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; AllianceGenome:HGNC:1974
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: BPS2; IKK1; IKKA; IKBKA; IKK-1; 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
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Genomic context

Location:: 10q24.31

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (100186319..100229596, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (101070354..101113853, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (101948057..101989353, 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?

GRP78 recognizes EV-F 3D protein and activates NF-kappaB to repress virus replication by interacting with CHUK/IKBKB.
Title: GRP78 recognizes EV-F 3D protein and activates NF-κB to repress virus replication by interacting with CHUK/IKBKB.
Cytokines-activated nuclear IKKalpha-FAT10 pathway induces breast cancer tamoxifen-resistance.
Title: Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance.
The host antiviral protein SAMHD1 suppresses NF-kappaB activation by interacting with the IKK complex during inflammatory responses and viral infection.
Title: The host antiviral protein SAMHD1 suppresses NF-κB activation by interacting with the IKK complex during inflammatory responses and viral infection.
IL-1beta stimulates a novel, IKKalpha -dependent, NIK -independent activation of non-canonical NFkappaB signalling.
Title: IL-1β stimulates a novel, IKKα -dependent, NIK -independent activation of non-canonical NFκB signalling.
IKKalpha kinase silencing increases doxorubicin-induced apoptosis through regulation of oxidative DNA damage response in colon cancer cells.
Title: IKKα kinase silencing increases doxorubicin-induced apoptosis through regulation of oxidative DNA damage response in colon cancer cells.
The inhibitor of kappaB kinase beta (IKKbeta) phosphorylates IkappaBalpha twice in a single binding event through a sequential mechanism.
Title: The inhibitor of κB kinase β (IKKβ) phosphorylates IκBα twice in a single binding event through a sequential mechanism.
Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer.
Title: Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer.
Enterovirus 2C Protein Suppresses IKKalpha Phosphorylation by Recruiting IKKbeta and IKKalpha into Viral Inclusion Bodies.
Title: Enterovirus 2C Protein Suppresses IKKα Phosphorylation by Recruiting IKKβ and IKKα into Viral Inclusion Bodies.
Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor B kinase alpha (IKKalpha).
Title: Combined immunodeficiency with autoimmunity caused by a homozygous missense mutation in inhibitor of nuclear factor 𝛋B kinase alpha (IKKα).
IKKalpha plays a major role in canonical NF-kappaB signalling in colorectal cells.
Title: IKKα plays a major role in canonical NF-κB signalling in colorectal cells.

Submit: New GeneRIF Correction See all GeneRIFs (205)

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
Bartsocas-Papas syndrome 2 MedGen: C5543445 OMIM: 619339 GeneReviews: Not available	not available
Cocoon syndrome MedGen: C3150891 OMIM: 613630 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. EBI GWAS Catalog EBI GWAS 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

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical NF-kappaB signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interferon-alpha production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in response to acetate	IEA Inferred from Electronic Annotation more info
involved_in response to amino acid	IEA Inferred from Electronic Annotation more info
involved_in response to cholecystokinin	IEA Inferred from Electronic Annotation more info
involved_in response to hydroperoxide	IEA Inferred from Electronic Annotation more info
involved_in response to toxic substance	IEA Inferred from Electronic Annotation more info
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in striated muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of CD40 receptor complex	ISS Inferred from Sequence or Structural Similarity more info
part_of IkappaB kinase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of IkappaB kinase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of IkappaB kinase complex	TAS Traceable Author Statement more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in 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; 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_016871101.1

EC 2.7.11.10

XP_047280496.1

EC 2.7.11.10

XP_047280497.1

EC 2.7.11.10

XP_047280498.1

EC 2.7.11.10

XP_047280499.1

EC 2.7.11.10

XP_054220630.1

EC 2.7.11.10

XP_054220631.1

EC 2.7.11.10

XP_054220632.1

EC 2.7.11.10

XP_054220633.1

EC 2.7.11.10

XP_054220634.1

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_028023.2 RefSeqGene

Range

5000..46296

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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

O14666, O15111, Q13132, Q5W0I4, Q92467

UniProtKB/TrEMBL

Q562E6

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_001320928.2 → NP_001307857.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform 2

Status: REVIEWED

Source sequence(s)

AI829429, AL138921, DA405845

UniProtKB/TrEMBL

Q59GT1

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000010.11 Reference GRCh38.p14 Primary Assembly

Range

100186319..100229596 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047424542.1 → XP_047280498.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3
XM_047424540.1 → XP_047280496.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1
XM_047424541.1 → XP_047280497.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2
XM_017015612.2 → XP_016871101.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X4
XM_047424543.1 → XP_047280499.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X5

Alternate T2T-CHM13v2.0

Genomic

NC_060934.1 Alternate T2T-CHM13v2.0

Range

101070354..101113853 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364655.1 → XP_054220630.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1
XM_054364657.1 → XP_054220632.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3
XM_054364656.1 → XP_054220631.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2
XM_054364658.1 → XP_054220633.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X4
XM_054364659.1 → XP_054220634.1 inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X5