Q9Y6K9 (NEMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	419 AA.
Sequence status	Complete.
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. 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 By similarity. 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 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 By similarity. 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.54 Ref.65
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.53
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.55 Ref.56 Ref.58 Ref.59 Ref.60 Ref.62 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.62 Ref.63 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.55 Ref.64 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.66 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.55 Ref.57 Ref.61 Ref.65 Ref.66
Sequence similarities	Contains 1 C2HC-type zinc finger.

Ontologies

Keywords
Biological process	Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Ectodermal dysplasia Osteopetrosis
Domain	Coiled coil Zinc-finger
Ligand	Metal-binding Zinc
PTM	Disulfide bond Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell homeostasis Inferred from electronic annotation. Source: Compara I-kappaB kinase/NF-kappaB cascade 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 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 Toll 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: Compara induction of apoptosis Traceable author statement Ref.1. Source: ProtInc inflammatory response Traceable author statement PubMed 18626576. Source: UniProtKB innate immune response Traceable author statement PubMed 18626576. Source: UniProtKB nucleotide-binding oligomerization domain containing signaling pathway Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade Traceable author statement. Source: Reactome positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.23. Source: UniProtKB positive regulation of type I interferon production Traceable author statement. Source: Reactome response to DNA damage stimulus Inferred from direct assay Ref.19. Source: UniProtKB response to virus Traceable author statement PubMed 18626576. Source: UniProtKB toll-like receptor 1 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 transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	IkappaB kinase complex Traceable author statement PubMed 18626576. Source: UniProtKB nucleus Inferred from direct assay Ref.19. Source: UniProtKB
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADAP2	Q9NPF8	2	EBI-81279,EBI-718895
ANXA1	P04083	6	EBI-81279,EBI-354007
ARL6IP4	Q66PJ3	2	EBI-81279,EBI-2683099
CALB1	P05937	3	EBI-81279,EBI-4286943
CDK2	P24941	4	EBI-81279,EBI-375096
CHUK	O15111	13	EBI-81279,EBI-81249
COPS3	Q9UNS2	2	EBI-81279,EBI-350590
FLT3	P36888	2	EBI-81279,EBI-3946257
GIT2	Q14161	6	EBI-81279,EBI-1046878
IKBKB	O14920	14	EBI-81279,EBI-81266
ipaH9.8	Q8VSC3	8	EBI-81279,EBI-6125799	From a different organism.
KRT18	P05783	3	EBI-81279,EBI-297888
KRT8	P05787	2	EBI-81279,EBI-297852
NFKBIA	P25963	2	EBI-81279,EBI-307386
RIPK1	Q13546	6	EBI-81279,EBI-358507
RNF7	Q9UBF6	3	EBI-81279,EBI-398632
RUSC1	Q9BVN2-2	4	EBI-81279,EBI-6257338
SENP2	Q9HC62	3	EBI-81279,EBI-714881
SRC	P12931	3	EBI-81279,EBI-621482
SYT1	P21579	3	EBI-81279,EBI-524909
TNFAIP3	P21580	2	EBI-81279,EBI-527670
TNIP1	Q15025	4	EBI-81279,EBI-357849
TNIP2	Q8NFZ5	6	EBI-81279,EBI-359372

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 419

419

NF-kappa-B essential modulator

PRO_0000096782

Regions

Zinc finger

396 – 417

22

C2HC-type

Region

44 – 111

68

Interaction with CHUK/IKBKB

Region

150 – 257

108

Interaction with TANK

Region

242 – 350

109

Ubiquitin-binding (UBD)

Region

246 – 365

120

Self-association

Region

251 – 419

169

Required for interaction with TNFAIP3

Region

322 – 343

22

Leucine-zipper Potential

Region

382 – 419

38

Interaction with CYLD

Coiled coil

49 – 356

308

Potential

Amino acid modifications

Modified residue

31

1

Phosphoserine; by IKKB Ref.20

Modified residue

43

1

Phosphoserine; by IKKB Ref.20

Modified residue

68

1

Phosphoserine Ref.35

Modified residue

85

1

Phosphoserine; by ATM Ref.31

Modified residue

376

1

Phosphoserine; by IKKB Ref.20

Disulfide bond

54

Interchain Ref.33

Disulfide bond

347

Interchain Ref.33

Cross-link

111

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

139

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

143

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

226

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

246

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

264

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

277

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.19 Ref.51

Cross-link

277

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate

Cross-link

283

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

285

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.23 Ref.40 Ref.51

Cross-link

292

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

302

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.51

Cross-link

309

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate Ref.19 Ref.40 Ref.42 Ref.51

Cross-link

309

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate

Cross-link

321

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.42

Cross-link

325

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

326

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

399

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.27

Natural variations

Alternative sequence

1

1

M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2.

VSP_041000

Alternative sequence

174 – 224

51

Missing in isoform 3.

VSP_041001

Alternative sequence

257 – 304

48

Missing in isoform 3.

VSP_041002

Natural variant

57

1

E → K in IP; shows the same luciferase activity as the control. Ref.57 Ref.61
Corresponds to variant rs148695964 [ dbSNP | Ensembl ].

VAR_026491

Natural variant

90

1

Missing in IP; only 46.3% of the activation obtained with the wild-type protein. Ref.61

VAR_026492

Natural variant

113

1

D → N. Ref.61
Corresponds to variant rs179363896 [ dbSNP | Ensembl ].

VAR_026493

Natural variant

123

1

R → W in IP; shows the same luciferase activity as the control. Ref.61
Corresponds to variant rs179363895 [ dbSNP | Ensembl ].

VAR_026494

Natural variant

153

1

L → R in EDAID. Ref.60 Ref.62

VAR_026495

Natural variant

173

1

R → G in IPD2. Ref.66
Corresponds to variant rs179363866 [ dbSNP | Ensembl ].

VAR_031958

Natural variant

175

1

R → P in EDAID. Ref.58
Corresponds to variant rs179363868 [ dbSNP | Ensembl ].

VAR_011320

Natural variant

227

1

L → P in EDAID. Ref.58
Corresponds to variant rs179363869 [ dbSNP | Ensembl ].

VAR_011321

Natural variant

288

1

A → G in EDAID. Ref.58

VAR_011322

Natural variant

311

1

D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. Ref.29 Ref.47 Ref.55 Ref.58
Corresponds to variant rs179363867 [ dbSNP | Ensembl ].

VAR_011323

Natural variant

315

1

E → A in AMCBX1; greatly impairs tandem ubiquitin binding. Ref.55 Ref.64

VAR_031959

Natural variant

319

1

R → Q in AMCBX1; impairs tandem ubiquitin binding. Ref.55 Ref.64

VAR_031960

Natural variant

323

1

A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Ref.55 Ref.65
Corresponds to variant rs179363865 [ dbSNP | Ensembl ].

VAR_042666

Natural variant

406

1

D → V in EDAID. Ref.59

VAR_011324

Natural variant

407

1

M → V in IP; impairs binding to ubiquitin. Ref.4 Ref.38 Ref.57

VAR_009182

Natural variant

417

1

C → F in EDAID. Ref.53 Ref.56 Ref.58
Corresponds to variant rs137853326 [ dbSNP | Ensembl ].

VAR_011325

Natural variant

417

1

C → R in EDAID; loss of sumoylation. Ref.19 Ref.56 Ref.58 Ref.59 Ref.60 Ref.62

VAR_011326

Natural variant

417

1

C → Y in NEMOID. Ref.62
Corresponds to variant rs137853326 [ dbSNP | Ensembl ].

VAR_026496

Experimental info

Mutagenesis

68

1

S → A: Increases formation of homodimers. Ref.35

Mutagenesis

68

1

S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. Ref.35

Mutagenesis

85

1

S → A: Decreases ubiquitination and abolishes nuclear export. Ref.31

Mutagenesis

115

1

K → R: No change in the ubiquitination level; when associated with R-399. Ref.23

Mutagenesis

224

1

K → R: No change in the ubiquitination level; when associated with R-399. Ref.23

Mutagenesis

277

1

K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. Ref.19

Mutagenesis

285

1

K → R: Important decrease in the ubiquitination level; when associated with R-399. Ref.23

Mutagenesis

296

1

E → 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

Mutagenesis

300

1

V → D: Greatly impairs tandem ubiquitin binding. Ref.55

Mutagenesis

301

1

L → A: Impairs tandem ubiquitin binding. Ref.55

Mutagenesis

304

1

Q → A: Impairs tandem ubiquitin binding. Ref.55

Mutagenesis

307

1

I → N: Greatly impairs tandem ubiquitin binding. Ref.55

Mutagenesis

308

1

Y → A: Greatly impairs tandem ubiquitin binding. Ref.55

Mutagenesis

309

1

K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. Ref.19

Mutagenesis

312

1

F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. Ref.41 Ref.55

Mutagenesis

312

1

F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). Ref.41 Ref.55

Mutagenesis

312

1

F → Y: Impairs tandem ubiquitin binding. Ref.41 Ref.55

Mutagenesis

313

1

Q → A: Impairs tandem ubiquitin binding. Ref.55

Mutagenesis

315

1

E → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Ref.41

Mutagenesis

315

1

E → Q: Greatly impairs tandem ubiquitin binding. Ref.41

Mutagenesis

317

1

Q → A or W: Greatly impairs tandem ubiquitin binding. Ref.55

Mutagenesis

323

1

A → D: Greatly impairs tandem ubiquitin binding. Ref.41

Mutagenesis

323

1

A → P: Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin, and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Ref.41

Mutagenesis

329

1

L → 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

Mutagenesis

329

1

L → P: Abolishes binding to polyubiquitin. Ref.29 Ref.41

Mutagenesis

336

1

L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. Ref.41

Mutagenesis

399

1

K → 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

Mutagenesis

414

1

V → S: Abolishes binding to polyubiquitin. Ref.38

Mutagenesis

415

1

M → S: Impairs binding to polyubiquitin. Ref.38

Sequence conflict

341

1

S → R in AAD12183. Ref.1

Sequence conflict

387

1

S → R in AAD12183. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

419

Helix Strand Turn

Details...

Helix

50 – 108

59

Turn

194 – 196

3

Helix

197 – 249

53

Turn

271 – 279

9

Helix

280 – 321

42

Beta strand

394 – 396

3

Beta strand

403 – 406

4

Helix

407 – 416

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 322D1037881447FF	FASTA	419	48,198
	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
	Isoform 2 [UniParc]. Checksum: 7A39E991E0013A73	FASTA	487	55,787
	10 20 30 40 50 60 MALVIQVGKL RPREVRTPQT INPSLFPSLP VKLSSIIEVP SGGERCCSRR TLVYKARAFW 70 80 90 100 110 120 KGAPLPCWMN RHLWKSQLCE MVQPSGGPAA DQDVLGEESP LGKPAMLHLP SEQGAPETLQ 130 140 150 160 170 180 RCLEENQELR DAIRQSNQIL RERCEELLHF QASQREEKEF LMCKFQEARK LVERLGLEKL 190 200 210 220 230 240 DLKRQKEQAL REVEHLKRCQ QQMAEDKASV KAQVTSLLGE LQESQSRLEA ATKECQALEG 250 260 270 280 290 300 RARAASEQAR QLESEREALQ QQHSVQVDQL RMQGQSVEAA LRMERQAASE EKRKLAQLQV 310 320 330 340 350 360 AYHQLFQEYD NHIKSSVVGS ERKRGMQLED LKQQLQQAEE ALVAKQEVID KLKEEAEQHK 370 380 390 400 410 420 IVMETVPVLK AQADIYKADF QAERQAREKL AEKKELLQEQ LEQLQREYSK LKASCQESAR 430 440 450 460 470 480 IEDMRKRHVE VSQAPLPPAP AYLSSPLALP SQRRSPPEEP PDFCCPKCQY QAPDMDTLQI HVMECIE
	Isoform 3 [UniParc]. Checksum: 3BEF2487C4446725	FASTA	320	36,953
	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 EGRRKLAQLQ 190 200 210 220 230 240 VAYHQLFQEY DNHIKSSVVG SERKRADIYK ADFQAERQAR EKLAEKKELL QEQLEQLQRE 250 260 270 280 290 300 YSKLKASCQE SARIEDMRKR HVEVSQAPLP PAPAYLSSPL ALPSQRRSPP EEPPDFCCPK 310 320 CQYQAPDMDT LQIHVMECIE

References

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[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.
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[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.
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[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.
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[30]	Erratum Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D. Nat. Cell Biol. 8:424-424(2006)
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[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.
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[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]	"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.
[54]	"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.
[55]	"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.
[56]	"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.
[57]	"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.
[58]	"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. , 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.
[59]	"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.
[60]	"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.
[61]	"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.
[62]	"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.
[63]	"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.
[64]	"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. , 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.
[65]	"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.
[66]	"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.

IPI

IPI00002411.
IPI00641117.
IPI00641409.

RefSeq

NP_001093326.2. NM_001099856.2.
NP_001093327.1. NM_001099857.1.
NP_001138727.1. NM_001145255.1.
NP_003630.1. NM_003639.3.

UniGene

Hs.43505.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JVX	NMR	-	A	394-419	[»]
2JVY	NMR	-	A	394-419	[»]
3BRT	X-ray	2.25	B/D	46-111	[»]
3BRV	X-ray	2.20	B/D	44-111	[»]
3CL3	X-ray	3.20	D/E	150-272	[»]
3FX0	X-ray	3.20	A/B	246-337	[»]

ProteinModelPortal

Q9Y6K9.

SMR

Q9Y6K9. Positions 49-109, 193-251, 263-333, 394-419.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27528N.

IntAct

Q9Y6K9. 134 interactions.

MINT

MINT-1133340.

STRING

9606.ENSP00000358622.

PTM databases

PhosphoSite

Q9Y6K9.

Polymorphism databases

DMDM

6685695.

Proteomic databases

PaxDb

Q9Y6K9.

PRIDE

Q9Y6K9.

Protocols and materials databases

DNASU

8517.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000369601; ENSP00000358614; ENSG00000073009.
ENST00000369602; ENSP00000358615; ENSG00000073009.
ENST00000369606; ENSP00000358619; ENSG00000073009.
ENST00000369607; ENSP00000358620; ENSG00000073009.
ENST00000369609; ENSP00000358622; ENSG00000073009.

GeneID

8517.

KEGG

hsa:8517.

UCSC

uc004fmb.4. human.
uc011mzr.2. human.
uc011mzs.2. human.

Organism-specific databases

CTD

8517.

GeneCards

GC0XP153769.

H-InvDB

HIX0203333.

HGNC

HGNC:5961. IKBKG.

HPA

CAB010373.
HPA000426.

MIM

300248. gene.
300291. phenotype.
300301. phenotype.
300584. phenotype.
300636. phenotype.
300640. phenotype.
308300. phenotype.

neXtProt

NX_Q9Y6K9.

Orphanet

69088. Anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema.
98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.
464. Incontinentia pigmenti.
748. Mendelian susceptibility to mycobacterial diseases.

PharmGKB

PA29777.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG138369.

HOGENOM

HOG000293233.

HOVERGEN

HBG000417.

InParanoid

Q9Y6K9.

KO

K07210.

OMA

QKFQEAR.

PhylomeDB

Q9Y6K9.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
il1pathway. IL1-mediated signaling events.
p75ntrpathway. p75(NTR)-mediated signaling.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
tnfpathway. TNF receptor signaling pathway.
trail_pathway. TRAIL signaling pathway.

Reactome

REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9Y6K9.

Bgee

Q9Y6K9.

CleanEx

HS_IKBKG.

Genevestigator

Q9Y6K9.

GermOnline

ENSG00000073009. Homo sapiens.

Family and domain databases

InterPro

IPR021063. NEMO_N.
[Graphical view]

Pfam

PF11577. NEMO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9Y6K9.

ChEMBL

CHEMBL4967.

ChiTaRS

IKBKG. human.

EvolutionaryTrace

Q9Y6K9.

GenomeRNAi

8517.

NextBio

31882.

SOURCE

Search...

Entry information

Entry name

NEMO_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 148 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.