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UniProtKB - Q9Y6K9 (NEMO_HUMAN)

Entry version 231 (23 Feb 2022)
Sequence version 2 (30 May 2000)
Previous versions | rss
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Protein

NF-kappa-B essential modulator

Gene

IKBKG

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:9751060, PubMed:14695475, PubMed:20724660).

Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:16547522, PubMed:18287044, PubMed:19033441, PubMed:21606507, PubMed:27777308, PubMed:19185524, PubMed:33567255).

Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:16547522, PubMed:18287044, PubMed:27777308, PubMed:19033441, PubMed:21606507, PubMed:19185524).

Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:19854139).

Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination (PubMed:20724660).

11 Publications

(Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B.

2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi397ZincPROSITE-ProRule annotation1
Metal bindingi400ZincPROSITE-ProRule annotation1
Metal bindingi413ZincPROSITE-ProRule annotation1
Metal bindingi417ZincPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processDNA damage, Host-virus interaction, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q9Y6K9

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1169091, Activation of NF-kappaB in B cells
R-HSA-1236974, ER-Phagosome pathway
R-HSA-168638, NOD1/2 Signaling Pathway
R-HSA-168927, TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476, RIP-mediated NFkB activation via ZBP1
R-HSA-202424, Downstream TCR signaling
R-HSA-2871837, FCERI mediated NF-kB activation
R-HSA-445989, TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-450302, activated TAK1 mediates p38 MAPK activation
R-HSA-450321, JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-4755510, SUMOylation of immune response proteins
R-HSA-5357905, Regulation of TNFR1 signaling
R-HSA-5357956, TNFR1-induced NFkappaB signaling pathway
R-HSA-5602636, IKBKB deficiency causes SCID
R-HSA-5603027, IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
R-HSA-5603029, IkBA variant leads to EDA-ID
R-HSA-5607764, CLEC7A (Dectin-1) signaling
R-HSA-5684264, MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-5689880, Ub-specific processing proteases
R-HSA-5689896, Ovarian tumor domain proteases
R-HSA-9020702, Interleukin-1 signaling
R-HSA-933542, TRAF6 mediated NF-kB activation
R-HSA-933543, NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-937039, IRAK1 recruits IKK complex
R-HSA-937041, IKK complex recruitment mediated by RIP1
R-HSA-975144, IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		Q9Y6K9

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q9Y6K9

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q9Y6K9

Protein family/group databases

MoonDB Database of extreme multifunctional and moonlighting proteins

More...MoonDBi		Q9Y6K9, Predicted

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
NF-kappa-B essential modulatorCurated
Short name:
NEMOCurated
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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:IKBKGImported
Synonyms:FIP3, NEMO
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome X

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:5961, IKBKG

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		300248, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q9Y6K9

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000269335

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Ectodermal dysplasia and immunodeficiency 1 (EDAID1)9 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDAID1 is an X-linked recessive disorder characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, and may be fatal in childhood.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_026495153L → R in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar.1
Natural variantiVAR_011320175R → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar.1
Natural variantiVAR_011321227L → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar.1
Natural variantiVAR_011322288A → G in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar.1
Natural variantiVAR_011323311D → N in EDAID1; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar.1
Natural variantiVAR_011324406D → V in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar.1
Natural variantiVAR_011325417C → F in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Natural variantiVAR_011326417C → R in EDAID1; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar.1
Immunodeficiency 33 (IMD33)6 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionAn X-linked recessive disorder characterized by variably impaired immunologic function and early-onset recurrent infections, usually due to pneumococcus, H. influenzae, and atypical mycobacteria. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031958173R → G in IMD33. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar.1
Natural variantiVAR_031959315E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs137853331EnsemblClinVar.1
Natural variantiVAR_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar.1
Natural variantiVAR_026496417C → Y in IMD33. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Incontinentia pigmenti (IP)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_072604173R → Q in IP. 1 PublicationCorresponds to variant dbSNP:rs1057520292EnsemblClinVar.1
Natural variantiVAR_072605183Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl.1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs179363865EnsemblClinVar.1
Natural variantiVAR_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi68S → A: Increases formation of homodimers. 1 Publication1
Mutagenesisi68S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. 1 Publication1
Mutagenesisi85S → A: Decreases ubiquitination and abolishes nuclear export. 1 Publication1
Mutagenesisi115K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi224K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi277K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. 1 Publication1
Mutagenesisi285K → R: Important decrease in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi296E → A: No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 1 Publication1
Mutagenesisi300V → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi301L → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi302K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi304Q → A: Complete loss of cleavage by HAV protease 3c. 1 Publication1
Mutagenesisi304Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi307I → N: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi308Y → A: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi309K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. No effect on MARCH2F-mediated K48-linked ubiquitination. 2 Publications1
Mutagenesisi312F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. 2 Publications1
Mutagenesisi312F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). 2 Publications1
Mutagenesisi312F → Y: Impairs tandem ubiquitin binding. 2 Publications1
Mutagenesisi313Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi315E → Q: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi317Q → A or W: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi321K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi323A → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi325K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi326K → R: Abolishes MARCH2F-mediated K48-linked ubiquitination and subsequent suppression of antiviral and antibacterial innate immune response. 1 Publication1
Mutagenesisi329L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336. 2 Publications1
Mutagenesisi329L → P: Abolished ubiquitin-binding. 3 Publications1
Mutagenesisi336L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. 1 Publication1
Mutagenesisi342K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi344K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi358K → R: No effect on MARCH2F-mediated K48-linked ubiquitination. 1 Publication1
Mutagenesisi399K → 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. 2 Publications1
Mutagenesisi414V → S: Abolishes binding to polyubiquitin. 1 Publication1
Mutagenesisi415M → S: Impairs binding to polyubiquitin. 1 Publication1

Keywords - Diseasei

Disease variant, Ectodermal dysplasia, Osteopetrosis

Organism-specific databases

DisGeNET

More...DisGeNETi		8517

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		IKBKG

MalaCards human disease database

More...MalaCardsi		IKBKG
MIMi300291, phenotype
300636, phenotype
308300, phenotype

Open Targets

More...OpenTargetsi		ENSG00000269335

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		69088, Anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome
98813, Hypohidrotic ectodermal dysplasia with immunodeficiency
464, Incontinentia pigmenti
319612, X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA29777

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q9Y6K9, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4967

Drug and drug target database

More...DrugBanki		DB04998, AGRO100
DB05289, Tarenflurbil

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		IKBKG

Domain mapping of disease mutations (DMDM)

More...DMDMi		6685695

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000967821 – 419NF-kappa-B essential modulatorAdd BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei31Phosphoserine; by IKKB1 Publication1
Modified residuei43Phosphoserine; by IKKB1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi54Interchain1 Publication
Modified residuei68Phosphoserine1 Publication1
Modified residuei85Phosphoserine; by ATM1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate2 Publications
Cross-linki283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)3 Publications
Cross-linki292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate4 Publications
Cross-linki321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin and interchain with MARCHF2)2 Publications
Disulfide bondi347Interchain1 Publication
Modified residuei376Phosphoserine; by IKKB1 Publication1
Modified residuei387PhosphoserineCombined sources1 Publication1
Cross-linki399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.1 Publication
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. Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage (PubMed:25861989). Ubiquitinated at Lys-326 by MARCHF2 following bacterial and viral infection which leads to its degradation (PubMed:32935379).8 Publications
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.5 Publications
Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.1 Publication
(Microbial infection) Cleaved by hepatitis A virus (HAV) protease 3C allowing the virus to disrupt the host innate immune signaling.1 Publication
(Microbial infection) 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.1 Publication
(Microbial infection) Polyubiquitination through 'Lys-63' is interrupted by interaction with SARS coronavirus-2/SARS-CoV-2 virus protein ORF9B which inhibits the NF-kappa-B pathway.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

The CPTAC Assay portal

More...CPTACi		CPTAC-1044
CPTAC-806

Encyclopedia of Proteome Dynamics

More...EPDi		Q9Y6K9

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q9Y6K9

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q9Y6K9

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q9Y6K9

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q9Y6K9

PeptideAtlas

More...PeptideAtlasi		Q9Y6K9

PRoteomics IDEntifications database

More...PRIDEi		Q9Y6K9

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		86716 [Q9Y6K9-1]
86717 [Q9Y6K9-2]
86718 [Q9Y6K9-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q9Y6K9, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q9Y6K9

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q9Y6K9

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000269335, Expressed in blood and 115 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q9Y6K9, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q9Y6K9, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000269335, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked (PubMed:18164680).

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 (PubMed:9751060, PubMed:9891086, PubMed:11080499, PubMed:18462684, PubMed:17977820, PubMed:32935379). The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex (PubMed:9751060, PubMed:9891086, PubMed:11080499). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (By similarity).

Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP (PubMed:11971985).

Interacts with COPS3, CYLD, NALP2, TRPC4AP and PIDD1 (PubMed:15456791, PubMed:16360037, PubMed:12917691, PubMed:11418127).

Interacts with ATM; the complex is exported from the nucleus (PubMed:16497931).

Interacts with TRAF6 (PubMed:17728323).

Interacts with IKBKE (PubMed:23453969).

Interacts with TANK; the interaction is enhanced by IKBKE and TBK1 (PubMed:12133833).

Part of a ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833).

Interacts with ZFAND5 (PubMed:14754897).

Interacts with RIPK2 (PubMed:18079694).

Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG (PubMed:11389905, PubMed:22099304).

Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin (PubMed:11389905, PubMed:22099304). Binds (via UBAN region) polyubiquitin; binds both 'Lys-63'-linked and linear polyubiquitin, with higher affinity for linear ubiquitin (PubMed:16547522, PubMed:19033441, PubMed:21606507, PubMed:19185524).

Interacts with NLRP10 (PubMed:22672233).

Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989).

Interacts with USP10; this interaction increases in response to DNA damage (PubMed:25861989).

Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989).

Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (PubMed:26334375).

Interacts with TRIM29; this interaction induces IKBKG/NEMO ubiquitination and proteolytic degradation (PubMed:27695001).

Interacts with TRIM13; this interaction leads to IKBKG/NEMO ubiquitination (PubMed:25152375).

Interacts with ARFIP2 (PubMed:26296658).

Interacts with RIPK1 (By similarity).

Interacts with (ubiquitinated) BCL10; interaction with polyubiquitinated BCL10 via both 'Lys-63'-linked and linear ubiquitin is required for TCR-induced NF-kappa-B activation (PubMed:18287044, PubMed:27777308).

Interacts with MARCHF2; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO (PubMed:32935379).

By similarity32 Publications

(Microbial infection) Interacts with Molluscum contagiosum virus protein MC005; this interaction inhibits NF-kappa-B activation.

1 Publication

(Microbial infection) Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG.

2 Publications

(Microbial infection) 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.

1 Publication

(Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF9B (via N-terminus); the interaction inhibits polyubiquitination through 'Lys-63' and NF-kappa-B activation.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Q9Y6K9
With#Exp.IntAct
ADAP2 [Q9NPF8]2EBI-81279,EBI-718895
AMOT [Q4VCS5]3EBI-81279,EBI-2511319
ANXA1 [P04083]6EBI-81279,EBI-354007
ARL6IP4 [Q66PJ3]2EBI-81279,EBI-2683099
ATM [Q13315]4EBI-81279,EBI-495465
ATR [Q13535]2EBI-81279,EBI-968983
BCL10 [O95999]7EBI-81279,EBI-958922
CALB1 [P05937]3EBI-81279,EBI-4286943
CDC37 [Q16543]6EBI-81279,EBI-295634
CDK2 [P24941]4EBI-81279,EBI-375096
CHUK [O15111]26EBI-81279,EBI-81249
COPS3 [Q9UNS2]2EBI-81279,EBI-350590
CWF19L2 [Q2TBE0]3EBI-81279,EBI-5453285
ENKD1 [Q9H0I2]3EBI-81279,EBI-744099
FLT3 [P36888]2EBI-81279,EBI-3946257
GIT2 [Q14161]6EBI-81279,EBI-1046878
GPKOW [Q92917]3EBI-81279,EBI-746309
HDDC2 [Q7Z4H3]3EBI-81279,EBI-6163836
HSP90AA1 [P07900]3EBI-81279,EBI-296047
HSP90AB1 [P08238]3EBI-81279,EBI-352572
IKBKB [O14920]36EBI-81279,EBI-81266
itself8EBI-81279,EBI-81279
KRT18 [P05783]3EBI-81279,EBI-297888
KRT8 [P05787]2EBI-81279,EBI-297852
LENG8 [Q96PV6]3EBI-81279,EBI-739546
MALT1 [Q9UDY8]4EBI-81279,EBI-1047372
MAP3K14 [Q99558]3EBI-81279,EBI-358011
MYC [P01106]3EBI-81279,EBI-447544
NFKBIA [P25963]6EBI-81279,EBI-307386
OSGIN1 [Q9UJX0]3EBI-81279,EBI-9057006
PPP2CA [P67775]4EBI-81279,EBI-712311
PRPF18 [Q99633]3EBI-81279,EBI-2798416
PSMB5 [P28074]3EBI-81279,EBI-357828
RBCK1 [Q9BYM8]9EBI-81279,EBI-2340624
RIPK1 [Q13546]8EBI-81279,EBI-358507
RNF31 [Q96EP0]10EBI-81279,EBI-948111
RNF7 [Q9UBF6]3EBI-81279,EBI-398632
RUSC1 - isoform 2 [Q9BVN2-2]4EBI-81279,EBI-6257338
SENP2 [Q9HC62]3EBI-81279,EBI-714881
SHARPIN [Q9H0F6]14EBI-81279,EBI-3942966
SLU7 [O95391]3EBI-81279,EBI-750559
SNW1 [Q13573]4EBI-81279,EBI-632715
SQSTM1 [Q13501]2EBI-81279,EBI-307104
SRC [P12931]3EBI-81279,EBI-621482
SUMO1 [P63165]3EBI-81279,EBI-80140
SYT1 [P21579]3EBI-81279,EBI-524909
TANK [Q92844]5EBI-81279,EBI-356349
TBK1 [Q9UHD2]4EBI-81279,EBI-356402
TNF [P01375]3EBI-81279,EBI-359977
TNFAIP3 [P21580]5EBI-81279,EBI-527670
TNIP1 [Q15025]6EBI-81279,EBI-357849
TNIP2 [Q8NFZ5]8EBI-81279,EBI-359372
UBC [P0CG48]4EBI-81279,EBI-3390054
UBE2D4 [Q9Y2X8]3EBI-81279,EBI-745527
ZC3H12A [Q5D1E8]2EBI-81279,EBI-747793
ZNF587 [Q96SQ5]3EBI-81279,EBI-6427977
ZNF835 [Q9Y2P0]3EBI-81279,EBI-5667516
ipaH9.8 [Q8VSC3] from Shigella flexneri.8EBI-81279,EBI-6125799
Proofreading exoribonuclease nsp14 (PRO_0000449631) from Severe acute respiratory syndrome coronavirus 2.3EBI-81279,EBI-25475920

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		114089, 427 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-3269, IkappaB kinase complex

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q9Y6K9

Database of interacting proteins

More...DIPi		DIP-27528N

Protein interaction database and analysis system

More...IntActi		Q9Y6K9, 268 interactors

Molecular INTeraction database

More...MINTi		Q9Y6K9

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000483825

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q9Y6K9

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q9Y6K9, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Biological Magnetic Resonance Data Bank

More...BMRBi		Q9Y6K9

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q9Y6K9

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q9Y6K9

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 197Required for interaction with and ubiquitination by MARCHF21 PublicationAdd BLAST197
Regioni44 – 111Interaction with CHUK/IKBKBAdd BLAST68
Regioni150 – 257Interaction with TANKAdd BLAST108
Regioni242 – 350Ubiquitin-binding (UBAN)Add BLAST109
Regioni246 – 365Self-associationAdd BLAST120
Regioni251 – 419Required for interaction with TNFAIP3Add BLAST169
Regioni322 – 343Leucine-zipperSequence analysisAdd BLAST22
Regioni358 – 395DisorderedSequence analysisAdd BLAST38
Regioni382 – 419Interaction with CYLD1 PublicationAdd BLAST38

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili49 – 356Sequence analysisAdd BLAST308

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The leucine-zipper domain and the CCHC NOA-type zinc-fingers constitute the UBAN region and are essential for polyubiquitin binding and for the activation of IRF3.2 Publications

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502R4ZD, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00530000063808

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q9Y6K9

Identification of Orthologs from Complete Genome Data

More...OMAi		KSPLCEM

Database of Orthologous Groups

More...OrthoDBi		745047at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q9Y6K9

TreeFam database of animal gene trees

More...TreeFami		TF326608

Family and domain databases

Database of protein disorder

More...DisProti		DP02269

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR032419, CC2-LZ_dom
IPR021063, NEMO_N
IPR034735, NEMO_ZF

Pfam protein domain database

More...Pfami		View protein in Pfam
PF16516, CC2-LZ, 1 hit
PF11577, NEMO, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51801, ZF_CCHC_NOA, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y6K9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET 
        60         70         80         90        100
LQRCLEENQE LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA 
       110        120        130        140        150
RKLVERLGLE KLDLKRQKEQ ALREVEHLKR CQQQMAEDKA SVKAQVTSLL 
       160        170        180        190        200
GELQESQSRL EAATKECQAL EGRARAASEQ ARQLESEREA LQQQHSVQVD 
       210        220        230        240        250
QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHIKSSVV 
       260        270        280        290        300
GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV 
       310        320        330        340        350
LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES 
       360        370        380        390        400
ARIEDMRKRH VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC 
       410 
QYQAPDMDTL QIHVMECIE
Length:419
Mass (Da):48,198
Last modified:May 30, 2000 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i322D1037881447FF
GO
Isoform 2 (identifier: Q9Y6K9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MALVIQVGKLRPREVRTPQTINPSLFPSLPVKLSSIIEVPSGGERCCSRRTLVYKARAFWKGAPLPCWM

Show »
Length:487
Mass (Da):55,787
Checksum:i7A39E991E0013A73
GO
Isoform 3 (identifier: Q9Y6K9-3) [UniParc]FASTAAdd to basket

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

Show »
Length:320
Mass (Da):36,953
Checksum:i3BEF2487C4446725
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087X1B1A0A087X1B1_HUMAN
NF-kappa-B essential modulator
IKBKG
418Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087X0G7A0A087X0G7_HUMAN
NF-kappa-B essential modulator
IKBKG
411Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087WUW6A0A087WUW6_HUMAN
NF-kappa-B essential modulator
IKBKG
412Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9J2V2C9J2V2_HUMAN
NF-kappa-B essential modulator
IKBKG
195Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9JCG6C9JCG6_HUMAN
NF-kappa-B essential modulator
IKBKG
138Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9JH59C9JH59_HUMAN
NF-kappa-B essential modulator
IKBKG
172Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9JN51C9JN51_HUMAN
NF-kappa-B essential modulator
IKBKG
250Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087X1K7A0A087X1K7_HUMAN
NF-kappa-B essential modulator
IKBKG
181Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087WV30A0A087WV30_HUMAN
NF-kappa-B essential modulator
IKBKG
115Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087WWQ9A0A087WWQ9_HUMAN
NF-kappa-B essential modulator
IKBKG
48Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti341S → R in AAD12183 (PubMed:9927690).Curated1
Sequence conflicti387S → R in AAD12183 (PubMed:9927690).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant dbSNP:rs148695964EnsemblClinVar.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026493113D → N1 PublicationCorresponds to variant dbSNP:rs179363896EnsemblClinVar.1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant dbSNP:rs179363895EnsemblClinVar.1
Natural variantiVAR_026495153L → R in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853328EnsemblClinVar.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_031958173R → G in IMD33. 1 PublicationCorresponds to variant dbSNP:rs179363866EnsemblClinVar.1
Natural variantiVAR_072604173R → Q in IP. 1 PublicationCorresponds to variant dbSNP:rs1057520292EnsemblClinVar.1
Natural variantiVAR_011320175R → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363868EnsemblClinVar.1
Natural variantiVAR_072605183Q → H in IP. 1 PublicationCorresponds to variant dbSNP:rs1198984417Ensembl.1
Natural variantiVAR_011321227L → P in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs179363869EnsemblClinVar.1
Natural variantiVAR_011322288A → G in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853330EnsemblClinVar.1
Natural variantiVAR_011323311D → N in EDAID1; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant dbSNP:rs179363867EnsemblClinVar.1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_031959315E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs137853331EnsemblClinVar.1
Natural variantiVAR_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant dbSNP:rs137853332EnsemblClinVar.1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant dbSNP:rs179363865EnsemblClinVar.1
Natural variantiVAR_011324406D → V in EDAID1. 1 PublicationCorresponds to variant dbSNP:rs137853327EnsemblClinVar.1
Natural variantiVAR_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant dbSNP:rs137853322EnsemblClinVar.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1
Natural variantiVAR_011325417C → F in EDAID1. 2 PublicationsCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1
Natural variantiVAR_011326417C → R in EDAID1; loss of sumoylation. 6 PublicationsCorresponds to variant dbSNP:rs137853325EnsemblClinVar.1
Natural variantiVAR_026496417C → Y in IMD33. 1 PublicationCorresponds to variant dbSNP:rs137853326EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0410001M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2. 1 Publication1
Alternative sequenceiVSP_041001174 – 224Missing in isoform 3. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_041002257 – 304Missing in isoform 3. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS14757.1 [Q9Y6K9-1]
CCDS48196.1 [Q9Y6K9-2]
CCDS48197.1 [Q9Y6K9-3]

NCBI Reference Sequences

More...RefSeqi		NP_001093326.2, NM_001099856.4 [Q9Y6K9-2]
NP_001093327.1, NM_001099857.2 [Q9Y6K9-1]
NP_001138727.1, NM_001145255.2 [Q9Y6K9-3]
NP_001308325.1, NM_001321396.1 [Q9Y6K9-1]
NP_001308326.1, NM_001321397.1
NP_003630.1, NM_003639.4 [Q9Y6K9-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000594239; ENSP00000471166; ENSG00000269335
ENST00000611071; ENSP00000479662; ENSG00000269335
ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		8517

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:8517

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000594239.6; ENSP00000471166.1; NM_001099857.5; NP_001093327.1

UCSC genome browser

More...UCSCi		uc033fbu.1, human [Q9Y6K9-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

IKBKGbase

IKBKG mutation db

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS14757.1 [Q9Y6K9-1]
CCDS48196.1 [Q9Y6K9-2]
CCDS48197.1 [Q9Y6K9-3]
RefSeqiNP_001093326.2, NM_001099856.4 [Q9Y6K9-2]
NP_001093327.1, NM_001099857.2 [Q9Y6K9-1]
NP_001138727.1, NM_001145255.2 [Q9Y6K9-3]
NP_001308325.1, NM_001321396.1 [Q9Y6K9-1]
NP_001308326.1, NM_001321397.1
NP_003630.1, NM_003639.4 [Q9Y6K9-1]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JVXNMR-A394-419[»]
2JVYNMR-A394-419[»]
3BRTX-ray2.25B/D44-111[»]
3BRVX-ray2.20B/D44-111[»]
3CL3X-ray3.20D/E150-272[»]
3FX0X-ray3.20A/B246-337[»]
4BWNX-ray2.27A/B258-344[»]
5AAYNMR-A392-419[»]
5LDEX-ray3.38R/S230-249[»]
6MI3X-ray1.78A/B38-129[»]
6MI4X-ray2.50A/B38-129[»]
6YEKX-ray3.20A/B258-344[»]
BMRBiQ9Y6K9
SMRiQ9Y6K9
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi114089, 427 interactors
ComplexPortaliCPX-3269, IkappaB kinase complex
CORUMiQ9Y6K9
DIPiDIP-27528N
IntActiQ9Y6K9, 268 interactors
MINTiQ9Y6K9
STRINGi9606.ENSP00000483825

Chemistry databases

BindingDBiQ9Y6K9
ChEMBLiCHEMBL4967
DrugBankiDB04998, AGRO100
DB05289, Tarenflurbil

Protein family/group databases

MoonDBiQ9Y6K9, Predicted

PTM databases

GlyGeniQ9Y6K9, 1 site, 1 O-linked glycan (1 site)
iPTMnetiQ9Y6K9
PhosphoSitePlusiQ9Y6K9

Genetic variation databases

BioMutaiIKBKG
DMDMi6685695

Proteomic databases

CPTACiCPTAC-1044
CPTAC-806
EPDiQ9Y6K9
jPOSTiQ9Y6K9
MassIVEiQ9Y6K9
MaxQBiQ9Y6K9
PaxDbiQ9Y6K9
PeptideAtlasiQ9Y6K9
PRIDEiQ9Y6K9
ProteomicsDBi86716 [Q9Y6K9-1]
86717 [Q9Y6K9-2]
86718 [Q9Y6K9-3]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		73338, 1269 antibodies from 46 providers

The DNASU plasmid repository

More...DNASUi		8517

Genome annotation databases

EnsembliENST00000594239; ENSP00000471166; ENSG00000269335
ENST00000611071; ENSP00000479662; ENSG00000269335
ENST00000611176; ENSP00000478616; ENSG00000269335 [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335 [Q9Y6K9-2]
GeneIDi8517
KEGGihsa:8517
MANE-SelectiENST00000594239.6; ENSP00000471166.1; NM_001099857.5; NP_001093327.1