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NFKBIA NFKB inhibitor alpha [ Homo sapiens (human) ]

Gene ID: 4792, updated on 6-May-2021

Summary

Official Symbol
NFKBIAprovided by HGNC
Official Full Name
NFKB inhibitor alphaprovided by HGNC
Primary source
HGNC:HGNC:7797
See related
Ensembl:ENSG00000100906 MIM:164008
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
IKBA; MAD-3; NFKBI; EDAID2
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]
Expression
Broad expression in bone marrow (RPKM 430.4), ovary (RPKM 112.0) and 21 other tissues See more
Orthologs
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Genomic context

See NFKBIA in Genome Data Viewer
Location:
14q13.2
Exon count:
6
Annotation release Status Assembly Chr Location
109.20210226 current GRCh38.p13 (GCF_000001405.39) 14 NC_000014.9 (35401513..35404749, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (35870719..35873955, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene PSMA6-RPLP0P3 intergenic CAGE-defined low expression enhancer Neighboring gene ribosomal protein lateral stalk subunit P0 pseudogene 3 Neighboring gene DnaJ heat shock protein family (Hsp40) member C8 pseudogene 1 Neighboring gene RPS3A pseudogene 4

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.
GeneReviews: Not available
Ectodermal dysplasia and immunodeficiency 2
MedGen: C2677481 OMIM: 612132 GeneReviews: Not available
Compare labs
Genome-wide association analysis identifies three psoriasis susceptibility loci.
GeneReviews: Not available

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-induced release of IL-6 is regulated by p38 MAPK, IkappaB-alpha, and p65 NF-kappaB activation in primary human monocyte-derived dendritic cells PubMed
env HIV-1 gp120 activates NF-kappaB by inducing phosphorylation of IkappaBalpha in human astrocyte cells PubMed
env HIV-1 gp120 induces degradation of IkappaBalpha in human astroglial cells PubMed
env The mRNA expression levels for alpha-tubulin, TRADD, IFN-gamma R2, GAS1, MADD, NF-kappaB, I-kappa B, 14-3-3 protein, APaf1, PARP, IGF-1 receptor, RB1, Rb2/p130, ARC, and caspase 6 are upregulated in human neuronal cells after treatment with HIV-1 gp120 PubMed
env HIV-1 gp120/CD4 interaction-induced NF-kappaB activation stimulates the hyperphosphorylation of IkappaB-alpha by IkappaB kinases (IKKs) PubMed
env Overexpression of NF-kappaB inhibitory subunit, IkappaBalpha, completely abrogates gp120-induced COX-2 activity PubMed
Envelope surface glycoprotein gp160, precursor env I kappa B alpha inhibits HIV replication and gp160 expression by negatively regulating Rev function, most likely acting through a cellular factor involved in Rev transactivation PubMed
Envelope transmembrane glycoprotein gp41 env Exposure of cells (primary human T cells, TZM-bl-2) to HIV gp41 increases phosphorylated NFKBIA (IkappaBalpha) PubMed
Nef nef HIV-1 Nef ultimately activates NFKBIA and CD28RE via lipid raft mediated AKT1 signaling PubMed
nef HIV-1 Nef induces phosphorylation of NFKIA (IkappaBalpha) PubMed
nef The interaction of HIV-1 Nef with TRAF2, TRAF5, and TRAF6 proteins activates NF-kappaB, leading to the degradation of IkappaB-alpha and the increased phosphorylation of IKK-alpha and IKK-beta in monocyte-derived macrophages PubMed
nef HIV-1 Nef suppresses immunoglobulin class-switch DNA recombination by inducing IkappaBalpha and SOCS proteins, which block CD154, IL-4 and IL-10 cytokine signaling via NF-kappaB and STAT transcription factors PubMed
nef The degradation of I-kappaB alpha in promonocytic cells treated with exogenous HIV-1 Nef results in the activation of NF-kappaB PubMed
Rev rev I kappa B alpha inhibits Rev function, most likely through a cellular factor involved in Rev transactivation PubMed
Tat tat HIV-1 Tat degrades NFKBIA (IkappaBalpha) in HUVEC and EA.hy926 cells PubMed
tat HIV-1 Tat causes proteasomal degradation of TIRAP and NFKBIA in THP-1 cells PubMed
tat HIV-1 Tat induces the phosphorylation and degradation of IkappaB leading to the activation of NF-kappa B, an effect that appears to be regulated by Tat induced expression of NOS-2 and NOS-3 PubMed
tat HIV-1 Tat degrades of NFKBIA (IKappaBalpha)) in CRT-MG human astroglioma cells PubMed
tat Primary human Muller glia cells treated with both HIV-1 clade B and clade C Tat induce phosphorylation of IkappaB-alpha PubMed
tat HIV-1 Tat enhances the NFkappaB activity by inhibiting IkappaB-alpha binding to p65 RelA PubMed
tat HIV-1 Tat upregulates the expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA, IkappaB alpha) in human primary T cells PubMed
tat HIV-1 Tat enhances the NFkappaB activity and promotes the transcriptional activation of MIP-1alpha by interacting with IkappaB-alpha and p65 RelA PubMed
tat HIV-1 Tat inhibits the LPS-induced activation of NFkappaB p65 via its induction of IkappaBalpha expression, which results in retention of NFkappaB p65 in the cytosol PubMed
tat Amino acids 72 to 287 of IkappaB-alpha are required for Tat inhibition. Amino acids 263 to 269 within the sixth ankrin of IkappaB-alpha are required for the binding to Tat PubMed
tat I kappa B potently inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter PubMed
Vpr vpr HIV-1 Vpr induces phosphorylation of IkappaB-alpha at serine positions 176 and 180 PubMed
vpr HIV-1 Vpr expression results in increased IkappaB-alpha levels in the presence of TNF-alpha treatment in differentiated U937 cells PubMed
vpr HIV-1 Vpr induced an increase in I kappa B alpha message in PBMCs, supporting the notion that Vpr diminishes NF-kappa B activity by upregulating I kappa B alpha transcription, an effect that is linked to Vpr regulation of apoptosis PubMed
Vpu vpu Vpu from primary isolates inhibits NFKBIA-dependent gene expression similarly to the inhibition observed when NL4-3 Vpu is utilized PubMed
vpu NL4-3 Vpu inhibits NFKBIA but not IRF3 signaling and requires serines at Vpu amino acid positions 52 and 56 to do so PubMed
vpu HIV-1 Vpu stabilizes IkappaB-alpha upon stimulation with TNF-alpha in 293T cells PubMed
vpu HIV-1 Vpu inhibits beta-TrCP-mediated degradation of phosphorylated IkappaB-alpha PubMed
capsid gag Exposure of human T cells to HIV CA (p24) increases phosphorylated NFKBIA (IkappaBalpha) PubMed
matrix gag Exposure of cells (primary human T cells, TZM-bl) to HIV MA (p17) increases phosphorylated NFKBIA (IkappaBalpha) PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables NF-kappaB binding IDA
Inferred from Direct Assay
more info
PubMed 
enables NF-kappaB binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables nuclear localization sequence binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables transcription factor binding TAS
Traceable Author Statement
more info
PubMed 
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
involved_in apoptotic process TAS
Traceable Author Statement
more info
PubMed 
involved_in cellular response to cold NAS
Non-traceable Author Statement
more info
PubMed 
involved_in cytoplasmic sequestering of NF-kappaB IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cytoplasmic sequestering of transcription factor IDA
Inferred from Direct Assay
more info
PubMed 
involved_in interleukin-1-mediated signaling pathway TAS
Traceable Author Statement
more info
 
involved_in lipopolysaccharide-mediated signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of DNA binding NAS
Non-traceable Author Statement
more info
PubMed 
acts_upstream_of_or_within negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of Notch signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 
involved_in negative regulation of lipid storage IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of macrophage derived foam cell differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of myeloid cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in nucleotide-binding oligomerization domain containing 1 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in nucleotide-binding oligomerization domain containing 2 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of NF-kappaB transcription factor activity TAS
Traceable Author Statement
more info
 
involved_in positive regulation of cellular protein metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of cholesterol efflux IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of inflammatory response IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in protein deubiquitination TAS
Traceable Author Statement
more info
 
involved_in protein import into nucleus IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of NIK/NF-kappaB signaling NAS
Non-traceable Author Statement
more info
PubMed 
involved_in regulation of cell population proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in response to exogenous dsRNA IEA
Inferred from Electronic Annotation
more info
 
involved_in response to muramyl dipeptide IEA
Inferred from Electronic Annotation
more info
 
involved_in response to muscle stretch IEA
Inferred from Electronic Annotation
more info
 
involved_in toll-like receptor 4 signaling pathway IEA
Inferred from Electronic Annotation
more info
 
involved_in tumor necrosis factor-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
part_of I-kappaB/NF-kappaB complex TAS
Traceable Author Statement
more info
PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 
located_in cytosol TAS
Traceable Author Statement
more info
 
located_in nucleoplasm TAS
Traceable Author Statement
more info
 
located_in nucleus IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 

General protein information

Preferred Names
NF-kappa-B inhibitor alpha
Names
I-kappa-B-alpha
IkappaBalpha
ikB-alpha
major histocompatibility complex enhancer-binding protein MAD3
nuclear factor of kappa light chain gene enhancer in B-cells
nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_007571.1 RefSeqGene

    Range
    4985..8229
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_89

mRNA and Protein(s)

  1. NM_020529.3NP_065390.1  NF-kappa-B inhibitor alpha

    See identical proteins and their annotated locations for NP_065390.1

    Status: REVIEWED

    Source sequence(s)
    AL133163, BC004983
    Consensus CDS
    CCDS9656.1
    UniProtKB/Swiss-Prot
    P25963
    Related
    ENSP00000216797.6, ENST00000216797.10
    Conserved Domains (3) summary
    cd00204
    Location:105237
    ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...
    sd00045
    Location:143180
    ANK; ANK repeat [structural motif]
    cl26073
    Location:27151
    Ank_2; Ankyrin repeats (3 copies)

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210226

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p13 Primary Assembly

    Range
    35401513..35404749 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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