NFAT5
Function
Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394). Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Also involved in the DNA damage response by preventing formation of R-loops; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:34049076).
Post-translational modifications
Phosphorylated (PubMed:10377394). Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization (PubMed:21209322).
Poly-ADP-ribosylated by PARP1 in response to DNA damage, promoting recruitment to sites of R-loop-associated DNA damage.
Tissue Specificity
Widely expressed, with highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes.
Cellular localization
- Nucleus
- Cytoplasm
- Chromosome
- Nuclear distribution increases under hypertonic conditions (By similarity). Recruited to sites of R-loop-associated DNA damage following poly-ADP-ribosylation by PARP1 (PubMed:34049076).
Alternative names
KIAA0827, TONEBP, NFAT5, Nuclear factor of activated T-cells 5, NF-AT5, T-cell transcription factor NFAT5, Tonicity-responsive enhancer-binding protein, TonE-binding protein, TonEBP