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Details on Person UniProt:Q13469 NFATC2
| Class:Id | ReferenceGeneProduct:60121 |
|---|---|
| _chainChangeLog | chain:1-925 added on Sat February 7 2015 |
| _displayName | UniProt:Q13469 NFATC2 |
| _timestamp | 2026-02-20 22:35:31 |
| chain | chain:1-925 |
| checksum | 8DAE86855CCB58D3 |
| comment | FUNCTION Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF or GM-CSF (PubMed:15790681). Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway (PubMed:21871017). Is involved in the negative regulation of chondrogenesis (PubMed:35789258). Recruited by AKAP5 to ORAI1 pore-forming subunit of CRAC channels in Ca(2+) signaling microdomains where store-operated Ca(2+) influx is coupled to calmodulin and calcineurin signaling and activation of NFAT-dependent transcriptional responses.SUBUNIT Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. The phosphorylated form specifically interacts with XPO1; which mediates nuclear export. NFATC proteins bind to DNA as monomers. Interacts with NFATC2IP (By similarity). Interacts with FOXP3 (PubMed:15790681). Interacts with TBX21 ('Thr-303' phosphorylated form) (By similarity). Interacts with KAT2A (By similarity). Interacts with HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC2 dephosphorylation and activation (PubMed:18218901). Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:26248042). Interacts with AKAP5 (via leucine zipper domain); this is required for NFATC2/NFAT1 recruitment to CRAC channels.INTERACTION Cytoplasmic for the phosphorylated form and 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 and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription.ALTERNATIVE PRODUCTS Additional isoforms seem to exist.TISSUE SPECIFICITY Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas. Isoform 1 is highly expressed in the small intestine, heart, testis, prostate, thymus, placenta and thyroid. Isoform 3 is highly expressed in stomach, uterus, placenta, trachea and thyroid.INDUCTION 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) and ionomycin.DOMAIN The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.DOMAIN Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.PTM 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 simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, Ser-53 or Ser-56 is phosphorylated; which is required for full transcriptional activity.PTM Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome.DISEASE The disease may be caused by variants affecting the gene represented in this entry. |
| description | recommendedName: Nuclear factor of activated T-cells, cytoplasmic 2 shortName: NF-ATc2 shortName: NFATc2 alternativeName: NFAT pre-existing subunit shortName: NF-ATp alternativeName: T-cell transcription factor NFAT1 |
| geneName | NFATC2 NFAT1 NFATP |
| identifier | Q13469 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Activator Alternative splicing Cytoplasm DNA-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | NFATC2 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8999638] ENSEMBL:ENSG00000101096 NFATC2 [Homo sapiens] |
| secondaryIdentifier | NFAC2_HUMAN B5B2N8 B5B2N9 B5B2P0 B5B2P2 B5B2P3 Q13468 Q5TFW7 Q5TFW8 Q9NPX6 Q9NQH3 Q9UJR2 |
| sequenceLength | 925 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:150981] UniProt:Q13469-2 NFATC2 [Homo sapiens] [ReferenceIsoform:405619] UniProt:Q13469-1 NFATC2 [Homo sapiens] [ReferenceIsoform:8971561] UniProt:Q13469-3 NFATC2 [Homo sapiens] [ReferenceIsoform:8971562] UniProt:Q13469-4 NFATC2 [Homo sapiens] [ReferenceIsoform:8971563] UniProt:Q13469-5 NFATC2 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:2025848] p-14S-NFATC2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2025894] p-S243-NFATC2 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:2685626] p-S243-NFATC2 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3791114] NFATC2 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:3791117] monoSUMO1-K682,895-NFATC2 [nucleoplasm] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2025862] O-phospho-L-serine at 177 [ModifiedResidue:2025866] O-phospho-L-serine at 174 [ModifiedResidue:2025870] O-phospho-L-serine at 268 [ModifiedResidue:2025883] O-phospho-L-serine at 171 [ModifiedResidue:2025884] O-phospho-L-serine at 175 [ModifiedResidue:2025895] O-phospho-L-serine at 221 [ModifiedResidue:2025940] O-phospho-L-serine at 326 [ModifiedResidue:2025961] O-phospho-L-serine at 217 [ModifiedResidue:2025964] O-phospho-L-serine at 276 [ModifiedResidue:2025965] O-phospho-L-serine at 213 |
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No pathways have been reviewed or authored by UniProt:Q13469 NFATC2 (60121)
