Browse NFATC2

Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
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
 
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
 
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
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
  Literatures describing the relation between NFATC2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26387540MelanomaInhibit immunityThe relevance of NFATc2-dependent melanoma dedifferentiation for immune escape was shown by cytolytic T-cell assays.
26324768Hepatocellular CarcinomaInhibit 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.
24777531Melanoma; Colon CarcinomaInhibit immunityHere 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.
22865456MelanomaInhibit 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
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
  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
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
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
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 Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1510.758
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0210.988
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2370.804
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.350.541
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.320.891
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3830.901
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.5660.227
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3040.838
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.8980.575
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9240.27
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9790.421
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1320.361
> Mutation difference between responders and non-responders
 
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 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) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916012.5-12.50.52
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59022.2-22.20.505
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 111307.7-7.71
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 51208.3-8.31
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
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
 
> Receptor
 
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NFATC2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NFATC2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNFATC2
Namenuclear 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 Location20q13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NFATC2 collected from DrugBank database.
> Drugs from DrugBank database
 

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