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. ,
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