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FLASH GENE
Symbol NFKB1 contributors: shn/npt/pgu - updated : 08-06-2019
HGNC name nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
HGNC id 7794
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a rel homology domain (RHD), in the N-terminal portion, mediating dimerization, interaction with each protein specific inhibitors, and DNA binding
  • a putative nuclear localization signal (NLS)
  • a glycine rich sequence (poly G)
  • six ankyrin repeats encoding domain, including a decameric consensus of NFKBs
  • one DEATH domain
  • HOMOLOGY
    interspecies homolog to Nfkb1, Mus musculus
    ortholog to nfkb1, Danio rerio
    ortholog to NFKB1, Pan troglodytes
    ortholog to Nfkb1, Rattus norvegicus
    Homologene
    FAMILY
  • NF-kappa B/REL family
  • CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • trapped in the cytoplasm when inactivated, translocated to the nucleus after activation
  • found in both the nucleus and the cytoplasm
  • basic FUNCTION
  • transcription factor of kappa light chain gene enhancer in B cells
  • regulating the expression of immune response, apoptosis, and cell-growth control genes
  • having dual functions such as cytoplasmic retention of attached NF-kappa-B proteins and generation of p50 by a cotranslational processing
  • involved in many cellular processes, including response to oxidative damage and other signaling, and in neuronal growth and pruning by apoptosis
  • NFKB1 and NFKB2 proteins serve both as NF-kappaB precursors and inhibitors of NF-kappaB dimers
  • induces SENP2 (and SENP1) transcription selectively in response to genotoxic stimuli, which involves ataxia telangiectasia mutated (ATM)-dependent histone methylation of SENP2 promoter κB regions and NFKB1 recruitment
  • major signal transducer by which IL15 affects cellular permeability, endocytosis, and intracellular trafficking at the level of the blood-brain barrier
  • plays a key role in the inflammatory processes of airway diseases
  • NFKB1 and STAT3, are activated simultaneously by an intrinsic mechanism during stressful conditions of cancer cells, and they cooperatively induce various survival factors
  • roles for TNFSF12, BIRC3, and noncanonical NFKB signaling in the regulation of myoblast fusion and highlight a role for cytokine signaling during adult skeletal myogenesis
  • key regulator of adult and developmental arteriogenesis and collateral formation
  • FAS and NFKB1 play a role in the initiation and development of breast cancer, while VEGFC appears to promote lymph node metastasis
  • plays a critical role in induction and mediation of pro-inflammatory response to infection and for development and maintenance of blood cells and immune tissues through modulation of apoptosis
  • role of NFKB1 as a master regulator of cellular transcription that is finely balanced depending on cell state and stimulation
  • CELLULAR PROCESS cell life, antiapoptosis
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    PATHWAY
    metabolism
    signaling
    a component
  • NFKB complex with REL, RELA, RELB
  • RELB/NFKB1 regulates CCL19 production, but fails to promote dendritic cells maturation
  • PLCB1/CAMK4-NFKB1 is involved in AGER mediated signaling pathway in human endothelial cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylated p65 associating with CREBBP and displaying the HDAC1-p50 complex
  • kappa light chain enhancer
  • governing the expression of genes encoding cytokines, chemokines, growth factors, cell adhesion molecules, acute phase proteins
  • interacting with TNIP1 (effects of TNIP1 on NFKB1 processing and of NFKB1 on stabilizing TNIP1 act to potentiate the NF-kappaB inhibitory activity of TNIP1)
  • NFKB1 activation by CSF2RB is dependent on TNFR-associated factor 6 (TRAF6) and association of TRAF6 with CSF2RB requires a consensus-binding motif found in other molecules known to interact with TRAF6
  • NFKB1 regulates the expression of UACA, a novel apoptosis regulator, with involvement of proteasome and caspase for its degradation
  • critical role for NFKB1 in USP6-mediated tumorigenesis, suggesting that NFKB1 inhibitors may function as effective therapeutic agents in the treatment of aneurysmal bone cyst (ABC)
  • IL15 can signal via IL15RA, JNK, and NFKB1 to drive CCL5 production by myeloid cells
  • SCGB1A1 gene transfer may inhibit airway inflammation through suppressing the activation of NFKB1, which may provide us a new consideration in the therapy of airway inflammation
  • NLRC3 inhibited TLR-dependent activation of the transcription factor NFKB1 by interacting with the TLR signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6 and activation of NFKB1
  • molecular link between two essential determinants of the circadian and immune mechanisms, the transcription factors CLOCK and NFKB1, respectively
  • GNB2 is required for starvation-induced NFKB1 activation and constitutive NFKB1 activity
  • FGFR2 serves as a scaffold for multiple components of the NFKB1 signaling complex
  • TBK1 negatively regulated IgA class switching by attenuating noncanonical signaling via the transcription factor NFKB1, an action that involved TBK1-mediated phosphorylation
  • its activity regulates mesenchymal stem cell accumulation at tumors, by inducing VCAM1 and thereby its interaction with tumor vessel endothelial cells
  • NFKB1 mediates TNFSF13-induced HOXC4 transcription
  • NFKB1 exerts an inhibitory effect on the ability of HES6 to promote cortical neuronal differentiation
  • PLK4 is a direct NFKB1 target gene
  • NFKB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent mechanisms
  • ZAP70 acts directly as an amplifier of NFKB1 signalling in Chronic lymphocytic leukaemia (CLL) cells which could be an underlying mechanism for its association with poor prognosis and which may represent a therapeutic target
  • KLF6 is an essential co-activator of NFKB1, suggesting new insight into the molecular regulation of RELA-dependent gene expression
  • IKBKB activates two "master" transcription factors of the innate immune system, IRF5 and NFKB1
  • ECSIT specifically interacted with RELA/NFKB1 proteins, which colocalized in the nucleus
  • NFKB1 may be involved in IL1B-induced activation of ADAMTS9 in human chondrocytes
  • CCL18 enhances hepatocellular carcinoma cell migration, invasion, and EMT through the expression of PITPNM3 and the activation of the NFKB1 signaling pathway
  • NFKB1 is a critical positive regulator, whereas YY1 is a negative regulator of the TGFA promoter
  • TRAF7 is involved in signal transduction pathways that lead either to activation or repression of NFKB1 transcription factor
  • cell & other
    REGULATION
    activated by numerous stimuli,cytokines,oxydant-free radicals, inhaled particles, ultraviolet irradiation, bacterial and viral products
    BCL10 through ubiquination of IKBKG
    GLUTAMATE
    induced by the phorbolester
    inhibited by NFKBIA, NFKBIB
    CYLD
    ASSOCIATED DISORDERS
    corresponding disease(s) CVID12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    bile acids evoke placental inflammation by activating GPBAR1/NFKB1 pathway in intrahepatic cholestasis of pregnancy
    Susceptibility
  • to ulcerative colitis and many inflammatory diseases
  • to alcohol dependence
  • to variation of risk of infection and allergy
  • Variant & Polymorphism SNP , other
  • 94delATTG increases the risk for ulcerative colitis
  • SNP significantly associated with alcohol dependence
  • insertion-deletion variant thought to affect NFKB1 expression (rs28362491), could play a key role in regulation of the immune response
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    inhibitor of activation of NFKB1 as therapy in ulcerative colitis
    cancerlung 
    potential companion drug target, together with EGFR, in EGFR-mutant lung cancers treated with EGFR TKI
    ANIMAL & CELL MODELS