nuclear factor of activated T-cells, cytoplasmic 2; T-cell transcription factor NFAT1; NFAT pre-existing subunit; NF-ATp (NFATC2, NFAT1, NFATp)

Function: - role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF - in resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-363 region - upon cell stimulation, all these sites except Ser-243 are dephosphorylated by calcineurin - dephosphorylation induces a conformational change that exposes an NLS & masks an NES, resulting in nuclear localization & Ser-53 or Ser-56 phosphorylation, which is required for full transcriptional activity - member of the multicomponent NFATC transcription complex - the phosphorylated form specifically interacts with XPO1 which mediates nuclear export - binds to DNA as monomer - interacts with NFATC2IP (putative) Structure: - Rel similarity domain (RSD) allows DNA-binding & cooperative interactions with AP1 factors (putative) - 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 - subcellular localization of NFATC plays a key role in the regulation of gene transcription Alternative splicing: named isoforms=2; C,B; additional isoforms seem to exist Expression: - expressed in thymus, spleen, heart, testis, brain, placenta, muscle & pancreas - inducibly expressed in T-lymphocytes upon activation of the T-cell receptor complex (TCR) - induced after co-addition of phorbol 12-myristate 13-acetate (PMA) & ionomycin

General

DNA-binding protein phosphoprotein

Properties

SIZE: entity length = 925 aa MW = 100 kD MOTIF: Ser phosphorylation site {S53} Ser phosphorylation site {S56} Ser phosphorylation site {S99} Ser phosphorylation site {S110} binding site SITE: 111-116 FOR-BINDING-OF: calcineurin transcriptional activation domain SITE: 119-199 MOTIF: cytoplasmic retention {161-175} Ser phosphorylation site {S168} Ser phosphorylation site {S171} Ser phosphorylation site {S172} Ser phosphorylation site {S174} Ser phosphorylation site {S175} Ser phosphorylation site {S177} Ser phosphorylation site {S180} 3 X approximate SP repeats {184-286} MOTIF: consensus repeat {184-200} consensus repeat {213-229} Ser phosphorylation site {S213} Ser phosphorylation site {S217} Ser phosphorylation site {S221} Ser phosphorylation site {S236} Ser phosphorylation site {S243} nuclear translocation signal {251-253} Ser phosphorylation site {S268} consensus repeat {272-286} Ser phosphorylation site {S274} Ser phosphorylation site {S276} Ser phosphorylation site {S280} Ser phosphorylation site {S326} Ser phosphorylation site {S330} Ser phosphorylation site {S363} RHD {392-574} MOTIF: DNA-binding motif SITE: 421-428 Thr phosphorylation site {T585} Thr phosphorylation site {T599} Ser phosphorylation site {S605} nuclear translocation signal {664-666} nuclear export signal {904-913}

Database Correlations

OMIM 600490 UniProt Q13469 PFAM correlations Entrez Gene 4773 Kegg hsa:4773

References

UniProt :accession Q13469