RCAN2 (regulator of calcineurin 2, also known as calcipressin-2) is encoded by a novel thyroid hormone-responsive gene ZAKI-4 that is abundantly expressed in human brain, heart and muscles []. It Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A [].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 [].
