Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0004393
UniProt IDP16220
Primary gene name(s)CREB1
Synonym gene name(s)unknown
Protein nameCyclic AMP-responsive element-binding protein 1
Protein functionPhosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element, CRE, a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Subcellular locationNucleus {ECO:0000255|PROSITE-ProRule:PRU00312, ECO:0000255|PROSITE-ProRule:PRU00978, ECO:0000269|PubMed:12552083}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P16220
Gene Ontology
(Biological Process)
Complete annatation
aging [GO:0007568];
axon guidance [GO:0007411];
cellular response to fatty acid [GO:0071398];
cellular response to hepatocyte growth factor stimulus [GO:0035729];
cellular response to insulin-like growth factor stimulus [GO:1990314];
cellular response to nerve growth factor stimulus [GO:1990090];
cellular response to platelet-derived growth factor stimulus [GO:0036120];
cellular response to zinc ion [GO:0071294];
chemotaxis to arachidonic acid [GO:0034670];
circadian rhythm [GO:0007623];
lactation [GO:0007595];
lung saccule development [GO:0060430];
memory [GO:0007613];
negative regulation of neuron death [GO:1901215];
negative regulation of transcription by competitive promoter binding [GO:0010944];
pituitary gland development [GO:0021983];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cardiac muscle tissue development [GO:0055025];
positive regulation of fat cell differentiation [GO:0045600];
positive regulation of hormone secretion [GO:0046887];
positive regulation of lipid biosynthetic process [GO:0046889];
positive regulation of long-term synaptic potentiation [GO:1900273];
positive regulation of multicellular organism growth [GO:0040018];
positive regulation of osteoclast differentiation [GO:0045672];
positive regulation of RNA polymerase II transcriptional preinitiation complex assembly [GO:0045899];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transforming growth factor beta3 production [GO:0032916];
protein phosphorylation [GO:0006468];
protein stabilization [GO:0050821];
regulation of cell size [GO:0008361];
regulation of circadian rhythm [GO:0042752];
regulation of fibroblast proliferation [GO:0048145];
regulation of glial cell proliferation [GO:0060251];
response to activity [GO:0014823];
response to drug [GO:0042493];
response to glucagon [GO:0033762];
response to hypoxia [GO:0001666];
response to L-glutamate [GO:1902065];
response to nicotine [GO:0035094];
response to organic substance [GO:0010033];
secretory granule organization [GO:0033363];
signal transduction [GO:0007165];
transforming growth factor beta receptor signaling pathway [GO:0007179];
Type I pneumocyte differentiation [GO:0060509];
viral process [GO:0016032];
visual learning [GO:0008542]
Gene Ontology
(Molecular Function)
Complete annatation
cAMP response element binding [GO:0035497];
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
RNA polymerase II activating transcription factor binding [GO:0001102];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
RNA polymerase II distal enhancer sequence-specific DNA binding [GO:0000980];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcriptional activator activity, RNA polymerase II transcription factor binding [GO:0001190];
transcription cofactor activity [GO:0003712];
transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding [GO:0003705];
transcription factor activity, sequence-specific DNA binding [GO:0003700]
Gene Ontology
(Cellular Component)
Complete annatation
ATF4-CREB1 transcription factor complex [GO:1990589];
axon [GO:0030424];
mitochondrial matrix [GO:0005759];
nuclear euchromatin [GO:0005719];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction107775
Phylogenetic treeP16220
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. CD30.1216165110212660.7101055964239960.794146438324736
AZA vs. DISU0.1415374981699820.5766006934268010.954304256505839
AZA vs. IL7-0.02988841078940560.8765625775979560.999311006273513
AZA vs. SAHA0.2371388355526020.3327169083014430.705017444134552
DISU vs. CD30.007239323068093350.9840937320388820.990004599356254
DISU vs. IL7-0.1802415122741820.4747823991733810.810714150984736
DISU vs. SAHA0.09629835001416970.7436343506353040.926453938862913
DMSO vs. AZA-0.09365785687502810.5767465908961121
DMSO vs. CD3-0.225938963958910.4797100987893610.589656710040937
DMSO vs. DISU-0.2368905545656290.3324721818943550.833813050486394
DMSO vs. IL70.07093919880050280.6934812876493160.936954851917814
DMSO vs. SAHA0.3231975412462460.1725770277864250.503077057208746
HIV vs. Mock in Activation0.1183589067778830.8499399844111810.999983755607037
HIV vs. Mock in Latency0.03646686821690.825271304266990.999834320637052
IL7 vs. CD3-0.1431131278983720.655852143224410.763312435705469
SAHA vs. CD30.09010292522330110.7990340596327120.857286293511674
SAHA vs. IL70.2626260790531540.2835442584838190.531345866780841
(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 -0.206408 0.197739
(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
0.96 0.989 0.985 0.991 1.075
(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
DB00131 Adenosine monophosphate approved, nutraceutical unknown activator
DB01183 Naloxone approved, vet_approved unknown other/unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2LXT NMR - C=116-149.

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

HIV Partner Interaction Type PubMed
matrix induces phosphorylation of 20402410
Vpr downregulates 21816823
Tat activates 16920714
Envelope surface glycoprotein gp120 inhibited by 19100722
Tat induces phosphorylation of 16339753
Tat regulated by 17202341
Tat downregulates 11156964
Tat requires 22219277

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04612 Antigen processing and presentation - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa04713 Circadian entrainment - Homo sapiens (human)
hsa04725 Cholinergic synapse - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04911 Insulin secretion - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04916 Melanogenesis - Homo sapiens (human)
hsa04918 Thyroid hormone synthesis - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04924 Renin secretion - Homo sapiens (human)
hsa04925 Aldosterone synthesis and secretion - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04962 Vasopressin-regulated water reabsorption - Homo sapiens (human)
hsa05016 Huntington's disease - Homo sapiens (human)
hsa05030 Cocaine addiction - Homo sapiens (human)
hsa05031 Amphetamine addiction - Homo sapiens (human)
hsa05034 Alcoholism - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)