Browse ATF6

Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
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 Endoplasmic reticulum membrane; Single-pass type II membrane protein.; SUBCELLULAR LOCATION: Processed cyclic AMP-dependent transcription factor ATF-6 alpha: Nucleus. Note=Under ER stress the cleaved N-terminal cytoplasmic domain translocates into the nucleus. THBS4 promotes its nuclear shuttling.
Domain PF00170 bZIP transcription factor
Function

Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates transcription of genes involved in the UPR. Binds DNA on the 5'-CCAC[GA]-3'half of the ER stress response element (ERSE) (5'-CCAAT-N(9)-CCAC[GA]-3') and of ERSE II (5'-ATTGG-N-CCACG-3'). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.

> Gene Ontology
 
Biological Process GO:0001654 eye development
GO:0006457 protein folding
GO:0006984 ER-nucleus signaling pathway
GO:0006986 response to unfolded protein
GO:0006990 positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response
GO:0007423 sensory organ development
GO:0007601 visual perception
GO:0030968 endoplasmic reticulum unfolded protein response
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:0036500 ATF6-mediated unfolded protein response
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:0050953 sensory perception of light stimulus
GO:1901522 positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus
GO:1990440 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
Molecular Function GO:0003713 transcription coactivator activity
GO:0031625 ubiquitin protein ligase binding
GO:0035497 cAMP response element binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0046982 protein heterodimerization activity
Cellular Component GO:0005635 nuclear envelope
GO:0030176 integral component of endoplasmic reticulum membrane
GO:0031227 intrinsic component of endoplasmic reticulum membrane
> KEGG and Reactome Pathway
 
KEGG hsa04141 Protein processing in endoplasmic reticulum
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
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between ATF6 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 ATF6 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25209846Hepatocellular CarcinomaInhibit immunityThe decreased expression level of CD155 was due to the involvement of the activating transcription factor 6 (ATF6) and inositol-requiring enzyme 1α (IRE1α) pathways.In addition, the IRE1α pathway contributed to the increased expression level of the ER-associated degradation (ERAD)-related molecule HRD1 and facilitated the degradation of CD155
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
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 ATF6 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
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
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 ATF6 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.3030.168
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2760.869
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.3230.79
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.3980.348
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.0890.965
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.0170.701
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1670.688
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0280.988
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3590.864
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2080.864
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6040.731
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2370.000615
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of ATF6 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.27.1-0.91
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ATF6. 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
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ATF6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ATF6.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ATF6. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of ATF6 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between ATF6 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolATF6
Nameactivating transcription factor 6
Aliases ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location1q23.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting ATF6 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting ATF6.
ID Name Drug Type Targets #Targets
DB00852PseudoephedrineSmall MoleculeADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......20