UniProtKB - A9QT41 (NEMO_PIG)
NF-kappa-B essential modulator
IKBKG
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 plays a key role in IKK activation by multiple signaling receptor pathways. Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much highr affinity for linear polyubiquitin. 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.
By similaritySites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 349 – 350 | (Microbial infection) Cleavage; by porcine reproductive and respiratory syndrome virus serine protease nsp41 Publication | 2 | |
Metal bindingi | 397 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 400 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 413 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 417 | ZincPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 389 – 419 | CCHC NOA-typePROSITE-ProRule annotationAdd BLAST | 31 |
GO - Molecular functioni
- K63-linked polyubiquitin modification-dependent protein binding Source: UniProtKB
- kinase activity Source: UniProtKB-KW
- linear polyubiquitin binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- cellular response to DNA damage stimulus Source: UniProtKB-KW
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of T cell receptor signaling pathway Source: UniProtKB
- regulation of I-kappaB kinase/NF-kappaB signaling Source: GO_Central
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | DNA damage, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-SSC-1169091, Activation of NF-kappaB in B cells R-SSC-168638, NOD1/2 Signaling Pathway R-SSC-1810476, RIP-mediated NFkB activation via ZBP1 R-SSC-202424, Downstream TCR signaling R-SSC-2871837, FCERI mediated NF-kB activation R-SSC-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-SSC-5357905, Regulation of TNFR1 signaling R-SSC-5357956, TNFR1-induced NFkappaB signaling pathway R-SSC-5607764, CLEC7A (Dectin-1) signaling R-SSC-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation R-SSC-5689880, Ub-specific processing proteases R-SSC-9020702, Interleukin-1 signaling R-SSC-933542, TRAF6 mediated NF-kB activation R-SSC-937039, IRAK1 recruits IKK complex R-SSC-937041, IKK complex recruitment mediated by RIP1 R-SSC-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
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 |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:89072, IKBKG |
Subcellular locationi
Cytosol
- IkappaB kinase complex Source: GO_Central
Nucleus
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000445606 | 1 – 419 | NF-kappa-B essential modulatorAdd BLAST | 419 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 31 | PhosphoserineBy similarity | 1 | |
Modified residuei | 43 | PhosphoserineBy similarity | 1 | |
Disulfide bondi | 54 | InterchainBy similarity | ||
Modified residuei | 68 | PhosphoserineBy similarity | 1 | |
Modified residuei | 85 | PhosphoserineBy similarity | 1 | |
Cross-linki | 111 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 139 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 143 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 226 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 246 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 264 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity | ||
Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Cross-linki | 283 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 285 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 292 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 302 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Cross-linki | 309 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity | ||
Cross-linki | 309 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity | ||
Cross-linki | 326 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Disulfide bondi | 347 | InterchainBy similarity | ||
Modified residuei | 376 | PhosphoserineBy similarity | 1 | |
Modified residuei | 387 | PhosphoserineBy similarity | 1 | |
Cross-linki | 399 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | A9QT41 |
PRIDEi | A9QT41 |
Expressioni
Gene expression databases
Bgeei | ENSSSCG00000012825, Expressed in adult mammalian kidney and 47 other tissues |
ExpressionAtlasi | A9QT41, baseline and differential |
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 (By similarity). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (By similarity).
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 (via UBAN region) polyubiquitin; binds both 'Lys-63'-linked and linear polyubiquitin, with higher affinity for linear ubiquitin.
Interacts with NLRP10.
Interacts with TANK; this interaction increases in response to DNA damage.
Interacts with USP10; this interaction increases in response to DNA damage.
Interacts with ZC3H12A; this interaction increases in response to DNA damage.
Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation.
Interacts with TRIM29; this interaction induces IKBKG/NEMO ubiquitination and proteolytic degradation.
Interacts with TRIM13; this interaction leads to IKBKG/NEMO ubiquitination.
Interacts with ARFIP2 (By similarity).
Interacts with RIPK1 (By similarity).
Interacts with (ubiquitinated) BCL10; interaction with polyubiquitinated BCL10 via both 'Lys-63'-linked and linear ubiquitin is required for TCR-induced NF-kappa-B activation (By similarity).
Interacts with MARCHF2; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (By similarity).
By similarityGO - Molecular functioni
- K63-linked polyubiquitin modification-dependent protein binding Source: UniProtKB
- linear polyubiquitin binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000031038 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 197 | Required for interaction with and ubiquitination by MARCHF2By similarityAdd BLAST | 197 | |
Regioni | 1 – 46 | DisorderedSequence analysisAdd BLAST | 46 | |
Regioni | 44 – 111 | Interaction with CHUK/IKBKBBy similarityAdd BLAST | 68 | |
Regioni | 150 – 257 | Interaction with TANKBy similarityAdd BLAST | 108 | |
Regioni | 242 – 350 | Ubiquitin-binding (UBAN)By similarityAdd BLAST | 109 | |
Regioni | 246 – 365 | Self-associationBy similarityAdd BLAST | 120 | |
Regioni | 251 – 419 | Required for interaction with TNFAIP3By similarityAdd BLAST | 169 | |
Regioni | 322 – 343 | Leucine-zipperSequence analysisAdd BLAST | 22 | |
Regioni | 363 – 394 | DisorderedSequence analysisAdd BLAST | 32 | |
Regioni | 382 – 419 | Interaction with CYLDBy similarityAdd BLAST | 38 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 100 – 353 | Sequence analysisAdd BLAST | 254 |
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 |
OMAi | KSPLCEM |
TreeFami | TF326608 |
Family and domain databases
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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MSRTPWKSQP CEMVQPSGGP AGDQDVLGEE SSLGKPTMLH LPSEQGAPET
60 70 80 90 100
FQRCLEENQE LRDAIRQSNQ MLRERCEELQ RFQGSQREEK EFLMQKFCEA
110 120 130 140 150
RRLVERLSLE KLELRRQREQ ALQEVELLKT CQQQMAEDKA SVKAQVTSLL
160 170 180 190 200
GELQESQSRL EAATKERQAL ESRVRATSEQ VRQLENEREA LQQQHSVQVD
210 220 230 240 250
QLRLQSQSME AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHIKSSVV
260 270 280 290 300
SSERNRGLQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
310 320 330 340 350
LKAQADIYKA DFQAERQARE QLAERKELLQ EQLEQLQREY SRLKTSCQES
360 370 380 390 400
ARIEDMRKRH VEVSQPTLPP APAHHSFHPA LPSQRRSPPE EPPNFCCPKC
410
QYQAPDMDTL QIHVMECIE
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7GSZ7 | K7GSZ7_PIG | NF-kappa-B essential modulator | IKBKG | 451 | Annotation score: | ||
K7GQV6 | K7GQV6_PIG | NF-kappa-B essential modulator | IKBKG | 320 | Annotation score: | ||
A0A5S8LD69 | A0A5S8LD69_PIG | NF-kappa-B essential modulator | IKBKG | 416 | Annotation score: | ||
A0A5S8LE56 | A0A5S8LE56_PIG | NF-kappa-B essential modulator | IKBKG | 393 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AEMK02000122 Genomic DNA No translation available. EU258760 mRNA Translation: ABX57883.1 |
RefSeqi | NP_001106524.1, NM_001113053.1 XP_005674095.1, XM_005674038.2 XP_005674097.1, XM_005674040.2 XP_013842025.1, XM_013986571.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AEMK02000122 Genomic DNA No translation available. EU258760 mRNA Translation: ABX57883.1 |
RefSeqi | NP_001106524.1, NM_001113053.1 XP_005674095.1, XM_005674038.2 XP_005674097.1, XM_005674040.2 XP_013842025.1, XM_013986571.1 |
3D structure databases
SMRi | A9QT41 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000031038 |
Proteomic databases
PaxDbi | A9QT41 |
PRIDEi | A9QT41 |
Genome annotation databases
Organism-specific databases
CTDi | 8517 |
VGNCi | VGNC:89072, IKBKG |
Phylogenomic databases
eggNOGi | ENOG502R4ZD, Eukaryota |
GeneTreei | ENSGT00530000063808 |
OMAi | KSPLCEM |
TreeFami | TF326608 |
Enzyme and pathway databases
Reactomei | R-SSC-1169091, Activation of NF-kappaB in B cells R-SSC-168638, NOD1/2 Signaling Pathway R-SSC-1810476, RIP-mediated NFkB activation via ZBP1 R-SSC-202424, Downstream TCR signaling R-SSC-2871837, FCERI mediated NF-kB activation R-SSC-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex R-SSC-5357905, Regulation of TNFR1 signaling R-SSC-5357956, TNFR1-induced NFkappaB signaling pathway R-SSC-5607764, CLEC7A (Dectin-1) signaling R-SSC-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation R-SSC-5689880, Ub-specific processing proteases R-SSC-9020702, Interleukin-1 signaling R-SSC-933542, TRAF6 mediated NF-kB activation R-SSC-937039, IRAK1 recruits IKK complex R-SSC-937041, IKK complex recruitment mediated by RIP1 R-SSC-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation |
Gene expression databases
Bgeei | ENSSSCG00000012825, Expressed in adult mammalian kidney and 47 other tissues |
ExpressionAtlasi | A9QT41, baseline and differential |
Family and domain databases
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | NEMO_PIG | |
Accessioni | A9QT41Primary (citable) accession number: A9QT41 Secondary accession number(s): F1RZ22, K7GSV8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 7, 2018 |
Last sequence update: | February 5, 2008 | |
Last modified: | February 23, 2022 | |
This is version 100 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |