TISIDB

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
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	Nucleus membrane Multi-pass membrane protein Endoplasmic reticulum membrane Multi-pass membrane protein Sarcoplasmic reticulum membrane Multi-pass membrane protein
Domain	PF00689 Cation transporting ATPase PF00690 Cation transporter/ATPase
Function	This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.

> Gene Ontology [ TOP ]
Biological Process	GO:0003013 circulatory system process GO:0003015 heart process GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0008015 blood circulation GO:0008016 regulation of heart contraction GO:0035637 multicellular organismal signaling GO:0044057 regulation of system process GO:0055074 calcium ion homeostasis GO:0060047 heart contraction GO:0061337 cardiac conduction GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:1903522 regulation of blood circulation GO:1903779 regulation of cardiac conduction
Molecular Function	GO:0005388 calcium-transporting ATPase activity GO:0015085 calcium ion transmembrane transporter activity GO:0015399 primary active transmembrane transporter activity GO:0015405 P-P-bond-hydrolysis-driven transmembrane transporter activity GO:0015662 ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism GO:0016820 hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances GO:0016887 ATPase activity GO:0019829 cation-transporting ATPase activity GO:0022804 active transmembrane transporter activity GO:0022853 active ion transmembrane transporter activity GO:0042623 ATPase activity, coupled GO:0042625 ATPase coupled ion transmembrane transporter activity GO:0042626 ATPase activity, coupled to transmembrane movement of substances GO:0043492 ATPase activity, coupled to movement of substances GO:0046873 metal ion transmembrane transporter activity GO:0072509 divalent inorganic cation transmembrane transporter activity
Cellular Component	GO:0005635 nuclear envelope GO:0016528 sarcoplasm GO:0016529 sarcoplasmic reticulum GO:0031094 platelet dense tubular network GO:0031095 platelet dense tubular network membrane GO:0031965 nuclear membrane GO:0033017 sarcoplasmic reticulum membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04022 cGMP-PKG signaling pathway hsa04972 Pancreatic secretion
Reactome	R-HSA-5576891: Cardiac conduction R-HSA-109582: Hemostasis R-HSA-983712: Ion channel transport R-HSA-5578775: Ion homeostasis R-HSA-936837: Ion transport by P-type ATPases R-HSA-397014: Muscle contraction R-HSA-418360: Platelet calcium homeostasis R-HSA-418346: Platelet homeostasis R-HSA-1912422: Pre-NOTCH Expression and Processing R-HSA-1912420: Pre-NOTCH Processing in Golgi R-HSA-418359: Reduction of cytosolic Ca++ levels R-HSA-162582: Signal Transduction R-HSA-157118: Signaling by NOTCH R-HSA-382551: Transmembrane transport of small molecules

> KEGG and Reactome Pathway

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KEGG

hsa04020 Calcium signaling pathway
hsa04022 cGMP-PKG signaling pathway
hsa04972 Pancreatic secretion

Reactome

R-HSA-5576891: Cardiac conduction
R-HSA-109582: Hemostasis
R-HSA-983712: Ion channel transport
R-HSA-5578775: Ion homeostasis
R-HSA-936837: Ion transport by P-type ATPases
R-HSA-397014: Muscle contraction
R-HSA-418360: Platelet calcium homeostasis
R-HSA-418346: Platelet homeostasis
R-HSA-1912422: Pre-NOTCH Expression and Processing
R-HSA-1912420: Pre-NOTCH Processing in Golgi
R-HSA-418359: Reduction of cytosolic Ca++ levels
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ATP2A3 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 ATP2A3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
22851172	Breast Carcinoma	Inhibit immunity	Here, we show that human CD4(+) T cells in the presence of tumor conditions manifested an up-regulation of SERCA3 expression that resulted in development of endoplasmic reticulum stress leading to CD4(+) T cell apoptosis. Gene manipulation and pharmacological approaches further established that an increase in SERCA expression also resulted in subsequent inhibition of PKCα and -θ and retention of NFκB in the cytosol; however, down-modulation of SERCA3 expression by a dihydropyrimidone derivative, ethyl-4-(3-nitro)-phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5 carboxylate (nifetepimine), protected the CD4(+) T cells from tumor-induced apoptosis.

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
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 ATP2A3 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	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
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 ATP2A3 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	-0.203	0.721
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.29	0.856
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.567	0.656
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.543	0.181
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.423	0.851
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.692	0.803
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.919	0.101
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.598	0.201
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.153	0.914
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.123	0.347
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	1.272	0.463
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.077	0.643

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ATP2A3 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	14.3	5.9	8.4	0.576
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	33.3	-13.3	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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
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	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	9.1	0	9.1	0.458
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	20	0	20	0.294

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ATP2A3. 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	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ATP2A3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ATP2A3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ATP2A3. 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	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ATP2A3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ATP2A3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ATP2A3
Name	ATPase, Ca++ transporting, ubiquitous
Aliases	SERCA3; sarcoplasmic/endoplasmic reticulum calcium ATPase 3; calcium pump 3; ATPase, Ca(2+)-transporting, ub ......
Chromosomal Location	17p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ATP2A3 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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