nuclear factor of activated T-cells, cytoplasmic 2; T-cell transcription factor NFAT1; NFAT pre-existing subunit; NF-ATp (NFATC2, NFAT1, NFATp)

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Function

role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF
in resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-363 region
upon cell stimulation, all these sites except Ser-243 are dephosphorylated by calcineurin
dephosphorylation induces a conformational change that exposes an NLS & masks an NES, resulting in nuclear localization & Ser-53 or Ser-56 phosphorylation, which is required for full transcriptional activity
member of the multicomponent NFATC transcription complex
the phosphorylated form specifically interacts with XPO1 which mediates nuclear export
binds to DNA as monomer
interacts with NFATC2IP (putative)

Rel similarity domain (RSD) allows DNA-binding & cooperative interactions with AP1 factors (putative)
contains 1 RHD (Rel-like) domain

cytoplasm. nucleus
cytoplasmic for the phosphorylated form
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 & transient Ca+2 signals
subcellular localization of NFATC plays a key role in the regulation of gene transcription

named isoforms=2; C,B additional isoforms seem to exist

expressed in thymus, spleen, heart, testis, brain, placenta, muscle & pancreas
inducibly expressed in T-lymphocytes upon activation of the T-cell receptor complex (TCR)
induced after co-addition of phorbol 12-myristate 13-acetate (PMA) & ionomycin