Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006022
UniProt IDQ00653
Primary gene name(s)NFKB2
Synonym gene name(s)LYT10
Protein nameNuclear factor NF-kappa-B p100 subunit
Protein functionNF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor, I-kappa-B family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases, IKKs in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. {ECO:0000269|PubMed:7925301}.
Subcellular locationNucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor, I-kappa-B.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q00653
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
extracellular matrix organization [GO:0030198];
follicular dendritic cell differentiation [GO:0002268];
germinal center formation [GO:0002467];
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of type I interferon production [GO:0032481];
regulation of transcription, DNA-templated [GO:0006355];
response to cytokine [GO:0034097];
response to lipopolysaccharide [GO:0032496];
rhythmic process [GO:0048511];
spleen development [GO:0048536]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin binding [GO:0003682];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcription coactivator activity [GO:0003713];
transcription factor activity, sequence-specific DNA binding [GO:0003700]
Gene Ontology
(Cellular Component)
Complete annatation
Bcl3/NF-kappaB2 complex [GO:0033257];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction110858
Phylogenetic treeQ00653
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. CD33.0997019510950400
AZA vs. DISU1.33937252856532.69684076736887e-070.000145186349026137
AZA vs. IL7-0.1435813023155120.4747428355850840.999311006273513
AZA vs. SAHA0.4614217120121460.183112393207930.546040794305904
DISU vs. CD3-1.774594460018332.46226297706542e-062.14296490278777e-05
DISU vs. IL7-1.492821492738441.04415942558944e-083.0270583347617e-06
DISU vs. SAHA-0.8747185637347240.0150976921842310.135559182427165
DMSO vs. AZA-0.05935781073515110.7445194827734631
DMSO vs. CD3-3.1706849391567300
DMSO vs. DISU-1.400844303518322.67321259572739e-081.86970208782e-05
DMSO vs. IL7-0.07680485455838230.6948513159761060.937070377919732
DMSO vs. SAHA0.5156625415928870.1331482181185370.437178097439702
HIV vs. Mock in Activation0.4045041010295930.5160713253431270.999983755607037
HIV vs. Mock in Latency-0.05410654755371230.74338201407460.999834320637052
IL7 vs. CD3-3.238253211627600
SAHA vs. CD3-2.66150250456873.75555142539952e-121.04037058788181e-10
SAHA vs. IL70.6028771852410480.09584318780070630.280251512694053
(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 0.0488258 0.797451
(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
1.005 0.977 0.938 0.937 0.859
(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
DB05212 HE3286 investigational unknown unknown
DB05451 P54 investigational unknown unknown
DB05464 NOX-700 investigational unknown unknown
DB05471 SGN-30 investigational unknown unknown
DB05767 HMPL-004 investigational unknown unknown
DB05487 CC-8490 investigational unknown unknown
DB01296 Glucosamine approved unknown antagonist
DB00945 Acetylsalicylic acid approved, vet_approved unknown antagonist

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1A3Q X-ray 2.1Å A/B=37-327.
2D96 NMR - A=766-859.
3DO7 X-ray 3.0Å B=37-329.
4OT9 X-ray 3.3Å A=407-765.

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

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa05134 Legionellosis - Homo sapiens (human)
hsa05166 HTLV-I 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)
hsa05224 Breast cancer - Homo sapiens (human)
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