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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CVID12 Immunodeficiency, common variable, 12
Location	4q24      Physical location : 103.422.485 - 103.538.458
Synonym name	nuclear factor NF-kappa-B p50 subunit
	DNA-binding factor KBF1
	nuclear factor kappa-B, subunit 1
Synonym symbol(s)	EVI157, KBF1, EBP-1, NF-kappa-B, NFKB-p105, NFKB-p50, p50, p105, MGC54151, DKFZp686C01211

DNA

TYPE	functioning gene
STRUCTURE	115.97 kb     24 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
motif	repetitive sequence   other
text structure	polymorphism -94ins/del ATTG in the promoter, proximal to binding sites important to promoter regulation

MAPPING

cloned

Y

linked

status

confirmed

Map	cen - D4S1591 - D4S2961 - NFKB1 - D4S3043 - D4S1572 - tel

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003998 24 - 4093 NP_003989 105 968 - 1999 10469655 NM_001165412 24 - 4090 NP_001158884 - 968 - 1999 10469655 p50 - - - 50 433 - 2015 26279205 assembles a heteromeric transcription factor, predominantly with RELA, that is complexed with IKBA

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Lymphoid/Immune lymph node       highly   spleen       highly   thymus       highly Reproductive male system prostate       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol   bone marrow     highly Connective bone       Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed immunology inflammatory   inhibitor of activation of NFKB1 as therapy in ulcerative colitis cancer lung   potential companion drug target, together with EGFR, in EGFR-mutant lung cancers treated with EGFR TKI

ANIMAL & CELL MODELS