ID:NFAC2_HUMAN DESCRIPTION: RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 2; Short=NF-ATc2; Short=NFATc2; AltName: Full=NFAT pre-existing subunit; Short=NF-ATp; AltName: Full=T-cell transcription factor NFAT1; 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-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. 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). INTERACTION: Q5S007:LRRK2; NbExp=3; IntAct=EBI-716258, EBI-5323863; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=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. 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 (By similarity). 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. SIMILARITY: Contains 1 RHD (Rel-like) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13469
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000976 transcription regulatory region sequence-specific DNA binding GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0019902 phosphatase binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001816 cytokine production GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006974 cellular response to DNA damage stimulus GO:0010628 positive regulation of gene expression GO:0014904 myotube cell development GO:0016477 cell migration GO:0030890 positive regulation of B cell proliferation GO:0033173 calcineurin-NFAT signaling cascade GO:0038095 Fc-epsilon receptor signaling pathway GO:0042493 response to drug GO:0045589 regulation of regulatory T cell differentiation GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0050853 B cell receptor signaling pathway GO:1901741 positive regulation of myoblast fusion GO:1905064 negative regulation of vascular smooth muscle cell differentiation
LP895140 - Sequence 4 from Patent EP3253886. AK226146 - Homo sapiens mRNA for nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 isoform C variant, clone: ah03087. AK304147 - Homo sapiens cDNA FLJ51454 complete cds, highly similar to Nuclear factor of activated T-cells, cytoplasmic 2. EU887573 - Homo sapiens nuclear factor of activated T-cells c2 isoform IB-IIL-Xa (NFATC2) mRNA, complete cds, alternatively spliced. EU887576 - Homo sapiens nuclear factor of activated T-cells c2 isoform IB-IIS-Xa (NFATC2) mRNA, complete cds, alternatively spliced. EU887574 - Homo sapiens nuclear factor of activated T-cells c2 isoform IA-IIL-Xa (NFATC2) mRNA, complete cds, alternatively spliced. EU887575 - Homo sapiens nuclear factor of activated T-cells c2 isoform IA-IIS-Xa (NFATC2) mRNA, complete cds, alternatively spliced. FJ573259 - Homo sapiens isolate L1231 EWSR1/NFATC2 fusion protein mRNA, complete cds. FJ573260 - Homo sapiens isolate L1857 EWSR1/NFATC2 fusion protein mRNA, complete cds. BC136418 - Homo sapiens nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2, mRNA (cDNA clone MGC:168029 IMAGE:9020406), complete cds. BC144074 - Homo sapiens nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2, mRNA (cDNA clone MGC:177611 IMAGE:9052594), complete cds. EU887578 - Homo sapiens nuclear factor of activated T-cells c2 isoform IB-IIL-deltaXa (NFATC2) mRNA, complete cds, alternatively spliced. EU887580 - Homo sapiens nuclear factor of activated T-cells c2 isoform IB-IIS-deltaXa (NFATC2) mRNA, complete cds, alternatively spliced. U43342 - Human transcription factor NFAT1 isoform C (NFAT1) mRNA, complete cds. EU887577 - Homo sapiens nuclear factor of activated T-cells c2 isoform IA-IIL-deltaXa (NFATC2) mRNA, complete cds, alternatively spliced. EU887579 - Homo sapiens nuclear factor of activated T-cells c2 isoform IA-IIS-deltaXa (NFATC2) mRNA, complete cds, alternatively spliced. AB590566 - Synthetic construct DNA, clone: pFN21AB0454, Homo sapiens NFATC2 gene for nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2, without stop codon, in Flexi system. U43341 - Human transcription factor NFAT1 isoform B (NFAT1) mRNA, complete cds. AK025758 - Homo sapiens cDNA: FLJ22105 fis, clone HEP17660. JD172926 - Sequence 153950 from Patent EP1572962. AY927566 - Homo sapiens mRNA sequence. JD129084 - Sequence 110108 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_calcineurinPathway - Effects of calcineurin in Keratinocyte Differentiation h_vipPathway - Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells h_tcrPathway - T Cell Receptor Signaling Pathway h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart) h_hdacPathway - Control of skeletal myogenesis by HDAC & calcium/calmodulin-dependent kinase (CaMK) h_mef2dPathway - Role of MEF2D in T-cell Apoptosis h_bcrPathway - BCR Signaling Pathway h_gpcrPathway - Signaling Pathway from G-Protein Families h_GATA3pathway - GATA3 participate in activating the Th2 cytokine genes expression h_fMLPpathway - fMLP induced chemokine gene expression in HMC-1 cells h_fcer1Pathway - Fc Epsilon Receptor I Signaling in Mast Cells
Reactome (by CSHL, EBI, and GO)
Protein Q13469 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
