NFAT5
Description
The NFAT5 (nuclear factor of activated T cells 5) is a protein-coding gene located on chromosome 16.
Nuclear factor of activated T-cells 5, also known as NFAT5 and sometimes TonEBP, is a human gene that encodes a transcription factor that regulates the expression of genes involved in the osmotic stress. The product of this gene is a member of the nuclear factors of activated T cells (NFAT) family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene.
== Osmotic stress == Tissues that comprise the kidneys, skin, and eyes are often subjected to osmotic stresses. When the extracellular environment is hypertonic, cells lose water and consequently, shrink. To counteract this, cells increase their sodium uptake in order to lose less water. However, an increase in intracellular ionic concentration is harmful to the cell.
NFAT5 is a transcription factor that regulates the expression of genes involved in osmoprotective and inflammatory responses. It binds to the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394) and mediates the transcriptional response to hypertonicity (PubMed:10051678). NFAT5 positively regulates the transcription of LCN2 and S100A4 genes, requiring the presence of DDX5/DDX17 for optimal transactivation (PubMed:22266867). It also plays a role in the DNA damage response by preventing the formation of R-loops, which are structures composed of DNA:RNA hybrids and associated non-template single-stranded DNA (PubMed:34049076).
NFAT5 is also known as NF-AT5, NFATL1, NFATZ, OREBP, TONEBP.
