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UniProtKB - O15111 (IKKA_HUMAN)

Entry version 226 (02 Jun 2021)
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:12789342, PubMed:15084260, PubMed:17434128, PubMed:20434986, PubMed:20501937, PubMed:21765415).

Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity).

By similarity6 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> 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

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

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

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.11.10, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O15111

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-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

More...SABIO-RKi		O15111

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

More...SignaLinki		O15111

SIGNOR Signaling Network Open Resource

More...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%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:
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%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:CHUK
Synonyms:IKKA, TCF16
<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 10

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:1974, CHUK

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		600664, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O15111

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000213341.10

<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

Cocoon syndrome (COCOS)1 Publication
The disease is caused by variants 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.
Related information in OMIM

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>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

More...DisGeNETi		1147

MalaCards human disease database

More...MalaCardsi		CHUK
MIMi613630, phenotype

Open Targets

More...OpenTargetsi		ENSG00000213341

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

More...Orphaneti		465824, Fetal encasement syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA26510

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O15111, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3476

Drug and drug target database

More...DrugBanki		DB06151, Acetylcysteine
DB00233, Aminosalicylic acid
DB00244, Mesalazine
DB00795, Sulfasalazine

DrugCentral

More...DrugCentrali		O15111

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1989

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...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 or proteolytic cleavage.<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 residuei179(Microbial infection) O-acetylthreonine; by Yersinia YopJ1 Publication1
Modified residuei180Phosphoserine; by SGK11 Publication1

<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

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

The CPTAC Assay portal

More...CPTACi		CPTAC-1220
CPTAC-1221

Encyclopedia of Proteome Dynamics

More...EPDi		O15111

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O15111

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O15111

MaxQB - The MaxQuant DataBase

More...MaxQBi		O15111

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

More...PaxDbi		O15111

PeptideAtlas

More...PeptideAtlasi		O15111

PRoteomics IDEntifications database

More...PRIDEi		O15111

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		48449

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O15111

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

More...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

More...Bgeei		ENSG00000213341, Expressed in islet of Langerhans and 118 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O15111, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000213341, 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

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).

Interacts with SASH1 (PubMed:23776175). Directly interacts with DDX3X after the physiological activation of the TLR7 and TLR8 pathways; this interaction enhances CHUK autophosphorylation (PubMed:30341167).

By similarity16 Publications

(Microbial infection) Interacts with InlC of Listeria monocytogenes.

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

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		107569, 157 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O15111

Database of interacting proteins

More...DIPi		DIP-27526N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		O15111

Protein interaction database and analysis system

More...IntActi		O15111, 73 interactors

Molecular INTeraction database

More...MINTi		O15111

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000359424

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O15111

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O15111, 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

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

3D structure databases

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

More...SMRi		O15111

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		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%5Fand%5Fdomains%5Fsection">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

More...eggNOGi		KOG4250, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00950000182937

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_101_2_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O15111

Identification of Orthologs from Complete Genome Data

More...OMAi		RMMNLDW

Database of Orthologous Groups

More...OrthoDBi		1013139at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O15111

TreeFam database of animal gene trees

More...TreeFami		TF324269

Family and domain databases

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00526

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR041185, IKBKB_SDD
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

More...Pfami		View protein in Pfam
PF18397, IKBKB_SDD, 1 hit
PF12179, IKKbetaNEMObind, 1 hit
PF00069, Pkinase, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...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%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>Sequencei

<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.

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

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

More...CCDSi		CCDS7488.1

NCBI Reference Sequences

More...RefSeqi		NP_001269.3, NM_001278.4

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000370397; ENSP00000359424; ENSG00000213341

Database of genes from NCBI RefSeq genomes

More...GeneIDi		1147

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:1147

UCSC genome browser

More...UCSCi		uc001kqp.4, human

<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

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

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
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[»]
SMRiO15111
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi107569, 157 interactors
ComplexPortaliCPX-3269, IkappaB kinase complex
CORUMiO15111
DIPiDIP-27526N
ELMiO15111
IntActiO15111, 73 interactors
MINTiO15111
STRINGi9606.ENSP00000359424

Chemistry databases

BindingDBiO15111
ChEMBLiCHEMBL3476
DrugBankiDB06151, Acetylcysteine
DB00233, Aminosalicylic acid
DB00244, Mesalazine
DB00795, Sulfasalazine
DrugCentraliO15111
GuidetoPHARMACOLOGYi1989

PTM databases

iPTMnetiO15111
PhosphoSitePlusiO15111

Genetic variation databases

BioMutaiCHUK

Proteomic databases

CPTACiCPTAC-1220
CPTAC-1221
EPDiO15111
jPOSTiO15111
MassIVEiO15111
MaxQBiO15111
PaxDbiO15111
PeptideAtlasiO15111
PRIDEiO15111
ProteomicsDBi48449

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		801, 1466 antibodies

The DNASU plasmid repository

More...DNASUi		1147

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		1147
DisGeNETi1147

GeneCards: human genes, protein and diseases

More...GeneCardsi		CHUK
HGNCiHGNC:1974, CHUK
HPAiENSG00000213341, Low tissue specificity
MalaCardsiCHUK
MIMi600664, gene
613630, phenotype
neXtProtiNX_O15111
OpenTargetsiENSG00000213341
Orphaneti465824, Fetal encasement syndrome
PharmGKBiPA26510
VEuPathDBiHostDB:ENSG00000213341.10

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG4250, Eukaryota
GeneTreeiENSGT00950000182937
HOGENOMiCLU_000288_101_2_1
InParanoidiO15111
OMAiRMMNLDW
OrthoDBi1013139at2759
PhylomeDBiO15111
TreeFamiTF324269

Enzyme and pathway databases

BRENDAi2.7.11.10, 2681
PathwayCommonsiO15111
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

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		1147, 32 hits in 1029 CRISPR screens

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

More...GeneWikii		CHUK

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

More...GenomeRNAii		1147
PharosiO15111, Tchem

Protein Ontology

More...PROi		PR:O15111
RNActiO15111, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000213341, Expressed in islet of Langerhans and 118 other tissues
GenevisibleiO15111, HS

Family and domain databases

IDEALiIID00526
InterProiView protein in InterPro
IPR041185, IKBKB_SDD
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
PF18397, IKBKB_SDD, 1 hit
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

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		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%5Fand%5Fisoforms">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: June 2, 2021
This is version 226 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, Direct protein sequencing, Reference proteome

Documents

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