| alternative products:Isoform C-alpha and isoform C-beta are the strongest activator of gene transcription, followed by isoform A-alpha and isoform A-beta, whereas isoform B-alpha and isoform B-beta are the weakest. Isoform B-alpha, isoform B-beta, isoform C-alpha and isoform C-beta, both present in T-cells, can modulate their transcriptional activity,domain: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.,domain:Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.,domain: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.,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.,induction:Only isoforms A are inducibly expressed in T lymphocytes upon activation of the T-cell receptor (TCR) complex. Induced after co-addition of phorbol 12-myristate 13-acetate (PMA) and ionomycin. Also induced after co-addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin. Weakly induced with PMA, ionomycin and cyclosporin A.,PTM:Phosphorylated by NFATC-kinase, dephosphorylated by calcineurin.,similarity:Contains 1 RHD (Rel-like) domain.,subcellular location: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.,subunit:Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC proteins bind to DNA as monomers.,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., |
