IKBKB inhibitor of nuclear factor kappa B kinase subunit beta [Homo sapiens (human)] - Gene

Summary

Official Symbol: IKBKBprovided by HGNC
Official Full Name: inhibitor of nuclear factor kappa B kinase subunit betaprovided by HGNC
Primary source: HGNC:HGNC:5960
See related: Ensembl:ENSG00000104365 MIM:603258; AllianceGenome:HGNC:5960
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: IKK2; IKKB; IMD15; IMD15A; IMD15B; NFKBIKB; IKK-beta
Summary: The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]
Expression: Ubiquitous expression in spleen (RPKM 14.6), lymph node (RPKM 12.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8p11.21

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (42271302..42332460)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (42545654..42606501)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (42128820..42189978)

Chromosome 8 - NC_000008.11 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?

NF-kappaB-inducing kinase (NIK) is activated in pancreatic beta-cells but does not contribute to the development of diabetes.
Title: NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes.
IKKbeta Alleviates Neuron Injury in Alzheimer's Disease via Regulating Autophagy and RIPK1-Mediated Necroptosis.
Title: IKKβ Alleviates Neuron Injury in Alzheimer's Disease via Regulating Autophagy and RIPK1-Mediated Necroptosis.
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.
Basal and IL-1beta enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKalpha and IKKbeta NF-kappaB activating kinases.
Title: Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases.
Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-kappaB/bone remodeling factors signaling.
Title: Circular RNA circIKBKB promotes breast cancer bone metastasis through sustaining NF-κB/bone remodeling factors signaling.
Clinicopathological analysis and prognostic significance of NF-kappaB p65 and IKKbeta protein and mRNA expression in nasopharyngeal carcinoma.
Title: Clinicopathological analysis and prognostic significance of NF-κB p65 and IKKβ protein and mRNA expression in nasopharyngeal carcinoma.
MAP3K7-IKK Inflammatory Signaling Modulates AR Protein Degradation and Prostate Cancer Progression.
Title: MAP3K7-IKK Inflammatory Signaling Modulates AR Protein Degradation and Prostate Cancer Progression.
Crosstalk of the IkappaB Kinase with Spliced X-Box Binding Protein 1 Couples Inflammation with Glucose Metabolic Reprogramming in Epithelial-Mesenchymal Transition.
Title: Crosstalk of the IκB Kinase with Spliced X-Box Binding Protein 1 Couples Inflammation with Glucose Metabolic Reprogramming in Epithelial-Mesenchymal Transition.
Inhibition of kinase IKKbeta suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6.
Title: Inhibition of kinase IKKβ suppresses cellular abnormalities induced by the human papillomavirus oncoprotein HPV 18E6.
Heterozygous IKKbeta activation loop mutation results in a complex immunodeficiency syndrome.
Title: Heterozygous IKKβ activation loop mutation results in a complex immunodeficiency syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (259)

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
Immunodeficiency 15a MedGen: C4748694 OMIM: 618204 GeneReviews: Not available	Compare labs
Severe combined immunodeficiency due to IKK2 deficiency MedGen: C4747743 OMIM: 615592 GeneReviews: Not available	Compare labs

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 JRFL (gp120) degrades IkappaBeta Kinases (IkB) in RPE cells	PubMed
	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 IKBKB (IKK2)	PubMed
	nef	HIV-1 and SIVcpz Nef proteins enhance TNF-alpha, IKK-beta, and RelA/p65-induced NF-kappaB activation in 293T cells	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	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 IKBKB (IKK2) in CRT-MG human astroglioma cells	PubMed
	tat	Curcumin and celastrol attenuate HIV-1 Tat-induced p65/NFKappaB phosphorylation and IKK phosphorylation	PubMed
	tat	HIV-1 Tat-mediated upregulation of ICAM-1 expression involves MEK1/2, JNK, and p38 MAPK proteins and downstream IKK2/NF-kappaB signaling pathways	PubMed
	tat	Nox2 is involved in HIV-1 Tat-induced NADPH oxidase p65 and IKK phosphorylation	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 each	PubMed
	vpr	Activation of TAK1 by HIV-1 Vpr leads to increased levels of phosphorylated IKK-beta and MKK7 in cells	PubMed
Vpu	vpu	Most HIV-1 and primate lentiviral Vpu proteins inhibit IKK-beta-induced NF-kappaB activation except HIV-1 group N Vpu proteins	PubMed

Go to the HIV-1, Human Interaction Database

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

RH104595 (e-PCR)
- UniSTS:99861

RH75091 (e-PCR)
- UniSTS:86861

L18426 (e-PCR)
- UniSTS:34648

D10S16 (e-PCR)
- UniSTS:155756

STS-N21119 (e-PCR)
- UniSTS:25813

D5S1597E (e-PCR)
- UniSTS:151019

Homology

Homologs of the IKBKB gene: The IKBKB gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 478 organisms have orthologs with human gene IKBKB
Orthologs

Clone Names

FLJ33771, FLJ36218, FLJ38368, FLJ40509, MGC131801

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
contributes_to IkappaB kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables IkappaB kinase activity	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction 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 kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	EXP Inferred from Experiment more info	PubMed
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement 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 Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in I-kappaB kinase/NF-kappaB signaling	TAS Traceable Author Statement more info	PubMed
involved_in I-kappaB phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS Traceable Author Statement more info
involved_in cellular response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
involved_in cortical actin cytoskeleton organization	IMP Inferred from Mutant Phenotype 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 interleukin-1-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interleukin-1-mediated signaling pathway	TAS Traceable Author Statement more info
involved_in negative regulation of bicellular tight junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of myosin-light-chain-phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NF-kappaB transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within positive regulation of NF-kappaB transcription factor activity	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 transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of tumor necrosis factor-mediated signaling pathway	TAS Traceable Author Statement more info
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in stimulatory C-type lectin receptor signaling pathway	TAS Traceable Author Statement more info
involved_in stress-activated MAPK cascade	TAS Traceable Author Statement more info
involved_in tumor necrosis factor-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	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	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 membrane raft	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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

Names: I-kappa-B kinase 2; I-kappa-B-kinase beta; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta; nuclear factor NF-kappa-B inhibitor kinase beta; nuclear factor kappa B kinase subunit beta; serine/threonine protein kinase IKBKB

NP_001177649.2

EC 2.7.11.1

EC 2.7.11.10

NP_001229707.1

EC 2.7.11.1

EC 2.7.11.10

NP_001547.1

EC 2.7.11.1

EC 2.7.11.10

XP_011542819.1

EC 2.7.11.1

EC 2.7.11.10

XP_011542822.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277713.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277714.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277715.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277716.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277717.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277718.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277719.1

EC 2.7.11.1

EC 2.7.11.10

XP_047277720.1

EC 2.7.11.1

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_041793.1 RefSeqGene

Range

5001..66159

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1241

mRNA and Protein(s)

NM_001190720.3 → NP_001177649.2 inhibitor of nuclear factor kappa-B kinase subunit beta isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' region, resulting in an upstream AUG start codon, as compared to variant 1. The resulting isoform (2) is slightly shorter and has a different N-terminus, as compared to isoform 1.

Source sequence(s)

AC083973, AK091297, AK302723

Consensus CDS

CCDS55228.2

UniProtKB/TrEMBL

A0A499FJS7

Related

ENSP00000430868.2, ENST00000520835.7

Conserved Domains (4) summary

cd17046
Location:246 → 326

Ubl_IKKA_like; ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins

pfam12179
Location:642 → 678

IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain

pfam18397
Location:325 → 599

IKBKB_SDD; IQBAL scaffold dimerization domain

cl21453
Location:1 → 245

PKc_like; Protein Kinases, catalytic domain
NM_001242778.2 → NP_001229707.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform 5

See identical proteins and their annotated locations for NP_001229707.1

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks an alternate exon in the 5' coding region and uses an alternate start codon, compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus, compared to variant 1.

Source sequence(s)

AC083973, AI379342, AK303528, DA159382

UniProtKB/Swiss-Prot

O14920

Conserved Domains (3) summary

smart00220
Location:8 → 231

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam12179
Location:649 → 683

IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain

cl21453
Location:8 → 250

PKc_like; Protein Kinases, catalytic domain
NM_001556.3 → NP_001547.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform 1

See identical proteins and their annotated locations for NP_001547.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF080158, AI379342, BC090865, DA709000

Consensus CDS

CCDS6128.1

UniProtKB/Swiss-Prot

O14920, O75327

Related

ENSP00000430684.1, ENST00000520810.6

Conserved Domains (4) summary

cd14038
Location:20 → 309

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

cd17046
Location:310 → 390

Ubl_IKKA_like; ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins

pfam12179
Location:708 → 742

IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain

pfam18397
Location:389 → 663

IKBKB_SDD; IQBAL scaffold dimerization domain

RNA

NR_033818.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) has an additional segment in the CDS, resulting in reading frame-shift and earlier translation termination, as compared to variant 1. The transcript is a nonsense-mediated mRNA decay candidate.

Source sequence(s)

AC083973, AI379342, BC090865, DA159382

Related

ENST00000342222.6
NR_033819.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an exon in the 3' CDS, resulting in reading frame-shift and earlier translation termination, as compared to variant 1. The transcript is a nonsense-mediated mRNA decay candidate.

Source sequence(s)

AC083973, AI379342, AK290952, BC108694, DA105584

Related

ENST00000416505.7
NR_040009.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (8) uses an alternate splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC083973, AI379342, BC144080, DA159382

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

42271302..42332460

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421762.1 → XP_047277718.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X8
XM_011544520.3 → XP_011542822.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5

Conserved Domains (4) summary

smart00220
Location:38 → 205

S_TKc; Serine/Threonine protein kinases, catalytic domain

pfam12179
Location:623 → 650

IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain

pfam13900
Location:700 → 720

GVQW; Putative domain of unknown function

cl21453
Location:45 → 224

PKc_like; Protein Kinases, catalytic domain
XM_011544517.3 → XP_011542819.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1

See identical proteins and their annotated locations for XP_011542819.1

Conserved Domains (3) summary

smart00220
Location:15 → 290

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14038
Location:20 → 309

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

pfam13900
Location:785 → 805

GVQW; Putative domain of unknown function
XM_047421758.1 → XP_047277714.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3
XM_047421764.1 → XP_047277720.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X10

UniProtKB/TrEMBL

G3V105

Related

ENSP00000428186.1, ENST00000521661.5
XM_047421757.1 → XP_047277713.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2

UniProtKB/Swiss-Prot

O75327
XM_047421760.1 → XP_047277716.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X6
XM_047421761.1 → XP_047277717.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X7
XM_047421759.1 → XP_047277715.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4
XM_047421763.1 → XP_047277719.1 inhibitor of nuclear factor kappa-B kinase subunit beta isoform X9

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

42545654..42606501

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001190721.1: Suppressed sequence

Description

NM_001190721.1: This RefSeq was permanently suppressed because currently there is not sufficient data to support this transcript.
NM_001190722.1: Suppressed sequence

Description

NM_001190722.1: This RefSeq was permanently suppressed because there is not sufficient data to support this transcript.