Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005329
UniProt IDQ9Y6K9
Primary gene name(s)IKBKG
Synonym gene name(s)FIP3, NEMO
Protein nameNF-kappa-B essential modulator
Protein functionRegulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation, either 'Lys-63'-linked or linear polyubiquitin and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination. {ECO:0000269|PubMed:14695475, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20724660}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:14651848}. Nucleus {ECO:0000269|PubMed:14651848}. Note=Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y6K9
Gene Ontology
(Biological Process)
Complete annatation
activation of MAPK activity [GO:0000187];
apoptotic process [GO:0006915];
cellular response to DNA damage stimulus [GO:0006974];
establishment of vesicle localization [GO:0051650];
Fc-epsilon receptor signaling pathway [GO:0038095];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
immune response [GO:0006955];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
JNK cascade [GO:0007254];
negative regulation of neuron death [GO:1901215];
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 from RNA polymerase II promoter [GO:0045944];
regulation of tumor necrosis factor-mediated signaling pathway [GO:0010803];
response to virus [GO:0009615];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
stress-activated MAPK cascade [GO:0051403];
T cell receptor signaling pathway [GO:0050852];
transcription, DNA-templated [GO:0006351];
TRIF-dependent toll-like receptor signaling pathway [GO:0035666]
Gene Ontology
(Molecular Function)
Complete annatation
K63-linked polyubiquitin binding [GO:0070530];
linear polyubiquitin binding [GO:1990450];
metal ion binding [GO:0046872];
protein domain specific binding [GO:0019904];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
signal transducer activity [GO:0004871];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
IkappaB kinase complex [GO:0008385];
intracellular [GO:0005622];
mitotic spindle [GO:0072686];
nucleus [GO:0005634];
spindle pole [GO:0000922];
ubiquitin ligase complex [GO:0000151]
Protein-protein interaction114089
Phylogenetic treeQ9Y6K9
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. CD3-0.1910811486715540.5610282750121260.670667900903189
AZA vs. DISU-0.1331669571332780.6004475065670230.955158276076142
AZA vs. IL7-0.08203511474393790.6719613886588520.999311006273513
AZA vs. SAHA-0.002565100015879070.9916690145139010.998223275042205
DISU vs. CD30.04537522509956570.9004369910466030.934792507096178
DISU vs. IL70.04119427888995240.8709128225435290.975375630725941
DISU vs. SAHA0.1334863473144160.6476196041510870.891335222691649
DMSO vs. AZA0.02750369318087190.870882027828191
DMSO vs. CD30.2083942395751880.5167288125837080.623609674082637
DMSO vs. DISU0.1591656763011540.5167389409187650.913889900204881
DMSO vs. IL7-0.102228079530110.5725734973951970.903878228908594
DMSO vs. SAHA-0.03547224267560320.8812725916882160.970940980432627
HIV vs. Mock in Activation0.2138578981752620.7322637955315030.999983755607037
HIV vs. Mock in Latency0.1085538226616480.5148713725294530.999834320637052
IL7 vs. CD30.1137541393166220.7248115147304290.81469679056911
SAHA vs. CD30.1657164023564170.6393819230135770.73054711961859
SAHA vs. IL70.07707232429486220.7536348857644530.889301476901753
(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 -0.121975 0.619269
(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
0.984 1.079 1.192 1.218 1.384
(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
209929_s_at 1.44 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB04998 AGRO100 investigational unknown unknown
DB05289 MPC-7869 investigational unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2JVX NMR - A=394-419.
2JVY NMR - A=394-419.
3BRT X-ray 2.2Å B/D=44-111.
3BRV X-ray 2.2Å B/D=44-111.
3CL3 X-ray 3.2Å D/E=150-272.
3FX0 X-ray 3.2Å A/B=246-337.
4BWN X-ray 2.2Å A/B=258-344.
5AAY NMR - A=392-419.

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

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 18187620
Envelope transmembrane glycoprotein gp41 cooperates with 22341466

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)
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)
hsa04920 Adipocytokine signaling pathway - 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)
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)
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)
hsa05340 Primary immunodeficiency - Homo sapiens (human)