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Details on Person UniProt:Q13469 NFATC2

Class:IdReferenceGeneProduct:60121
_chainChangeLogchain:1-925 added on Sat February 7 2015
_displayNameUniProt:Q13469 NFATC2
_timestamp2026-02-20 22:35:31
chainchain:1-925
checksum8DAE86855CCB58D3
commentFUNCTION 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.
descriptionrecommendedName: 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
geneNameNFATC2
NFAT1
NFATP
identifierQ13469
isSequenceChangedFALSE
keyword3D-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
nameNFATC2
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8999638] ENSEMBL:ENSG00000101096 NFATC2 [Homo sapiens]
secondaryIdentifierNFAC2_HUMAN
B5B2N8
B5B2N9
B5B2P0
B5B2P2
B5B2P3
Q13468
Q5TFW7
Q5TFW8
Q9NPX6
Q9NQH3
Q9UJR2
sequenceLength925
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)