Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003825
UniProt IDP15336
Primary gene name(s)ATF2
Synonym gene name(s)CREB2, CREBP1
Protein nameCyclic AMP-dependent transcription factor ATF-2
Protein functionTranscriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE, cAMP response element consensus sequences, 5'-TGACGTCA-3' or to AP-1, activator protein 1 consensus sequences, 5'-TGACTCA-3'. In the nucleus, contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. In the cytoplasm, interacts with and perturbs HK1- and VDAC1-containing complexes at the mitochondrial outer membrane, thereby impairing mitochondrial membrane potential, inducing mitochondrial leakage and promoting cell death. The phosphorylated form, mediated by ATM plays a role in the DNA damage response and is involved in the ionizing radiation, IR-induced S phase checkpoint control and in the recruitment of the MRN complex into the IR-induced foci, IRIF. Exhibits histone acetyltransferase, HAT activity which specifically acetylates histones H2B and H4 in vitro. In concert with CUL3 and RBX1, promotes the degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. Can elicit oncogenic or tumor suppressor activities depending on the tissue or cell type. {ECO:0000269|PubMed:10821277, ECO:0000269|PubMed:15916964, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:22304920}.
Subcellular locationNucleus. Cytoplasm. Mitochondrion outer membrane. Note=Shuttles between the cytoplasm and the nucleus and heterodimerization with JUN is essential for the nuclear localization. Localization to the cytoplasm is observed under conditions of cellular stress and in disease states. Localizes at the mitochondrial outer membrane in response to genotoxic stress. Phosphorylation at Thr-52 is required for its nuclear localization and negatively regulates its mitochondrial localization. Co-localizes with the MRN complex in the IR-induced foci, IRIF.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P15336
Gene Ontology
(Biological Process)
Complete annatation
adipose tissue development [GO:0060612];
amelogenesis [GO:0097186];
cellular response to DNA damage stimulus [GO:0006974];
fat cell differentiation [GO:0045444];
intra-S DNA damage checkpoint [GO:0031573];
negative regulation of epithelial cell proliferation [GO:0050680];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
outflow tract morphogenesis [GO:0003151];
positive regulation of mitochondrial membrane permeability involved in apoptotic process [GO:1902110];
positive regulation of neuron apoptotic process [GO:0043525];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transforming growth factor beta2 production [GO:0032915];
regulation of sequence-specific DNA binding transcription factor activity [GO:0051090];
regulation of transcription, DNA-templated [GO:0006355];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
response to osmotic stress [GO:0006970];
response to water deprivation [GO:0009414]
Gene Ontology
(Molecular Function)
Complete annatation
cAMP response element binding [GO:0035497];
cAMP response element binding protein binding [GO:0008140];
chromatin binding [GO:0003682];
enhancer sequence-specific DNA binding [GO:0001158];
histone acetyltransferase activity [GO:0004402];
metal ion binding [GO:0046872];
protein kinase binding [GO:0019901];
RNA polymerase II activating transcription factor binding [GO:0001102];
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 transcription regulatory region sequence-specific binding [GO:0001228];
transcription coactivator activity [GO:0003713];
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0003705];
transcription factor activity, RNA polymerase II transcription factor binding [GO:0001076];
transcription factor activity, sequence-specific DNA binding [GO:0003700]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
mitochondrial outer membrane [GO:0005741];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
site of double-strand break [GO:0035861]
Protein-protein interaction107776
Phylogenetic treeP15336
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. CD30.3753731571397570.2522948444733070.365001717786685
AZA vs. DISU0.3024086391153140.2350323992281250.819764548625228
AZA vs. IL70.04356649010680350.8211858021365530.999311006273513
AZA vs. SAHA-0.127478562772960.6018743024395170.868743947405718
DISU vs. CD3-0.08535895518889030.815425548411550.874233621390875
DISU vs. IL7-0.2675227124695610.2910263061196990.676904802665525
DISU vs. SAHA-0.4294586930660790.143766049661930.487446149483678
DMSO vs. AZA-0.1045940173098370.5342282991456341
DMSO vs. CD3-0.4911732037387680.1253746794653870.205078126617378
DMSO vs. DISU-0.4087817088736750.09654159945731930.561988951844643
DMSO vs. IL70.1553699688434610.3890818386268870.839354424341775
DMSO vs. SAHA-0.03044317208134470.8974050934313580.975026503245809
HIV vs. Mock in Activation-0.06935007776622770.9114090374258060.999983755607037
HIV vs. Mock in Latency0.07780729832891240.6385405212907830.999834320637052
IL7 vs. CD3-0.3230690011620910.3152399775274180.453225122212015
SAHA vs. CD3-0.5285174273427320.1355638712942140.222107799565536
SAHA vs. IL7-0.175468326415940.4719041179091630.705772663296232
(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 2.41998 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
0.895 0.895 1.038 0.945 0.858
(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
DB00852 Pseudoephedrine approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BHI NMR - A=19-56.
1T2K X-ray 3.0Å D=354-414.
4H36 X-ray 3.0Å B=48-55.

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

HIV Partner Interaction Type PubMed
Nef interacts with 25961023
Nef inhibits 20068037
Envelope surface glycoprotein gp120 upregulates 16179804

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04911 Insulin secretion - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04918 Thyroid hormone synthesis - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04925 Aldosterone synthesis and secretion - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
hsa05031 Amphetamine addiction - Homo sapiens (human)
hsa05034 Alcoholism - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)