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Protein

NF-kappa-B essential modulator

Gene

IKBKG

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. 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 (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri396 – 41722C2HC-typeAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-BTA-1169091. Activation of NF-kappaB in B cells.
R-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-1810476. RIP-mediated NFkB activation via ZBP1.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-450302. activated TAK1 mediates p38 MAPK activation.
R-BTA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-BTA-933542. TRAF6 mediated NF-kB activation.
R-BTA-937039. IRAK1 recruits IKK complex.
R-BTA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.

Names & Taxonomyi

Protein namesi
Recommended name:
NF-kappa-B essential modulator
Short name:
NEMO
Alternative name(s):
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:NEMO
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome X

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 419419NF-kappa-B essential modulatorPRO_0000269196Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei31 – 311Phosphoserine; by IKKBBy similarity
Modified residuei43 – 431Phosphoserine; by IKKBBy similarity
Disulfide bondi54 – 54InterchainBy similarity
Modified residuei68 – 681PhosphoserineBy similarity
Cross-linki111 – 111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki139 – 139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki143 – 143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki226 – 226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki246 – 246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki264 – 264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki277 – 277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki277 – 277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki283 – 283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki285 – 285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki292 – 292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki302 – 302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki309 – 309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki309 – 309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Cross-linki321 – 321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki325 – 325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki326 – 326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Disulfide bondi347 – 347InterchainBy similarity
Modified residuei376 – 3761Phosphoserine; by IKKBBy similarity
Modified residuei387 – 3871PhosphoserineBy similarity
Cross-linki399 – 399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.By similarity
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 (By similarity).By similarity
Sumoylated on Lys-277 and Lys-309 with SUMO1.By similarity
Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.By similarity

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ95KU9.
PRIDEiQ95KU9.

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 LRDD. 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. Interacts with NLRP10 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi159166. 4 interactions.
STRINGi9913.ENSBTAP00000008224.

Structurei

3D structure databases

ProteinModelPortaliQ95KU9.
SMRiQ95KU9. Positions 49-109, 196-253, 394-419.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni44 – 11168Interaction with CHUK/IKBKBBy similarityAdd
BLAST
Regioni150 – 257108Interaction with TANKBy similarityAdd
BLAST
Regioni242 – 350109Ubiquitin-binding (UBD)Add
BLAST
Regioni246 – 365120Self-associationBy similarityAdd
BLAST
Regioni251 – 419169Required for interaction with TNFAIP3By similarityAdd
BLAST
Regioni322 – 34322Leucine-zipperSequence analysisAdd
BLAST
Regioni382 – 41938Interaction with CYLDBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili49 – 353305Sequence analysisAdd
BLAST

Domaini

The leucine-zipper domain and the C2HC-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3.By similarity

Sequence similaritiesi

Contains 1 C2HC-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri396 – 41722C2HC-typeAdd
BLAST

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJBJ. Eukaryota.
ENOG410Y1FG. LUCA.
GeneTreeiENSGT00530000063808.
HOGENOMiHOG000293233.
HOVERGENiHBG000417.
InParanoidiQ95KU9.
KOiK07210.
OMAiEFLMQKF.
OrthoDBiEOG7D2FD7.
TreeFamiTF326608.

Family and domain databases

InterProiIPR032419. CC2-LZ_dom.
IPR021063. NEMO_N.
[Graphical view]
PfamiPF16516. CC2-LZ. 1 hit.
PF11577. NEMO. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q95KU9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRPPWKSPL CEMVQPSGSP AGDQDMLGEE SSLGKPAMLH VPSEQGTPET
60 70 80 90 100
FQRCLEENQE LRDAIRQSNQ MLRERCEELQ HFQGNQREEK AFLMQKFQEA
110 120 130 140 150
RDLVVRLSLE KRELRQQREQ ALKEVERLKT CQQQMAEDKA SVKAQVTSLL
160 170 180 190 200
GELQESQSRL EAATKERQAL ESRARVASEK ARQLESEREA LEQRHSVQVD
210 220 230 240 250
QLVLQNESME AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHMKSSMV
260 270 280 290 300
SSERNRGLQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
310 320 330 340 350
LKAQADIYKA DFQAERQARE KLAEKKEFLQ EQLEQLQREY SRLKTSCQES
360 370 380 390 400
ARIEDMRKRH VEVSQPPLAP GPAHHSFHLN PSSQRRSPPD EPPKFCCPKC
410
QYQAPDIDTL QIHVMECIE
Length:419
Mass (Da):48,570
Last modified:December 1, 2001 - v1
Checksum:i95DBC093DC464F78
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti211 – 2111A → T in AAX08770 (PubMed:16305752).Curated
Sequence conflicti262 – 2654DLKQ → ISA in AAX08857 (PubMed:16305752).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414557 mRNA. Translation: CAC93688.1.
BT020840 mRNA. Translation: AAX08857.1.
BT020753 mRNA. Translation: AAX08770.1.
BT020767 mRNA. Translation: AAX08784.1.
BT020872 mRNA. Translation: AAX08889.1.
BC133306 mRNA. Translation: AAI33307.1.
RefSeqiNP_776779.1. NM_174354.3.
XP_005227784.1. XM_005227727.3.
XP_005227785.1. XM_005227728.3.
XP_005227786.1. XM_005227729.3.
XP_015316989.1. XM_015461503.1.
UniGeneiBt.98727.

Genome annotation databases

EnsembliENSBTAT00000008224; ENSBTAP00000008224; ENSBTAG00000006268.
GeneIDi281855.
KEGGibta:281855.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ414557 mRNA. Translation: CAC93688.1.
BT020840 mRNA. Translation: AAX08857.1.
BT020753 mRNA. Translation: AAX08770.1.
BT020767 mRNA. Translation: AAX08784.1.
BT020872 mRNA. Translation: AAX08889.1.
BC133306 mRNA. Translation: AAI33307.1.
RefSeqiNP_776779.1. NM_174354.3.
XP_005227784.1. XM_005227727.3.
XP_005227785.1. XM_005227728.3.
XP_005227786.1. XM_005227729.3.
XP_015316989.1. XM_015461503.1.
UniGeneiBt.98727.

3D structure databases

ProteinModelPortaliQ95KU9.
SMRiQ95KU9. Positions 49-109, 196-253, 394-419.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159166. 4 interactions.
STRINGi9913.ENSBTAP00000008224.

Proteomic databases

PaxDbiQ95KU9.
PRIDEiQ95KU9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000008224; ENSBTAP00000008224; ENSBTAG00000006268.
GeneIDi281855.
KEGGibta:281855.

Organism-specific databases

CTDi8517.

Phylogenomic databases

eggNOGiENOG410IJBJ. Eukaryota.
ENOG410Y1FG. LUCA.
GeneTreeiENSGT00530000063808.
HOGENOMiHOG000293233.
HOVERGENiHBG000417.
InParanoidiQ95KU9.
KOiK07210.
OMAiEFLMQKF.
OrthoDBiEOG7D2FD7.
TreeFamiTF326608.

Enzyme and pathway databases

ReactomeiR-BTA-1169091. Activation of NF-kappaB in B cells.
R-BTA-168638. NOD1/2 Signaling Pathway.
R-BTA-1810476. RIP-mediated NFkB activation via ZBP1.
R-BTA-202424. Downstream TCR signaling.
R-BTA-2871837. FCERI mediated NF-kB activation.
R-BTA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-BTA-446652. Interleukin-1 signaling.
R-BTA-450302. activated TAK1 mediates p38 MAPK activation.
R-BTA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-BTA-5357905. Regulation of TNFR1 signaling.
R-BTA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-BTA-5607764. CLEC7A (Dectin-1) signaling.
R-BTA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-BTA-933542. TRAF6 mediated NF-kB activation.
R-BTA-937039. IRAK1 recruits IKK complex.
R-BTA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.

Family and domain databases

InterProiIPR032419. CC2-LZ_dom.
IPR021063. NEMO_N.
[Graphical view]
PfamiPF16516. CC2-LZ. 1 hit.
PF11577. NEMO. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the regulatory subunit NEMO and their substrate IkappaBalpha."
    Rottenberg S., Schmuckli-Maurer J., Grimm S., Heussler V.T., Dobbelaere D.A.E.
    Gene 299:293-300(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT OF THE IKK COMPLEX.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Fetal skin.

Entry informationi

Entry nameiNEMO_BOVIN
AccessioniPrimary (citable) accession number: Q95KU9
Secondary accession number(s): A2VDM3, Q5E9T0, Q5EA16
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 1, 2001
Last modified: June 8, 2016
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.