Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000767
UniProt IDP35638
Primary gene name(s)DDIT3
Synonym gene name(s)CHOP, CHOP10, GADD153
Protein nameDNA damage-inducible transcript 3 protein
Protein functionMultifunctional transcription factor in ER stress response. Plays an essential role in the response to a wide variety of cell stresses and induces cell cycle arrest and apoptosis in response to ER stress. Plays a dual role both as an inhibitor of CCAAT/enhancer-binding protein, C/EBP function and as an activator of other genes. Acts as a dominant-negative regulator of C/EBP-induced transcription: dimerizes with members of the C/EBP family, impairs their association with C/EBP binding sites in the promoter regions, and inhibits the expression of C/EBP regulated genes. Positively regulates the transcription of TRIB3, IL6, IL8, IL23, TNFRSF10B/DR5, PPP1R15A/GADD34, BBC3/PUMA, BCL2L11/BIM and ERO1L. Negatively regulates; expression of BCL2 and MYOD1, ATF4-dependent transcriptional activation of asparagine synthetase, ASNS, CEBPA-dependent transcriptional activation of hepcidin, HAMP and CEBPB-mediated expression of peroxisome proliferator-activated receptor gamma, PPARG. Inhibits the canonical Wnt signaling pathway by binding to TCF7L2/TCF4, impairing its DNA-binding properties and repressing its transcriptional activity. Plays a regulatory role in the inflammatory response through the induction of caspase-11, CASP4/CASP11 which induces the activation of caspase-1, CASP1 and both these caspases increase the activation of pro-IL1B to mature IL1B which is involved in the inflammatory response. {ECO:0000269|PubMed:15322075, ECO:0000269|PubMed:15775988, ECO:0000269|PubMed:16434966, ECO:0000269|PubMed:17709599, ECO:0000269|PubMed:18940792, ECO:0000269|PubMed:19672300, ECO:0000269|PubMed:20829347, ECO:0000269|PubMed:20876114, ECO:0000269|PubMed:22761832}.
Subcellular locationCytoplasm. Nucleus. Note=Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P35638
Gene Ontology
(Biological Process)
Complete annatation
ATF6-mediated unfolded protein response [GO:0036500];
blood vessel maturation [GO:0001955];
cell cycle arrest [GO:0007050];
cell redox homeostasis [GO:0045454];
cellular response to DNA damage stimulus [GO:0006974];
ER overload response [GO:0006983];
establishment of protein localization to mitochondrion [GO:0072655];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
intrinsic apoptotic signaling pathway in response to nitrosative stress [GO:1990442];
mRNA transcription from RNA polymerase II promoter [GO:0042789];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of CREB transcription factor activity [GO:0032792];
negative regulation of determination of dorsal identity [GO:2000016];
negative regulation of fat cell differentiation [GO:0045599];
negative regulation of myoblast differentiation [GO:0045662];
negative regulation of protein kinase B signaling [GO:0051898];
negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding [GO:1903026];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
PERK-mediated unfolded protein response [GO:0036499];
positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway [GO:1902237];
positive regulation of interleukin-8 production [GO:0032757];
positive regulation of neuron apoptotic process [GO:0043525];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress [GO:1990440];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
regulation of DNA-templated transcription in response to stress [GO:0043620];
regulation of transcription, DNA-templated [GO:0006355];
regulation of transcription involved in anterior/posterior axis specification [GO:0044324];
release of sequestered calcium ion into cytosol [GO:0051209];
response to endoplasmic reticulum stress [GO:0034976];
response to starvation [GO:0042594];
response to unfolded protein [GO:0006986];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
cAMP response element binding protein binding [GO:0008140];
DNA binding [GO:0003677];
leucine zipper domain binding [GO:0043522];
protein heterodimerization activity [GO:0046982];
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 corepressor activity [GO:0003714];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
transcription regulatory region DNA binding [GO:0044212];
transcription regulatory region sequence-specific DNA binding [GO:0000976]
Gene Ontology
(Cellular Component)
Complete annatation
AP1 complex [GO:0035976];
CHOP-ATF3 complex [GO:1990622];
CHOP-ATF4 complex [GO:1990617];
CHOP-C/EBP complex [GO:0036488];
cytosol [GO:0005829];
late endosome [GO:0005770];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
protein-DNA complex [GO:0032993]
Protein-protein interaction108016
Phylogenetic treeP35638
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. CD3-0.6607489130557280.04773377713997320.0960282286510512
AZA vs. DISU0.5938631021455160.02053742858425080.340000936255075
AZA vs. IL7-0.2602507721539130.1879853263835570.952505417553304
AZA vs. SAHA-0.1636066637203980.5115771405908760.828090503058109
DISU vs. CD31.23991916270460.0008889074894629090.00374389256668452
DISU vs. IL7-0.8632507533452060.0007735778761320810.0229948874055723
DISU vs. SAHA-0.7541220756532320.0112706428245580.111456599743382
DMSO vs. AZA-0.009775074435187890.9549791646643131
DMSO vs. CD30.6392940592487530.04938266891083890.0954026554426504
DMSO vs. DISU-0.6053298932741220.01439910127609470.251150991007809
DMSO vs. IL7-0.2432968494304960.1884409963428710.699385449417225
DMSO vs. SAHA-0.1591247851985560.5080599925393210.818402324450632
HIV vs. Mock in Activation-0.07272321757385160.9078229511663320.999983755607037
HIV vs. Mock in Latency0.00802824259964640.9615772351405020.999834320637052
IL7 vs. CD30.4063192161705680.2124247387466880.337430507654002
SAHA vs. CD30.4739419404098070.1840438829834780.283101083654283
SAHA vs. IL70.09447491664497930.7034060714573540.863055411171111
(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) 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 0.871183 0.097748
(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
unknown unknown unknown unknown unknown
(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
Tat enhanced by 16511829

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04141 Protein processing in endoplasmic reticulum - Homo sapiens (human)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
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