NFATC3
Description
The NFATC3 (nuclear factor of activated T cells 3) is a protein-coding gene located on chromosome 16.
Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene. It is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Four transcript variants encoding distinct isoforms have been identified for this gene.
NFATC3 acts as a transcription activator, binding to the TNFSF11/RANKL promoter to promote TNFSF11 transcription. This binding is enhanced by high levels of calcium, which in turn induces NFATC3 expression, potentially regulating TNFSF11 expression in osteoblasts. NFATC3 plays a role in mesenteric arterial wall remodeling in response to intermittent hypoxia-induced EDN1 and ROCK signaling, colocalizing with F-actin filaments and translocating to the nucleus to promote ACTA2 transcription, a marker for smooth muscle hypertrophy and differentiation. It also promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes. Following JAK/STAT signaling activation, NFATC3 forms a complex with NFATC4 and STAT3, binding to the alpha-beta E4 promoter region of CRYAB and activating transcription in cardiomyocytes. Working with NFATC4, it contributes to embryonic heart development by supporting cardiomyocyte survival, proliferation, and differentiation. NFATC3 contributes to the inducible expression of cytokine genes in T-cells, particularly IL-2, and is necessary for thymocyte maturation during the DN3 to DN4 transition and positive selection. NFATC3 positively regulates macrophage-derived polymicrobial clearance by binding to the promoter region of NOS2 and promoting its transcription, leading to nitric oxide production. It is involved in calcium-mediated transcriptional responses upon calcium influx through ORAI1 CRAC channels.
NFATC3 is also known as NF-AT4c, NFAT4, NFATX, n339260.
