Browse NFATC1

Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
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 (PubMed:16511445). Nuclear translocation of NFATC1 is enhanced in the presence of TNFSF11. Nuclear translocation is decreased in the presence of FBN1 which can bind and sequester TNFSF11 (By similarity).
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 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (PubMed:10358178). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (By similarity).

> Gene Ontology
 
Biological Process GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0007223 Wnt signaling pathway, calcium modulating pathway
GO:0016055 Wnt signaling pathway
GO:0019722 calcium-mediated signaling
GO:0019932 second-messenger-mediated signaling
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0033173 calcineurin-NFAT signaling cascade
GO:0035567 non-canonical Wnt signaling pathway
GO:0038093 Fc receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0048016 inositol phosphate-mediated signaling
GO:0097720 calcineurin-mediated signaling
GO:0198738 cell-cell signaling by wnt
Molecular Function GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001158 enhancer sequence-specific DNA binding
GO:0001205 transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0001221 transcription cofactor binding
GO:0001223 transcription coactivator binding
GO:0001224 RNA polymerase II transcription cofactor binding
GO:0001225 RNA polymerase II transcription coactivator binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0005527 macrolide binding
GO:0005528 FK506 binding
GO:0008134 transcription factor binding
GO:0008144 drug binding
GO:0035326 enhancer binding
GO:0048273 mitogen-activated protein kinase p38 binding
GO:0051019 mitogen-activated protein kinase binding
Cellular Component GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0044454 nuclear chromosome part
> KEGG and Reactome Pathway
 
KEGG hsa04010 MAPK signaling pathway
hsa04022 cGMP-PKG signaling pathway
hsa04024 cAMP signaling pathway
hsa04310 Wnt 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-3858494: Beta-catenin independent WNT signaling
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-4086398: Ca2+ pathway
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
R-HSA-162582: Signal Transduction
R-HSA-195721: Signaling by Wnt
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between NFATC1 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 NFATC1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25851535MelanomaInhibit immunity (T cell function)Together, we propose that targeting the unrecognized ADAP-SKAP55-NFATc1-PD-1 pathway might increase efficacy of anti-tumor immunotherapy.
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
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 NFATC1 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
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
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 NFATC1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.460.241
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1430.913
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.8940.413
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2890.615
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3860.86
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.1620.955
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.4390.242
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.6670.554
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1140.932
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.1590.285
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.6930.266
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1860.231
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of NFATC1 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) 277311.11.49.70.0589
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275911.11.79.40.0895
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
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
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of NFATC1. 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
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of NFATC1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by NFATC1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of NFATC1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of NFATC1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between NFATC1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolNFATC1
Namenuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
Aliases NF-ATC; NFATc; NFAT2; NF-ATc1.2; NFAT transcription complex cytosolic component; nuclear factor of activated ......
Chromosomal Location18q23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting NFATC1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting NFATC1.
ID Name Drug Type Targets #Targets
DB00852PseudoephedrineSmall MoleculeADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......20