Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006023
UniProt IDP25963
Primary gene name(s)NFKBIA
Synonym gene name(s)IKBA, MAD3, NFKBI
Protein nameNF-kappa-B inhibitor alpha
Protein functionInhibits 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. {ECO:0000269|PubMed:7479976}.
Subcellular locationCytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal, NLS and a CRM1-dependent nuclear export. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P25963
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
cellular response to cold [GO:0070417];
cellular response to cytokine stimulus [GO:0071345];
cellular response to organic cyclic compound [GO:0071407];
cytoplasmic sequestering of NF-kappaB [GO:0007253];
cytoplasmic sequestering of transcription factor [GO:0042994];
Fc-epsilon receptor signaling pathway [GO:0038095];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
liver regeneration [GO:0097421];
negative regulation of apoptotic process [GO:0043066];
negative regulation of DNA binding [GO:0043392];
negative regulation of lipid storage [GO:0010888];
negative regulation of macrophage derived foam cell differentiation [GO:0010745];
negative regulation of myeloid cell differentiation [GO:0045638];
negative regulation of NF-kappaB transcription factor activity [GO:0032088];
negative regulation of Notch signaling pathway [GO:0045746];
nucleotide-binding oligomerization domain containing 1 signaling pathway [GO:0070427];
nucleotide-binding oligomerization domain containing 2 signaling pathway [GO:0070431];
positive regulation of cellular protein metabolic process [GO:0032270];
positive regulation of cholesterol efflux [GO:0010875];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
protein import into nucleus, translocation [GO:0000060];
regulation of cell proliferation [GO:0042127];
regulation of NF-kappaB import into nucleus [GO:0042345];
response to exogenous dsRNA [GO:0043330];
response to muramyl dipeptide [GO:0032495];
response to muscle stretch [GO:0035994];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell receptor signaling pathway [GO:0050852];
toll-like receptor 4 signaling pathway [GO:0034142];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
NF-kappaB binding [GO:0051059];
nuclear localization sequence binding [GO:0008139];
transcription factor binding [GO:0008134];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
I-kappaB/NF-kappaB complex [GO:0033256];
nucleus [GO:0005634];
plasma membrane [GO:0005886]
Protein-protein interaction110859
Phylogenetic treeP25963
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD33.6229700963427500
AZA vs. DISU0.8792762228116860.0006103443017322350.0578637107189416
AZA vs. IL7-0.2313143745343130.2337986287425440.990920320206469
AZA vs. SAHA-0.2769250310789840.2596143537389670.632421908251646
DISU vs. CD3-2.757986503131261.18105525359624e-124.14028532388599e-11
DISU vs. IL7-1.11996773379271.3495389570406e-050.0011178186690872
DISU vs. SAHA-1.153413664595490.0001071748118266490.00413102708194227
DMSO vs. AZA-0.1059756179995360.5323055271893241
DMSO vs. CD3-3.7425520482496400
DMSO vs. DISU-0.9878707686513296.91265814826147e-050.0118379270788978
DMSO vs. IL7-0.1177690815205810.5170373376559970.889301967358611
DMSO vs. SAHA-0.1763736926355150.4572144363513250.786786797242614
HIV vs. Mock in Activation-0.1468561693327870.8139184184301090.999983755607037
HIV vs. Mock in Latency-0.1173003109036540.479962644034110.999834320637052
IL7 vs. CD3-3.84742012397300
SAHA vs. CD3-3.9244482231729100
SAHA vs. IL7-0.04870912768975860.8424115603070640.93295950775613
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.411304 0.00199466
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.23 0.96 1.068 1.088 0.945
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00945 Acetylsalicylic acid approved, vet_approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1IKN X-ray 2.3Å D=67-302.
1NFI X-ray 2.7Å E/F=70-282.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef induces phosphorylation of 26075907
Tat activates 19622906
Rev inhibited by 7878004
Tat upregulates 23898208
Vpu stabilizes 11278695
Vpr induces phosphorylation of 23453579
Envelope surface glycoprotein gp120 upregulates 15103018
Envelope surface glycoprotein gp120 regulated by 25008924
matrix increases 26347747
Nef degrades 12419805
Envelope surface glycoprotein gp160; precursor downregulated by 7878004
Envelope surface glycoprotein gp120 induces phosphorylation of 11959143
Tat interacts with 22187158
Vpu inhibits 26178989
Tat inhibits 21951552
Envelope surface glycoprotein gp120 inhibited by 16001969
Tat inhibited by 8615004
Tat induces phosphorylation of 25943894
Vpr upregulates 23001849
Tat binds 17942396
Tat degrades 26031809
capsid increases 26347747
Envelope surface glycoprotein gp120 degrades 21175585
Envelope transmembrane glycoprotein gp41 increases 26347747
Nef upregulates 16429138

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa04623 Cytosolic DNA-sensing pathway - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05140 Leishmaniasis - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)