The NFATC2 gene consists of 11 exons of which the last is the biggest. There are five known transcripts, varying from 7525 to 620 base pairs of which the largest four lead to a protein product (ensembl, last viewed at 10-04-2012) (Macian, 2005).

Transcription of the gene is from the - strand. Transcribed sequence contains both a 5and a 3-UTR region. The 5-UTR is located in exon 10 and the full exon 11 and is > 4500 bases in size. The large UTR indicates transcription control by small non-coding RNA and/or large non-coding RNA sequences (ensembl, last viewed at 10-04-2012).

NFATc2 is part of the NFAT family of transcription factors. The conserved region of all NFAT proteins consists of two domains. The first is the NFAT Homology region (NHR) which is the regulatory domain. It contains a strong transactivation domain and many serine residues that are phosphorylated when the protein is inactive and resides in the cytoplasm. There are two serine rich regions (SRRs) and three SPXX-repeat motifs (SPs), where X stands for any amino acid. Calcineurin and NFAT kinases regulate the activity of the NFAT proteins by determining the phosphorylation status of the serine residues, interacting with NFAT proteins at the NHR.
Another, highly conserved region of the NFAT family is the DNA binding domain that is structurally related to the DNA binding domain of the Rel-Family of transcription factors. This domain, called the REL homology region (RHR) is also responsible for binding partner proteins like the AP1 complex.
There are three alternative splice variants of the NFATC2 protein, all of which occur in the C-terminal domain of the protein (Macian, 2005).

Inactive NFATC2 normally resides in the cytoplasm where the serine residues in the NHR are phosphorylated. This phosphorylated state of the NHR results in configuration changes of the protein shielding the nuclear localisation signal (NLS). Activation of NFATC2 is regulated by a pathway including calcium influx to the cytoplasm, calmodulin and calcineurin. In response to various stimuli, calcium enters the cytoplasm from the environment and intracellular stores. Calcium binds calmodulin and this complex activates calcineurin. The activated calcineurin will dephosphorylate the SRRs and SPs of the NHR, resulting in the exposure of the NLS and translocation of the protein to the nucleus. Translocated NFAT binds to consensus DNA sites (WGGAAANHN (H is not G, N is any of the four nucleotides)) and control gene transcription with the help of other nuclear complexes such as the AP1 protein complex (Macian, 2005).
Several kinases have been identified to rephosphorylate NFAT proteins at multiple sites, thereby controlling their nuclear shuttling. These kinases include glycogen-synthase kinase 3 (GSK3), casein kinase 1 (CK1), p38, and JUN N-terminal kinase (JNK). Some of them act as maintenance kinases, to keep the NFAT proteins in the cytosol in a fully phosphorylated state, preventing them from nuclear shuttling. Others act as export kinases; they rephosphorylate NFAT in the nucleus and thereby promote the nuclear export of NFAT, stopping the NFAT driven transcription after calcineurin activity declines.
Another regulatory mechanism has been discovered for NFAT proteins which uses a non-coding RNA (ncRNA). Functional analysis of ncRNAs found a Non-coding repressor of NFAT (NRON). When NRON was deactivated by small hairpin RNA (shRNA), a dramatic increase in NFAT activity was measured. NRON directly binds to 11 proteins, of which four are repressors of NFAT. NRON probably interacts with the nuclear shuttling of NFAT proteins which is demonstrated by an increase in nuclear localisation upon treatment with NRON shRNA (Rao et al., 1997; Willingham et al., 2005; Macian, 2005).
At this moment, 8 different microRNAs, which target 5 locations on the NFATC2 gene have been discovered (ensembl last viewed at 10-04-2012).

In its inactive form, NFATC2 resides in the cytoplasm. When activated it translocates to the nucleus (Macian, 2005).

NFATC2 is a transcription factor that forms complexes with other nuclear proteins including the AP-1 complex and regulates transcription of a large number of genes. It thereby regulates many processes including cell differentiation, migration and angiogenesis. It is, together with the other NFATs, essential for the development of multiple organ systems, including the nerve and immune system, the heart and skeletal muscles, the vasculature, the lungs and the skeletal structures. Because of their multiple functions, dysfunction of NFATs may play a role in pathobiology of cancer (Wu et al., 2007; Macian, 2005).

NFATC2 shows great similarity with the NFATC1, NFATC3 and NFATC4 proteins. The RHR shows great similarity with the DNA binding sites of proteins of the REL family of transcription factors (Hogan et al., 2003).