Phospho-NFAT3 (Ser676) Antibody - #AF3587

Ca(2+)-regulated transcription factor that is involved in several processes, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems. Involved in T-cell activation, stimulating the transcription of cytokine genes, including that of IL2 and IL4. Along with NFATC3, involved in embryonic heart development. Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function (By similarity). Transactivates many genes involved in the cardiovascular system, including AGTR2, NPPB/BNP (in synergy with GATA4), NPPA/ANP/ANF and MYH7/beta-MHC (By similarity). Involved in the regulation of adult hippocampal neurogenesis. Involved in BDNF-driven pro-survival signaling in hippocampal adult-born neurons. Involved in the formation of long-term spatial memory and long-term potentiation (By similarity). In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during the developmental critical period, when auditory neurons depend on afferent input for survival (By similarity). Binds to and activates the BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic processing of the amyloid precursor protein (APP). Plays a role in adipocyte differentiation. May be involved in myoblast differentiation into myotubes. Binds the consensus DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF transcription. Binds to PPARG gene promoter and regulates its activity. Binds to PPARG and REG3G gene promoters (By similarity).

Phosphorylated by NFATC-kinases; dephosphorylated by calcineurin/PPP3CA. Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8/JNK1 and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3. Phosphorylated by GSK3B. Phosphorylation by GSK3B markedly increases NFATC4 ubiquitination (By similarity). Phosphorylation at Ser-168 and Ser-170 is stimulated by UV irradiation. Phosphorylation determines subcellular location: the hyperphosphorylated protein is cytosolic, while the dephosphorylated form is targeted to the nucleus.

Ubiquitinated, leading to degradation by the proteasome. Ubiquitination may be stimulated by GSK3B-dependent phosphorylation. Polyubiquitin linkage mainly occurs through 'Lys-48'.

Cytoplasm>Cytosol. Nucleus.
Note: 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).

Widely expressed, with high levels in placenta, lung, kidney, testis and ovary. Weakly expressed in spleen and thymus. In the hippocampus, expressed in the granular layer of the dentate gyrus, in the pyramidal neurons of CA3 region, and in the hippocampal fissure. Expressed in the heart (at protein level).

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 NFAT proteins, such as NFATC3, or members of the activating protein-1 (AP-1) family and MAF can also bind the complex. NFAT proteins can bind DNA as monomers or dimers. Interacts with CREBBP; this interaction potentiates transcription activation. Interacts with MAPK8/JNK1 and MAPK9/JNK2. Interacts with GATA4 (via the second Zn finger) (By similarity). Interacts (via N-terminus) with IRAK1 (via C-terminus). Interacts with RPS6KA3. Interacts with HOMER1, HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC4 dephosphorylation and activation. Interacts with ESR1 and ESR2; this interaction decreases NFATC4 transcriptional activity. Interacts with MTOR and MAPK7/ERK5.

Rel similarity domain (RSD) or Rel homology domain (RHD) allows DNA-binding and cooperative interactions with AP-1 factors.