Calcipressin-3 (RCAN3) is a member of the calcipressin family. Overexpressed RCAN3 has been found to bind and inhibit the Ca2+/calmodulin-dependent phosphatase calcineurin, and further down-regulates nuclear factor of activated T cells (NFAT)-dependent cytokine gene expression in activated human Jurkat T cells []. RCAN3 can also interact with cardiac troponin I (TNNI3), a heart-specific inhibitory subunit of the troponin complex, and may play a role in cardiac contraction [].Calcipressins (RCANs) are a novel family of calcineurin regulators that have been suggested as key factors contributing to Down syndrome in humans. Three human calcipressins have been identified, calcipressin 1-3. Calcipressin 1 is also known as modulatory calcineurin-interacting protein 1 (MCIP1), Adapt78 and Down syndrome critical region 1 (DSCR1). Calcipressin 2 is variously known as MCIP2, ZAKI-4 and DSCR1-like 1. Calcipressin 3 is also called MCIP3 and DSCR1-like 2 []. Calcipressins contain an N-terminal RNA recognition motif (RRM), a highly conserved SP repeat domain containing the phosphorylation site by GSK-3, a well-known PxIxIT motif responsible for docking many substrates to calcineurin, and a C-terminal TxxP motif [].Calcineurin is a calcium-responsive enzyme that dephosphorylates the nuclear factor of activated T cells (NFAT). In doing so, it promotes its nuclear translocation and uniquely links calcium signalling to transcriptional regulation [].
