TISIDB

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
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 [ TOP ]
Subcellular Location	Cytoplasm. Nucleus. Note=Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription.
Domain	PF16179 Rel homology dimerisation domain PF00554 Rel homology DNA-binding domain
Function	Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway.

> Gene Ontology [ TOP ]
Biological Process	GO:0000768 syncytium formation by plasma membrane fusion GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006949 syncytium formation GO:0007520 myoblast fusion GO:0010830 regulation of myotube differentiation GO:0010831 positive regulation of myotube differentiation GO:0014902 myotube differentiation GO:0014904 myotube cell development GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0030888 regulation of B cell proliferation GO:0030890 positive regulation of B cell proliferation GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0033173 calcineurin-NFAT signaling cascade GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0042100 B cell proliferation GO:0042113 B cell activation GO:0042493 response to drug GO:0042692 muscle cell differentiation GO:0046651 lymphocyte proliferation GO:0048016 inositol phosphate-mediated signaling GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050851 antigen receptor-mediated signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050864 regulation of B cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050871 positive regulation of B cell activation GO:0051146 striated muscle cell differentiation GO:0051147 regulation of muscle cell differentiation GO:0051149 positive regulation of muscle cell differentiation GO:0051153 regulation of striated muscle cell differentiation GO:0051155 positive regulation of striated muscle cell differentiation GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0055001 muscle cell development GO:0055002 striated muscle cell development GO:0060142 regulation of syncytium formation by plasma membrane fusion GO:0060143 positive regulation of syncytium formation by plasma membrane fusion GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0097720 calcineurin-mediated signaling GO:1901739 regulation of myoblast fusion GO:1901741 positive regulation of myoblast fusion
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:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0008134 transcription factor binding
Cellular Component	GO:0005667 transcription factor complex GO:0015629 actin cytoskeleton GO:0044798 nuclear transcription factor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04022 cGMP-PKG signaling pathway hsa04310 Wnt signaling pathway hsa04360 Axon guidance hsa04370 VEGF signaling pathway hsa04380 Osteoclast differentiation hsa04650 Natural killer cell mediated cytotoxicity hsa04660 T cell receptor signaling pathway hsa04662 B cell receptor signaling pathway hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5607763: CLEC7A (Dectin-1) induces NFAT activation R-HSA-5607764: CLEC7A (Dectin-1) signaling R-HSA-2871809: FCERI mediated Ca+2 mobilization R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between NFATC2 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

[ TOP ]

Literatures describing the relation between NFATC2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
26387540	Melanoma	Inhibit immunity	The relevance of NFATc2-dependent melanoma dedifferentiation for immune escape was shown by cytolytic T-cell assays.
26324768	Hepatocellular Carcinoma	Inhibit immunity (T cell function)	FOXP3/NFAT interaction is required to repress expression of IL-2, upregulate expression of the Treg markers CTLA4 and CD25, and confer suppressor function to Tregs.
24777531	Melanoma; Colon Carcinoma	Inhibit immunity	Here we identified the DUB USP15 as a crucial negative regulator of T cell activation. USP15 stabilized the E3 ubiquitin ligase MDM2, which in turn negatively regulated T cell activation by targeting the degradation of the transcription factor NFATc2. USP15 deficiency promoted T cell activation in vitro and enhanced T cell responses to bacterial infection and tumor challenge in vivo. USP15 also stabilized MDM2 in cancer cells and regulated p53 function and cancer-cell survival.
22865456	Melanoma	Inhibit immunity (T cell function)	NFAT1 supports tumor-induced anergy of CD4(+) T cells. NFAT1 deficiency blunted the induction of anergy in tumor antigen-specific CD4+ T cells, enhancing antitumor responses.

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
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

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Statistical results of NFATC2 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	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
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

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Points in the above scatter plot represent the expression difference of NFATC2 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	-0.151	0.758
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.021	0.988
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.237	0.804
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.35	0.541
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.32	0.891
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.383	0.901
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.566	0.227
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.304	0.838
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.898	0.575
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.924	0.27
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	0.979	0.421
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.132	0.361

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of NFATC2 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	0	3.7	0.27
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	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
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	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
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	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	0	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NFATC2. 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	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NFATC2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NFATC2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NFATC2. 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	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of NFATC2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between NFATC2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	NFATC2
Name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2
Aliases	NF-ATP; NFATp; NFAT1; NF-ATc2; NFAT pre-existing subunit; NFAT transcription complex, preexisting component; ......
Chromosomal Location	20q13.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting NFATC2 collected from DrugBank database.

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

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