CHUK component of inhibitor of nuclear factor kappa B kinase complex [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHUKprovided by HGNC
Official Full Name: component of inhibitor of nuclear factor kappa B kinase complexprovided by HGNC
Primary source: HGNC:HGNC:1974
See related: Ensembl:ENSG00000213341 MIM:600664
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IKK1; IKKA; IKBKA; TCF16; NFKBIKA; IKK-alpha
Summary: This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in kidney (RPKM 4.9), bone marrow (RPKM 4.7) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 10q24.31

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	10	NC_000010.11 (100188298..100229610, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (101948123..101989367, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Reduced expression of adenomatous polyposis coli (Apc) gene and IkappaB kinase alpha (IkappaBalpha), and increased expression of NF-kappaB p65 were found in Intracranial aneurysm (IA) tissues.
Title: <i>Apc</i> gene suppresses intracranial aneurysm formation and rupture through inhibiting the NF-κB signaling pathway mediated inflammatory response.
data indicate that the IKKs restrict infection but HCMV targets their signaling to modulate the cellular inflammatory environment.
Title: The IκB Kinases Restrict Human Cytomegalovirus Infection.
IKKalpha(p45) is rapidly activated by DNA damage independent of ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, and is required for robust ATM activation and efficient DNA repair.
Title: IKKα Kinase Regulates the DNA Damage Response and Drives Chemo-resistance in Cancer.
miR379 inhibits cell proliferation and epithelialmesenchymal transition by targeting CHUK through the NFkappaB pathway in nonsmall cell lung cancer.
Title: miR‑379 inhibits cell proliferation and epithelial‑mesenchymal transition by targeting CHUK through the NF‑κB pathway in non‑small cell lung cancer.
Data suggest a linkage between notch receptor 1 (NOTCH1), IKK-alpha protein (IKKalpha), and NF-kappa B (NF-kappaB) pathway activation in maintaining the CD133(+) stem cutaneous squamous cell carcinoma (cSCC) phenotypes.
Title: Targeting Notch1 and IKKα Enhanced NF-κB Activation in CD133<sup>+</sup> Skin Cancer Stem Cells.
mRNA expression of individual inhibitory kappaB kinases and SIKE are associated with unique prognostic significance and may act as valuable prognostic biomarkers and potential targets for future therapeutic interventions in gastric cancer.
Title: Prognostic values of inhibitory κB kinases mRNA expression in human gastric cancer.
Data indicate that DEAD-box helicase 3 (DDX3) directly interacts with IkappaB kinase alpha (IKKalpha) and enhances its autophosphorylation and -activation.
Title: DDX3 directly facilitates IKKα activation and regulates downstream signalling pathways.
A core element of NF-kappaB activation is the IKK complex built from two catalytic subunits, IKKa and IKKb kinases, and a regulatory subunit, NF-kappaB essential modulator (NEMO)/IKKc. (Review)
Title: IKKs and tumor cell plasticity.
Depletion of human IKK1, IKK2 or IKK1/2 leads to strongly impaired NF-kappaB activation. Only IKK1/2 double-deficient cells are sensitized to TNF-alpha induced cell death. Cell death is mediated independently on NF-kappaB via RIPK1.
Title: IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner.
AMBRA1 regulates mitophagy through a novel pathway, in which HUWE1 and IKKalpha are key factors, shedding new lights on the regulation of mitochondrial quality control and homoeostasis in mammalian cells.
Title: HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα.

Submit: New GeneRIF Correction See all GeneRIFs (183)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cocoon syndrome MedGen: C3150891 OMIM: 613630 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120/CD4 interaction-induced NF-kappaB activation stimulates the hyperphosphorylation of IkappaB-alpha by IkappaB kinases (IKKs)	PubMed
Nef	nef	HIV-1 Nef induces phosphorylation of CHUK (IKKalpha)	PubMed
	nef	HIV-1 Nef-induced strong activation of MAP kinases (p38/MAPK14, JNK/MAPK8, and ERK1/2) and NF-kappaB pathway (IKK alpha/beta) in M2-macrophages is mediated by TAK1	PubMed
	nef	HIV-1 Nef induces phosphorylation of IKKalpha in M2-type macrophages	PubMed
	nef	The interaction of HIV-1 Nef with TRAF2, TRAF5, and TRAF6 proteins activates NF-kappaB, leading to the degradation of IkappaB-alpha and the increased phosphorylation of IKK-alpha and IKK-beta in monocyte-derived macrophages	PubMed
	nef	HIV-1 Nef myristoylation is required for the rapid and transient phosphorylation of the alpha- and beta- subunits of the Ikappa-B kinase complex and activation of JNK, ERK1/2 and p38 MAPK family members	PubMed
Tat	tat	HIV-1 Tat induces phosphorylation of CHUK (IKKalpha) in CRT-MG human astroglioma cells	PubMed
	tat	HIV-1 Tat induces phosphorylation of IKK-alpha/IKK-beta in human astroglioma cells	PubMed
	tat	HIV-1 Tat induces phosphorylation of IKK in HeLa-CD4-long terminal repeat (LTR)-beta-gal (MAGI) cells	PubMed
	tat	Tat stimulates NF-kappaB-inducing kinase IKKalpha translocation from the cytoplasm to the nucleus in monocytes, which leads to IKKalpha and CBP/p300 recruitment to the IL-10 promoter and histone H3 phosphorylation (Ser 10) and acetylation (Lys 14)	PubMed
	tat	Tat activates at least three signaling pathways concurrently, including NF-kappaB, PKC, ERK1/2 and p38 MAP kinases and IKKalpha pathways, to promote production of IL-10	PubMed
Vpr	vpr	HIV-1 Vpr requires CHUK (IKKa) or IKBKB (IKKb) to induce G2/M arrest in HeLa cells as shown through siRNA knockdown of CHUK (IKKa) or IKBKB (IKKb)	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

RH15687 (e-PCR)
- UniSTS:78910

CHUK_1668 (e-PCR)
- UniSTS:280502

GDB:335751 (e-PCR)
- UniSTS:156601

SHGC-68297 (e-PCR)
- UniSTS:95425

L29953 (e-PCR)
- UniSTS:52164

SHGC-83371 (e-PCR)
- UniSTS:101061

Homology

Homologs of the CHUK gene: The CHUK gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 272 organisms have orthologs with human gene CHUK
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
contributes_to IkappaB kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
IkappaB kinase activity	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein heterodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
protein-containing complex binding	IEA Inferred from Electronic Annotation more info
scaffold protein binding	IDA Inferred from Direct Assay more info	PubMed
transferrin receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
I-kappaB kinase/NF-kappaB signaling	TAS Traceable Author Statement more info	PubMed
I-kappaB phosphorylation	TAS Traceable Author Statement more info	PubMed
MyD88-independent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
NIK/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
NIK/NF-kappaB signaling	TAS Traceable Author Statement more info
Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
T cell receptor signaling pathway	TAS Traceable Author Statement more info
TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS Traceable Author Statement more info
cellular response to cadmium ion	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to reactive oxygen species	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
cellular response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
immune response	TAS Traceable Author Statement more info	PubMed
inflammatory response	TAS Traceable Author Statement more info	PubMed
innate immune response	TAS Traceable Author Statement more info	PubMed
interleukin-1-mediated signaling pathway	TAS Traceable Author Statement more info
negative regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	TAS Traceable Author Statement more info
positive regulation of NF-kappaB transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of NF-kappaB transcription factor activity	TAS Traceable Author Statement more info	PubMed
positive regulation of interferon-alpha secretion	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
response to acetate	IEA Inferred from Electronic Annotation more info
response to amino acid	IEA Inferred from Electronic Annotation more info
response to cholecystokinin	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to hydroperoxide	IEA Inferred from Electronic Annotation more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to toxic substance	IEA Inferred from Electronic Annotation more info
response to virus	TAS Traceable Author Statement more info	PubMed
skeletal muscle contraction	IEA Inferred from Electronic Annotation more info
stimulatory C-type lectin receptor signaling pathway	TAS Traceable Author Statement more info
stress-activated MAPK cascade	TAS Traceable Author Statement more info
striated muscle cell differentiation	IEA Inferred from Electronic Annotation more info
tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
IkappaB kinase complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
IkappaB kinase complex	TAS Traceable Author Statement more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
cytosol	IDA Inferred from Direct Assay more info
cytosol	TAS Traceable Author Statement more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: inhibitor of nuclear factor kappa-B kinase subunit alpha

Names: I-kappa-B kinase 1; I-kappa-B kinase-alpha; IKK-a kinase; IkB kinase alpha subunit; Nuclear factor NFkappaB inhibitor kinase alpha; TCF-16; conserved helix-loop-helix ubiquitous kinase; transcription factor 16

NP_001269.3

EC 2.7.11.10

NP_001307857.1

EC 2.7.11.10

XP_016871100.1

EC 2.7.11.10

XP_016871101.1

EC 2.7.11.10

XP_016871102.1

EC 2.7.11.10

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_028023.1 RefSeqGene

Range

4992..46288

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001278.5 → NP_001269.3 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 1

See identical proteins and their annotated locations for NP_001269.3

Status: REVIEWED

Source sequence(s)

AF080157, AI829429, BC034796, BM800404, DA405845

Consensus CDS

CCDS7488.1

UniProtKB/Swiss-Prot

O15111

Related

ENSP00000359424.6, ENST00000370397.8

Conserved Domains (2) summary

cd14039
Location:21 → 309

STKc_IKK_alpha; Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha

pfam12179
Location:709 → 743

IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain
NM_001320928.1 → NP_001307857.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 2

Status: REVIEWED

Source sequence(s)

AI829429, AL138921, DA405845

Conserved Domains (2) summary

smart00220
Location:15 → 298

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14039
Location:21 → 309

STKc_IKK_alpha; Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p13 Primary Assembly

Range

100188298..100229610 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017015611.1 → XP_016871100.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1
XM_017015613.1 → XP_016871102.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3
XM_017015612.1 → XP_016871101.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2