Nfatc2 phospho S54
Developmental stage
Expressed in the developing heart at 13.5 and 16.5 dpc, during the transition from spongy to compact myocardium (PubMed:17198697). Not detected in the skeletal system at 11 and 13.5 dpc (PubMed:10620601).
Domain
Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.
Function
Plays a 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. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (By similarity). Is involved in the negative regulation of chondrogenesis (PubMed:10620601). Recruited by AKAP5 to ORAI1 pore-forming subunit of CRAC channels in Ca(2+) signaling microdomains where store-operated Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT-dependent transcriptional responses.
Post-translational modifications
In resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-365 region. Upon cell stimulation, all these sites except Ser-245 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, one site among Ser-53; Ser-54 and Ser-56 is phosphorylated; which is required for full transcriptional activity.
Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome.
Tissue Specificity
Expressed in spleen, heart, testis, brain, placenta, muscle and pancreas (PubMed:18675896). Expressed in the thymus (PubMed:17579027, PubMed:18675896). Expressed in the lung (PubMed:17579027). Expressed in cartilage (PubMed:10620601).
Cellular localization
- Cytoplasm
- 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.
Alternative names
Nfat1, Nfatp, Nfatc2, NF-ATc2, NFATc2, NFAT pre-existing subunit, T-cell transcription factor NFAT1, NF-ATp