Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002470
UniProt IDQ04864
Primary gene name(s)REL
Synonym gene name(s)unknown
Protein nameProto-oncogene c-Rel
Protein functionProto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator.
Subcellular locationNucleus {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q04864
Gene Ontology
(Biological Process)
Complete annatation
I-kappaB kinase/NF-kappaB signaling [GO:0007249];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
negative regulation of gene expression [GO:0010629];
negative regulation of interferon-beta production [GO:0032688];
negative regulation of neuron death [GO:1901215];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
NIK/NF-kappaB signaling [GO:0038061];
positive regulation of I-kappaB kinase/NF-kappaB signaling [GO:0043123];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
response to cytokine [GO:0034097]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin binding [GO:0003682];
RNA polymerase II distal enhancer sequence-specific DNA binding [GO:0000980];
transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0001205];
transcription factor activity, sequence-specific DNA binding [GO:0003700]
Gene Ontology
(Cellular Component)
Complete annatation
cytosol [GO:0005829];
I-kappaB/NF-kappaB complex [GO:0033256];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcription factor complex [GO:0005667]
Protein-protein interaction111898
Phylogenetic treeQ04864
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. CD33.300349433925396.59139409719955e-121.39923227933791e-10
AZA vs. DISU0.3167676331308980.2175739312194730.806023455198412
AZA vs. IL7-0.2811901842590820.1561108384401130.922364014369591
AZA vs. SAHA0.4521652228567410.06947012470710010.324509655976085
DISU vs. CD3-2.997458547635791.18877430121955e-092.33937125542866e-08
DISU vs. IL7-0.6065088175282380.01789081859217860.16710290599572
DISU vs. SAHA0.1368032452432530.6460328303211310.89062941692003
DMSO vs. AZA-0.055030740081340.7516448488667041
DMSO vs. CD3-3.366296412115332.37965203098156e-124.91088463653934e-11
DMSO vs. DISU-0.373581301623210.1311989014493960.621518013007355
DMSO vs. IL7-0.2187998264368770.2384787062595880.744318806053491
DMSO vs. SAHA0.499807595073130.0384995326718350.216826030230652
HIV vs. Mock in Activation0.8938138345966160.3470821853943640.999983755607037
HIV vs. Mock in Latency0.189873722718550.2618401008643360.999834320637052
IL7 vs. CD3-3.574214841769182.19602114270856e-137.10313877340045e-12
SAHA vs. CD3-2.873576910760951.03869949308333e-081.37550099830982e-07
SAHA vs. IL70.728999578320530.003638237771711240.0306707742881911
(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
-1.2 0.121251884 -1.2 0.066977119 -1.7 0.004154137
(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) TRUE
(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 0.57138 0.000305467
(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
1.046 1.032 1.141 1.319 1.054
(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

not found

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

HIV Partner Interaction Type PubMed
Vpr upregulates 20801175
Tat upregulates 9510190
Tat downregulates 11254713
Tat interacts with 1727488

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)