | 1 | |
Natural variantiVAR_072604 | 173 | R → Q in IP. 1 PublicationCorresponds to variant dbSNP:rs1057520292EnsemblClinVar. | 1 | |
Natural variantiVAR_072605 | 183 | Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl. | 1 | |
Natural variantiVAR_072606 | 314 | A → P in IP. 1 Publication | 1 | |
Natural variantiVAR_072607 | 322 | L → P in IP. 1 Publication | 1 | |
Natural variantiVAR_042666 | 323 | A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs179363865EnsemblClinVar. | 1 | |
Natural variantiVAR_009182 | 407 | M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar. | 1 | |
Natural variantiVAR_072608 | 413 | H → Y in IP. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 68 | S → A: Increases formation of homodimers. 1 Publication | 1 | |
Mutagenesisi | 68 | S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. 1 Publication | 1 | |
Mutagenesisi | 85 | S → A: Decreases ubiquitination and abolishes nuclear export. 1 Publication | 1 | |
Mutagenesisi | 115 | K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication | 1 | |
Mutagenesisi | 224 | K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication | 1 | |
Mutagenesisi | 277 | K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. 1 Publication | 1 | |
Mutagenesisi | 285 | K → R: Important decrease in the ubiquitination level; when associated with R-399. 1 Publication | 1 | |
Mutagenesisi | 296 | E → A: No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 1 Publication | 1 | |
Mutagenesisi | 300 | V → D: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 301 | L → A: Impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 304 | Q → A: Complete loss of cleavage by HAV protease 3c. 1 Publication | 1 | |
Mutagenesisi | 304 | Q → A: Impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 307 | I → N: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 308 | Y → A: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 309 | K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. 1 Publication | 1 | |
Mutagenesisi | 312 | F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. 2 Publications | 1 | |
Mutagenesisi | 312 | F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). 2 Publications | 1 | |
Mutagenesisi | 312 | F → Y: Impairs tandem ubiquitin binding. 2 Publications | 1 | |
Mutagenesisi | 313 | Q → A: Impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 315 | E → Q: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 317 | Q → A or W: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 323 | A → D: Greatly impairs tandem ubiquitin binding. 1 Publication | 1 | |
Mutagenesisi | 329 | L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336. 2 Publications | 1 | |
Mutagenesisi | 329 | L → P: Abolishes binding to polyubiquitin. 2 Publications | 1 | |
Mutagenesisi | 336 | L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. 1 Publication | 1 | |
Mutagenesisi | 399 | K → R: Abolishes BCL10-mediated but not RIPK2-mediated ubiquitination. Important decrease in the ubiquitination level; when associated with R-285. No change in the ubiquitination level; when associated with R-115 or R-224. 2 Publications | 1 | |
Mutagenesisi | 414 | V → S: Abolishes binding to polyubiquitin. 1 Publication | 1 | |
Mutagenesisi | 415 | M → S: Impairs binding to polyubiquitin. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Ectodermal dysplasia, OsteopetrosisOrganism-specific databases
DisGeNETi | 8517 |
GeneReviewsi | IKBKG |
MalaCardsi | IKBKG |
MIMi | 300291, phenotype 300636, phenotype 308300, phenotype |
OpenTargetsi | ENSG00000269335 |
Orphaneti | 69088, Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome 98813, Hypohidrotic ectodermal dysplasia with immunodeficiency 464, Incontinentia pigmenti 319612, X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency |
PharmGKBi | PA29777 |
Miscellaneous databases
Pharosi | Q9Y6K9, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4967 |
DrugBanki | DB04998, AGRO100 DB05289, Tarenflurbil |
Genetic variation databases
BioMutai | IKBKG |
DMDMi | 6685695 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000096782 | 1 – 419 | NF-kappa-B essential modulatorAdd BLAST | 419 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 31 | Phosphoserine; by IKKB1 Publication | 1 | |
Modified residuei | 43 | Phosphoserine; by IKKB1 Publication | 1 | |
Disulfide bondi | 54 | Interchain1 Publication | ||
Modified residuei | 68 | Phosphoserine1 Publication | 1 | |
Modified residuei | 85 | Phosphoserine; by ATM1 Publication | 1 | |
Cross-linki | 111 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 139 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 143 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 226 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 246 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 264 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | ||
Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate2 Publications | ||
Cross-linki | 283 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 285 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)3 Publications | ||
Cross-linki | 292 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 302 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 309 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | ||
Cross-linki | 309 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate4 Publications | ||
Cross-linki | 321 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 325 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 326 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Disulfide bondi | 347 | Interchain1 Publication | ||
Modified residuei | 376 | Phosphoserine; by IKKB1 Publication | 1 | |
Modified residuei | 387 | PhosphoserineCombined sources1 Publication | 1 | |
Cross-linki | 399 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
CPTACi | CPTAC-1044 CPTAC-806 |
EPDi | Q9Y6K9 |
jPOSTi | Q9Y6K9 |
MassIVEi | Q9Y6K9 |
PaxDbi | Q9Y6K9 |
PeptideAtlasi | Q9Y6K9 |
PRIDEi | Q9Y6K9 |
ProteomicsDBi | 86716 [Q9Y6K9-1] 86717 [Q9Y6K9-2] 86718 [Q9Y6K9-3] |
PTM databases
iPTMneti | Q9Y6K9 |
PhosphoSitePlusi | Q9Y6K9 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000269335, Expressed in blood and 114 other tissues |
ExpressionAtlasi | Q9Y6K9, baseline and differential |
Genevisiblei | Q9Y6K9, HS |
Organism-specific databases
HPAi | ENSG00000269335, Tissue enhanced (blood) |
Interactioni
Subunit structurei
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. 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 PIDD1.
Interacts with ATM; the complex is exported from the nucleus.
Interacts with TRAF6.
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 NLRP10.
Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989).
Interacts with USP10; this interaction increases in response to DNA damage (PubMed:25861989).
Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989).
Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (PubMed:26334375).
Interacts with TRIM29; this interaction induces IKBKG/NEMO ubiquitination and proteolytic degradation (PubMed:27695001).
Interacts with TRIM13; this interaction leads to IKBKG/NEMO ubiquitination (PubMed:25152375).
Interacts with ARFIP2 (PubMed:26296658).
Interacts with RIPK1 (By similarity).
By similarity22 Publications(Microbial infection) Interacts with Molluscum contagiosum virus protein MC005; this interaction inhibits NF-kappa-B activation.
1 Publication(Microbial infection) Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG.
2 Publications(Microbial infection) 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.
1 PublicationBinary interactionsi
Q9Y6K9
GO - Molecular functioni
- identical protein binding Source: IntAct
- K63-linked polyubiquitin modification-dependent protein binding Source: GO_Central
- linear polyubiquitin binding Source: ParkinsonsUK-UCL
- peroxisome proliferator activated receptor binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- transferrin receptor binding Source: ARUK-UCL
- ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 114089, 396 interactors |
ComplexPortali | CPX-3269, IkappaB kinase complex |
CORUMi | Q9Y6K9 |
DIPi | DIP-27528N |
IntActi | Q9Y6K9, 242 interactors |
MINTi | Q9Y6K9 |
STRINGi | 9606.ENSP00000483825 |
Chemistry databases
BindingDBi | Q9Y6K9 |
Miscellaneous databases
RNActi | Q9Y6K9, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | Q9Y6K9 |
SMRi | Q9Y6K9 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9Y6K9 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 44 – 111 | Interaction with CHUK/IKBKBAdd BLAST | 68 | |
Regioni | 150 – 257 | Interaction with TANKAdd BLAST | 108 | |
Regioni | 242 – 350 | Ubiquitin-binding (UBD)Add BLAST | 109 | |
Regioni | 246 – 365 | Self-associationAdd BLAST | 120 | |
Regioni | 251 – 419 | Required for interaction with TNFAIP3Add BLAST | 169 | |
Regioni | 322 – 343 | Leucine-zipperSequence analysisAdd BLAST | 22 | |
Regioni | 382 – 419 | Interaction with CYLD1 PublicationAdd BLAST | 38 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 49 – 356 | Sequence analysisAdd BLAST | 308 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 389 – 419 | CCHC NOA-typePROSITE-ProRule annotationAdd BLAST | 31 |
Keywords - Domaini
Coiled coil, Zinc-fingerPhylogenomic databases
eggNOGi | ENOG502R4ZD, Eukaryota |
GeneTreei | ENSGT00530000063808 |
InParanoidi | Q9Y6K9 |
OMAi | AHPSFHL |
OrthoDBi | 745047at2759 |
PhylomeDBi | Q9Y6K9 |
TreeFami | TF326608 |
Family and domain databases
DisProti | DP02269 |
InterProi | View protein in InterPro IPR032419, CC2-LZ_dom IPR021063, NEMO_N IPR034735, NEMO_ZF |
Pfami | View protein in Pfam PF16516, CC2-LZ, 1 hit PF11577, NEMO, 1 hit |
PROSITEi | View protein in PROSITE PS51801, ZF_CCHC_NOA, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET
60 70 80 90 100
LQRCLEENQE LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA
110 120 130 140 150
RKLVERLGLE KLDLKRQKEQ ALREVEHLKR CQQQMAEDKA SVKAQVTSLL
160 170 180 190 200
GELQESQSRL EAATKECQAL EGRARAASEQ ARQLESEREA LQQQHSVQVD
210 220 230 240 250
QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHIKSSVV
260 270 280 290 300
GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
310 320 330 340 350
LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES
360 370 380 390 400
ARIEDMRKRH VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC
410
QYQAPDMDTL QIHVMECIE
Computationally mapped potential isoform sequencesi
There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087X1B1 | A0A087X1B1_HUMAN | NF-kappa-B essential modulator | IKBKG | 418 | Annotation score: | ||
A0A087X0G7 | A0A087X0G7_HUMAN | NF-kappa-B essential modulator | IKBKG | 411 | Annotation score: | ||
A0A087WUW6 | A0A087WUW6_HUMAN | NF-kappa-B essential modulator | IKBKG | 412 | Annotation score: | ||
C9J2V2 | C9J2V2_HUMAN | NF-kappa-B essential modulator | IKBKG | 195 | Annotation score: | ||
C9JCG6 | C9JCG6_HUMAN | NF-kappa-B essential modulator | IKBKG | 138 | Annotation score: | ||
C9JH59 | C9JH59_HUMAN | NF-kappa-B essential modulator | IKBKG | 172 | Annotation score: | ||
A0A087X1K7 | A0A087X1K7_HUMAN | NF-kappa-B essential modulator | IKBKG | 181 | Annotation score: | ||
C9JN51 | C9JN51_HUMAN | NF-kappa-B essential modulator | IKBKG | 250 | Annotation score: | ||
A0A087WV30 | A0A087WV30_HUMAN | NF-kappa-B essential modulator | IKBKG | 115 | Annotation score: | ||
A0A087WWQ9 | A0A087WWQ9_HUMAN | NF-kappa-B essential modulator | IKBKG | 48 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 341 | S → R in AAD12183 (PubMed:9927690).Curated | 1 | |
Sequence conflicti | 387 | S → R in AAD12183 (PubMed:9927690).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026491 | 57 | E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar. | 1 | |
Natural variantiVAR_026492 | 90 | Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication | 1 | |
Natural variantiVAR_026493 | 113 | D → N1 PublicationCorresponds to variant dbSNP:rs179363896EnsemblClinVar. | 1 | |
Natural variantiVAR_026494 | 123 | R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar. | 1 | |
Natural variantiVAR_026495 | 153 | L → R in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar. | 1 | |
Natural variantiVAR_072603 | 170 | L → P in IP. 1 Publication | 1 | |
Natural variantiVAR_031958 | 173 | R → G in IMD33. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar. | 1 | |
Natural variantiVAR_072604 | 173 | R → Q in IP. 1 PublicationCorresponds to variant dbSNP:rs1057520292EnsemblClinVar. | 1 | |
Natural variantiVAR_011320 | 175 | R → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar. | 1 | |
Natural variantiVAR_072605 | 183 | Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl. | 1 | |
Natural variantiVAR_011321 | 227 | L → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar. | 1 | |
Natural variantiVAR_011322 | 288 | A → G in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar. | 1 | |
Natural variantiVAR_011323 | 311 | D → N in EDAID1; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar. | 1 | |
Natural variantiVAR_072606 | 314 | A → P in IP. 1 Publication | 1 | |
Natural variantiVAR_031959 | 315 | E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs137853331EnsemblClinVar. | 1 | |
Natural variantiVAR_031960 | 319 | R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar. | 1 | |
Natural variantiVAR_072607 | 322 | L → P in IP. 1 Publication | 1 | |
Natural variantiVAR_042666 | 323 | A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs179363865EnsemblClinVar. | 1 | |
Natural variantiVAR_011324 | 406 | D → V in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar. | 1 | |
Natural variantiVAR_009182 | 407 | M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar. | 1 | |
Natural variantiVAR_072608 | 413 | H → Y in IP. 1 Publication | 1 | |
Natural variantiVAR_011325 | 417 | C → F in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar. | 1 | |
Natural variantiVAR_011326 | 417 | C → R in EDAID1; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar. | 1 | |
Natural variantiVAR_026496 | 417 | C → Y in IMD33. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_041000 | 1 | M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2. 1 Publication | 1 | |
Alternative sequenceiVSP_041001 | 174 – 224 | Missing in isoform 3. 1 PublicationAdd BLAST | 51 | |
Alternative sequenceiVSP_041002 | 257 – 304 | Missing in isoform 3. 1 PublicationAdd BLAST | 48 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF062089 mRNA Translation: AAD12183.1 AF091453 mRNA Translation: AAD38081.1 AF074382 mRNA Translation: AAC36330.1 AJ271718 Genomic DNA Translation: CAB93146.1 AF261086 mRNA Translation: AAF99679.1 AY114157 mRNA Translation: AAM44073.1 AK000593 mRNA No translation available. BT019621 mRNA Translation: AAV38427.1 AF277315 Genomic DNA Translation: AAL27012.1 BC000299 mRNA Translation: AAH00299.1 BC012114 mRNA Translation: AAH12114.1 BC046922 mRNA Translation: AAH46922.1 BC050612 mRNA Translation: AAH50612.1 |
CCDSi | CCDS14757.1 [Q9Y6K9-1] CCDS48196.1 [Q9Y6K9-2] CCDS48197.1 [Q9Y6K9-3] |
RefSeqi | NP_001093326.2, NM_001099856.4 [Q9Y6K9-2] NP_001093327.1, NM_001099857.2 [Q9Y6K9-1] NP_001138727.1, NM_001145255.2 [Q9Y6K9-3] NP_001308325.1, NM_001321396.1 [Q9Y6K9-1] NP_001308326.1, NM_001321397.1 NP_003630.1, NM_003639.4 [Q9Y6K9-1] |
Genome annotation databases
Ensembli | ENST00000594239; ENSP00000471166; ENSG00000269335 [Q9Y6K9-1] ENST00000611071; ENSP00000479662; ENSG00000269335 [Q9Y6K9-1] ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3] ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2] |
GeneIDi | 8517 |
KEGGi | hsa:8517 |
UCSCi | uc033fbu.1, human [Q9Y6K9-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
IKBKGbase IKBKG mutation db |
Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG) Leiden Open Variation Database (LOVD) |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF062089 mRNA Translation: AAD12183.1 AF091453 mRNA Translation: AAD38081.1 AF074382 mRNA Translation: AAC36330.1 AJ271718 Genomic DNA Translation: CAB93146.1 AF261086 mRNA Translation: AAF99679.1 AY114157 mRNA Translation: AAM44073.1 AK000593 mRNA No translation available. BT019621 mRNA Translation: AAV38427.1 AF277315 Genomic DNA Translation: AAL27012.1 BC000299 mRNA Translation: AAH00299.1 BC012114 mRNA Translation: AAH12114.1 BC046922 mRNA Translation: AAH46922.1 BC050612 mRNA Translation: AAH50612.1 |
CCDSi | CCDS14757.1 [Q9Y6K9-1] CCDS48196.1 [Q9Y6K9-2] CCDS48197.1 [Q9Y6K9-3] |
RefSeqi | NP_001093326.2, NM_001099856.4 [Q9Y6K9-2] NP_001093327.1, NM_001099857.2 [Q9Y6K9-1] NP_001138727.1, NM_001145255.2 [Q9Y6K9-3] NP_001308325.1, NM_001321396.1 [Q9Y6K9-1] NP_001308326.1, NM_001321397.1 NP_003630.1, NM_003639.4 [Q9Y6K9-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2JVX | NMR | - | A | 394-419 | [»] | |
2JVY | NMR | - | A | 394-419 | [»] | |
3BRT | X-ray | 2.25 | B/D | 44-111 | [»] | |
3BRV | X-ray | 2.20 | B/D | 44-111 | [»] | |
3CL3 | X-ray | 3.20 | D/E | 150-272 | [»] | |
3FX0 | X-ray | 3.20 | A/B | 246-337 | [»] | |
4BWN | X-ray | 2.27 | A/B | 258-344 | [»] | |
5AAY | NMR | - | A | 392-419 | [»] | |
5LDE | X-ray | 3.38 | R/S | 230-249 | [»] | |
6MI3 | X-ray | 1.78 | A/B | 38-129 | [»] | |
6MI4 | X-ray | 2.50 | A/B | 38-129 | [»] | |
BMRBi | Q9Y6K9 | |||||
SMRi | Q9Y6K9 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114089, 396 interactors |
ComplexPortali | CPX-3269, IkappaB kinase complex |
CORUMi | Q9Y6K9 |
DIPi | DIP-27528N |
IntActi | Q9Y6K9, 242 interactors |
MINTi | Q9Y6K9 |
STRINGi | 9606.ENSP00000483825 |
Chemistry databases
BindingDBi | Q9Y6K9 |
ChEMBLi | CHEMBL4967 |
DrugBanki | DB04998, AGRO100 DB05289, Tarenflurbil |
Protein family/group databases
MoonDBi | Q9Y6K9, Predicted |
PTM databases
iPTMneti | Q9Y6K9 |
PhosphoSitePlusi | Q9Y6K9 |
Genetic variation databases
BioMutai | IKBKG |
DMDMi | 6685695 |
Proteomic databases
CPTACi | CPTAC-1044 CPTAC-806 |
EPDi | Q9Y6K9 |
jPOSTi | Q9Y6K9 |
MassIVEi | Q9Y6K9 |
PaxDbi | Q9Y6K9 |
PeptideAtlasi | Q9Y6K9 |
PRIDEi | Q9Y6K9 |
ProteomicsDBi | 86716 [Q9Y6K9-1] 86717 [Q9Y6K9-2] 86718 [Q9Y6K9-3] |
Protocols and materials databases
Antibodypediai | 73338, 1214 antibodies |
DNASUi | 8517 |
Genome annotation databases
Ensembli | ENST00000594239; ENSP00000471166; ENSG00000269335 [Q9Y6K9-1] ENST00000611071; ENSP00000479662; ENSG00000269335 [Q9Y6K9-1] ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3] ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2] |
GeneIDi | 8517 |
KEGGi | hsa:8517 |
UCSCi | uc033fbu.1, human [Q9Y6K9-1] |
Organism-specific databases
CTDi | 8517 |
DisGeNETi | 8517 |
GeneCardsi | IKBKG |
GeneReviewsi | IKBKG |
HGNCi | HGNC:5961, IKBKG |
HPAi | ENSG00000269335, Tissue enhanced (blood) |
MalaCardsi | IKBKG |
MIMi | 300248, gene 300291, phenotype 300636, phenotype 308300, phenotype |
neXtProti | NX_Q9Y6K9 |
OpenTargetsi | ENSG00000269335 |
Orphaneti | 69088, Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome 98813, Hypohidrotic ectodermal dysplasia with immunodeficiency 464, Incontinentia pigmenti 319612, X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency |
PharmGKBi | PA29777 |
VEuPathDBi | HostDB:ENSG00000269335.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502R4ZD, Eukaryota |
GeneTreei | ENSGT00530000063808 |
InParanoidi | Q9Y6K9 |
OMAi | AHPSFHL |
OrthoDBi | 745047at2759 |
PhylomeDBi | Q9Y6K9 |
TreeFami | TF326608 |
Enzyme and pathway databases
PathwayCommonsi | Q9Y6K9 |
Reactomei | R-HSA-1169091, Activation of NF-kappaB in B cells R-HSA-1236974, ER-Phagosome pathway R-HSA-168638, NOD1/2 Signaling Pathway R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment R-HSA-1810476, RIP-mediated NFkB activation via ZBP1 R-HSA-202424, Downstream TCR signaling R-HSA-2871837, FCERI mediated NF-kB activation R-HSA-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-HSA-450302, activated TAK1 mediates p38 MAPK activation R-HSA-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 R-HSA-4755510, SUMOylation of immune response proteins R-HSA-5357905, Regulation of TNFR1 signaling R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway R-HSA-5602636, IKBKB deficiency causes SCID R-HSA-5603027, IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) R-HSA-5603029, IkBA variant leads to EDA-ID R-HSA-5607764, CLEC7A (Dectin-1) signaling R-HSA-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-9020702, Interleukin-1 signaling R-HSA-933542, TRAF6 mediated NF-kB activation R-HSA-933543, NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-937039, IRAK1 recruits IKK complex R-HSA-937041, IKK complex recruitment mediated by RIP1 R-HSA-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
SABIO-RKi | Q9Y6K9 |
SIGNORi | Q9Y6K9 |
Miscellaneous databases
BioGRID-ORCSi | 8517, 44 hits in 501 CRISPR screens |
ChiTaRSi | IKBKG, human |
EvolutionaryTracei | Q9Y6K9 |
GeneWikii | IKBKG |
GenomeRNAii | 8517 |
Pharosi | Q9Y6K9, Tbio |
PROi | PR:Q9Y6K9 |
RNActi | Q9Y6K9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000269335, Expressed in blood and 114 other tissues |
ExpressionAtlasi | Q9Y6K9, baseline and differential |
Genevisiblei | Q9Y6K9, HS |
Family and domain databases
DisProti | DP02269 |
InterProi | View protein in InterPro IPR032419, CC2-LZ_dom IPR021063, NEMO_N IPR034735, NEMO_ZF |
Pfami | View protein in Pfam PF16516, CC2-LZ, 1 hit PF11577, NEMO, 1 hit |
PROSITEi | View protein in PROSITE PS51801, ZF_CCHC_NOA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NEMO_HUMAN | |
Accessioni | Q9Y6K9Primary (citable) accession number: Q9Y6K9 Secondary accession number(s): Q7LBY6, Q7Z7F1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | May 30, 2000 | |
Last modified: | February 10, 2021 | |
This is version 227 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants