NFATC1

The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]

Full Name

NFATC1

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).

Biological Process

Aortic valve morphogenesis Source: BHF-UCL
Calcineurin-NFAT signaling cascade Source: UniProtKB
Intracellular signal transduction Source: MGI
Negative regulation of vascular associated smooth muscle cell differentiation Source: BHF-UCL
Negative regulation of Wnt signaling pathway Source: ParkinsonsUK-UCL
Positive regulation of transcription, DNA-templated Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Pulmonary valve morphogenesis Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: GO_Central

Cellular Location

Nucleus
Cytoplasm
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).

PTM

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.