NFKBIA NFKB inhibitor alpha [Homo sapiens (human)] - Gene

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; AllianceGenome:HGNC:7797
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: mouse all
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Genomic context

Location:: 14q13.2

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (35401513..35404749, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (29589207..29592460, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (35870719..35873955, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IkBalpha ubiquitination and activating NF-kB signaling.
Title: ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling.
Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IkappaBalpha axis in liver inflammation.
Title: Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IκBα axis in liver inflammation.
Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-kappaB /NLRP3 pathway.
Title: Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-κB /NLRP3 pathway.
Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.
Title: Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas.
IKBA phosphorylation governs human sperm motility through ACC-mediated fatty acid beta-oxidation.
Title: IKBA phosphorylation governs human sperm motility through ACC-mediated fatty acid beta-oxidation.
Identification of Key Genes and miRNAs Affecting Osteosarcoma Based on Bioinformatics.
Title: Identification of Key Genes and miRNAs Affecting Osteosarcoma Based on Bioinformatics.
A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia.
Title: A Novel De Novo NFKBIA Missense Mutation Associated to Ectodermal Dysplasia with Dysgammaglobulinemia.
Genetic variants in the NF-kappaB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients.
Title: Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients.
The role of NFKB1/NFKBIA genetic variants in HPV infection: A cross-sectional cohort study.
Title: The role of NFKB1/NFKBIA genetic variants in HPV infection: A cross-sectional cohort study.
IkappaBalpha is required for full transcriptional induction of some NFkappaB-regulated genes in response to TNF in MCF-7 cells.
Title: IκBα is required for full transcriptional induction of some NFκB-regulated genes in response to TNF in MCF-7 cells.

Submit: New GeneRIF Correction See all GeneRIFs (267)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Ectodermal dysplasia and immunodeficiency 2 MedGen: C2677481 OMIM: 612132 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies three psoriasis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D14S1326 (e-PCR)
- UniSTS:35158

PMC152543P2 (e-PCR)
- UniSTS:271226

GDB:366518 (e-PCR)
- UniSTS:156813

G44344 (e-PCR)
- UniSTS:95131

NFKBIA (e-PCR)
- UniSTS:480425

PMC135646P3 (e-PCR)
- UniSTS:270767

NFKBIA (e-PCR)
- UniSTS:264121

RH69167 (e-PCR)
- UniSTS:75491

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NF-kappaB binding	IBA Inferred from Biological aspect of Ancestor more info
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 molecular sequestering activity	IDA Inferred from Direct Assay 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 protein sequestering activity	IDA Inferred from Direct Assay more info	PubMed
enables transcription regulator inhibitor activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to cold	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to tumor necrosis factor	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytoplasmic sequestering of NF-kappaB	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytoplasmic sequestering of NF-kappaB	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in interleukin-1-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
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 canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
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 non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
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 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 protein metabolic process	IMP Inferred from Mutant Phenotype 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 positive regulation of transcription initiation by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in protein import into nucleus	IEA Inferred from Electronic Annotation more info
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	IBA Inferred from Biological aspect of Ancestor more info
involved_in toll-like receptor 4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
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
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
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

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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

NG_007571.1 RefSeqGene

Range

4985..8229

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_89

mRNA and Protein(s)

NM_020529.3 → NP_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

B2R8L6, P25963

UniProtKB/TrEMBL

A0A8V8TLC3

Related

ENSP00000216797.6, ENST00000216797.10

Conserved Domains (3) summary

cd00204
Location:105 → 237

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:143 → 180

ANK; ANK repeat [structural motif]

cl26073
Location:27 → 151

Ank_2; Ankyrin repeats (3 copies)