Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:Q12968 NFATC3
| Class:Id | ReferenceGeneProduct:60123 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-1075 added on Fri February 6 2015;initiator methionine:1 for 60123 removed on Fri Nov 03 2023;initiator methionine: for 60123 added on Fri Nov 03 2023;initiator methionine: for 60123 removed on Fri Aug 15 2025;initiator methionine:1 for 60123 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q12968 NFATC3 |
| _timestamp | 2025-08-15 21:54:52 |
| chain | initiator methionine:1 chain:2-1075 |
| checksum | 0B25D61A2B56D898 |
| comment | FUNCTION Acts as a regulator of transcriptional activation. Binds to the TNFSF11/RANKL promoter region and promotes TNFSF11 transcription (By similarity). Binding to the TNFSF11 promoter region is increased by high levels of Ca(2+) which induce NFATC3 expression and may lead to regulation of TNFSF11 expression in osteoblasts (By similarity). Plays a role in promoting mesenteric arterial wall remodeling in response to the intermittent hypoxia-induced increase in EDN1 and ROCK signaling (By similarity). As a result NFATC3 colocalizes with F-actin filaments, translocates to the nucleus and promotes transcription of the smooth muscle hypertrophy and differentiation marker ACTA2 (By similarity). Promotes lipopolysaccharide-induced apoptosis and hypertrophy in cardiomyocytes (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC4 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity). In conjunction with NFATC4, involved in embryonic heart development via maintenance of cardiomyocyte survival, proliferation and differentiation (By similarity). Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 (PubMed:18815128). Required for thymocyte maturation during DN3 to DN4 transition and during positive selection (By similarity). Positively regulates macrophage-derived polymicrobial clearance, via binding to the promoter region and promoting transcription of NOS2 resulting in subsequent generation of nitric oxide (By similarity). Involved in Ca(2+)-mediated transcriptional responses upon Ca(2+) influx via ORAI1 CRAC channels.SUBUNIT NFATC proteins bind to DNA as monomers (PubMed:7749981). 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 (By similarity). Other members such as NFATC4, or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex (By similarity). Component of a promoter-binding complex composed of STAT3, NFATC3 and NFATC4; complex formation is enhanced by calcineurin (By similarity). Interacts with TRIM17; this interaction prevents NFATC3 nuclear localization (By similarity). Interacts with and ubiquitinated by STUB1/CHIP; HSPA1A/HSP70 is required as a co-chaperone (PubMed:30980393).INTERACTION The subcellular localization of NFATC plays a key role in the regulation of gene transcription (By similarity). Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals (By similarity). Cytoplasmic when phosphorylated and nuclear after activation, that is controlled by calcineurin-mediated dephosphorylation (By similarity). Translocation to the nucleus is increased in the presence of calcium in pre-osteoblasts (By similarity). Translocates to the nucleus in the presence of EDN1 following colocalization with F-actin filaments, translocation is ROCK-dependent (By similarity). Translocates to the nucleus in response to lipopolysaccharide treatment of macrophages (By similarity).ALTERNATIVE PRODUCTS Predominantly expressed in thymus and is also found in peripheral blood leukocytes and kidney.TISSUE SPECIFICITY Predominantly expressed in skeletal muscle (PubMed:9759864). Also found weakly expressed in the thymus, kidney, testis, spleen, prostate, ovary, small intestine, heart, placenta and pancreas (PubMed:9759864).TISSUE SPECIFICITY Expressed in thymus and kidney.TISSUE SPECIFICITY Expressed in thymus and skeletal muscle.DOMAIN Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.PTM Ubiquitinated by STUB1/CHIP, leading to proteasomal degradation.PTM Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin. |
| description | recommendedName: fullName evidence="17"Nuclear factor of activated T-cells, cytoplasmic 3 shortName: NF-ATc3 shortName evidence="3"NFATc3 alternativeName: fullName evidence="14"NFATx alternativeName: fullName evidence="15"T-cell transcription factor NFAT4 shortName evidence="15"NF-AT4 shortName evidence="15"NF-AT4c |
| geneName | NFATC3 NFAT4 |
| identifier | Q12968 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Activator Alternative splicing Cytoplasm Developmental protein Direct protein sequencing DNA-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | NFATC3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9003096] ENSEMBL:ENSG00000072736 NFATC3 [Homo sapiens] |
| secondaryIdentifier | NFAC3_HUMAN O75211 Q14516 Q99840 Q99841 Q99842 |
| sequenceLength | 1075 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:150984] UniProt:Q12968-2 NFATC3 [Homo sapiens] [ReferenceIsoform:150985] UniProt:Q12968-3 NFATC3 [Homo sapiens] [ReferenceIsoform:150986] UniProt:Q12968-4 NFATC3 [Homo sapiens] [ReferenceIsoform:150987] UniProt:Q12968-5 NFATC3 [Homo sapiens] [ReferenceIsoform:150988] UniProt:Q12968-6 NFATC3 [Homo sapiens] [ReferenceIsoform:405543] UniProt:Q12968-1 NFATC3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:445161] NFATC3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:2025920] p-13S-NFATC3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:2025988] p-S265-NFATC3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:2685614] p-S265-NFATC3 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:2025845] O-phospho-L-serine at 168 [ModifiedResidue:2025851] O-phospho-L-serine at 240 [ModifiedResidue:2025877] O-phospho-L-serine at 344 [ModifiedResidue:2025888] O-phospho-L-serine at 296 [ModifiedResidue:2025916] O-phospho-L-serine at 169 [ModifiedResidue:2025918] O-phospho-L-serine at 174 [ModifiedResidue:2025930] O-phospho-L-serine at 236 [ModifiedResidue:2025939] O-phospho-L-serine at 300 [ModifiedResidue:2025943] O-phospho-L-serine at 171 [ModifiedResidue:2025969] O-phospho-L-serine at 288 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q12968 NFATC3 (60123)
