Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm Cell membrane Nucleus Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Note=Colocalizes with GABBR1 in hippocampal neuron dendritic membranes (By similarity). Colocalizes with NEK6 at the centrosome (PubMed:20873783). |
Domain |
PF00170 bZIP transcription factor |
Function |
Transcriptional activator. Binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Cooperates with FOXO1 in osteoblasts to regulate glucose homeostasis through suppression of beta-cell production and decrease in insulin production (By similarity). It binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I. Regulates the induction of DDIT3/CHOP and asparagine synthetase (ASNS) in response to endoplasmic reticulum (ER) stress. In concert with DDIT3/CHOP, activates the transcription of TRIB3 and promotes ER stress-induced neuronal apoptosis by regulating the transcriptional induction of BBC3/PUMA. Activates transcription of SIRT4. Regulates the circadian expression of the core clock component PER2 and the serotonin transporter SLC6A4. Binds in a circadian time-dependent manner to the cAMP response elements (CRE) in the SLC6A4 and PER2 promoters and periodically activates the transcription of these genes. During ER stress response, activates the transcription of NLRP1, possibly in concert with other factors (PubMed:26086088). |
Biological Process |
GO:0001819 positive regulation of cytokine production GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006094 gluconeogenesis GO:0006356 regulation of transcription from RNA polymerase I promoter GO:0006360 transcription from RNA polymerase I promoter GO:0006413 translational initiation GO:0006417 regulation of translation GO:0006446 regulation of translational initiation GO:0006520 cellular amino acid metabolic process GO:0006813 potassium ion transport GO:0006979 response to oxidative stress GO:0006984 ER-nucleus signaling pathway GO:0006986 response to unfolded protein GO:0007214 gamma-aminobutyric acid signaling pathway GO:0007623 circadian rhythm GO:0009267 cellular response to starvation GO:0009299 mRNA transcription GO:0009314 response to radiation GO:0009411 response to UV GO:0009416 response to light stimulus GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010042 response to manganese ion GO:0010573 vascular endothelial growth factor production GO:0010574 regulation of vascular endothelial growth factor production GO:0010575 positive regulation of vascular endothelial growth factor production GO:0010608 posttranscriptional regulation of gene expression GO:0010959 regulation of metal ion transport GO:0015672 monovalent inorganic cation transport GO:0016051 carbohydrate biosynthetic process GO:0017148 negative regulation of translation GO:0019318 hexose metabolic process GO:0019319 hexose biosynthetic process GO:0030968 endoplasmic reticulum unfolded protein response GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0032055 negative regulation of translation in response to stress GO:0032057 negative regulation of translational initiation in response to stress GO:0032922 circadian regulation of gene expression GO:0034198 cellular response to amino acid starvation GO:0034248 regulation of cellular amide metabolic process GO:0034249 negative regulation of cellular amide metabolic process GO:0034599 cellular response to oxidative stress GO:0034620 cellular response to unfolded protein GO:0034644 cellular response to UV 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:0036091 positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0036473 cell death in response to oxidative stress GO:0036475 neuron death in response to oxidative stress GO:0036499 PERK-mediated unfolded protein response GO:0042149 cellular response to glucose starvation GO:0042594 response to starvation GO:0042789 mRNA transcription from RNA polymerase II promoter GO:0043266 regulation of potassium ion transport GO:0043267 negative regulation of potassium ion transport GO:0043271 negative regulation of ion transport GO:0043523 regulation of neuron apoptotic process GO:0043525 positive regulation of neuron apoptotic process GO:0043555 regulation of translation in response to stress GO:0043558 regulation of translational initiation in response to stress GO:0043618 regulation of transcription from RNA polymerase II promoter in response to stress GO:0043619 regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0043620 regulation of DNA-templated transcription in response to stress GO:0044283 small molecule biosynthetic process GO:0044723 single-organism carbohydrate metabolic process GO:0045943 positive regulation of transcription from RNA polymerase I promoter GO:0045947 negative regulation of translational initiation GO:0046364 monosaccharide biosynthetic process GO:0046685 response to arsenic-containing substance GO:0048511 rhythmic process GO:0051051 negative regulation of transport GO:0051402 neuron apoptotic process GO:0061394 regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance GO:0061395 positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070997 neuron death GO:0071214 cellular response to abiotic stimulus GO:0071241 cellular response to inorganic substance GO:0071243 cellular response to arsenic-containing substance GO:0071248 cellular response to metal ion GO:0071287 cellular response to manganese ion GO:0071478 cellular response to radiation GO:0071482 cellular response to light stimulus GO:0071496 cellular response to external stimulus GO:0097193 intrinsic apoptotic signaling pathway GO:1900407 regulation of cellular response to oxidative stress GO:1900408 negative regulation of cellular response to oxidative stress GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death GO:1901216 positive regulation of neuron death GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus GO:1902882 regulation of response to oxidative stress GO:1902883 negative regulation of response to oxidative stress GO:1903201 regulation of oxidative stress-induced cell death GO:1903202 negative regulation of oxidative stress-induced cell death GO:1903203 regulation of oxidative stress-induced neuron death GO:1903204 negative regulation of oxidative stress-induced neuron death GO:1990267 response to transition metal nanoparticle GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990737 response to manganese-induced endoplasmic reticulum stress |
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:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001085 RNA polymerase II transcription factor binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor 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:0016234 inclusion body GO:0031252 cell leading edge GO:0031253 cell projection membrane GO:0031256 leading edge membrane GO:0032589 neuron projection membrane GO:0032590 dendrite membrane GO:0034399 nuclear periphery GO:0044798 nuclear transcription factor complex GO:0090575 RNA polymerase II transcription factor complex GO:0097413 Lewy body GO:1990037 Lewy body core GO:1990589 ATF4-CREB1 transcription factor complex GO:1990590 ATF1-ATF4 transcription factor complex GO:1990617 CHOP-ATF4 complex |
KEGG |
hsa04010 MAPK signaling pathway hsa04022 cGMP-PKG signaling pathway hsa04141 Protein processing in endoplasmic reticulum hsa04151 PI3K-Akt signaling pathway hsa04210 Apoptosis hsa04261 Adrenergic signaling in cardiomyocytes hsa04668 TNF signaling pathway hsa04720 Long-term potentiation hsa04722 Neurotrophin signaling pathway hsa04725 Cholinergic synapse hsa04728 Dopaminergic synapse hsa04911 Insulin secretion hsa04912 GnRH signaling pathway hsa04915 Estrogen signaling pathway hsa04918 Thyroid hormone synthesis hsa04922 Glucagon signaling pathway |
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 | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between ATF4 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. |
Literatures describing the relation between ATF4 and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
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
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Statistical results of ATF4 in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
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 |
Points in the above scatter plot represent the expression difference of ATF4 in various data sets.
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Points in the above scatter plot represent the mutation difference of ATF4 in various data sets.
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Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ATF4. 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. |
Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ATF4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ATF4. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ATF4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of ATF4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between ATF4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | ATF4 |
Name | activating transcription factor 4 |
Aliases | TAXREB67; tax-responsive enhancer element B67; TXREB; activating transcription factor 4 (tax-responsive enha ...... |
Chromosomal Location | 22q13.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting ATF4 collected from DrugBank database. |
Details on drugs targeting ATF4.
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