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

Gene ID: 3551, updated on 5-Jan-2025

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; IKK-2; 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
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Genomic context

See IKBKB in Genome Data Viewer
Location:
8p11.21
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (42271302..42332460)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (42545654..42606501)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (42128820..42189978)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene small nucleolar RNA U13 Neighboring gene IKBKB divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27303 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27304 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42127815-42128314 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19154 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27305 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr8:42150166-42151365 Neighboring gene uncharacterized LOC105379395 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42163399-42164071 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:42164072-42164743 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:42179455-42179956 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:42179957-42180456 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:42188156-42188656 Neighboring gene ribosomal protein L5 pseudogene 23 Neighboring gene DNA polymerase beta Neighboring gene dickkopf WNT signaling pathway inhibitor 4

Genomic regions, transcripts, and products

Expression

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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

HIV-1 interactions

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

Pathways from PubChem

Interactions

General gene information

Clone Names

  • FLJ33771, FLJ36218, FLJ38368, FLJ40509, MGC131801

Gene Ontology Provided by GOA

Items 1 - 25 of 36
Function Evidence Code Pubs
enables 3-phosphoinositide-dependent protein kinase activity  
enables AMP-activated protein kinase activity  
enables ATP binding  
enables DNA-dependent protein kinase activity  
enables IkappaB kinase activity PubMed 
enables IkappaB kinase activity PubMed 
enables Rho-dependent protein serine/threonine kinase activity  
enables eukaryotic translation initiation factor 2alpha kinase activity  
enables histone H2AS1 kinase activity  
enables histone H2AS121 kinase activity  
enables histone H2AT120 kinase activity  
enables histone H2AXS139 kinase activity  
enables histone H2BS14 kinase activity  
enables histone H2BS36 kinase activity  
enables histone H3S10 kinase activity  
enables histone H3S28 kinase activity  
enables histone H3S57 kinase activity  
enables histone H3T11 kinase activity  
enables histone H3T3 kinase activity  
enables histone H3T45 kinase activity  
enables histone H3T6 kinase activity  
enables histone H4S1 kinase activity  
enables identical protein binding PubMed 
enables protein binding PubMed 
enables protein heterodimerization activity PubMed 
enables protein homodimerization activity PubMed 
enables protein kinase activity PubMed 
enables protein kinase binding PubMed 
enables protein serine kinase activity  
enables protein serine/threonine kinase activity PubMed 
enables protein serine/threonine kinase activity  
enables protein serine/threonine kinase activity PubMed 
enables protein serine/threonine kinase activity  
enables ribosomal protein S6 kinase activity  
enables scaffold protein binding PubMed 
enables transferrin receptor binding PubMed 
Items 1 - 25 of 36
Items 1 - 25 of 38
Process Evidence Code Pubs
involved_in Fc-epsilon receptor signaling pathway  
involved_in MyD88-dependent toll-like receptor signaling pathway  
involved_in T cell receptor signaling pathway  
involved_in TRIF-dependent toll-like receptor signaling pathway  
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent  
involved_in canonical NF-kappaB signal transduction PubMed 
involved_in canonical NF-kappaB signal transduction PubMed 
involved_in canonical NF-kappaB signal transduction PubMed 
involved_in cellular response to tumor necrosis factor PubMed 
involved_in chromatin remodeling  
involved_in inflammatory response PubMed 
involved_in innate immune response PubMed 
involved_in interleukin-1-mediated signaling pathway PubMed 
involved_in interleukin-1-mediated signaling pathway  
involved_in negative regulation of bicellular tight junction assembly PubMed 
involved_in peptidyl-serine phosphorylation PubMed 
involved_in positive regulation of DNA-templated transcription PubMed 
acts_upstream_of_or_within positive regulation of NF-kappaB transcription factor activity PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction  
involved_in positive regulation of canonical NF-kappaB signal transduction PubMed 
involved_in positive regulation of canonical NF-kappaB signal transduction PubMed 
involved_in positive regulation of transcription by RNA polymerase II  
involved_in positive regulation of transcription by RNA polymerase II PubMed 
involved_in protein localization to plasma membrane PubMed 
involved_in protein maturation PubMed 
involved_in protein phosphorylation PubMed 
involved_in protein phosphorylation PubMed 
involved_in regulation of establishment of endothelial barrier PubMed 
involved_in regulation of phosphorylation PubMed 
involved_in regulation of toll-like receptor signaling pathway  
involved_in regulation of tumor necrosis factor-mediated signaling pathway  
involved_in response to virus PubMed 
involved_in stimulatory C-type lectin receptor signaling pathway  
involved_in stress-activated MAPK cascade  
involved_in toll-like receptor 3 signaling pathway  
involved_in tumor necrosis factor-mediated signaling pathway  
involved_in tumor necrosis factor-mediated signaling pathway PubMed 
Items 1 - 25 of 38
Component Evidence Code Pubs
part_of CD40 receptor complex  
part_of IkappaB kinase complex  
part_of IkappaB kinase complex PubMed 
part_of IkappaB kinase complex PubMed 
is_active_in cytoplasm  
is_active_in cytoplasm PubMed 
located_in cytoplasmic side of plasma membrane  
located_in cytosol  
located_in cytosol  
located_in membrane raft  
located_in nucleus  

General protein information

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
NP_001229707.1
NP_001547.1
XP_011542819.1
XP_011542822.1
XP_047277713.1
XP_047277714.1
XP_047277715.1
XP_047277716.1
XP_047277717.1
XP_047277718.1
XP_047277719.1
XP_047277720.1
XP_054216402.1
XP_054216403.1
XP_054216404.1
XP_054216405.1
XP_054216406.1
XP_054216407.1
XP_054216408.1
XP_054216409.1
XP_054216410.1
XP_054216411.1

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

  1. NG_041793.1 RefSeqGene

    Range
    5001..66159
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1241

mRNA and Protein(s)

  1. NM_001190720.3NP_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, B4DP95
    Related
    ENSP00000430868.2, ENST00000520835.7
    Conserved Domains (4) summary
    cd17046
    Location:246326
    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:642678
    IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain
    pfam18397
    Location:325599
    IKBKB_SDD; IQBAL scaffold dimerization domain
    cl21453
    Location:1245
    PKc_like; Protein Kinases, catalytic domain
  2. NM_001242778.2NP_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/TrEMBL
    B4DP95
    Conserved Domains (3) summary
    smart00220
    Location:8231
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    pfam12179
    Location:649683
    IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain
    cl21453
    Location:8250
    PKc_like; Protein Kinases, catalytic domain
  3. NM_001556.3NP_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
    B4DZ30, B4E0U4, O14920, O75327
    UniProtKB/TrEMBL
    B4DP95
    Related
    ENSP00000430684.1, ENST00000520810.6
    Conserved Domains (4) summary
    cd14038
    Location:20309
    STKc_IKK_beta; Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta
    cd17046
    Location:310390
    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:708742
    IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain
    pfam18397
    Location:389663
    IKBKB_SDD; IQBAL scaffold dimerization domain

RNA

  1. 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
  2. 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
  3. 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: 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

  1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    42271302..42332460
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421762.1XP_047277718.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X8

    UniProtKB/TrEMBL
    B4DP95
  2. XM_011544520.3XP_011542822.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5

    UniProtKB/TrEMBL
    B4DP95
    Conserved Domains (4) summary
    smart00220
    Location:38205
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    pfam12179
    Location:623650
    IKKbetaNEMObind; I-kappa-kinase-beta NEMO binding domain
    pfam13900
    Location:700720
    GVQW; Putative domain of unknown function
    cl21453
    Location:45224
    PKc_like; Protein Kinases, catalytic domain
  3. XM_011544517.3XP_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:15290
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14038
    Location:20309
    STKc_IKK_beta; Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta
    pfam13900
    Location:785805
    GVQW; Putative domain of unknown function
  4. XM_047421758.1XP_047277714.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3

  5. XM_047421764.1XP_047277720.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X10

    UniProtKB/TrEMBL
    A8K4I7, G3V105
    Related
    ENSP00000428186.1, ENST00000521661.5
  6. XM_047421757.1XP_047277713.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2

    UniProtKB/Swiss-Prot
    B4DZ30, B4E0U4, O14920, O75327
    UniProtKB/TrEMBL
    B4DP95
  7. XM_047421760.1XP_047277716.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X6

    UniProtKB/TrEMBL
    B4DP95
  8. XM_047421761.1XP_047277717.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X7

    UniProtKB/TrEMBL
    B4DP95
  9. XM_047421759.1XP_047277715.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4

    UniProtKB/TrEMBL
    B4DP95
  10. XM_047421763.1XP_047277719.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X9

    UniProtKB/TrEMBL
    B3KRB7

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    42545654..42606501
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054360434.1XP_054216409.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X8

    UniProtKB/TrEMBL
    B4DP95
  2. XM_054360431.1XP_054216406.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X5

    UniProtKB/TrEMBL
    B4DP95
  3. XM_054360429.1XP_054216404.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3

  4. XM_054360427.1XP_054216402.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1

  5. XM_054360436.1XP_054216411.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X10

    UniProtKB/TrEMBL
    A8K4I7, G3V105
  6. XM_054360428.1XP_054216403.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2

    UniProtKB/Swiss-Prot
    B4DZ30, B4E0U4, O14920, O75327
    UniProtKB/TrEMBL
    B4DP95
  7. XM_054360432.1XP_054216407.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X6

    UniProtKB/TrEMBL
    B4DP95
  8. XM_054360433.1XP_054216408.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X7

    UniProtKB/TrEMBL
    B4DP95
  9. XM_054360430.1XP_054216405.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4

    UniProtKB/TrEMBL
    B4DP95
  10. XM_054360435.1XP_054216410.1  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X9

    UniProtKB/TrEMBL
    B3KRB7

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