Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006740
UniProt IDQ04206
Primary gene name(s)RELA
Synonym gene name(s)NFKB3
Protein nameTranscription factor p65
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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and p65-c-Rel complexes are transcriptional activators. The NF-kappa-B p65-p65 complex appears to be involved in invasin-mediated activation of IL-8 expression. The inhibitory effect of I-kappa-B upon NF-kappa-B the cytoplasm is exerted primarily through the interaction with p65. p65 shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells, PubMed:15790681. {ECO:0000269|PubMed:10928981, ECO:0000269|PubMed:12748188, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:17000776, ECO:0000269|PubMed:17620405, ECO:0000269|PubMed:19058135, ECO:0000269|PubMed:19103749, ECO:0000269|PubMed:20547752}.
Subcellular locationNucleus. Cytoplasm. Note=Colocalized with DDX1 in the nucleus upon TNF-alpha induction, By similarity. Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor, I-kappa-B. Colocalizes with GFI1 in the nucleus after LPS stimulation. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q04206
Gene Ontology
(Biological Process)
Complete annatation
acetaldehyde metabolic process [GO:0006117];
aging [GO:0007568];
animal organ morphogenesis [GO:0009887];
cellular defense response [GO:0006968];
cellular response to hepatocyte growth factor stimulus [GO:0035729];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to interleukin-1 [GO:0071347];
cellular response to interleukin-6 [GO:0071354];
cellular response to lipopolysaccharide [GO:0071222];
cellular response to nicotine [GO:0071316];
cellular response to peptide hormone stimulus [GO:0071375];
cellular response to tumor necrosis factor [GO:0071356];
cytokine-mediated signaling pathway [GO:0019221];
defense response to virus [GO:0051607];
Fc-epsilon receptor signaling pathway [GO:0038095];
hair follicle development [GO:0001942];
inflammatory response [GO:0006954];
liver development [GO:0001889];
membrane protein intracellular domain proteolysis [GO:0031293];
negative regulation of apoptotic process [GO:0043066];
negative regulation of extrinsic apoptotic signaling pathway [GO:2001237];
negative regulation of insulin receptor signaling pathway [GO:0046627];
negative regulation of NIK/NF-kappaB signaling [GO:1901223];
negative regulation of protein catabolic process [GO:0042177];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
nucleotide-binding oligomerization domain containing 2 signaling pathway [GO:0070431];
positive regulation of cell proliferation [GO:0008284];
positive regulation of chondrocyte differentiation [GO:0032332];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of interleukin-12 biosynthetic process [GO:0045084];
positive regulation of miRNA metabolic process [GO:2000630];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of pri-miRNA transcription from RNA polymerase II promoter [GO:1902895];
positive regulation of Schwann cell differentiation [GO:0014040];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of type I interferon production [GO:0032481];
regulation of inflammatory response [GO:0050727];
response to amino acid [GO:0043200];
response to cAMP [GO:0051591];
response to cobalamin [GO:0033590];
response to drug [GO:0042493];
response to insulin [GO:0032868];
response to interleukin-1 [GO:0070555];
response to morphine [GO:0043278];
response to muramyl dipeptide [GO:0032495];
response to muscle stretch [GO:0035994];
response to organic substance [GO:0010033];
response to progesterone [GO:0032570];
response to UV-B [GO:0010224];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
T cell receptor signaling pathway [GO:0050852]
Gene Ontology
(Molecular Function)
Complete annatation
actinin binding [GO:0042805];
activating transcription factor binding [GO:0033613];
chromatin binding [GO:0003682];
chromatin DNA binding [GO:0031490];
DNA binding [GO:0003677];
histone deacetylase binding [GO:0042826];
identical protein binding [GO:0042802];
NF-kappaB binding [GO:0051059];
phosphate ion binding [GO:0042301];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
protein kinase binding [GO:0019901];
protein N-terminus binding [GO:0047485];
repressing transcription factor binding [GO:0070491];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
RNA polymerase II distal enhancer sequence-specific DNA binding [GO:0000980];
RNA polymerase II regulatory region sequence-specific DNA binding [GO:0000977];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0001205];
transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001078];
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0003705];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
transcription regulatory region DNA binding [GO:0044212];
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];
NF-kappaB complex [GO:0071159];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcription factor complex [GO:0005667]
Protein-protein interaction111902
Phylogenetic treeQ04206
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
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. CD3-0.01389195096683280.9662622973704230.977413935680275
AZA vs. DISU0.2355088330993020.3518106818382920.888431548241123
AZA vs. IL7-0.08076631572425390.6747259619419440.999311006273513
AZA vs. SAHA0.02108286886281260.9311297535880860.984833700925261
DISU vs. CD30.2367100860017770.5152374383523680.638741022941944
DISU vs. IL7-0.32590540516910.1960464423371140.570559784940047
DISU vs. SAHA-0.2115230779654880.4677648099431040.802731342023029
DMSO vs. AZA0.01765621579974980.9161818284603321
DMSO vs. CD30.0193657702346690.9519638034594080.96633210020322
DMSO vs. DISU-0.2198347621640440.3675876836363080.851059516423285
DMSO vs. IL7-0.09096612452705880.61320337000070.915237658574009
DMSO vs. SAHA-0.00130597513462070.9955825736030240.999029560341645
HIV vs. Mock in Activation0.1954287358558690.7535121423739380.999983755607037
HIV vs. Mock in Latency-0.01292324725500130.9375725131861730.999834320637052
IL7 vs. CD3-0.06164547841381260.8487178406459820.901975887474927
SAHA vs. CD30.0119332019015050.9730956529285840.981569813750586
SAHA vs. IL70.09963580034024890.6826785671020830.849803419341424
(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 -0.435568 0.000580925
(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
1.001 0.921 0.991 1.065 0.944
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1NFI X-ray 2.7Å A/C=20-320.
2LSP NMR - A=304-316.
2N22 NMR - B=521-551.
2O61 X-ray 2.8Å A=20-291.
3GUT X-ray 3.5Å A/C/E/G=20-291.
3QXY X-ray 2.0Å P/Q=302-316.
3RC0 X-ray 2.1Å P/Q=302-316.
4KV1 X-ray 1.5Å C/D=308-314.
4KV4 X-ray 2.0Å B=308-314.

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

HIV Partner Interaction Type PubMed
matrix inhibits 25265071
Envelope surface glycoprotein gp120 interacts with 22528837
Vpr regulated by 24225433
Tat activates 10393859
capsid inhibits 25265071
Tat increases nuclear localization of 26446987
Tat upregulates 22187158
Envelope transmembrane glycoprotein gp41 inhibits 25265071
Envelope surface glycoprotein gp120 co-localizes with 24043886
Nef induces 26075907
Vpr induces phosphorylation of 23453579
Vpr inhibits 17023015
Tat cooperates with 23555914
Tat regulated by 11704662
Envelope surface glycoprotein gp120 regulated by 25008924
Tat downregulates 23287597
Vpr activates 9560267
matrix increases 26347747
Tat enhances 21344388
Nef interacts with 24658403
Tat recruits 9566873
Tat acetylates 11739381
HIV-1 virus replication enhanced by expression of human gene 18854154
Tat regulates 23103739
Tat interacts with 22187158
Vpu inhibits 25620704
Tat inhibits 19622906
Vpr cooperates with 19204000
Vpr downregulates 22552851
Tat induces phosphorylation of 21344388
Nef enhances 25620704
Tat binds 22187158
Vpu inhibited by 23164059
Envelope surface glycoprotein gp120 activates 23554973
Envelope transmembrane glycoprotein gp41 increases 26347747
Envelope transmembrane glycoprotein gp41 cooperates with 22341466
Tat increases binding of 26446987

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)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04064 NF-kappa B signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04211 Longevity regulating pathway - 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)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
hsa05120 Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
hsa05131 Shigellosis - Homo sapiens (human)
hsa05132 Salmonella infection - Homo sapiens (human)
hsa05133 Pertussis - 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)
hsa05146 Amoebiasis - Homo sapiens (human)
hsa05152 Tuberculosis - 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)
hsa05202 Transcriptional misregulation 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)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)