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Q6TMG5 (NEMO_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ikbkg
Synonyms:Nemo
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length412 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subunit structure

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 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.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity.

Domain

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

Post-translational modification

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization By similarity.

Polyubiquitinated on Lys-278 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-392 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-270 and Lys-302; 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-270, Lys-278, Lys-285, Lys-295, Lys-302 and Lys-319; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation By similarity.

Sumoylated on Lys-270 and Lys-302 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 By similarity.

Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity By similarity.

Sequence similarities

Contains 1 C2HC-type zinc finger.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainCoiled coil
Zinc-finger
   LigandMetal-binding
Zinc
   PTMDisulfide bond
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from electronic annotation. Source: Ensembl

NF-kappaB import into nucleus

Traceable author statement Ref.1. Source: RGD

activation of NF-kappaB-inducing kinase activity

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Traceable author statement Ref.1. Source: RGD

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentIkappaB kinase complex

Inferred from direct assay PubMed 17419723. Source: RGD

cytosol

Inferred from direct assay PubMed 17419723. Source: RGD

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein heterodimerization activity

Inferred from physical interaction PubMed 17419723. Source: RGD

protein homodimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 412412NF-kappa-B essential modulator
PRO_0000269197

Regions

Zinc finger389 – 41022C2HC-type
Region44 – 11168Interaction with CHUK/IKBKB By similarity
Region150 – 250101Interaction with TANK By similarity
Region242 – 343102Ubiquitin-binding (UBD)
Region246 – 358113Self-association By similarity
Region249 – 412164Required for interaction with TNFAIP3 By similarity
Region315 – 33622Leucine-zipper Potential
Region375 – 41238Interaction with CYLD By similarity
Coiled coil49 – 343295 Potential

Amino acid modifications

Modified residue311Phosphoserine; by IKKB By similarity
Modified residue431Phosphoserine; by IKKB By similarity
Modified residue681Phosphoserine By similarity
Modified residue851Phosphoserine; by ATM By similarity
Modified residue3691Phosphoserine; by IKKB By similarity
Modified residue3801Phosphoserine By similarity
Disulfide bond54Interchain By similarity
Disulfide bond340Interchain By similarity
Cross-link111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Cross-link270Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link278Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link295Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity
Cross-link302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity
Cross-link314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link319Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link392Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q6TMG5 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 6D5D96B08A4CCEC2

FASTA41248,066
        10         20         30         40         50         60 
MSRHLWKNQL SEMVQPSGGP AEDQDMLGEE SSLGKPAMLH LPSEQGTPET LQRCLEENQE 

        70         80         90        100        110        120 
LRDAIRQSNQ MLRERCEELL HFQVSQREEK EFLMCKFQEA RKLVERLSLE KLDLRRQREQ 

       130        140        150        160        170        180 
ALEDLEHLKK CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKERQTL EGRIRAVSEQ 

       190        200        210        220        230        240 
VRQLESEREV LQQQHSVQVD QLRMQNQSVE AALRMERQAA SEEKRKLAQL QAAYHQLFQD 

       250        260        270        280        290        300 
YDSHIKSSKG MQLEDLRQQL QQAEEALVAK QELIDKLKEE AEQHKIVMET VPVLKAQADI 

       310        320        330        340        350        360 
YKADFQAERH AREKLVERKE LLQEQLEQLQ REFNKLKVGC HESARIEDMR KRHVETSQPP 

       370        380        390        400        410 
LLPAPAHHSF HLALSNQRRS PPEEPPDFCC PKCQYQAPDM DTLQIHVMEC IE 

« Hide

References

[1]"Two carboxyl-terminal activation regions of Epstein-Barr virus latent membrane protein 1 activate NF-kappaB through distinct signaling pathways in fibroblast cell lines."
Saito N., Courtois G., Chiba A., Yamamoto N., Nitta T., Hironaka N., Rowe M., Yamamoto N., Yamaoka S.
J. Biol. Chem. 278:46565-46575(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Fischer 344.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY392762 mRNA. Translation: AAQ94056.1.
RefSeqNP_954534.1. NM_199103.1.
XP_006229646.1. XM_006229584.1.
XP_006229647.1. XM_006229585.1.
XP_006229648.1. XM_006229586.1.
UniGeneRn.214715.

3D structure databases

ProteinModelPortalQ6TMG5.
SMRQ6TMG5. Positions 49-109, 193-248, 387-412.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid259339. 1 interaction.
STRING10116.ENSRNOP00000053114.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000056275; ENSRNOP00000053114; ENSRNOG00000037237.
GeneID309295.
KEGGrno:309295.

Organism-specific databases

CTD8517.
RGD735223. Ikbkg.

Phylogenomic databases

eggNOGNOG138369.
GeneTreeENSGT00530000063808.
HOGENOMHOG000293233.
HOVERGENHBG000417.
InParanoidQ6TMG5.
KOK07210.
OMAQKFQEAR.
OrthoDBEOG7D2FD7.
PhylomeDBQ6TMG5.

Gene expression databases

GenevestigatorQ6TMG5.

Family and domain databases

InterProIPR021063. NEMO_N.
[Graphical view]
PfamPF11577. NEMO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio660548.

Entry information

Entry nameNEMO_RAT
AccessionPrimary (citable) accession number: Q6TMG5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 71 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families