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FLASH GENE
Symbol IKBKB contributors: mct - updated : 14-03-2016
HGNC name inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta
HGNC id 5960
Corresponding disease
IMD15 Immunodeficiency 15
Location 8p11.21      Physical location : 42.128.819 - 42.190.171
Synonym name
  • nuclear factor of kappa light chain gene
  • inhibitor of nuclear factor kappa B kinase beta subunit
  • I-kappa-B-kinase beta
  • I-kappa-B kinase 2
  • Synonym symbol(s) IKKB, IKK2, NFKBIKB, IKK-beta, FLJ40509, MGC131801, IMD15
    EC.number 2.7.11.10
    DNA
    TYPE functioning gene
    STRUCTURE 61.35 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    C8orf4 8p11.2 chromosome 8 open reading frame 4 FLJ13842 8p11.21 hypothetical protein FLJ13842 SFRP1 8p12-p11.2 secreted frizzled-related protein 1 GCP16 LOC392214 8 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) MGC14799 8p11.21 hypothetical protein MGC14799 DKFZp586M1819 8p11.21 putative lysophosphatidic acid acyltransferase FLJ25169 8p11.21 hypothetical protein FLJ25169 ANK1 8p11.2 ankyrin 1, erythrocytic MYST3 8p11 MYST histone acetyltransferase (monocytic leukemia) 3 AP3M2 8p11.2 adaptor-related protein complex 3, mu 2 subunit PLAT 8p12-p11.2 plasminogen activator, tissue LOC389650 8 LOC389650 IKBKB 8p11.2 inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta POLB 8p11.2 polymerase (DNA directed), beta DKK4 8p11.2-p11.1 dickkopf homolog 4 (Xenopus laevis) VDAC3 8q11.2 voltage-dependent anion channel 3 SLC20A2 8p12-q21 solute carrier family 20 (phosphate transporter), member 2 LOC114926 8p11.21 hypothetical protein BC013035 CHRNB3 8p11.2 cholinergic receptor, nicotinic, beta polypeptide 3 CHRNA6 8p22 cholinergic receptor, nicotinic, alpha polypeptide 6 THAP1 8p11.1 THAP domain containing, apoptosis associated protein 1 DKFZP564A022 8p11.21 hypothetical protein DKFZp564A022 HOOK3 8p11.21 hook homolog 3 (Drosophila) FNTA 8p22-q11 farnesyltransferase, CAAX box, alpha FLJ23356 8p11.21 hypothetical protein FLJ23356 FLJ32731 8p11.1 hypothetical protein FLJ32731 LOC347028 8p11.21 similar to AFG3-like protein 2 (Paraplegin-like protein) LOC340441 8p11.21 similar to pote protein; Expressed in prostate, ovary, testis, and placenta LOC389651 8 similar to hypothetical protein (L1H 3 region) - human
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 4131 86.4 756 - 1997 9346241
    11 - 1631 - 420 - 1997 9346241
    20 - 3695 - 668 - 1997 9346241
    21 - 3992 - 754 - 1997 9346241
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Endocrinepancreas   moderately
    Nervousbrain   moderately
    Reproductivemale systemprostate  moderately
    Respiratorylung   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Lymphoid    
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N- terminal leucine zipper domain
  • a kinase domain, displaying CK2-like phosphorylation specificity
  • an ubiquitination-like domain (ULD) has been shown essential for IKBKB activation, and regulates osteoclastogenesis and osteolysis
  • helix-loop-helix (HLH) domain, necessary for restricting substrate specificity toward Ser-32 and Ser-36 in CHUK
  • NBD (NEMO-binding domain) C terminal domain, conserved region in the C-terminal tail AAs 734-745 important for interaction with IKBKG
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Ikbkb
    intraspecies homolog to IKKA
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • I-kappa-B kinase subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • inhibitor of kappa light polypeptide enhancer in B cells, kinase beta
  • suppression of apoptosis
  • central coordinator of inflammatory responses through activation of NF-kappaB
  • cooperate with CHUK to maintain bile duct integrity in the liver
  • playing a central role in allergic reactions
  • involved in the phosphorytion of SNAP23
  • is critical for activation of T cells and differentiation of B cells
  • novel function for IKBKB and NFKB modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response
  • IKBKB, IKBKG and REL control the levels of Claspin in the cells by an alternative mechanism to cell cycle
  • important function of IKBKB and REL in the DNA-damage response pathway
  • essential roles for IKBKB in regulating endothelial permeability and migration, as well as an unanticipated connection between IKBKB and AKT1 signalling
  • essential role for IKBKB in production of type 1 interferons by plasmacytoid dendritic cells
  • regulates Myosin light chain (MLC) phosphorylation as an MLC kinase (MLCK) and, thus, vascular function and blood pressure
  • IKBKB interacted with RICTOR and regulated CRTC2
  • IKBKG together with the catalytic subunits CHUK and IKBKB, plays an essential role in the formation of the IKK complex and in the activation of the canonical NFKB pathway
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer with IKBKG/CHUK (catalytic subunits with CHUK)
  • IKBKG together with catalytic subunits CHUK and IKBKB, forms the IKB kinase (IKK) complex, a key regulator of NFKB pathway signaling
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with NFKB (activation of IKBKB causes insulin resistance)
  • cooperating with CHUK for regulating liver immune homeostasis and bile duct integrity (share a redundant function in mediating canonical NFKB signaling in hepatocytes and protecting the liver from TNF toxicity)
  • interacts with FAF1 in response to proinflammatory stimuli (such as tumor necrosis factor-alpha, interleukin-1beta, and lipopolysaccharide) and suppresses IKK activation
  • PPM1A and PPM1B, are IKBKB phosphatases
  • IKBKB physically associated with NAA10 and phosphorylated it at Ser209)
  • NMRAL1 interacts and colocalizes with IKBKB, and inhibits the phosphorylation of IKBKB
  • IKBKG is essential for IKBKB activation by inflammatory stimuli, and also a specificity factor that directs IKBKB activity toward CHUK
  • IKBKB directly phosphorylated MAP3K8 on three serines, including the critical regulatory site, S400
  • SLC39A8 is a transcriptional target of NFKB1 and functions to negatively regulate proinflammatory responses through zinc-mediated down-modulation of IKBKB activity
  • VDR physically interacts with IKBKB to block NFKB1 activation
  • CHUK and IKBKB physically interacted with RICTOR
  • PHLPP2 interacts with IKBKB, decreases its phosphorylation and the subsequent NFKB1 activation in cancer cells (
  • NLK functions as a pivotal negative regulator in TNF-induced activation of NFKB1 via disrupting the interaction of MAP3K7 with IKBKB
  • activation of NFKB1 induced translocation of ASAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of ASAP1 and IKBKB
  • IKBKB regulates endothelial thrombomodulin in a KLF2-dependent manner
  • CHUK and IKBKB are RELB interacting partners whose activation by TNF promotes RELB phosphorylation at serine 472
  • IKBKB is an IRF5 kinase that instigates inflammation
  • IKBKB activates two "master" transcription factors of the innate immune system, IRF5 and NFKB1
  • IKBKB, an upstream IRF5 activator, is phosphorylated in response to the agonist-induced TLR signaling
  • IRAK4 activity regulates likely MAP3K7 and IKBKB activation, leading to the nuclear translocation of IRF5 and induction of inflammatory cytokines in human monocytes
  • unique innate immune activation cascade in which TBK1-IKBKB formed a positive feedback loop to assure robust cytokine production during CGAS-TMEM173 activation
  • cell & other
    REGULATION
    activated by TRAF6
    inhibited by CYLD
    Other regulated by IKBKG (increase the kinase activity of IKBKB)
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD15
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    protecting against neurodegeneration in cerebral ischemia
    constitutional       loss of function
    in myeloid cells ameliorates Alzheimer disease-related symptoms and pathology
    tumoral somatic mutation      
    in splenic marginal zone lymphomas and multiple myeloma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • treatment of insulin resistance by inhibition of IKBKB, especially in myeloid cells
  • IKBKB inhibitors for stroke therapy
  • inhibition of IKKgamma/NEMO oligomerization induces apoptosis in high-risk myelodysplastic syndrome and acute myeloid leukemia
  • Marker
    Therapy target
    ANIMAL & CELL MODELS