Reviewed, UniProtKB/Swiss-Prot O88522 (NEMO_MOUSE)

Names and origin

Protein names

Recommended name:
    NF-kappa-B essential modulator
      Short name=NEMO
Alternative name(s):
    NF-kappa-B essential modifier
    Inhibitor of nuclear factor kappa-B kinase subunit gamma
      Short name=IkB kinase subunit gamma
      Short name=I-kappa-B kinase gamma
      Short name=IKK-gamma
      Short name=IKKG
    IkB kinase-associated protein 1
      Short name=IKKAP1
      Short name=mFIP-3

Gene names

Name:	Ikbkg
Synonyms:	Nemo

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	412 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein 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. 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 By similarity.
Subunit structure	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. 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 By similarity. Interacts with IKBKG; the interaction is enhanced by TBK1 and IKBKE. Part of a ternary complex consisting of TANK, IKBKB and IKBKG.
Subcellular location	Cytoplasm By similarity. Nucleus By similarity.
Sequence similarities	Contains 1 C2HC-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
PTM	Disulfide bond Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	B cell homeostasis Inferred from mutant phenotype. Source: MGI activation of NF-kappaB-inducing kinase activity Inferred from direct assay. Source: MGI regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Irf7	P70434	1	EBI-998011,EBI-997907

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 412	412	NF-kappa-B essential modulator		PRO_0000096783
Regions
	Domain	315 – 336	22	Leucine-zipper Potential
	Zinc finger	389 – 410	22	C2HC-type
	Region	44 – 111	68	Interaction with CHUK/IKBKB By similarity
	Region	150 – 250	101	Interaction with TANK
	Coiled coil	49 – 345	297	Potential
Amino acid modifications
	Modified residue	369	1	Phosphoserine; by IKKB Ref.5
	Modified residue	380	1	Phosphoserine By similarity
	Disulfide bond	54		Interchain By similarity
	Disulfide bond	340		Interchain By similarity
	Cross-link	314		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7
	Cross-link	318		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
	Cross-link	319		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Probable
Experimental info
	Mutagenesis	318	1	K → R: Slightly decreases ubiquitination; when associated with R-319. Ref.7
	Mutagenesis	319	1	K → R: Slightly decreases ubiquitination; when associated with R-318. Ref.7
	Mutagenesis	369	1	S → A: Decreases phosphorylation and increases NF-kappa-B activity. Ref.5
	Mutagenesis	375	1	S → A: Decreases phosphorylation and increases NF-kappa-B activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O88522-1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 30ED68B5A2383608	FASTA	412	47,942
	10 20 30 40 50 60 MNKHPWKNQL SETVQPSGGP AEDQDMLGEE SSLGKPAMLH LPSEQGTPET LQRCLEENQE 70 80 90 100 110 120 LRDAIRQSNQ MLRERCEELL HFQVSQREEK EFLMCKFQEA RKLVERLSLE KLDLRSQREQ 130 140 150 160 170 180 ALKELEQLKK CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKDRQAL 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 AREKLVEKKE YLQEQLEQLQ REFNKLKVGC HESARIEDMR KRHVETPQPP 370 380 390 400 410 LLPAPAHHSF HLALSNQRRS PPEEPPDFCC PKCQYQAPDM DTLQIHVMEC IE

References

[1]	"Complementation cloning of NEMO, a component of the I-kappaB kinase complex essential for NF-kappaB activation." Yamaoka S., Courtois G., Bessia C., Whiteside S.T., Weil R., Agou F., Kirk H.E., Kay R.J., Israel A. Cell 93:1231-1240(1998) [PubMed: 9657155] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[2]	"IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex." Mercurio F., Murray B.W., Shevchenko A., Bennett B.L., Young D.B., Li J.W., Pascual G., Motiwala A., Zhu H., Mann M., Manning A.M. Mol. Cell. Biol. 19:1526-1538(1999) [PubMed: 9891086] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-412, PROTEIN SEQUENCE OF 144-159. Tissue: Cervix carcinoma.
[3]	"Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis." Li Y., Kang J., Friedman J., Tarassishin L., Ye J., Kovalenko A., Wallach D., Horwitz M.S. Proc. Natl. Acad. Sci. U.S.A. 96:1042-1047(1999) [PubMed: 9927690] [Abstract] Cited for: FUNCTION.
[4]	"Role of ikkgamma/nemo in assembly of the IkappaB kinase complex." Li X.-H., Fang X., Gaynor R.B. J. Biol. Chem. 276:4494-4500(2001) [PubMed: 11080499] [Abstract] Cited for: IKK COMPLEX.
[5]	"Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta -mediated phosphorylation." Prajapati S., Gaynor R.B. J. Biol. Chem. 277:24331-24339(2002) [PubMed: 11971901] [Abstract] Cited for: PHOSPHORYLATION AT SER-369, MUTAGENESIS OF SER-369 AND SER-375.
[6]	"Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases." Chariot A., Leonardi A., Muller J., Bonif M., Brown K., Siebenlist U. J. Biol. Chem. 277:37029-37036(2002) [PubMed: 12133833] [Abstract] Cited for: INTERACTION WITH TANK AND IKBKB.
[7]	"Identification of TRAF6-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti." Sebban-Benin H., Pescatore A., Fusco F., Pascuale V., Gautheron J., Yamaoka S., Moncla A., Ursini M.V., Courtois G. Hum. Mol. Genet. 16:2805-2815(2007) [PubMed: 17728323] [Abstract] Cited for: UBIQUITINATION AT LYS-314; LYS-318 AND LYS-319, MUTAGENESIS OF LYS-318 AND LYS-319.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF069542 mRNA. Translation: AAC40153.1.

IPI

IPI00914699.

RefSeq

NP_034677.1.

UniGene

Mm.12967

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZVN	X-ray	3.00	B/D/F/H	253-337	[»]
2ZVO	X-ray	2.90	B/D	250-339	[»]
3F89	X-ray	2.80	A/B	250-339	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O88522. 1 interaction.

PTM databases

PhosphoSite

O88522.

Proteomic databases

PRIDE

O88522.

Genome annotation databases

Ensembl

ENSMUSG00000004221. Mus musculus. [Contig view]

GeneID

16151.

Organism-specific databases

MGI

MGI:1338074. Ikbkg.

Phylogenomic databases

HOVERGEN

O88522.

Gene expression databases

ArrayExpress

O88522.

Bgee

O88522.

CleanEx

MM_IKBKG.

GermOnline

ENSMUSG00000004221. Mus musculus.

Family and domain databases

ProtoNet

Search...

Other Resources

NextBio

288945.

SOURCE

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Entry information

Entry name

NEMO_MOUSE

Accession

Primary (citable) accession number: O88522

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)