Homo sapiens Gene: NFKBIA
Summary
InnateDB Gene IDBG-4758.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NFKBIA
Gene Name nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Synonyms IKBA; MAD-3; NFKBI;
Species Homo sapiens
Ensembl Gene ENSG00000100906
Encoded Proteins
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
NFKBIA is a common component of the heterogeneous IKK complex that mediates an essential step of the NF-kappaB signal transduction cascade by acting as an inhibitor of NF-kappaB.
Tyrosine phosphorylation of NFKBIA is c-Src-dependent, leading to the subsequent activation of NF-kappaB.
Nuclear transport of the NFKBIA : RELA complex, required for the appropriate regulation of NF-kappaB signalling, is facilitated by 14-3-3 proteins.
NFKBIA ubiquitination and degradation is inhibited by ChlaDub1, a protein of Chlamydia trachomatis, suppressing NF-kappaB activation as a result.
NFKBIA degradation occurs through the TNF-stimulated formation of autophagosomes in epithelial cells, which results in the prolonged activation of NFKB activity.
Polymorphisms in the NFKBIA promoter are associated with pediatric lung diseases, including childhood asthma, bronchiolitis and bronchopulmonary dysplasia.
Haploinsufficiency of A20 (HA20) is caused by high-penetrance loss-of-function germline mutations in TNFAIP3 with increased degradation of NFKBIA, nuclear translocation of RELA, increased expression of NFκB mediated proinflammatory cytokines, and defective deubiquitinating activity.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Nfkbia degradation occurs through the TNF-stimulated formation of autophagosomes in epithelial cells, which results in the prolonged activation of NFKB activity.
Entrez Gene
Summary This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]
Gene Information
Type Protein coding
Genomic Location Chromosome 14:35401511-35404749
Strand Reverse strand
Band q13.2
Transcripts
ENST00000216797 ENSP00000216797
ENST00000554001 ENSP00000450537
ENST00000557140 ENSP00000451257
ENST00000557389 ENSP00000450514
ENST00000555371
ENST00000557100
ENST00000556664
ENST00000557459
ENST00000555629
ENST00000553342 ENSP00000451281
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 234 experimentally validated interaction(s) in this database.
They are also associated with 30 interaction(s) predicted by orthology.
Experimentally validated
Total 234 [view]
Protein-Protein 210 [view]
Protein-DNA 23 [view]
Protein-RNA 0
DNA-DNA 1 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 30 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0008139 nuclear localization sequence binding
GO:0019899 enzyme binding
GO:0031072 heat shock protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0032403 protein complex binding
GO:0042802 identical protein binding
GO:0051059 NF-kappaB binding
Biological Process
GO:0000060 protein import into nucleus, translocation
GO:0002224 toll-like receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006915 apoptotic process
GO:0007253 cytoplasmic sequestering of NF-kappaB
GO:0010468 regulation of gene expression
GO:0010745 negative regulation of macrophage derived foam cell differentiation
GO:0010875 positive regulation of cholesterol efflux
GO:0010888 negative regulation of lipid storage
GO:0016032 viral process
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032270 positive regulation of cellular protein metabolic process
GO:0032481 positive regulation of type I interferon production
GO:0032495 response to muramyl dipeptide
GO:0032496 response to lipopolysaccharide
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042127 regulation of cell proliferation
GO:0042345 regulation of NF-kappaB import into nucleus
GO:0042994 cytoplasmic sequestering of transcription factor
GO:0043066 negative regulation of apoptotic process
GO:0043330 response to exogenous dsRNA
GO:0043392 negative regulation of DNA binding
GO:0045087 innate immune response (InnateDB)
GO:0045638 negative regulation of myeloid cell differentiation
GO:0045746 negative regulation of Notch signaling pathway
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0070417 cellular response to cold
GO:0070427 nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0033256 I-kappaB/NF-kappaB complex
GO:0043234 protein complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
TGF_beta_Receptor pathway
TNFalpha pathway
TCR pathway
BCR pathway
IL1 pathway
IL4 pathway
IL5 pathway
IL6 pathway
RANKL pathway
Leptin pathway
TSH pathway
TSLP pathway
TWEAK pathway
Prolactin pathway
Oncostatin_M pathway
REACTOME
RIP-mediated NFkB activation via ZBP1 pathway
MyD88 dependent cascade initiated on endosome pathway
FCERI mediated NF-kB activation pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TCR signaling pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
MyD88 cascade initiated on plasma membrane pathway
Innate Immune System pathway
NF-kB is activated and signals survival pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated NF-kB activation pathway
Fc epsilon receptor (FCERI) signaling pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Signal Transduction pathway
Activation of NF-kappaB in B cells pathway
Adaptive Immune System pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Downstream TCR signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
Signaling by the B Cell Receptor (BCR) pathway
Downstream signaling events of B Cell Receptor (BCR) pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
KEGG
Chemokine signaling pathway pathway
Apoptosis pathway
Osteoclast differentiation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
T cell receptor signaling pathway pathway
B cell receptor signaling pathway pathway
Neurotrophin signaling pathway pathway
Adipocytokine signaling pathway pathway
Epithelial cell signaling in Helicobacter pylori infection pathway
Shigellosis pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Toxoplasmosis pathway
Hepatitis C pathway
Pathways in cancer pathway
Prostate cancer pathway
Chronic myeloid leukemia pathway
Small cell lung cancer pathway
INOH
TNFR1 signaling pathway pathway
CD4 T cell receptor signaling pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
B cell receptor signaling pathway
PID BIOCARTA
Atm signaling pathway [Biocarta view]
Toll-like receptor pathway [Biocarta view]
Chaperones modulate interferon signaling pathway [Biocarta view]
Mechanism of gene regulation by peroxisome proliferators via ppara [Biocarta view]
Nf-kb signaling pathway [Biocarta view]
Role of egf receptor transactivation by gpcrs in cardiac hypertrophy [Biocarta view]
Tnfr2 signaling pathway [Biocarta view]
Acetylation and deacetylation of rela in nucleus [Biocarta view]
Inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages [Biocarta view]
Keratinocyte differentiation [Biocarta view]
Bone remodeling [Biocarta view]
Double stranded rna induced gene expression [Biocarta view]
Trefoil factors initiate mucosal healing [Biocarta view]
Signal transduction through il1r [Biocarta view]
Fmlp induced chemokine gene expression in hmc-1 cells [Biocarta view]
Cd40l signaling pathway [Biocarta view]
Hiv-1 nef: negative effector of fas and tnf [Biocarta view]
Ceramide signaling pathway [Biocarta view]
T cell receptor signaling pathway [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
Erythropoietin mediated neuroprotection through nf-kb [Biocarta view]
Influence of ras and rho proteins on g1 to s transition [Biocarta view]
Akt signaling pathway [Biocarta view]
Cadmium induces dna synthesis and proliferation in macrophages [Biocarta view]
PID NCI
CD40/CD40L signaling
Atypical NF-kappaB pathway
Ceramide signaling pathway
LPA receptor mediated events
Aurora A signaling
Signaling events mediated by HDAC Class I
BCR signaling pathway
IL23-mediated signaling events
Canonical NF-kappaB pathway
HIV-1 Nef: Negative effector of Fas and TNF-alpha
Osteopontin-mediated events
Cross-References
SwissProt
TrEMBL G3V286 Q9UGJ5
UniProt Splice Variant
Entrez Gene 4792
UniGene
RefSeq NM_020529
HUGO HGNC:7797
OMIM 164008
CCDS CCDS9656
HPRD 01235
IMGT
EMBL AJ249290 AL133163
GenPept CAB65113
RNA Seq Atlas 4792