TISIDB

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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

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Literatures describing the relation between ATF6 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25209846	Hepatocellular Carcinoma	Inhibit immunity	The 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
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.303	0.168
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.276	0.869
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.323	0.79
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.398	0.348
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.089	0.965
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.017	0.701
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.167	0.688
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.028	0.988
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.359	0.864
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.208	0.864
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.604	0.731
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.237	0.000615

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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 [ TOP ]

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ATF6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ATF6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ATF6
Name	activating transcription factor 6
Aliases	ATF6A; activating transcription factor 6 alpha; cAMP-dependent transcription factor ATF-6 alpha; ATF6-alpha; ......
Chromosomal Location	1q23.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ATF6 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ATF6.

ID	Name	Drug Type	Targets	#Targets
DB00852	Pseudoephedrine	Small Molecule	ADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......	20

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