NFATC1
GeneName
NFATC1
Summary
NFATC1, also known as NFAT2 or NFATc, is a 101 kDa transcription factor that plays a pivotal role in regulating gene expression in response to various extracellular signals. It is predominantly expressed in the nucleus, where it binds to specific DNA sequences to modulate the transcription of target genes. NFATC1 is involved in key biological processes such as the calcineurin-NFAT signaling cascade, which is crucial for T cell activation and differentiation, as well as in the morphogenesis of heart valves. Its activity is regulated by calcium signalling and it interacts with several proteins, including those involved in mitogen-activated protein kinase pathways and protein phosphatase 2B.
Importance
NFATC1 is relevant to: - Immune response regulation, particularly in T cell activation and differentiation, influencing adaptive immunity - Cardiovascular development and disease through its role in heart valve morphogenesis - Vascular biology, as it negatively regulates smooth muscle cell differentiation and Wnt signalling - Potential therapeutic targets in autoimmune diseases and heart conditions due to its involvement in critical signalling pathways
Top Products
For researchers investigating NFATC1, we recommend the well-cited polyclonal antibody, Anti-NFAT2 antibody (ab25916). This antibody has garnered 80 citations, reflecting its reliability and trust within the scientific community. It is particularly effective for Western blotting (WB) and immunocytochemistry (ICC), making it a valuable tool for various experimental applications. Its proven performance in these techniques ensures that you can confidently explore the role of NFATC1 in your research. The NFATC1 ELISA Kit (ab25916), supported by 80 citations, is an excellent option for researchers looking to accurately measure NFATC1 levels in their samples.
Abcam Product Citation Summary
The use of Abcam antibody ab2796 for NFATC1 detection highlights its role in nuclear translocation studies, particularly in RAW264.7 cells, which are a model for macrophage behaviour. This suggests that NFATC1 may be significant in understanding cellular responses in immune contexts.
Abcam Product Citation Table
Domain
Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.
The N-terminal transactivation domain (TAD-A) binds to and is activated by Cbp/p300. The dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus.
Isoforms C have a C-terminal part with an additional transactivation domain, TAD-B, which acts as a transcriptional activator. Isoforms B have a shorter C-terminal part without complete TAD-B which acts as a transcriptional repressor.
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).
Post-translational modifications
Phosphorylated by NFATC-kinase and GSK3B; phosphorylation induces NFATC1 nuclear exit and dephosphorylation by calcineurin promotes nuclear import. Phosphorylation by PKA and DYRK2 negatively modulates nuclear accumulation, and promotes subsequent phosphorylation by GSK3B or casein kinase 1.
Tissue Specificity
Expressed in thymus, peripheral leukocytes as T-cells and spleen. Isoforms A are preferentially expressed in effector T-cells (thymus and peripheral leukocytes) whereas isoforms B and isoforms C are preferentially expressed in naive T-cells (spleen). Isoforms B are expressed in naive T-cells after first antigen exposure and isoforms A are expressed in effector T-cells after second antigen exposure. Isoforms IA are widely expressed but not detected in liver nor pancreas, neural expression is strongest in corpus callosum. Isoforms IB are expressed mostly in muscle, cerebellum, placenta and thymus, neural expression in fetal and adult brain, strongest in corpus callosum.
Cellular localization
- Cytoplasm
- Nucleus
- 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. Translocation to the nucleus is increased in the presence of calcium in pre-osteoblasts (By similarity). 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).
Alternative names
NFAT2, NFATC, NFATC1, NF-ATc1, NFATc1, NFAT transcription complex cytosolic component, NF-ATc, NFATc
Database links
swissprot:O95644 omim:600489 entrezGene:4772
Other research areas
- Epigenetics
- Immuno-oncology