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Aliases for IKBKB Gene

Aliases for IKBKB Gene

  • Inhibitor Of Kappa Light Polypeptide Gene Enhancer In B-Cells, Kinase Beta 2 3
  • NFKBIKB 3 4 6
  • Nuclear Factor NF-Kappa-B Inhibitor Kinase Beta 3 4
  • I-Kappa-B-Kinase Beta 3 4
  • I-Kappa-B Kinase 2 3 4
  • EC 2.7.11.10 4 64
  • IKK-Beta 3 4
  • IMD15 3 6
  • IKK-B 3 4
  • IKK2 3 4
  • IKKB 3 4
  • Inhibitor Of Nuclear Factor Kappa-B Kinase Subunit Beta 3
  • EC 2.7.11 64
  • IkBKB 4

External Ids for IKBKB Gene

Summaries for IKBKB Gene

Entrez Gene Summary for IKBKB Gene

  • 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]

GeneCards Summary for IKBKB Gene

IKBKB (Inhibitor Of Kappa Light Polypeptide Gene Enhancer In B-Cells, Kinase Beta) is a Protein Coding gene. Diseases associated with IKBKB include immunodeficiency 15 and severe combined immunodeficiency due to ikk2 deficiency. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include protein homodimerization activity and protein heterodimerization activity. An important paralog of this gene is CHUK.

UniProtKB/Swiss-Prot for IKBKB Gene

  • 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 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.

Tocris Summary for IKBKB Gene

  • IkappaB Kinase (IKK) is an enzyme complex that forms part of the NF-kappaB signaling pathway. The complex is comprised of three subunits (IKKalpha (IKK1), IKKbeta (IKK2) and IKKgamma (NEMO)), the alpha- and beta-subunits are catalytically active whereas the gamma-subunit serves a regulatory function. Activation of NF-kappaB occurs via degradation of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated IkappaB becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene expression.

Gene Wiki entry for IKBKB Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IKBKB Gene

Genomics for IKBKB Gene

Genomic Location for IKBKB Gene

Start:
42,271,302 bp from pter
End:
42,332,653 bp from pter
Size:
61,352 bases
Orientation:
Plus strand

Genomic View for IKBKB Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for IKBKB Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IKBKB Gene

Regulatory Elements for IKBKB Gene

Proteins for IKBKB Gene

  • Protein details for IKBKB Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14920-IKKB_HUMAN
    Recommended name:
    Inhibitor of nuclear factor kappa-B kinase subunit beta
    Protein Accession:
    O14920
    Secondary Accessions:
    • B4DZ30
    • B4E0U4
    • O75327

    Protein attributes for IKBKB Gene

    Size:
    756 amino acids
    Molecular mass:
    86564 Da
    Quaternary structure:
    • 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. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, IKBKAP and MAP3K14. Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB. Interacts with SQSTM1 through PRKCZ or PRKCI. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6. May interact with MAVS/IPS1. Interacts with NALP2. Interacts with TICAM1. Interacts with Yersinia yopJ. Interacts with FAF1; the interaction disrupts the IKK complex formation. Interacts with ATM. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with NIBP; the interaction is direct. Interacts with ARRB1 and ARRB2. Interacts with TRIM21. Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity. Interacts with PDPK1. Interacts with EIF2AK2/PKR. The phosphorylated form interacts with PPM1A and PPM1B. Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-alpha-dependent manner. Interacts with IKBKE. Interacts with NAA10, leading to NAA10 degradation (By similarity).

    Three dimensional structures from OCA and Proteopedia for IKBKB Gene

    Alternative splice isoforms for IKBKB Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IKBKB Gene

Proteomics data for IKBKB Gene at MOPED

Post-translational modifications for IKBKB Gene

  • Acetylation of Thr-180 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.
  • Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappaB.
  • Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to PubMed:19675099, Ser-163 does not serve as a monoubiquitination site. According to PubMed:16267042, ubiquitination on Ser-163 modulates phosphorylation on C-terminal serine residues. Monoubiquitination by TRIM21 is disrupted by Yersinia yopJ.
  • Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription. Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys106, Lys163, and Lys555

Domains for IKBKB Gene

UniProtKB/Swiss-Prot:

IKKB_HUMAN
Domain:
  • 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.:
    • O14920
  • Contains 1 protein kinase domain.:
    • O14920
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.:
    • O14920
genes like me logo Genes that share domains with IKBKB: view

Function for IKBKB Gene

Molecular function for IKBKB Gene

GENATLAS Biochemistry: inhibitor of kappa light polypeptide enhancer in B cells,kinase beta,complexing with IKBKA
UniProtKB/Swiss-Prot CatalyticActivity: ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein]
UniProtKB/Swiss-Prot Function: 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 2 critical 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. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.

Enzyme Numbers (IUBMB) for IKBKB Gene

Gene Ontology (GO) - Molecular Function for IKBKB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IDA 20434986
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 10521409
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with IKBKB: view
genes like me logo Genes that share phenotypes with IKBKB: view

Animal Models for IKBKB Gene

MGI Knock Outs for IKBKB:

No data available for Transcription Factor Targeting and HOMER Transcription for IKBKB Gene

Localization for IKBKB Gene

Subcellular locations from UniProtKB/Swiss-Prot for IKBKB Gene

Cytoplasm. Nucleus. Membrane raft. Note=Colocalized with DPP4 in membrane rafts.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IKBKB Gene COMPARTMENTS Subcellular localization image for IKBKB gene
Compartment Confidence
cytosol 5
nucleus 5
plasma membrane 3

Gene Ontology (GO) - Cellular Components for IKBKB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0008385 IkappaB kinase complex TAS 18626576
GO:0009898 cytoplasmic side of plasma membrane ISS --
genes like me logo Genes that share ontologies with IKBKB: view

Pathways for IKBKB Gene

SuperPathways for IKBKB Gene

genes like me logo Genes that share pathways with IKBKB: view

Gene Ontology (GO) - Biological Process for IKBKB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001782 B cell homeostasis IEA --
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with IKBKB: view

Compounds for IKBKB Gene

(5) Tocris Compounds for IKBKB Gene

Compound Action Cas Number
ACHP Selective IKKalpha and IKKbeta inhibitor [406208-42-2]
Amlexanox Inhibitor of TBK1 and IKKepsilon; antiallergic agent [68302-57-8]
IKK 16 Selective inhibitor of IKK [1186195-62-9]
PF 184 Potent and selective IKKbeta inhibitor [1187460-81-6]
TPCA-1 Potent, selective inhibitor of IKKbeta [507475-17-4]

(3) HMDB Compounds for IKBKB Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Sumatriptan
  • Imigran
103628-46-2

(4) Drugbank Compounds for IKBKB Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Arsenic trioxide
  • Acide Arsenieux [French]
1327-53-3 target inducer
Auranofin
34031-32-8 target inhibitor
Mesalazine
  • 5-aminosalicylate
89-57-6 target inhibitor
Sulfasalazine
  • Sulfasalazin
599-79-1 target inhibitor

(57) Novoseek inferred chemical compound relationships for IKBKB Gene

Compound -log(P) Hits PubMed IDs
tab-1 72.7 6
bortezomib 50.1 1
serine 48.9 24
parthenolide 43.6 2
sp 600125 41.8 2
genes like me logo Genes that share compounds with IKBKB: view

Transcripts for IKBKB Gene

Unigene Clusters for IKBKB Gene

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IKBKB Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b · 17c ^ 18 ^ 19 ^ 20a ·
SP1: - - - - -
SP2: - - - - -
SP3: - - - - - - - - - - -
SP4: - -
SP5: -
SP6:
SP7:
SP8:

ExUns: 20b ^ 21 ^ 22a · 22b ^ 23a · 23b · 23c
SP1: -
SP2: -
SP3: -
SP4:
SP5:
SP6: -
SP7: -
SP8:

Relevant External Links for IKBKB Gene

GeneLoc Exon Structure for
IKBKB
ECgene alternative splicing isoforms for
IKBKB

Expression for IKBKB Gene

mRNA expression in normal human tissues for IKBKB Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for IKBKB Gene

SOURCE GeneReport for Unigene cluster for IKBKB Gene Hs.597664

mRNA Expression by UniProt/SwissProt for IKBKB Gene

O14920-IKKB_HUMAN
Tissue specificity: Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood
genes like me logo Genes that share expressions with IKBKB: view

Orthologs for IKBKB Gene

This gene was present in the common ancestor of animals.

Orthologs for IKBKB Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IKBKB 36
  • 98.48 (n)
  • 98.53 (a)
IKBKB 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia IKBKB 36
  • 86.86 (n)
  • 93.79 (a)
IKBKB 37
  • 93 (a)
OneToOne
dog
(Canis familiaris)
Mammalia IKBKB 36
  • 90.11 (n)
  • 95.1 (a)
IKBKB 37
  • 95 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ikbkb 36
  • 87.15 (n)
  • 92.72 (a)
Ikbkb 16
Ikbkb 37
  • 92 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia IKBKB 37
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia IKBKB 37
  • 89 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ikbkb 36
  • 87.11 (n)
  • 91.66 (a)
chicken
(Gallus gallus)
Aves IKBKB 36
  • 67.94 (n)
  • 69.49 (a)
IKBKB 37
  • 71 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia IKBKB 37
  • 75 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ikbkb 36
  • 70.54 (n)
  • 73.32 (a)
Str.17591 36
zebrafish
(Danio rerio)
Actinopterygii ikbkb 36
  • 62.47 (n)
  • 61.71 (a)
ikbkb 37
  • 59 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta ird5 37
  • 22 (a)
OneToMany
ird5 38
  • 34 (a)
Species with no ortholog for IKBKB:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for IKBKB Gene

ENSEMBL:
Gene Tree for IKBKB (if available)
TreeFam:
Gene Tree for IKBKB (if available)

Paralogs for IKBKB Gene

Paralogs for IKBKB Gene

genes like me logo Genes that share paralogs with IKBKB: view

Variants for IKBKB Gene

Sequence variations from dbSNP and Humsavar for IKBKB Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type MAF
rs1057741 -- 42,331,032(+) TGTGC(A/G)GTGGG utr-variant-3-prime, nc-transcript-variant, downstream-variant-500B
rs1057763 -- 42,322,458(+) AAGCG(A/G)CAGAA synonymous-codon, reference, nc-transcript-variant
rs1057764 -- 42,322,466(+) GAAGG(A/G)GCTCT reference, missense, nc-transcript-variant
rs1316995 -- 42,281,979(-) AGGTG(C/T)CTGGC intron-variant
rs1317130 -- 42,291,746(-) GCCTT(G/T)GTATG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for IKBKB Gene

Variant ID Type Subtype PubMed ID
nsv831301 CNV Loss 17160897
nsv508508 CNV Loss 20534489
nsv6169 CNV Loss 18451855
nsv398024 CNV Loss 16902084
esv1003654 CNV Deletion 20482838
esv2736935 CNV Deletion 23290073
esv1761681 CNV Deletion 17803354
dgv128n16 CNV Deletion 17901297

Relevant External Links for IKBKB Gene

HapMap Linkage Disequilibrium report
IKBKB
Human Gene Mutation Database (HGMD)
IKBKB

Disorders for IKBKB Gene

(1) OMIM Diseases for IKBKB Gene (603258)

UniProtKB/Swiss-Prot

IKKB_HUMAN
  • Immunodeficiency 15 (IMD15) [MIM:615592]: An autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T-cells, and impaired differentiation and activation of immune cells. {ECO:0000269 PubMed:24369075}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(31) Novoseek inferred disease relationships for IKBKB Gene

Disease -log(P) Hits PubMed IDs
necrosis 70.8 35
leukemia t-cell 57.7 2
tumors 56.6 48
inflammation 52.3 19
cancer 42.4 14

Relevant External Links for IKBKB

Genetic Association Database (GAD)
IKBKB
Human Genome Epidemiology (HuGE) Navigator
IKBKB
genes like me logo Genes that share disorders with IKBKB: view

Publications for IKBKB Gene

  1. IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF- kappaB activation. (PMID: 9346484) Mercurio F. … Rao A. (Science 1997) 3 4 23
  2. IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. (PMID: 9346485) Woronicz J.D. … Goeddel D.V. (Science 1997) 3 4 23
  3. Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation. (PMID: 10195894) Delhase M. … Karin M. (Science 1999) 3 4 23
  4. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. (PMID: 9819420) Nemoto S. … Lin A. (Mol. Cell. Biol. 1998) 3 4 23
  5. Activation of IkappaB kinase beta by protein kinase C isoforms. (PMID: 10022904) Lallena M.J. … Moscat J. (Mol. Cell. Biol. 1999) 3 4 23

Products for IKBKB Gene

  • Addgene plasmids for IKBKB

Sources for IKBKB Gene

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