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UniProtKB - Q9Y6K9 (NEMO_HUMAN)

Protein

NF-kappa-B essential modulator

Gene

IKBKG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processDNA damage, Host-virus interaction, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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-RKiQ9Y6K9
SIGNORiQ9Y6K9

Protein family/group databases

MoonDBiQ9Y6K9 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
NF-kappa-B essential modulator
Short 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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000269335.5
HGNCiHGNC:5961 IKBKG
MIMi300248 gene
neXtProtiNX_Q9Y6K9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ectodermal dysplasia, anhidrotic, with immunodeficiency X-linked (EDAID)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300291
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026495153L → R in EDAID. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar.1
Natural variantiVAR_011320175R → P in EDAID. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar.1
Natural variantiVAR_011321227L → P in EDAID. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar.1
Natural variantiVAR_011322288A → G in EDAID. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar.1
Natural variantiVAR_011323311D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar.1
Natural variantiVAR_011324406D → V in EDAID. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar.1
Natural variantiVAR_011325417C → F in EDAID. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Natural variantiVAR_011326417C → R in EDAID; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar.1
Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema (OLEDAID)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300301
Immunodeficiency, NEMO-related, without anhidrotic ectodermal dysplasia (NEMOID)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients manifest immunodeficiency not associated with other abnormalities, and resulting in increased susceptibility to infections. Patients suffer from multiple episodes of infectious diseases.
See also OMIM:300584
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026496417C → Y in NEMOID. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Immunodeficiency 33 (IMD33)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:300636
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031959315E → 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_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar.1
Recurrent isolated invasive pneumococcal disease 2 (IPD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRecurrent 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.
See also OMIM:300640
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031958173R → G in IPD2. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar.1
Incontinentia pigmenti (IP)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:308300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_072604173R → Q in IP. 1 Publication1
Natural variantiVAR_072605183Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl.1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → 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_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68S → A: Increases formation of homodimers. 1 Publication1
Mutagenesisi68S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. 1 Publication1
Mutagenesisi85S → A: Decreases ubiquitination and abolishes nuclear export. 1 Publication1
Mutagenesisi115K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi224K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi277K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. 1 Publication1
Mutagenesisi285K → R: Important decrease in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi296E → A: No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 1 Publication1
Mutagenesisi300V → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi301L → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi304Q → A: Complete loss of cleavage by HAV protease 3c. 1 Publication1
Mutagenesisi304Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi307I → N: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi308Y → A: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi309K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. 1 Publication1
Mutagenesisi312F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. 2 Publications1
Mutagenesisi312F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). 2 Publications1
Mutagenesisi312F → Y: Impairs tandem ubiquitin binding. 2 Publications1
Mutagenesisi313Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi315E → Q: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi317Q → A or W: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi323A → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi329L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336. 2 Publications1
Mutagenesisi329L → P: Abolishes binding to polyubiquitin. 2 Publications1
Mutagenesisi336L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. 1 Publication1
Mutagenesisi399K → 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 Publications1
Mutagenesisi414V → S: Abolishes binding to polyubiquitin. 1 Publication1
Mutagenesisi415M → S: Impairs binding to polyubiquitin. 1 Publication1

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia, Osteopetrosis

Organism-specific databases

DisGeNETi8517
GeneReviewsiIKBKG
MalaCardsiIKBKG
MIMi300291 phenotype
300301 phenotype
300584 phenotype
300636 phenotype
300640 phenotype
308300 phenotype
OpenTargetsiENSG00000269335
Orphaneti69088 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
PharmGKBiPA29777

Chemistry databases

ChEMBLiCHEMBL4967
DrugBankiDB04998 AGRO100
DB05289 MPC-7869

Polymorphism and mutation databases

DMDMi6685695

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967821 – 419NF-kappa-B essential modulatorAdd BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31Phosphoserine; by IKKB1 Publication1
Modified residuei43Phosphoserine; by IKKB1 Publication1
Disulfide bondi54Interchain1 Publication
Modified residuei68Phosphoserine1 Publication1
Modified residuei85Phosphoserine; by ATM1 Publication1
Cross-linki111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate2 Publications
Cross-linki283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)3 Publications
Cross-linki292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate4 Publications
Cross-linki321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Disulfide bondi347Interchain1 Publication
Modified residuei376Phosphoserine; by IKKB1 Publication1
Modified residuei387PhosphoserineCombined sources1 Publication1
Cross-linki399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.1 Publication
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. 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. Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage (PubMed:25861989).7 Publications
Sumoylated 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.5 Publications
Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.1 Publication
(Microbial infection) Cleaved by hepatitis A virus (HAV) protease 3C allowing the virus to disrupt the host innate immune signaling.1 Publication
(Microbial infection) 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.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y6K9
PaxDbiQ9Y6K9
PeptideAtlasiQ9Y6K9
PRIDEiQ9Y6K9
ProteomicsDBi86716
86717 [Q9Y6K9-2]
86718 [Q9Y6K9-3]

PTM databases

iPTMnetiQ9Y6K9
PhosphoSitePlusiQ9Y6K9

Expressioni

Tissue specificityi

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Gene expression databases

BgeeiENSG00000269335 Expressed in 90 organ(s), highest expression level in blood
CleanExiHS_IKBKG
ExpressionAtlasiQ9Y6K9 baseline and differential
GenevisibleiQ9Y6K9 HS

Organism-specific databases

HPAiCAB010373
HPA000426

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).21 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 Publication

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi114089, 331 interactors
ComplexPortaliCPX-3269 IkappaB kinase complex
CORUMiQ9Y6K9
DIPiDIP-27528N
IntActiQ9Y6K9, 198 interactors
MINTiQ9Y6K9
STRINGi9606.ENSP00000358622

Chemistry databases

BindingDBiQ9Y6K9

Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y6K9
SMRiQ9Y6K9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6K9

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni44 – 111Interaction with CHUK/IKBKBAdd BLAST68
Regioni150 – 257Interaction with TANKAdd BLAST108
Regioni242 – 350Ubiquitin-binding (UBD)Add BLAST109
Regioni246 – 365Self-associationAdd BLAST120
Regioni251 – 419Required for interaction with TNFAIP3Add BLAST169
Regioni322 – 343Leucine-zipperSequence analysisAdd BLAST22
Regioni382 – 419Interaction with CYLD1 PublicationAdd BLAST38

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili49 – 356Sequence analysisAdd BLAST308

Domaini

The leucine-zipper domain and the CCHC NOA-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3.2 Publications

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJBJ Eukaryota
ENOG410Y1FG LUCA
GeneTreeiENSGT00530000063808
HOGENOMiHOG000293233
HOVERGENiHBG000417
InParanoidiQ9Y6K9
KOiK07210
OMAiEFLMQKF
OrthoDBiEOG091G0576
PhylomeDBiQ9Y6K9
TreeFamiTF326608

Family and domain databases

InterProiView protein in InterPro
IPR032419 CC2-LZ_dom
IPR021063 NEMO_N
IPR034735 NEMO_ZF
PfamiView protein in Pfam
PF16516 CC2-LZ, 1 hit
PF11577 NEMO, 1 hit
PROSITEiView protein in PROSITE
PS51801 ZF_CCHC_NOA, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y6K9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:419
Mass (Da):48,198
Last modified:May 30, 2000 - v2
Checksum:i322D1037881447FF
GO
Isoform 2 (identifier: Q9Y6K9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MALVIQVGKLRPREVRTPQTINPSLFPSLPVKLSSIIEVPSGGERCCSRRTLVYKARAFWKGAPLPCWM

Show »
Length:487
Mass (Da):55,787
Checksum:i7A39E991E0013A73
GO
Isoform 3 (identifier: Q9Y6K9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     174-224: Missing.
     257-304: Missing.

Show »
Length:320
Mass (Da):36,953
Checksum:i3BEF2487C4446725
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X1B1A0A087X1B1_HUMAN
NF-kappa-B essential modulator
IKBKG
418Annotation score:
A0A087X0G7A0A087X0G7_HUMAN
NF-kappa-B essential modulator
IKBKG
411Annotation score:
A0A087WUW6A0A087WUW6_HUMAN
NF-kappa-B essential modulator
IKBKG
412Annotation score:
C9J2V2C9J2V2_HUMAN
NF-kappa-B essential modulator
IKBKG
195Annotation score:
C9JCG6C9JCG6_HUMAN
NF-kappa-B essential modulator
IKBKG
138Annotation score:
C9JH59C9JH59_HUMAN
NF-kappa-B essential modulator
IKBKG
172Annotation score:
C9JN51C9JN51_HUMAN
NF-kappa-B essential modulator
IKBKG
250Annotation score:
A0A087X1K7A0A087X1K7_HUMAN
NF-kappa-B essential modulator
IKBKG
181Annotation score:
A0A087WV30A0A087WV30_HUMAN
NF-kappa-B essential modulator
IKBKG
115Annotation score:
A0A087WWQ9A0A087WWQ9_HUMAN
NF-kappa-B essential modulator
IKBKG
48Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti341S → R in AAD12183 (PubMed:9927690).Curated1
Sequence conflicti387S → R in AAD12183 (PubMed:9927690).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026493113D → N1 PublicationCorresponds to variant dbSNP:rs179363896EnsemblClinVar.1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar.1
Natural variantiVAR_026495153L → R in EDAID. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_031958173R → G in IPD2. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar.1
Natural variantiVAR_072604173R → Q in IP. 1 Publication1
Natural variantiVAR_011320175R → P in EDAID. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar.1
Natural variantiVAR_072605183Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl.1
Natural variantiVAR_011321227L → P in EDAID. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar.1
Natural variantiVAR_011322288A → G in EDAID. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar.1
Natural variantiVAR_011323311D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar.1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_031959315E → 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_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar.1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → 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_011324406D → V in EDAID. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar.1
Natural variantiVAR_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1
Natural variantiVAR_011325417C → F in EDAID. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Natural variantiVAR_011326417C → R in EDAID; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar.1
Natural variantiVAR_026496417C → Y in NEMOID. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0410001M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2. 1 Publication1
Alternative sequenceiVSP_041001174 – 224Missing in isoform 3. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_041002257 – 304Missing in isoform 3. 1 PublicationAdd BLAST48

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
CCDSiCCDS14757.1 [Q9Y6K9-1]
CCDS48196.1 [Q9Y6K9-2]
CCDS48197.1 [Q9Y6K9-3]
RefSeqiNP_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]
UniGeneiHs.43505

Genome annotation databases

EnsembliENST00000594239; ENSP00000471166; ENSG00000269335 [Q9Y6K9-1]
ENST00000611071; ENSP00000479662; ENSG00000269335 [Q9Y6K9-1]
ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2]
GeneIDi8517
KEGGihsa:8517
UCSCiuc033fbu.1 human [Q9Y6K9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
CCDSiCCDS14757.1 [Q9Y6K9-1]
CCDS48196.1 [Q9Y6K9-2]
CCDS48197.1 [Q9Y6K9-3]
RefSeqiNP_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]
UniGeneiHs.43505

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JVXNMR-A394-419[»]
2JVYNMR-A394-419[»]
3BRTX-ray2.25B/D44-111[»]
3BRVX-ray2.20B/D44-111[»]
3CL3X-ray3.20D/E150-272[»]
3FX0X-ray3.20A/B246-337[»]
4BWNX-ray2.27A/B258-344[»]
5AAYNMR-A392-419[»]
5LDEX-ray3.38R/S230-249[»]
ProteinModelPortaliQ9Y6K9
SMRiQ9Y6K9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114089, 331 interactors
ComplexPortaliCPX-3269 IkappaB kinase complex
CORUMiQ9Y6K9
DIPiDIP-27528N
IntActiQ9Y6K9, 198 interactors
MINTiQ9Y6K9
STRINGi9606.ENSP00000358622

Chemistry databases

BindingDBiQ9Y6K9
ChEMBLiCHEMBL4967
DrugBankiDB04998 AGRO100
DB05289 MPC-7869

Protein family/group databases

MoonDBiQ9Y6K9 Predicted

PTM databases

iPTMnetiQ9Y6K9
PhosphoSitePlusiQ9Y6K9

Polymorphism and mutation databases

DMDMi6685695

Proteomic databases

EPDiQ9Y6K9
PaxDbiQ9Y6K9
PeptideAtlasiQ9Y6K9
PRIDEiQ9Y6K9
ProteomicsDBi86716
86717 [Q9Y6K9-2]
86718 [Q9Y6K9-3]

Protocols and materials databases

DNASUi8517
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000594239; ENSP00000471166; ENSG00000269335 [Q9Y6K9-1]
ENST00000611071; ENSP00000479662; ENSG00000269335 [Q9Y6K9-1]
ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2]
GeneIDi8517
KEGGihsa:8517
UCSCiuc033fbu.1 human [Q9Y6K9-1]

Organism-specific databases

CTDi8517
DisGeNETi8517
EuPathDBiHostDB:ENSG00000269335.5
GeneCardsiIKBKG
GeneReviewsiIKBKG
H-InvDBiHIX0203333
HGNCiHGNC:5961 IKBKG
HPAiCAB010373
HPA000426
MalaCardsiIKBKG
MIMi300248 gene
300291 phenotype
300301 phenotype
300584 phenotype
300636 phenotype
300640 phenotype
308300 phenotype
neXtProtiNX_Q9Y6K9
OpenTargetsiENSG00000269335
Orphaneti69088 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
PharmGKBiPA29777
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJBJ Eukaryota
ENOG410Y1FG LUCA
GeneTreeiENSGT00530000063808
HOGENOMiHOG000293233
HOVERGENiHBG000417
InParanoidiQ9Y6K9
KOiK07210
OMAiEFLMQKF
OrthoDBiEOG091G0576
PhylomeDBiQ9Y6K9
TreeFamiTF326608

Enzyme and pathway databases

ReactomeiR-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-RKiQ9Y6K9
SIGNORiQ9Y6K9

Miscellaneous databases

ChiTaRSiIKBKG human
EvolutionaryTraceiQ9Y6K9
GeneWikiiIKBKG
GenomeRNAii8517
PROiPR:Q9Y6K9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000269335 Expressed in 90 organ(s), highest expression level in blood
CleanExiHS_IKBKG
ExpressionAtlasiQ9Y6K9 baseline and differential
GenevisibleiQ9Y6K9 HS

Family and domain databases

InterProiView protein in InterPro
IPR032419 CC2-LZ_dom
IPR021063 NEMO_N
IPR034735 NEMO_ZF
PfamiView protein in Pfam
PF16516 CC2-LZ, 1 hit
PF11577 NEMO, 1 hit
PROSITEiView protein in PROSITE
PS51801 ZF_CCHC_NOA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNEMO_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6K9
Secondary accession number(s): Q7LBY6, Q7Z7F1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: November 7, 2018
This is version 209 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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