FunctionPlays 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.
Tissue specificityExpressed 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.
DomainRel 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 trans-activation 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.
Post-translational modificationsPhosphorylated by NFATC-kinase; dephosphorylated by calcineurin.
Cellular localizationCytoplasm. 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. The subcellular localization of NFATC plays a key role in the regulation of gene transcription.