Browse NFKBIA

Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.
Domain PF00023 Ankyrin repeat
PF12796 Ankyrin repeats (3 copies)
Function

Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals. On cellular stimulation by immune and proinflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.

> Gene Ontology
 
Biological Process GO:0000060 protein import into nucleus, translocation
GO:0001889 liver development
GO:0002218 activation of innate immune response
GO:0002220 innate immune response activating cell surface receptor signaling pathway
GO:0002221 pattern recognition receptor signaling pathway
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002237 response to molecule of bacterial origin
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002683 negative regulation of immune system process
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway
GO:0002757 immune response-activating signal transduction
GO:0002758 innate immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0006606 protein import into nucleus
GO:0006869 lipid transport
GO:0006913 nucleocytoplasmic transport
GO:0007219 Notch signaling pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007253 cytoplasmic sequestering of NF-kappaB
GO:0008593 regulation of Notch signaling pathway
GO:0009266 response to temperature stimulus
GO:0009409 response to cold
GO:0009612 response to mechanical stimulus
GO:0010742 macrophage derived foam cell differentiation
GO:0010743 regulation of macrophage derived foam cell differentiation
GO:0010745 negative regulation of macrophage derived foam cell differentiation
GO:0010874 regulation of cholesterol efflux
GO:0010875 positive regulation of cholesterol efflux
GO:0010876 lipid localization
GO:0010883 regulation of lipid storage
GO:0010888 negative regulation of lipid storage
GO:0015850 organic hydroxy compound transport
GO:0015918 sterol transport
GO:0017038 protein import
GO:0019915 lipid storage
GO:0030099 myeloid cell differentiation
GO:0030301 cholesterol transport
GO:0030522 intracellular receptor signaling pathway
GO:0031099 regeneration
GO:0031100 animal organ regeneration
GO:0031349 positive regulation of defense response
GO:0031503 protein complex localization
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032368 regulation of lipid transport
GO:0032370 positive regulation of lipid transport
GO:0032371 regulation of sterol transport
GO:0032373 positive regulation of sterol transport
GO:0032374 regulation of cholesterol transport
GO:0032376 positive regulation of cholesterol transport
GO:0032386 regulation of intracellular transport
GO:0032387 negative regulation of intracellular transport
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0032507 maintenance of protein location in cell
GO:0033157 regulation of intracellular protein transport
GO:0033344 cholesterol efflux
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034504 protein localization to nucleus
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0035994 response to muscle stretch
GO:0038093 Fc receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042306 regulation of protein import into nucleus
GO:0042308 negative regulation of protein import into nucleus
GO:0042345 regulation of NF-kappaB import into nucleus
GO:0042347 negative regulation of NF-kappaB import into nucleus
GO:0042348 NF-kappaB import into nucleus
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0042994 cytoplasmic sequestering of transcription factor
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0043331 response to dsRNA
GO:0043392 negative regulation of DNA binding
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0044744 protein targeting to nucleus
GO:0045088 regulation of innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045185 maintenance of protein location
GO:0045637 regulation of myeloid cell differentiation
GO:0045638 negative regulation of myeloid cell differentiation
GO:0045746 negative regulation of Notch signaling pathway
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046823 negative regulation of nucleocytoplasmic transport
GO:0048732 gland development
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0051051 negative regulation of transport
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051101 regulation of DNA binding
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051220 cytoplasmic sequestering of protein
GO:0051224 negative regulation of protein transport
GO:0051235 maintenance of location
GO:0051651 maintenance of location in cell
GO:0061008 hepaticobiliary system development
GO:0070417 cellular response to cold
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070427 nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0090077 foam cell differentiation
GO:0090317 negative regulation of intracellular protein transport
GO:0097421 liver regeneration
GO:1900180 regulation of protein localization to nucleus
GO:1900181 negative regulation of protein localization to nucleus
GO:1901652 response to peptide
GO:1902532 negative regulation of intracellular signal transduction
GO:1902593 single-organism nuclear import
GO:1903533 regulation of protein targeting
GO:1903706 regulation of hemopoiesis
GO:1903707 negative regulation of hemopoiesis
GO:1903828 negative regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904590 negative regulation of protein import
GO:1904950 negative regulation of establishment of protein localization
Molecular Function GO:0005048 signal sequence binding
GO:0008134 transcription factor binding
GO:0008139 nuclear localization sequence binding
GO:0031072 heat shock protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0033218 amide binding
GO:0042277 peptide binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0051059 NF-kappaB binding
Cellular Component GO:0033256 I-kappaB/NF-kappaB complex
> KEGG and Reactome Pathway
 
KEGG hsa04024 cAMP signaling pathway
hsa04062 Chemokine signaling pathway
hsa04064 NF-kappa B signaling pathway
hsa04210 Apoptosis
hsa04380 Osteoclast differentiation
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04623 Cytosolic DNA-sensing pathway
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
hsa04668 TNF signaling pathway
hsa04722 Neurotrophin signaling pathway
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-166054: Activated TLR4 signalling
R-HSA-1169091: Activation of NF-kappaB in B cells
R-HSA-1280218: Adaptive Immune System
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-5607764: CLEC7A (Dectin-1) signaling
R-HSA-1834949: Cytosolic sensors of pathogen-associated DNA
R-HSA-5688426: Deubiquitination
R-HSA-1643685: Disease
R-HSA-5602358: Diseases associated with the TLR signaling cascade
R-HSA-5260271: Diseases of Immune System
R-HSA-202424: Downstream TCR signaling
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2871837: FCERI mediated NF-kB activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-5603027: IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
R-HSA-5603029: IkBA variant leads to EDA-ID
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-166058: MyD88
R-HSA-209560: NF-kB is activated and signals survival
R-HSA-597592: Post-translational protein modification
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-1810476: RIP-mediated NFkB activation via ZBP1
R-HSA-162582: Signal Transduction
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-445989: TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-HSA-202403: TCR signaling
R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines
R-HSA-933542: TRAF6 mediated NF-kB activation
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-5689880: Ub-specific processing proteases
R-HSA-1606322: ZBP1(DAI) mediated induction of type I IFNs
R-HSA-193704: p75 NTR receptor-mediated signalling
R-HSA-193639: p75NTR signals via NF-kB
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NFKBIA and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between NFKBIA and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
17210719SacromaInhibit immunity (T cell function)Tumor-induced oxidative stress increased cytosolic IkappaBalpha retention and inhibited NF-kappaB nuclear translocation in thymic T cells. These NF-kappaB-perturbed cells became vulnerable to tumor-secreted tumor necrosis factor (TNF)-alpha (TNF-alpha)-mediated apoptosis through the activation of TNF receptor-associated protein death domain-associated Fas-associated protein death domain and caspase-8.
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of NFKBIA in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of NFKBIA in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0850.803
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1960.938
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0040.998
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0180.97
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.5620.828
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6770.848
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1270.775
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0950.952
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.070.97
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3860.838
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8330.772
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0570.551
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NFKBIA in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.115.4-6.31
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5122016.73.31
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NFKBIA. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NFKBIA. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NFKBIA.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NFKBIA. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NFKBIA expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NFKBIA and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNFKBIA
Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Aliases IKBA; MAD-3; IkappaBalpha; NFKBI; I-kappa-B-alpha; ikB-alpha; major histocompatibility complex enhancer-bind ......
Chromosomal Location14q13
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NFKBIA collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting NFKBIA.
ID Name Drug Type Targets #Targets
DB00945Acetylsalicylic acidSmall MoleculeAKR1C1, EDNRA, HSPA5, IKBKB, NFKB1, NFKB2, NFKBIA, PRKAA1, PRKAA2, ......18
DB05983Bardoxolone methylSmall MoleculeNFKBIA1
DB06543AstaxanthinSmall MoleculeNFKBIA1