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Browse DDIT3

Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Note=Present in the cytoplasm under non-stressed conditions and ER stress leads to its nuclear accumulation.
Domain PF07716 Basic region leucine zipper
Function

Multifunctional 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.

> Gene Ontology
 
Biological Process GO:0001819 positive regulation of cytokine production
GO:0001955 blood vessel maturation
GO:0003002 regionalization
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0006983 ER overload response
GO:0006984 ER-nucleus signaling pathway
GO:0006986 response to unfolded protein
GO:0007050 cell cycle arrest
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007389 pattern specification process
GO:0009299 mRNA transcription
GO:0009798 axis specification
GO:0009799 specification of symmetry
GO:0009855 determination of bilateral symmetry
GO:0009948 anterior/posterior axis specification
GO:0009952 anterior/posterior pattern specification
GO:0009953 dorsal/ventral pattern formation
GO:0009991 response to extracellular stimulus
GO:0010498 proteasomal protein catabolic process
GO:0016055 Wnt signaling pathway
GO:0021700 developmental maturation
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031667 response to nutrient levels
GO:0032637 interleukin-8 production
GO:0032677 regulation of interleukin-8 production
GO:0032757 positive regulation of interleukin-8 production
GO:0032792 negative regulation of CREB transcription factor activity
GO:0032844 regulation of homeostatic process
GO:0032845 negative regulation of homeostatic process
GO:0034620 cellular response to unfolded protein
GO:0034976 response to endoplasmic reticulum stress
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0036003 positive regulation of transcription from RNA polymerase II promoter in response to stress
GO:0036499 PERK-mediated unfolded protein response
GO:0036500 ATF6-mediated unfolded protein response
GO:0042594 response to starvation
GO:0042692 muscle cell differentiation
GO:0042789 mRNA transcription from RNA polymerase II promoter
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043392 negative regulation of DNA binding
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043491 protein kinase B signaling
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress
GO:0043620 regulation of DNA-templated transcription in response to stress
GO:0044324 regulation of transcription involved in anterior/posterior axis specification
GO:0045444 fat cell differentiation
GO:0045445 myoblast differentiation
GO:0045454 cell redox homeostasis
GO:0045598 regulation of fat cell differentiation
GO:0045599 negative regulation of fat cell differentiation
GO:0045661 regulation of myoblast differentiation
GO:0045662 negative regulation of myoblast differentiation
GO:0045786 negative regulation of cell cycle
GO:0048262 determination of dorsal/ventral asymmetry
GO:0048263 determination of dorsal identity
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051101 regulation of DNA binding
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051208 sequestering of calcium ion
GO:0051209 release of sequestered calcium ion into cytosol
GO:0051235 maintenance of location
GO:0051238 sequestering of metal ion
GO:0051282 regulation of sequestering of calcium ion
GO:0051283 negative regulation of sequestering of calcium ion
GO:0051402 neuron apoptotic process
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051896 regulation of protein kinase B signaling
GO:0051898 negative regulation of protein kinase B signaling
GO:0055074 calcium ion homeostasis
GO:0060070 canonical Wnt signaling pathway
GO:0060401 cytosolic calcium ion transport
GO:0060402 calcium ion transport into cytosol
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0070509 calcium ion import
GO:0070588 calcium ion transmembrane transport
GO:0070838 divalent metal ion transport
GO:0070997 neuron death
GO:0071216 cellular response to biotic stimulus
GO:0071695 anatomical structure maturation
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072511 divalent inorganic cation transport
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097553 calcium ion transmembrane import into cytosol
GO:0198738 cell-cell signaling by wnt
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1902235 regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1902237 positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1902532 negative regulation of intracellular signal transduction
GO:1902656 calcium ion import into cytosol
GO:1903025 regulation of RNA polymerase II regulatory region sequence-specific DNA binding
GO:1903026 negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding
GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
GO:2000015 regulation of determination of dorsal identity
GO:2000016 negative regulation of determination of dorsal identity
GO:2000021 regulation of ion homeostasis
GO:2000677 regulation of transcription regulatory region DNA binding
GO:2000678 negative regulation of transcription regulatory region DNA binding
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001159 core promoter proximal region DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003714 transcription corepressor activity
GO:0008134 transcription factor binding
GO:0008140 cAMP response element binding protein binding
GO:0030275 LRR domain binding
GO:0043522 leucine zipper domain binding
GO:0046982 protein heterodimerization activity
Cellular Component GO:0005667 transcription factor complex
GO:0005770 late endosome
GO:0032993 protein-DNA complex
GO:0035976 transcription factor AP-1 complex
GO:0036488 CHOP-C/EBP complex
GO:0044798 nuclear transcription factor complex
GO:0090575 RNA polymerase II transcription factor complex
GO:1990617 CHOP-ATF4 complex
GO:1990622 CHOP-ATF3 complex
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04141 Protein processing in endoplasmic reticulum
hsa04210 Apoptosis
Reactome R-HSA-380994: ATF4 activates genes
R-HSA-381183: ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-381033: ATF6 (ATF6-alpha) activates chaperones
R-HSA-392499: Metabolism of proteins
R-HSA-381042: PERK regulates gene expression
R-HSA-381119: Unfolded Protein Response (UPR)
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between DDIT3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between DDIT3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25238096lung carcinoma; melanoma; colon carcinomaInhibit immunity (T cell function)Here, we show the critical role of the cellular stress sensor C/EBP-homologous protein (Chop) in the accumulation and immune inhibitory activity of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). MDSCs lacking Chop had decreased immune-regulatory functions and showed the ability to prime T cell function and induce antitumor responses.
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of DDIT3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of DDIT3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.7240.0906
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.790.764
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.670.717
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4960.465
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2880.848
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.4930.442
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.1380.722
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.280.83
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0810.953
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0460.98
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.1710.951
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0410.653
> Mutation difference between responders and non-responders
 

There is no record.
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DDIT3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DDIT3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DDIT3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DDIT3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of DDIT3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between DDIT3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolDDIT3
NameDNA-damage-inducible transcript 3
Aliases CHOP10; GADD153; CHOP; C/EBP zeta; CHOP-10; CCAAT/enhancer-binding protein homologous protein; DDIT-3; c/EBP ......
Chromosomal Location12q13.1-q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting DDIT3 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.