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Q9Y6K9 (NEMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:IKBKG
Synonyms:FIP3, NEMO
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length419 AA.
Sequence statusComplete.
Protein existenceEvidence 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. 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. Ref.27 Ref.39 Ref.43

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 HTLV-1 Tax oncoprotein; the interaction activates IKBKG. 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 Shigella flexneri ipah9.8; the interaction promotes TNIP1-dependent 'Lys-27'-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. Interacts with NLRP10. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.24 Ref.25 Ref.28 Ref.31 Ref.33 Ref.34 Ref.35 Ref.42 Ref.48 Ref.52 Ref.53 Ref.56 Ref.67

Subcellular location

Cytoplasm. Nucleus. Note: Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress. Ref.19

Tissue specificity

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

Domain

The leucine-zipper domain and the C2HC-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3. Ref.39 Ref.55

Post-translational modification

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.

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. 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.

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. Ref.19

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

Involvement in disease

Ectodermal dysplasia, anhidrotic, with immunodeficiency X-linked (EDAID) [MIM:300291]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.29 Ref.47 Ref.57 Ref.58 Ref.60 Ref.61 Ref.62 Ref.64

Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema (OLEDAID) [MIM:300301]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Immunodeficiency, NEMO-related, without anhidrotic ectodermal dysplasia (NEMOID) [MIM:300584]: Patients manifest immunodeficiency not associated with other abnormalities, and resulting in increased susceptibility to infections. Patients suffer from multiple episodes of infectious diseases.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.64 Ref.65

X-linked familial atypical micobacteriosis 1 (AMCBX1) [MIM:300636]: X-linked recessive form of Mendelian susceptibility to mycobacterial disease (MSMD). MSMD is a congenital syndrome resulting in predisposition to clinical disease caused by weakly virulent mycobacterial species, such as bacillus Calmette-Guerin vaccines and non-tuberculous, environmental mycobacteria. Patients are also susceptible to the more virulent species Mycobacterium tuberculosis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.57 Ref.66

Recurrent isolated invasive pneumococcal disease 2 (IPD2) [MIM:300640]: Recurrent 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.68

Incontinentia pigmenti (IP) [MIM:308300]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.38 Ref.42 Ref.57 Ref.59 Ref.63 Ref.67 Ref.68

Sequence similarities

Contains 1 C2HC-type zinc finger.

Ontologies

Keywords
   Biological processHost-virus interaction
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Ectodermal dysplasia
Osteopetrosis
   DomainCoiled coil
Zinc-finger
   LigandMetal-binding
Zinc
   PTMDisulfide bond
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell homeostasis

Inferred from electronic annotation. Source: Ensembl

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

I-kappaB kinase/NF-kappaB signaling

Traceable author statement PubMed 18626576. Source: UniProtKB

JNK cascade

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Non-traceable author statement Ref.26. Source: UniProtKB

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of MAPK activity

Traceable author statement. Source: Reactome

activation of NF-kappaB-inducing kinase activity

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Traceable author statement Ref.1. Source: ProtInc

cellular response to DNA damage stimulus

Inferred from direct assay Ref.19. Source: UniProtKB

immune response

Traceable author statement Ref.3. Source: ProtInc

inflammatory response

Traceable author statement PubMed 18626576. Source: UniProtKB

innate immune response

Traceable author statement PubMed 18626576. Source: UniProtKB

nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway

Traceable author statement. Source: Reactome

nucleotide-binding oligomerization domain containing signaling pathway

Traceable author statement. Source: Reactome

positive regulation of I-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Inferred from direct assay Ref.23. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 23091055. Source: UniProtKB

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

response to virus

Traceable author statement PubMed 18626576. Source: UniProtKB

stress-activated MAPK cascade

Traceable author statement. Source: Reactome

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentIkappaB kinase complex

Traceable author statement PubMed 18626576. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 11113112Ref.19. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

intracellular

Inferred from direct assay. Source: LIFEdb

nucleus

Inferred from direct assay Ref.19. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein domain specific binding

Inferred from physical interaction PubMed 15341735. Source: UniProtKB

protein heterodimerization activity

Inferred from direct assay PubMed 23091055. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 23091055. Source: UniProtKB

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y6K9-1)

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.
Isoform 2 (identifier: Q9Y6K9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MALVIQVGKLRPREVRTPQTINPSLFPSLPVKLSSIIEVPSGGERCCSRRTLVYKARAFWKGAPLPCWM
Isoform 3 (identifier: Q9Y6K9-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 419419NF-kappa-B essential modulator
PRO_0000096782

Regions

Zinc finger396 – 41722C2HC-type
Region44 – 11168Interaction with CHUK/IKBKB
Region150 – 257108Interaction with TANK
Region242 – 350109Ubiquitin-binding (UBD)
Region246 – 365120Self-association
Region251 – 419169Required for interaction with TNFAIP3
Region322 – 34322Leucine-zipper Potential
Region382 – 41938Interaction with CYLD
Coiled coil49 – 356308 Potential

Amino acid modifications

Modified residue311Phosphoserine; by IKKB Ref.20
Modified residue431Phosphoserine; by IKKB Ref.20
Modified residue681Phosphoserine Ref.35
Modified residue851Phosphoserine; by ATM Ref.31
Modified residue3761Phosphoserine; by IKKB Ref.20
Modified residue3871Phosphoserine Ref.54
Disulfide bond54Interchain Ref.33
Disulfide bond347Interchain Ref.33
Cross-link111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.19 Ref.51
Cross-link277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross-link283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23 Ref.40 Ref.51
Cross-link292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51
Cross-link309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.19 Ref.40 Ref.42 Ref.51
Cross-link309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross-link321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.42
Cross-link325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.27

Natural variations

Alternative sequence11M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2.
VSP_041000
Alternative sequence174 – 22451Missing in isoform 3.
VSP_041001
Alternative sequence257 – 30448Missing in isoform 3.
VSP_041002
Natural variant571E → K in IP; shows the same luciferase activity as the control. Ref.59 Ref.63
Corresponds to variant rs148695964 [ dbSNP | Ensembl ].
VAR_026491
Natural variant901Missing in IP; only 46.3% of the activation obtained with the wild-type protein. Ref.63
VAR_026492
Natural variant1131D → N. Ref.63
Corresponds to variant rs179363896 [ dbSNP | Ensembl ].
VAR_026493
Natural variant1231R → W in IP; shows the same luciferase activity as the control. Ref.63
Corresponds to variant rs179363895 [ dbSNP | Ensembl ].
VAR_026494
Natural variant1531L → R in EDAID. Ref.62 Ref.64
VAR_026495
Natural variant1731R → G in IPD2. Ref.68
Corresponds to variant rs179363866 [ dbSNP | Ensembl ].
VAR_031958
Natural variant1751R → P in EDAID. Ref.60
Corresponds to variant rs179363868 [ dbSNP | Ensembl ].
VAR_011320
Natural variant2271L → P in EDAID. Ref.60
Corresponds to variant rs179363869 [ dbSNP | Ensembl ].
VAR_011321
Natural variant2881A → G in EDAID. Ref.60
VAR_011322
Natural variant3111D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. Ref.29 Ref.47 Ref.57 Ref.60
Corresponds to variant rs179363867 [ dbSNP | Ensembl ].
VAR_011323
Natural variant3151E → A in AMCBX1; greatly impairs tandem ubiquitin binding. Ref.57 Ref.66
VAR_031959
Natural variant3191R → Q in AMCBX1; impairs tandem ubiquitin binding. Ref.57 Ref.66
VAR_031960
Natural variant3231A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Ref.57 Ref.67
Corresponds to variant rs179363865 [ dbSNP | Ensembl ].
VAR_042666
Natural variant4061D → V in EDAID. Ref.61
VAR_011324
Natural variant4071M → V in IP; impairs binding to ubiquitin. Ref.4 Ref.38 Ref.59
VAR_009182
Natural variant4171C → F in EDAID. Ref.55 Ref.58 Ref.60
Corresponds to variant rs137853326 [ dbSNP | Ensembl ].
VAR_011325
Natural variant4171C → R in EDAID; loss of sumoylation. Ref.19 Ref.58 Ref.60 Ref.61 Ref.62 Ref.64
VAR_011326
Natural variant4171C → Y in NEMOID. Ref.64
Corresponds to variant rs137853326 [ dbSNP | Ensembl ].
VAR_026496

Experimental info

Mutagenesis681S → A: Increases formation of homodimers. Ref.35
Mutagenesis681S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. Ref.35
Mutagenesis851S → A: Decreases ubiquitination and abolishes nuclear export. Ref.31
Mutagenesis1151K → R: No change in the ubiquitination level; when associated with R-399. Ref.23
Mutagenesis2241K → R: No change in the ubiquitination level; when associated with R-399. Ref.23
Mutagenesis2771K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. Ref.19
Mutagenesis2851K → R: Important decrease in the ubiquitination level; when associated with R-399. Ref.23
Mutagenesis2961E → A: No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Ref.41
Mutagenesis3001V → D: Greatly impairs tandem ubiquitin binding. Ref.57
Mutagenesis3011L → A: Impairs tandem ubiquitin binding. Ref.57
Mutagenesis3041Q → A: Impairs tandem ubiquitin binding. Ref.57
Mutagenesis3071I → N: Greatly impairs tandem ubiquitin binding. Ref.57
Mutagenesis3081Y → A: Greatly impairs tandem ubiquitin binding. Ref.57
Mutagenesis3091K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. Ref.19
Mutagenesis3121F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. Ref.41 Ref.57
Mutagenesis3121F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). Ref.41 Ref.57
Mutagenesis3121F → Y: Impairs tandem ubiquitin binding. Ref.41 Ref.57
Mutagenesis3131Q → A: Impairs tandem ubiquitin binding. Ref.57
Mutagenesis3151E → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Ref.41
Mutagenesis3151E → Q: Greatly impairs tandem ubiquitin binding. Ref.41
Mutagenesis3171Q → A or W: Greatly impairs tandem ubiquitin binding. Ref.57
Mutagenesis3231A → D: Greatly impairs tandem ubiquitin binding. Ref.41
Mutagenesis3231A → P: Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin, and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Ref.41
Mutagenesis3291L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336. Ref.29 Ref.41
Mutagenesis3291L → P: Abolishes binding to polyubiquitin. Ref.29 Ref.41
Mutagenesis3361L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. Ref.41
Mutagenesis3991K → 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. Ref.23 Ref.27
Mutagenesis4141V → S: Abolishes binding to polyubiquitin. Ref.38
Mutagenesis4151M → S: Impairs binding to polyubiquitin. Ref.38
Sequence conflict3411S → R in AAD12183. Ref.1
Sequence conflict3871S → R in AAD12183. Ref.1

Secondary structure

.............. 419
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 322D1037881447FF

FASTA41948,198
        10         20         30         40         50         60 
MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET LQRCLEENQE 

        70         80         90        100        110        120 
LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA RKLVERLGLE KLDLKRQKEQ 

       130        140        150        160        170        180 
ALREVEHLKR CQQQMAEDKA SVKAQVTSLL GELQESQSRL EAATKECQAL EGRARAASEQ 

       190        200        210        220        230        240 
ARQLESEREA LQQQHSVQVD QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE 

       250        260        270        280        290        300 
YDNHIKSSVV GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV 

       310        320        330        340        350        360 
LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES ARIEDMRKRH 

       370        380        390        400        410 
VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC QYQAPDMDTL QIHVMECIE 

« Hide

Isoform 2 [UniParc].

Checksum: 7A39E991E0013A73
Show »

FASTA48755,787
Isoform 3 [UniParc].

Checksum: 3BEF2487C4446725
Show »

FASTA32036,953

References

« Hide 'large scale' references
[1]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28."
Jin D.-Y., Jeang K.-T.
J. Biomed. Sci. 6:115-120(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Mammary cancer.
[3]"IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex."
Rothwarf D.M., Zandi E., Natoli G., Karin M.
Nature 395:297-300(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
Tissue: Cervix carcinoma.
[4]"Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti."
Smahi A., Courtois G., Vabres P., Yamaoka S., Heuertz S., Munnich A., Israel A., Heiss N.S., Klauck S.M., Kioschis P., Wiemann S., Poustka A., Esposito T., Bardaro T., Gianfrancesco F., Ciccodicola A., D'Urso M., Woffendin H. expand/collapse author list , Jakins T., Donnai D., Stewart H., Kenwrick S.J., Aradhya S., Yamagata T., Levy M., Lewis R.A., Nelson D.L.
Nature 405:466-472(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT IP VAL-407.
[5]"cDNA cloning by amplification of circularized first strand cDNAs reveals non-IRE-regulated iron-responsive mRNAs."
Ye Z., Connor J.R.
Biochem. Biophys. Res. Commun. 275:223-227(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Astrocytoma.
[6]"Ikbkg gene modulates the herpes virus susceptibility in mice."
Perelygin A.A., Perelygina L.M.
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[7]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
[8]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung, Placenta and Skin.
[11]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-419 (ISOFORM 1), PROTEIN SEQUENCE OF 144-159.
Tissue: Cervix carcinoma.
[12]"Role of adapter function in oncoprotein-mediated activation of NF-kappaB: human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma."
Jin D.-Y., Giordano V., Kibler K.V., Nakano H., Jeang K.-T.
J. Biol. Chem. 274:17402-17405(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTLV-1 TAX-1.
[13]"Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein."
Xiao G., Sun S.C.
Oncogene 19:5198-5203(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HTLV-1 TAX-1.
[14]"Functional redundancy of the zinc fingers of A20 for inhibition of NF-kappaB activation and protein-protein interactions."
Klinkenberg M., Van Huffel S., Heyninck K., Beyaert R.
FEBS Lett. 498:93-97(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFAIP3.
[15]"CSN3 interacts with IKKgamma and inhibits TNF- but not IL-1-induced NF-kappaB activation."
Hong X., Xu L.-G., Li X., Zhai Z., Shu H.-B.
FEBS Lett. 499:133-136(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COPS3.
[16]"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] [Europe PMC] [Abstract]
Cited for: SUBUNIT OF THE IKK COMPLEX.
[17]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TANK AND IKBKB.
[18]"Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) coactivator activity by I kappa B kinase."
Wu R.-C., Qin J., Hashimoto Y., Wong J., Xu J., Tsai S.Y., Tsai M.-J., O'Malley B.W.
Mol. Cell. Biol. 22:3549-3561(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT OF A COMPLEX CONTAINING CREBBP; NCOA2; NCOA3; IKKA AND IKKB.
[19]"Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress."
Huang T.T., Wuerzberger-Davis S.M., Wu Z.H., Miyamoto S.
Cell 115:565-576(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-277 AND LYS-309, UBIQUITINATION AT LYS-277 AND LYS-309, MUTAGENESIS OF LYS-277 AND LYS-309, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT EDAID ARG-417.
[20]"In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase."
Carter R.S., Pennington K.N., Ungurait B.J., Ballard D.W.
J. Biol. Chem. 278:19642-19648(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-31; SER-43 AND SER-376.
[21]"Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation."
Tegethoff S., Behlke J., Scheidereit C.
Mol. Cell. Biol. 23:2029-2041(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SELF-ASSOCIATION, COMPOSITION OF THE IKK COMPLEX.
[22]"The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination."
Kovalenko A., Chable-Bessia C., Cantarella G., Israeel A., Wallach D., Courtois G.
Nature 424:801-805(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CYLD.
[23]"The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO."
Abbott D.W., Wilkins A., Asara J.M., Cantley L.C.
Curr. Biol. 14:2217-2227(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-285, MUTAGENESIS OF LYS-115; LYS-224; LYS-285 AND LYS-399.
[24]"ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor of NFkappaB activation."
Huang J., Teng L., Li L., Liu T., Li L., Chen D., Xu L.-G., Zhai Z., Shu H.-B.
J. Biol. Chem. 279:16847-16853(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZFAND5.
[25]"PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages."
Bruey J.-M., Bruey-Sedano N., Newman R., Chandler S., Stehlik C., Reed J.C.
J. Biol. Chem. 279:51897-51907(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NALP2.
[26]"The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[27]"Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO."
Zhou H., Wertz I., O'Rourke K., Ultsch M., Seshagiri S., Eby M., Xiao W., Dixit V.M.
Nature 427:167-171(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION AT LYS-399, MUTAGENESIS OF LYS-399.
[28]"PIDD mediates NF-kappaB activation in response to DNA damage."
Janssens S., Tinel A., Lippens S., Tschopp J.
Cell 123:1079-1092(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRDD.
[29]"Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation."
Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D.
Nat. Cell Biol. 8:398-406(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITIN-BINDING, MUTAGENESIS OF LEU-329, CHARACTERIZATION OF VARIANT EDAID ASN-311.
[30]Erratum
Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D.
Nat. Cell Biol. 8:424-424(2006)
[31]"Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli."
Wu Z.H., Shi Y., Tibbetts R.S., Miyamoto S.
Science 311:1141-1146(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATM, PHOSPHORYLATION AT SER-85, MUTAGENESIS OF SER-85.
[32]"Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[33]"Intermolecular disulfide bond formation in the NEMO dimer requires Cys54 and Cys347."
Herscovitch M., Comb W., Ennis T., Coleman K., Yong S., Armstead B., Kalaitzidis D., Chandani S., Gilmore T.D.
Biochem. Biophys. Res. Commun. 367:103-108(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, DISULFIDE BONDS.
[34]"A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation."
Hasegawa M., Fujimoto Y., Lucas P.C., Nakano H., Fukase K., Nunez G., Inohara N.
EMBO J. 27:373-383(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RIPK2.
[35]"Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity."
Palkowitsch L., Leidner J., Ghosh S., Marienfeld R.B.
J. Biol. Chem. 283:76-86(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IKBKB, PHOSPHORYLATION AT SER-68, MUTAGENESIS OF SER-68.
[36]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[37]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[38]"The zinc finger of NEMO is a functional ubiquitin-binding domain."
Cordier F., Grubisha O., Traincard F., Veron M., Delepierre M., Agou F.
J. Biol. Chem. 284:2902-2907(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITIN-BINDING, MUTAGENESIS OF VAL-414 AND MET-415, CHARACTERIZATION OF VARIANT IP VAL-407.
[39]"Key role of Ubc5 and lysine-63 polyubiquitination in viral activation of IRF3."
Zeng W., Xu M., Liu S., Sun L., Chen Z.J.
Mol. Cell 36:315-325(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN LEUCINE-ZIPPER AND C2HC-TYPE ZINC-FINGER.
[40]"Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation."
Tokunaga F., Sakata S., Saeki Y., Satomi Y., Kirisako T., Kamei K., Nakagawa T., Kato M., Murata S., Yamaoka S., Yamamoto M., Akira S., Takao T., Tanaka K., Iwai K.
Nat. Cell Biol. 11:123-132(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-285 AND LYS-309.
[41]"DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding."
Grubisha O., Kaminska M., Duquerroy S., Fontan E., Cordier F., Haouz A., Raynal B., Chiaravalli J., Delepierre M., Israel A., Veron M., Agou F.
J. Mol. Biol. 395:89-104(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-296; PHE-312; GLU-315; ALA-323; LEU-329 AND LEU-336.
[42]"A bacterial E3 ubiquitin ligase IpaH9.8 targets NEMO/IKKgamma to dampen the host NF-kappaB-mediated inflammatory response."
Ashida H., Kim M., Schmidt-Supprian M., Ma A., Ogawa M., Sasakawa C.
Nat. Cell Biol. 12:66-73(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SHIGELLA FLEXNERI IPAH9.8, UBIQUITINATION AT LYS-309 AND LYS-321.
[43]"Polyubiquitin conjugation to NEMO by tripartite motif protein 23 (TRIM23) is critical in antiviral defense."
Arimoto K., Funami K., Saeki Y., Tanaka K., Okawa K., Takeuchi O., Akira S., Murakami Y., Shimotohno K.
Proc. Natl. Acad. Sci. U.S.A. 107:15856-15861(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION.
[44]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[45]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[46]"TRIM40 promotes neddylation of IKKgamma and is downregulated in gastrointestinal cancers."
Noguchi K., Okumura F., Takahashi N., Kataoka A., Kamiyama T., Todo S., Hatakeyama S.
Carcinogenesis 32:995-1004(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: NEDDYLATION BY TRIM40.
[47]"Polyubiquitin binding to ABIN1 is required to prevent autoimmunity."
Nanda S.K., Venigalla R.K., Ordureau A., Patterson-Kane J.C., Powell D.W., Toth R., Arthur J.S., Cohen P.
J. Exp. Med. 208:1215-1228(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITIN-BINDING, CHARACTERIZATION OF VARIANT EDAID ASN-311.
[48]"Direct, noncatalytic mechanism of IKK inhibition by A20."
Skaug B., Chen J., Du F., He J., Ma A., Chen Z.J.
Mol. Cell 44:559-571(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TNFAIP3.
[49]"Linear ubiquitination prevents inflammation and regulates immune signalling."
Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E., Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., Nachbur U., Gangoda L., Warnken U., Purcell A.W., Silke J., Walczak H.
Nature 471:591-596(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY THE LUBAC COMPLEX.
[50]"SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex."
Tokunaga F., Nakagawa T., Nakahara M., Saeki Y., Taniguchi M., Sakata S., Tanaka K., Nakano H., Iwai K.
Nature 471:633-636(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY THE LUBAC COMPLEX.
[51]"SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis."
Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C., Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J., Tokunaga F., Androulidaki A., Nakagawa T., Pasparakis M., Iwai K., Sundberg J.P., Schaefer L., Rittinger K., Macek B., Dikic I.
Nature 471:637-641(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-277; LYS-285; LYS-309; LYS-326; LYS-111; LYS-143; LYS-226; LYS-246; LYS-264; LYS-292 AND LYS-302 BY THE LUBAC COMPLEX, UBIQUITINATION AT LYS-139 AND LYS-283.
[52]"NLRP10 enhances Shigella-induced pro-inflammatory responses."
Lautz K., Damm A., Menning M., Wenger J., Adam A.C., Zigrino P., Kremmer E., Kufer T.A.
Cell. Microbiol. 14:1568-1583(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NLRP10.
[53]"IKKepsilon-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex."
Zhou A.Y., Shen R.R., Kim E., Lock Y.J., Xu M., Chen Z.J., Hahn W.C.
Cell Rep. 3:724-733(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IKBKE.
[54]"Identifying post-translational modifications of NEMO by tandem mass spectrometry after high affinity purification."
Jackson S.S., Coughlin E.E., Coon J.J., Miyamoto S.
Protein Expr. Purif. 92:48-53(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-387.
[55]"Solution structure of NEMO zinc finger and impact of an anhidrotic ectodermal dysplasia with immunodeficiency-related point mutation."
Cordier F., Vinolo E., Veron M., Delepierre M., Agou F.
J. Mol. Biol. 377:1419-1432(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 394-419 OF WILD-TYPE AND MUTANT PHE-417, DOMAIN ZINC-FINGER.
[56]"Structure of a NEMO/IKK-associating domain reveals architecture of the interaction site."
Rushe M., Silvian L., Bixler S., Chen L.L., Cheung A., Bowes S., Cuervo H., Berkowitz S., Zheng T., Guckian K., Pellegrini M., Lugovskoy A.
Structure 16:798-808(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 44-111 IN COMPLEX WITH CHUK AND IKBKB, SUBUNIT.
[57]"Structural basis for recognition of diubiquitins by NEMO."
Lo Y.C., Lin S.C., Rospigliosi C.C., Conze D.B., Wu C.J., Ashwell J.D., Eliezer D., Wu H.
Mol. Cell 33:602-615(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 246-337, UBIQUITIN-BINDING, MUTAGENESIS OF VAL-300; LEU-301; GLN-304; ILE-307; TYR-308; PHE-312; GLN-313 AND GLN-317, CHARACTERIZATION OF VARIANT EDAID ASN-311, CHARACTERIZATION OF VARIANT AMCBX1 ALA-315, CHARACTERIZATION OF VARIANTS GLN-319 AND IP PRO-323.
[58]"A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO)."
Zonana J., Elder M.E., Schneider L.C., Orlow S.J., Moss C., Golabi M., Shapira S.K., Farndon P.A., Wara D.W., Emmal S.A., Ferguson B.M.
Am. J. Hum. Genet. 67:1555-1562(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDAID ARG-417 AND PHE-417.
[59]"A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations."
Aradhya S., Woffendin H., Jakins T., Bardaro T., Esposito T., Smahi A., Shaw C., Levy M., Munnich A., D'Urso M., Lewis R.A., Kenwrick S., Nelson D.L.
Hum. Mol. Genet. 10:2171-2179(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IP LYS-57 AND VAL-407.
[60]"X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa B signaling."
Doeffinger R., Smahi A., Bessia C., Geissmann F., Feinberg J., Durandy A., Bodemer C., Kenwrick S.J., Dupuis-Girod S., Blanche S., Wood P., Rabia S.H., Headon D.J., Overbeek P.A., Le Deist F., Holland S.M., Belani K., Kumararatne D.S. expand/collapse author list , Fischer A., Shapiro R., Conley M.E., Reimund E., Kalhoff H., Abinun M., Munnich A., Israael A., Courtois G., Casanova J.-L.
Nat. Genet. 27:277-285(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDAID PRO-175; PRO-227; GLY-288; ASN-311; ARG-417 AND PHE-417.
[61]"Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia."
Jain A., Ma C.A., Liu S., Brown M., Cohen J., Strober W.
Nat. Immunol. 2:223-228(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDAID VAL-406 AND ARG-417.
[62]"Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations."
Orange J.S., Brodeur S.R., Jain A., Bonilla F.A., Schneider L.C., Kretschmer R., Nurko S., Rasmussen W.L., Koehler J.R., Gellis S.E., Ferguson B.M., Strominger J.L., Zonana J., Ramesh N., Ballas Z.K., Geha R.S.
J. Clin. Invest. 109:1501-1509(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDAID ARG-153 AND ARG-417.
[63]"Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation."
Fusco F., Bardaro T., Fimiani G., Mercadante V., Miano M.G., Falco G., Israeel A., Courtois G., D'Urso M., Ursini M.V.
Hum. Mol. Genet. 13:1763-1773(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123, VARIANT ASN-113, CHARACTERIZATION OF VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123, CHARACTERIZATION OF VARIANT ASN-113.
[64]"The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation."
Orange J.S., Jain A., Ballas Z.K., Schneider L.C., Geha R.S., Bonilla F.A.
J. Allergy Clin. Immunol. 113:725-733(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EDAID ARG-153 AND ARG-417, VARIANT NEMOID TYR-417.
[65]"Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia."
Orange J.S., Levy O., Brodeur S.R., Krzewski K., Roy R.M., Niemela J.E., Fleisher T.A., Bonilla F.A., Geha R.S.
J. Allergy Clin. Immunol. 114:650-656(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN NEMOID.
[66]"X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production."
Filipe-Santos O., Bustamante J., Haverkamp M.H., Vinolo E., Ku C.-L., Puel A., Frucht D.M., Christel K., von Bernuth H., Jouanguy E., Feinberg J., Durandy A., Senechal B., Chapgier A., Vogt G., de Beaucoudrey L., Fieschi C., Picard C. expand/collapse author list , Garfa M., Chemli J., Bejaoui M., Tsolia M.N., Kutukculer N., Plebani A., Notarangelo L., Bodemer C., Geissmann F., Israeel A., Veron M., Knackstedt M., Barbouche R., Abel L., Magdorf K., Gendrel D., Agou F., Holland S.M., Casanova J.-L.
J. Exp. Med. 203:1745-1759(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AMCBX1 ALA-315 AND GLN-319.
[67]"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] [Europe PMC] [Abstract]
Cited for: VARIANT IP PRO-323, CHARACTERIZATION OF VARIANT IP PRO-323, INTERACTION WITH TRAF6.
[68]"IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease."
Ku C.-L., Picard C., Erdos M., Jeurissen A., Bustamante J., Puel A., von Bernuth H., Filipe-Santos O., Chang H.-H., Lawrence T., Raes M., Marodi L., Bossuyt X., Casanova J.-L.
J. Med. Genet. 44:16-23(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT IPD2 GLY-173.
+Additional computationally mapped references.

Web resources

IKBKGbase

IKBKG mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001093326.2. NM_001099856.3.
NP_001093327.1. NM_001099857.2.
NP_001138727.1. NM_001145255.2.
NP_003630.1. NM_003639.4.
XP_005274820.1. XM_005274763.2.
UniGeneHs.43505.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JVXNMR-A394-419[»]
2JVYNMR-A394-419[»]
3BRTX-ray2.25B/D46-111[»]
3BRVX-ray2.20B/D44-111[»]
3CL3X-ray3.20D/E150-272[»]
3FX0X-ray3.20A/B246-337[»]
ProteinModelPortalQ9Y6K9.
SMRQ9Y6K9. Positions 49-109, 193-251, 263-333, 394-419.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114089. 275 interactions.
DIPDIP-27528N.
IntActQ9Y6K9. 166 interactions.
MINTMINT-128245.
STRING9606.ENSP00000358622.

Chemistry

BindingDBQ9Y6K9.
ChEMBLCHEMBL4967.

PTM databases

PhosphoSiteQ9Y6K9.

Polymorphism databases

DMDM6685695.

Proteomic databases

PaxDbQ9Y6K9.
PRIDEQ9Y6K9.

Protocols and materials databases

DNASU8517.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000369601; ENSP00000358614; ENSG00000073009. [Q9Y6K9-1]
ENST00000369602; ENSP00000358615; ENSG00000073009. [Q9Y6K9-3]
ENST00000369606; ENSP00000358619; ENSG00000073009. [Q9Y6K9-1]
ENST00000369607; ENSP00000358620; ENSG00000073009. [Q9Y6K9-1]
ENST00000369609; ENSP00000358622; ENSG00000073009. [Q9Y6K9-2]
GeneID8517.
KEGGhsa:8517.
UCSCuc004fmb.4. human. [Q9Y6K9-1]
uc011mzr.2. human. [Q9Y6K9-2]
uc011mzs.2. human. [Q9Y6K9-3]

Organism-specific databases

CTD8517.
GeneCardsGC0XP153769.
H-InvDBHIX0203333.
HGNCHGNC:5961. IKBKG.
HPACAB010373.
HPA000426.
MIM300248. gene.
300291. phenotype.
300301. phenotype.
300584. phenotype.
300636. phenotype.
300640. phenotype.
308300. phenotype.
neXtProtNX_Q9Y6K9.
Orphanet69088. Anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema.
98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.
464. Incontinentia pigmenti.
319612. X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency.
PharmGKBPA29777.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG138369.
HOGENOMHOG000293233.
HOVERGENHBG000417.
InParanoidQ9Y6K9.
KOK07210.
OMAQKFQEAR.
PhylomeDBQ9Y6K9.
TreeFamTF326608.

Enzyme and pathway databases

ReactomeREACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SABIO-RKQ9Y6K9.

Gene expression databases

ArrayExpressQ9Y6K9.
BgeeQ9Y6K9.
CleanExHS_IKBKG.
GenevestigatorQ9Y6K9.

Family and domain databases

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

Other

ChiTaRSIKBKG. human.
EvolutionaryTraceQ9Y6K9.
GeneWikiIKBKG.
GenomeRNAi8517.
NextBio31882.
PROQ9Y6K9.
SOURCESearch...

Entry information

Entry nameNEMO_HUMAN
AccessionPrimary (citable) accession number: Q9Y6K9
Secondary accession number(s): Q7LBY6, Q7Z7F1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM