nuclear factor of activated T-cells cytoplasmic 4 (NFATc4, NFAT3)

Function: - role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 & IL-4 - transcriptionally repressed by estrogen receptors; inhibition is further enhanced by estrogen - increases transcriptional activity of PPARG - role in adipocyte differentiation - may play a role in myotube differentiation - may play a role in cardiac development & hypertrophy - may play a role in deafferentation-induced apoptosis of sensory neurons - phosphorylated by NFATC-kinases - dephosphorylated by calcineurin - phosphorylated on Ser-168 & Ser-170 by FRAP1, IRAK1, MAPK7 & MAPK14, on Ser-213 & Ser-217 by MAPK8 & MAPK9, & on Ser-289 & Ser-344 by RPS6KA3 - phosphorylated by GSK3B - ubiquitinated, leading to its degradation by the proteasome - ubiquitination can be further facilitated via GSK3B-dependent phosphorylation - polyubiquitin linkage is mainly through Lys-48 - member of the multicomponent NFATC transcription complex - binds to DNA as monomer - interacts with CREBBP, GATA4, IRAK1, MAPK8, MAPK9 & RPS6KA3 Structure: - Rel similarity domain (RSD) allows DNA-binding & cooperative interactions with AP1 factors (putative) - contains 1 IPT/TIG domain - contains 1 RHD (Rel-like) domain Compartment: - cytoplasm. nucleus - cytoplasmic for the phosphorylated form - nuclear after activation that is controlled by calcineurin-mediated dephosphorylation - rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained & transient Ca⁺² signals - the subcellular localization of NFATC plays a key role in regulation of gene transcription Alternative splicing: named isoforms=24 Expression: - highly expressed in placenta, lung, kidney, testis & ovary - weakly expressed in spleen & thymus - not expressed in peripheral blood lymphocytes - detected in hippocampus

General

DNA-binding protein phosphoprotein

Properties

SIZE: MW = 95 kD entity length = 902 aa MOTIF: proline residue {62-69} (8) binding site SITE: 114-119 FOR-BINDING-OF: calcineurin Ser phosphorylation site SP {213-229} nuclear translocation signal {268-270} SP {277-293} proline residue {297-304} (8) DNA-binding motif SITE: 430-437 nuclear translocation signal {672-674}

Database Correlations

OMIM 602699 UniProt Q14934 PFAM correlations Entrez Gene 4776 Kegg hsa:4776

References

UniProt :accession Q14934