NFATC4

Nuclear factor of activated T-cells,cytoplasmic 4 ;
NF-ATc4 ;
NFATc4 ;
T-cell transcription factor NFAT3 ;
NF-AT3 ;

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 and IL-4. Transcriptionally repressed by estrogen receptors; this inhibition is further enhanced by estrogen. Increases the transcriptional activity of PPARG and has a direct role in adipocyte differentiation. May play an important role in myotube differentiation. May play a critical role in cardiac development and hypertrophy. May play a role in deafferentation-induced apoptosis of sensory neurons. ,PTM:Phosphorylated by NFATC-kinases; dephosphorylated by calcineurin. Phosphorylated on Ser-168 and Ser-170 by FRAP1 , IRAK1 , MAPK7 and MAPK14 , on Ser-213 and Ser-217 by MAPK8 and MAPK9 , and on Ser-289 and Ser-344 by RPS6KA3. Phosphorylated by GSK3B. ,PTM:Ubiquitinated , leading to its degradation by the proteasome and reduced transcriptional activity. Ubiquitination and reduction in transcriptional activity can be further facilitated through GSK3B-dependent phosphorylation. Polyubiquitin linkage is mainly through 'Lys-48'. ,similarity:Contains 1 IPT/TIG domain. ,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. Interacts with CREBBP , GATA4 , IRAK1 , MAPK8 , MAPK9 and RPS6KA3. ,tissue specificity:Highly expressed in placenta , lung , kidney , testis and ovary. Weakly expressed in spleen and thymus. Not expressed in peripheral blood lymphocytes. Detected in hippocampus. ,

generation of precursor metabolites and energy , transcription , transcription , DNA-dependent , regulation of transcription , DNA-dependent , transcription from RNA polymerase II promoter , defense response , inflammatory response , heart development , response to wounding , energy derivation by oxidation of organic compounds , RNA biosynthetic process , cellular respiration , regulation of transcription , regulation of RNA metabolic process ,

Cytoplasm , cytosol . Nucleus . When hyperphosphorylated , localizes in the cytosol. When intracellular Ca (2+) levels increase , dephosphorylation by calcineurin/PPP3CA leads to translocation into the nucleus (PubMed:11997522 , PubMed:18347059) . MAPK7/ERK5 and MTOR regulate NFATC4 nuclear export through phosphorylation at Ser-168 and Ser-170 (PubMed:18347059) . .