Human Gene NFATC2 (ENST00000609507.1) Description and Page Index
  Description: Homo sapiens nuclear factor of activated T cells 2 (NFATC2), transcript variant 5, mRNA. (from RefSeq NM_001258294)
RefSeq Summary (NM_001258294): This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants encoding different isoforms have been characterized. [provided by RefSeq, Apr 2012].
Gencode Transcript: ENST00000609507.1
Gencode Gene: ENSG00000101096.20
Transcript (Including UTRs)
   Position: hg38 chr20:51,391,228-51,562,831 Size: 171,604 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr20:51,398,687-51,523,583 Size: 124,897 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:51,391,228-51,562,831)mRNA (may differ from genome)Protein (702 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
LynxMGIneXtProtOMIMPubMedReactome
Stanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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.

-  MalaCards Disease Associations
  MalaCards Gene Search: NFATC2
Diseases sorted by gene-association score: leukostasis (8), fibrosarcoma of bone (4), narcolepsy (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.63 RPKM in Spleen
Total median expression: 79.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -120.70285-0.424 Picture PostScript Text
3' UTR -54.30268-0.203 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013783 - Ig-like_fold
IPR014756 - Ig_E-set
IPR002909 - IPT_TIG_rcpt
IPR008366 - NFAT
IPR008967 - p53-like_TF_DNA-bd
IPR011539 - RHD

Pfam Domains:
PF00554 - Rel homology DNA-binding domain
PF01833 - IPT/TIG domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1A02
- X-ray MuPIT

1OWR
- X-ray MuPIT

1P7H
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1PZU - X-ray MuPIT 1S9K - X-ray MuPIT 2AS5 - X-ray MuPIT
2O93 - X-ray MuPIT 3QRF - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13469
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  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

Cellular Component:
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0044798 nuclear transcription factor complex
GO:1990904 ribonucleoprotein complex


-  Descriptions from all associated GenBank mRNAs
  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.
JD172926 - Sequence 153950 from Patent EP1572962.
AY927566 - Homo sapiens mRNA sequence.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway
hsa04310 - Wnt signaling pathway
hsa04360 - Axon guidance
hsa04370 - VEGF signaling pathway
hsa04650 - Natural killer cell mediated cytotoxicity
hsa04660 - T cell receptor signaling pathway
hsa04662 - B cell receptor signaling pathway

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):

R-HSA-8877338 RUNX1 and NFATC2 bind the IL2 gene promoter
R-HSA-8877348 RUNX1, FOXP3 and NFATC2 bind the IL2 gene promoter
R-HSA-2025890 Calcineurin binds NFATC1,2,3
R-HSA-2730867 Translocation of CaN:CaM:NFAT to nucleus
R-HSA-8877330 RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)
R-HSA-2025928 Calcineurin activates NFAT
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation
R-HSA-8878171 Transcriptional regulation by RUNX1
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-212436 Generic Transcription Pathway
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-168249 Innate Immune System
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: B5B2N8, B5B2N9, NFAC2_HUMAN, NFAT1, NFATP, NM_001258294, Q13468, Q13469, Q5TFW7, Q5TFW8, Q9NPX6, Q9NQH3, Q9UJR2, uc010zyy.1, uc010zyy.2, uc010zyy.3, uc010zyy.4
UCSC ID: uc010zyy.4
RefSeq Accession: NM_001258294
Protein: Q13469 (aka NFAC2_HUMAN)
CCDS: CCDS68156.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.