nuclear factor of activated T-cells, cytoplasmic 1; NF-ATc1; NFAT transcription complex cytosolic component; NF-ATc; NFATc (NFATC1, NFAT2, NFATC)

Function: - role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 or IL-4 gene transcription - also controls gene expression in embryonic cardiac cells - may regulate not only the activation & proliferation, but also differentiation & programmed death of T-lymphocytes as well as other lymphoid & non-lymphoid cells - phosphorylated by NFATC-kinase - dephosphorylated by calcineurin - member of the multicomponent NFATC transcription complex - binds to DNA as monomer Structure: - Rel similarity domain (RSD) allows DNA-binding & cooperative interactions with AP1 factors - the N-terminal transactivation domain (TAD-A) binds to & is activated by Cbp/p300 - dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus - isoform C has a C-terminal part with an additional trans-activation domain, TAD-B, which acts as a transcriptional activator - isoform B has a shorter C-terminal part without complete TAD-B which acts as a transcriptional repressor - 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: Alternative initiation; Named isoforms=9; potency in activation of gene transcription: isoforms C > A > B; isoforms A, B & C have alpha & beta forms Expression: - expressed in T-cells within thymus, peripheral blood & spleen - isoform A is preferentially expressed in effector T-cells (thymus & peripheral blood) - isoforms B & C are preferentially expressed in naive T-cells (spleen) - isoforms B is expressed in naive T-cells after first antigen exposure - isoform A is expressed in effector T-cells after second antigen exposure - only isoform A is inducibly expressed in T lymphocytes upon activation of the T-cell receptor (TCR) complex - induced after co-addition of phorbol 12-myristate 13-acetate (PMA) or 12-O-tetradecanoylphorbol-13-acetate (TPA) & ionomycin; further addition of cyclosporin A seems to inhibit induction

General

DNA-binding protein phosphoprotein

Properties

SIZE: entity length = 943 aa MW = 101 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ser phosphorylation site {S117} binding site SITE: 118-123 FOR-BINDING-OF: calcineurin transcriptional activation domain SITE: 126-218 3 X SP repeats {203-298} MOTIF: consensus repeat {203-219} consensus repeat {233-249} nuclear translocation signal {265-267} consensus repeat {282-298} nuclear export signal {310-321} RHD {410-592} MOTIF: DNA-binding motif SITE: 439-446 nuclear translocation signal {682-684} transcriptional activation domain SITE: 703-943 MOTIF: nuclear export signal {924-933}

Database Correlations

OMIM 600489 UniProt O95644 PFAM correlations Entrez Gene 4772 Kegg hsa:4772

References

UniProt :accession O95644