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Entry version 211 (10 Apr 2019)
Sequence version 2 (11 Jan 2011)
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Protein

Inhibitor of nuclear factor kappa-B kinase subunit alpha

Gene

CHUK

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

Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Negatively regulates the pathway by phosphorylating the scaffold protein TAXBP1 and thus promoting the assembly of the A20/TNFAIP3 ubiquitin-editing complex (composed of A20/TNFAIP3, TAX1BP1, and the E3 ligases ITCH and RNF11). Therefore, CHUK plays a key role in the negative feedback of NF-kappa-B canonical signaling to limit inflammatory gene activation. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. In turn, these complexes regulate genes encoding molecules involved in B-cell survival and lymphoid organogenesis. Participates also in the negative feedback of the non-canonical NF-kappa-B signaling pathway by phosphorylating and destabilizing MAP3K14/NIK. Within the nucleus, phosphorylates CREBBP and consequently increases both its transcriptional and histone acetyltransferase activities. Modulates chromatin accessibility at NF-kappa-B-responsive promoters by phosphorylating histones H3 at 'Ser-10' that are subsequently acetylated at 'Lys-14' by CREBBP. Additionally, phosphorylates the CREBBP-interacting protein NCOA3. Also phosphorylates FOXO3 and may regulate this pro-apoptotic transcription factor (PubMed:15084260).6 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated when phosphorylated and inactivated when dephosphorylated.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei44ATPPROSITE-ProRule annotation1
<p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei144Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi21 – 29ATPPROSITE-ProRule annotation9

<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

GO - Biological processi

<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

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.10 2681

Reactome - a knowledgebase of biological pathways and processes

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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-198323 AKT phosphorylates targets in the cytosol
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-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-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
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

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SABIO-RKi
O15111

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

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SignaLinki
O15111

SIGNOR Signaling Network Open Resource

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SIGNORi
O15111

<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_and_taxonomy_section">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:
Inhibitor of nuclear factor kappa-B kinase subunit alpha (EC:2.7.11.10)
Short name:
I-kappa-B kinase alpha
Short name:
IKK-A
Short name:
IKK-alpha
Short name:
IkBKA
Short name:
IkappaB kinase
Alternative name(s):
Conserved helix-loop-helix ubiquitous kinase
I-kappa-B kinase 1
Short name:
IKK1
Nuclear factor NF-kappa-B inhibitor kinase alpha
Short name:
NFKBIKA
Transcription factor 16
Short name:
TCF-16
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:CHUK
Synonyms:IKKA, TCF16
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_manual">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 10

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000213341.10

Human Gene Nomenclature Database

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HGNCi
HGNC:1974 CHUK

Online Mendelian Inheritance in Man (OMIM)

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MIMi
600664 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O15111

<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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

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

Cocoon syndrome (COCOS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA lethal syndrome characterized by multiple fetal malformations including defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin.
See also OMIM:613630

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'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>Mutagenesisi23T → A: Loss of phosphorylation and decrease of kinase activity. 1 Publication1
Mutagenesisi44K → A: Loss of kinase activity. 2 Publications1
Mutagenesisi44K → M: Loss of autophosphorylation. 2 Publications1
Mutagenesisi176S → A: Loss of phosphorylation and of activity. 2 Publications1
Mutagenesisi176S → E: Full activation. 2 Publications1
Mutagenesisi179T → A: No change in phosphorylation. 1 Publication1
Mutagenesisi180S → A: No change in phosphorylation. 1 Publication1

Organism-specific databases

DisGeNET

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DisGeNETi
1147

MalaCards human disease database

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MalaCardsi
CHUK
MIMi613630 phenotype

Open Targets

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OpenTargetsi
ENSG00000213341

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

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Orphaneti
465824 Fetal encasement syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA26510

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL3476

Drug and drug target database

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DrugBanki
DB06151 Acetylcysteine
DB00233 Aminosalicylic Acid
DB00244 Mesalazine
DB00795 Sulfasalazine

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1989

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
CHUK

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000860111 – 745Inhibitor of nuclear factor kappa-B kinase subunit alphaAdd BLAST745

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 residuei23Phosphothreonine; by PKB/AKT1 and SGK12 Publications1
Modified residuei176Phosphoserine; by MAP3K141 Publication1
Modified residuei179O-acetylthreonine; by Yersinia yopJ1 Publication1
Modified residuei180Phosphoserine; by SGK11 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

Phosphorylated by MAP3K14/NIK, AKT and to a lesser extent by MEKK1, and dephosphorylated by PP2A. Autophosphorylated.
(Microbial infection) Acetylation of Thr-179 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O15111

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O15111

MaxQB - The MaxQuant DataBase

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MaxQBi
O15111

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

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PaxDbi
O15111

PeptideAtlas

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PeptideAtlasi
O15111

PRoteomics IDEntifications database

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PRIDEi
O15111

ProteomicsDB human proteome resource

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ProteomicsDBi
48449

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O15111

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

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PhosphoSitePlusi
O15111

<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

Widely expressed.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000213341 Expressed in 92 organ(s), highest expression level in caudate nucleus

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O15111 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB004240
CAB018564
HPA001402

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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 (PubMed:10195894, PubMed:12612076). 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). Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (PubMed:9751059). Directly interacts with TRPC4AP (By similarity). May interact with TRAF2 (PubMed:19150425). Interacts with NALP2 (PubMed:15456791). May interact with MAVS/IPS1 (PubMed:16177806). Interacts with ARRB1 and ARRB2 (PubMed:15173580). Interacts with NLRC5; prevents CHUK phosphorylation and kinase activity (PubMed:20434986). Interacts with PIAS1; this interaction induces PIAS1 phosphorylation (PubMed:17540171). Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-alpha-dependent manner (PubMed:23091055). Interacts with FOXO3 (PubMed:15084260). Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (PubMed:26334375). Interacts with LRRC14 (PubMed:27426725).By similarity14 Publications
(Microbial infection) Interacts with InlC of Listeria monocytogenes.1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">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="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
107569, 143 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-3269 IkappaB kinase complex

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O15111

Database of interacting proteins

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DIPi
DIP-27526N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
O15111

Protein interaction database and analysis system

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IntActi
O15111, 70 interactors

Molecular INTeraction database

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MINTi
O15111

STRING: functional protein association networks

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STRINGi
9606.ENSP00000359424

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O15111

<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

1745
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C732-745[»]
5EBZX-ray4.50A/B/C/D/E/F/G/H/I/J/K/L10-660[»]
5TQWelectron microscopy5.60A/B10-660[»]
5TQXelectron microscopy5.40A/B10-660[»]
5TQYelectron microscopy5.20A/B10-660[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O15111

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

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SMRi
O15111

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O15111

<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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini15 – 302Protein kinasePROSITE-ProRule annotationAdd BLAST288

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>Regioni455 – 476Leucine-zipperAdd BLAST22
Regioni738 – 743NEMO-binding6

<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 kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG.1 Publication

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.PROSITE-ProRule annotation

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4250 Eukaryota
ENOG410XRMU LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00950000182937

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000038048

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG018241

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O15111

KEGG Orthology (KO)

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KOi
K04467

Identification of Orthologs from Complete Genome Data

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OMAi
TPQASAW

Database of Orthologous Groups

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OrthoDBi
1013139at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O15111

TreeFam database of animal gene trees

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TreeFami
TF324269

Family and domain databases

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR022007 IKKbetaNEMObind
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS

Pfam protein domain database

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Pfami
View protein in Pfam
PF12179 IKKbetaNEMObind, 1 hit
PF00069 Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM01239 IKKbetaNEMObind, 1 hit
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 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_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

O15111-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MERPPGLRPG AGGPWEMRER LGTGGFGNVC LYQHRELDLK IAIKSCRLEL
60 70 80 90 100
STKNRERWCH EIQIMKKLNH ANVVKACDVP EELNILIHDV PLLAMEYCSG
110 120 130 140 150
GDLRKLLNKP ENCCGLKESQ ILSLLSDIGS GIRYLHENKI IHRDLKPENI
160 170 180 190 200
VLQDVGGKII HKIIDLGYAK DVDQGSLCTS FVGTLQYLAP ELFENKPYTA
210 220 230 240 250
TVDYWSFGTM VFECIAGYRP FLHHLQPFTW HEKIKKKDPK CIFACEEMSG
260 270 280 290 300
EVRFSSHLPQ PNSLCSLVVE PMENWLQLML NWDPQQRGGP VDLTLKQPRC
310 320 330 340 350
FVLMDHILNL KIVHILNMTS AKIISFLLPP DESLHSLQSR IERETGINTG
360 370 380 390 400
SQELLSETGI SLDPRKPASQ CVLDGVRGCD SYMVYLFDKS KTVYEGPFAS
410 420 430 440 450
RSLSDCVNYI VQDSKIQLPI IQLRKVWAEA VHYVSGLKED YSRLFQGQRA
460 470 480 490 500
AMLSLLRYNA NLTKMKNTLI SASQQLKAKL EFFHKSIQLD LERYSEQMTY
510 520 530 540 550
GISSEKMLKA WKEMEEKAIH YAEVGVIGYL EDQIMSLHAE IMELQKSPYG
560 570 580 590 600
RRQGDLMESL EQRAIDLYKQ LKHRPSDHSY SDSTEMVKII VHTVQSQDRV
610 620 630 640 650
LKELFGHLSK LLGCKQKIID LLPKVEVALS NIKEADNTVM FMQGKRQKEI
660 670 680 690 700
WHLLKIACTQ SSARSLVGSS LEGAVTPQTS AWLPPTSAEH DHSLSCVVTP
710 720 730 740
QDGETSAQMI EENLNCLGHL STIIHEANEE QGNSMMNLDW SWLTE
Length:745
Mass (Da):84,640
Last modified:January 11, 2011 - 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:i4EA55C6FFC66FA16
GO

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 conflicti543E → G in AAC51671 (PubMed:9252186).Curated1
Sequence conflicti604L → R in AAC50713 (PubMed:8777433).Curated1
Sequence conflicti679 – 680TS → AY in AAC50713 (PubMed:8777433).Curated2
Sequence conflicti684P → A no nucleotide entry (PubMed:9346484).Curated1
Sequence conflicti684P → A in AAC50713 (PubMed:8777433).Curated1
Sequence conflicti686 – 687TS → DL in AAC50713 (PubMed:8777433).Curated2

Natural variant

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_040565126S → C1 PublicationCorresponds to variant dbSNP:rs34427437Ensembl.1
Natural variantiVAR_040566155V → A1 PublicationCorresponds to variant dbSNP:rs2230803Ensembl.1
Natural variantiVAR_021359268V → I6 PublicationsCorresponds to variant dbSNP:rs2230804Ensembl.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
AF012890 mRNA Translation: AAC51662.1
AF009225 mRNA Translation: AAC51671.1
AF080157 mRNA Translation: AAD08996.1
AY652653 Genomic DNA Translation: AAT49098.1
AL138921 Genomic DNA No translation available.
U22512 mRNA Translation: AAC50713.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS7488.1

NCBI Reference Sequences

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RefSeqi
NP_001269.3, NM_001278.4

UniGene gene-oriented nucleotide sequence clusters

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UniGenei
Hs.198998

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000370397; ENSP00000359424; ENSG00000213341

Database of genes from NCBI RefSeq genomes

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GeneIDi
1147

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:1147

UCSC genome browser

More...
UCSCi
uc001kqp.4 human

Keywords - Coding sequence diversityi

Polymorphism

<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_references_section">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

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF012890 mRNA Translation: AAC51662.1
AF009225 mRNA Translation: AAC51671.1
AF080157 mRNA Translation: AAD08996.1
AY652653 Genomic DNA Translation: AAT49098.1
AL138921 Genomic DNA No translation available.
U22512 mRNA Translation: AAC50713.1
CCDSiCCDS7488.1
RefSeqiNP_001269.3, NM_001278.4
UniGeneiHs.198998

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C732-745[»]
5EBZX-ray4.50A/B/C/D/E/F/G/H/I/J/K/L10-660[»]
5TQWelectron microscopy5.60A/B10-660[»]
5TQXelectron microscopy5.40A/B10-660[»]
5TQYelectron microscopy5.20A/B10-660[»]
ProteinModelPortaliO15111
SMRiO15111
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107569, 143 interactors
ComplexPortaliCPX-3269 IkappaB kinase complex
CORUMiO15111
DIPiDIP-27526N
ELMiO15111
IntActiO15111, 70 interactors
MINTiO15111
STRINGi9606.ENSP00000359424

Chemistry databases

BindingDBiO15111
ChEMBLiCHEMBL3476
DrugBankiDB06151 Acetylcysteine
DB00233 Aminosalicylic Acid
DB00244 Mesalazine
DB00795 Sulfasalazine
GuidetoPHARMACOLOGYi1989

PTM databases

iPTMnetiO15111
PhosphoSitePlusiO15111

Polymorphism and mutation databases

BioMutaiCHUK

Proteomic databases

EPDiO15111
jPOSTiO15111
MaxQBiO15111
PaxDbiO15111
PeptideAtlasiO15111
PRIDEiO15111
ProteomicsDBi48449

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370397; ENSP00000359424; ENSG00000213341
GeneIDi1147
KEGGihsa:1147
UCSCiuc001kqp.4 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
1147
DisGeNETi1147
EuPathDBiHostDB:ENSG00000213341.10

GeneCards: human genes, protein and diseases

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GeneCardsi
CHUK

H-Invitational Database, human transcriptome db

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H-InvDBi
HIX0201495
HGNCiHGNC:1974 CHUK
HPAiCAB004240
CAB018564
HPA001402
MalaCardsiCHUK
MIMi600664 gene
613630 phenotype
neXtProtiNX_O15111
OpenTargetsiENSG00000213341
Orphaneti465824 Fetal encasement syndrome
PharmGKBiPA26510

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4250 Eukaryota
ENOG410XRMU LUCA
GeneTreeiENSGT00950000182937
HOGENOMiHOG000038048
HOVERGENiHBG018241
InParanoidiO15111
KOiK04467
OMAiTPQASAW
OrthoDBi1013139at2759
PhylomeDBiO15111
TreeFamiTF324269

Enzyme and pathway databases

BRENDAi2.7.11.10 2681
ReactomeiR-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-198323 AKT phosphorylates targets in the cytosol
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-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-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation
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-RKiO15111
SignaLinkiO15111
SIGNORiO15111

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
CHUK human
EvolutionaryTraceiO15111

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
CHUK

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
1147

Protein Ontology

More...
PROi
PR:O15111

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000213341 Expressed in 92 organ(s), highest expression level in caudate nucleus
GenevisibleiO15111 HS

Family and domain databases

InterProiView protein in InterPro
IPR022007 IKKbetaNEMObind
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF12179 IKKbetaNEMObind, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM01239 IKKbetaNEMObind, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiIKKA_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O15111
Secondary accession number(s): O14666
, Q13132, Q5W0I4, Q92467
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 11, 2011
Last modified: April 10, 2019
This is version 211 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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