Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005328
UniProt IDO14920
Primary gene name(s)IKBKB
Synonym gene name(s)IKKB
Protein nameInhibitor of nuclear factor kappa-B kinase subunit beta
Protein functionSerine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. {ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:20797629}. Nucleus {ECO:0000269|PubMed:20797629}. Membrane raft {ECO:0000269|PubMed:17287217}. Note=Colocalized with DPP4 in membrane rafts. {ECO:0000269|PubMed:17287217}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14920
Gene Ontology
(Biological Process)
Complete annatation
cellular response to tumor necrosis factor [GO:0071356];
cortical actin cytoskeleton organization [GO:0030866];
establishment of protein localization to plasma membrane [GO:0090002];
Fc-epsilon receptor signaling pathway [GO:0038095];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
interleukin-1-mediated signaling pathway [GO:0070498];
negative regulation of apoptotic process [GO:0043066];
negative regulation of bicellular tight junction assembly [GO:1903347];
negative regulation of myosin-light-chain-phosphatase activity [GO:0035509];
nucleotide-binding oligomerization domain containing signaling pathway [GO:0070423];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
protein phosphorylation [GO:0006468];
regulation of establishment of endothelial barrier [GO:1903140];
regulation of phosphorylation [GO:0042325];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to virus [GO:0009615];
serine phosphorylation of STAT protein [GO:0042501];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666];
tumor necrosis factor-mediated signaling pathway [GO:0033209]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
IkappaB kinase activity [GO:0008384];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
protein kinase activity [GO:0004672];
protein kinase binding [GO:0019901];
protein serine/threonine kinase activity [GO:0004674];
scaffold protein binding [GO:0097110]
Gene Ontology
(Cellular Component)
Complete annatation
CD40 receptor complex [GO:0035631];
cytoplasm [GO:0005737];
cytoplasmic side of plasma membrane [GO:0009898];
cytosol [GO:0005829];
IkappaB kinase complex [GO:0008385];
membrane raft [GO:0045121];
nucleus [GO:0005634]
Protein-protein interaction109767
Phylogenetic treeO14920
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD3-0.4436964492513840.1756280530289710.275850981164302
AZA vs. DISU0.1927162067941550.4455456556184030.91814655876178
AZA vs. IL7-0.1681691298876680.3811363146291450.999311006273513
AZA vs. SAHA-0.1471088937856230.5462161575941760.845739823260084
DISU vs. CD30.6233134184724450.08627616847013190.166074187654038
DISU vs. IL7-0.3700957935518980.1418356509391520.491140422005528
DISU vs. SAHA-0.3375763095516530.2465410265617150.624704935827561
DMSO vs. AZA0.05791160903173570.7290202415183471
DMSO vs. CD30.4896585872376030.126043784324440.205948981653763
DMSO vs. DISU-0.1366590873931360.5748230091947030.931469777531738
DMSO vs. IL7-0.2187319197196010.2232641383439960.730634444581427
DMSO vs. SAHA-0.2108055179602530.3709599137745610.718603709575374
HIV vs. Mock in Activation0.1865033217811210.7643580848931780.999983755607037
HIV vs. Mock in Latency0.1669007215958980.3111505105482720.999834320637052
IL7 vs. CD30.281877128031030.3799149450331730.516781695378126
SAHA vs. CD30.2729277339351680.4399368412150890.552910403706479
SAHA vs. IL70.01801165365129980.9410200152234710.977311325505629
(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 -0.18231 0.216557
(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
1.002 1.048 1.258 1.35 1.334
(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
DB00995 Auranofin approved yes inhibitor
DB01169 Arsenic trioxide approved, investigational yes inducer
DB05183 MLN0415 investigational unknown unknown
DB00795 Sulfasalazine approved unknown inhibitor
DB00244 Mesalazine approved unknown inhibitor
DB06151 Acetylcysteine approved unknown inhibitor
DB00945 Acetylsalicylic acid approved, vet_approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
3BRT X-ray 2.2Å A/C=701-730.
3BRV X-ray 2.2Å A/C=701-745.
4E3C X-ray 3.9Å A/B/C/D/E/F=11-669.
4KIK X-ray 2.8Å A/B=2-664.

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

HIV Partner Interaction Type PubMed
Vpu inhibits 25620704
Nef induces phosphorylation of 17182689
23774506
2487473926075907
Vpr induces phosphorylation of 24912525
Envelope surface glycoprotein gp120 stimulates 11959143
Tat induces phosphorylation of 21029719
2134438821344388
22435562
22748238
2506415926031809
Tat cooperates with 23555914
Nef enhances 25620704
Nef activates 24874739
25620704

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01523 Antifolate resistance - Homo sapiens (human)
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt 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)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04930 Type II diabetes mellitus - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - 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)
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)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
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