N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins and similar proteins
Proteins containing the Rel homology domain (RHD) are metazoan transcription factors. The RHD is composed of two structural sub-domains; this model characterizes the N-terminal RHD sub-domain of the NFAT family of transcription factors. NFAT transcription complexes are a target of calcineurin, a calcium dependent phosphatase, and activate genes that are mainly involved in cell-cell interaction. Upon de-phosphorylation of the nuclear localization signal, NFAT enters the nucleus and acts as a transcription factor; its export from the nucleus is triggered by phosphorylation via export kinases. NFATs play important roles in mediating the immune response, and are found in T cells, B Cells, NK cells, mast cells, and monocytes. NFATs are also found in various non-hematopoietic cell types, where they play roles in development. This group also contains the N-terminal RHD sub-domain of the non-calcium regulated tonicity-responsive enhancer binding protein (TonEBP), also called NFAT5. Mammalian TonEBP regulates the expression of genes in response to tonicity. It plays a pivotal role in urinary concentrating mechanisms in kidney medulla, by triggering the accumulation of osmolytes that enable renal medullary cells to tolerate high levels of urea and salt.