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 (PubMed:17198697). Along with NFATC3, involved in embryonic heart development (PubMed:12750314, PubMed:17198697). Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function (PubMed:12750314). Transactivates many genes involved in heart physiology. Along with GATA4, binds to and activates NPPB/BNP promoter (PubMed:9568714). Activates NPPA/ANP/ANF and MYH7/beta-MHC transcription (By similarity). Binds to and transactivates AGTR2 gene promoter (PubMed:17198697). 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 (PubMed:22586092). In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during a developmental critical period when auditory neurons depend on afferent input for survival (PubMed:18354019). 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 (By similarity). 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 (By similarity). Binds to PPARG and REG3G gene promoters (PubMed:17198697). 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 (Probable). Interacts with CREBBP; this interaction potentiates transcription activation (By similarity). Interacts with MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with GATA4 (via the second Zn finger) (PubMed:9568714). Interacts (via N-terminus) with IRAK1 (via C-terminus) (By similarity). Interacts with RPS6KA3 (By similarity). Interacts with HOMER1, HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC4 dephosphorylation and activation (By similarity). Interacts with ESR1 and ESR2; this interaction decreases NFATC4 transcriptional activity (By similarity). Interacts with MTOR and MAPK7/ERK5 (By similarity). Interacts with TRIM17; this interaction prevents NFATC3 nuclear localization (PubMed:25215946). When hyperphosphorylated, localizes in the cytosol. When intracellular Ca(2+) levels increase, dephosphorylation by calcineurin/PPP3CA leads to translocation into the nucleus (By similarity). MAPK7/ERK5 and MTOR regulate NFATC4 nuclear export through phosphorylation at Ser-168 and Ser-170 (By similarity). Widely expressed (PubMed:18675896). In the brain, expressed in neurons (PubMed:18675896, PubMed:25663301). Expressed in the hippocampus (at protein level) (PubMed:25663301). In the hippocampus, expressed in both the CA1-CA3 pyramidal cells and the dentate gyrus granular cells (PubMed:22586092). Expressed in a subset of hippocampal cells representing adult-born neurons (at protein level) (PubMed:22586092). Expressed in the submandibular gland (at protein level) (PubMed:21435446). In the olfactory system, expressed at low levels in the glomerular and granular layers and in the mitral cell layer (PubMed:18675896). In the cerebellum, expressed at moderate levels in granular neurons (PubMed:18675896). Expressed at moderate levels in the choroid plexus and ependymal cells (PubMed:18675896). Expressed in neurons of the cochlear nucleus (at protein level) (PubMed:18354019). Expressed at low levels in the heart (at protein level) (PubMed:12370307). Expressed at high levels in the embryonic brain at 13.5 dpc (PubMed:18675896, PubMed:22586092). Expression decreases thereafter, reaching the lowest levels at postnatal day 14 and remaining unchanged in adulthood (PubMed:18675896). Expressed in the developing heart at 13.5 and 16.5 dpc, during the transition from spongy to compact myocardium (PubMed:17198697). Up-regulated by BDNF. Rel similarity domain (RSD) or Rel homology domain (RHD) allows DNA-binding and cooperative interactions with AP-1 factors. 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 and MAPK9, and on Ser-289 and Ser-344 by RPS6KA3 (PubMed:18691762). Phosphorylated by GSK3B (By similarity). Phosphorylation by GSK3B markedly increases NFATC4 ubiquitination (By similarity). Phosphorylation by MAPK8/JNK1, MAPK9/JNK2 and RPS6KA3 may stimulate NFATC4 transcriptional activity. Phosphorylation at Ser-168 and Ser-170 is stimulated by UV irradiation (By similarity). Ubiquitinated, leading to degradation by the proteasome. Ubiquitination may be stimulated by GSK3B-dependent phosphorylation. Polyubiquitin linkage mainly occurs through 'Lys-48'. No visible phenotype (PubMed:12370307). However, adult mutant animals show selective impairment in the formation of spatial long-term memory and long-term potentiation. They exhibit a reduced number of hippocampal adult-born neurons compared to wild-type littermates (PubMed:22586092). Simultaneous knockout of NFATC3 and NFATC4 results in embryonic death soon after 10.5 dpc. Embryos appear normal at 9.5 dpc. At 10.5 dpc, they exhibit defects in cardiac development, including dilated thin translucent hearts, pericardial effusion and anemia. Despite a mild generalized developmental delay, the heads, tails, and limb buds are well developed. By 11.5 dpc, mutant embryos are either necrotic or resorbed (PubMed:12750314).