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    NFATC3 nuclear factor of activated T cells 3 [ Homo sapiens (human) ]

    Gene ID: 4775, updated on 11-Apr-2024

    Summary

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    Official Symbol
    NFATC3provided by HGNC
    Official Full Name
    nuclear factor of activated T cells 3provided by HGNC
    Primary source
    HGNC:HGNC:7777
    See related
    Ensembl:ENSG00000072736 MIM:602698; AllianceGenome:HGNC:7777
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NFAT4; NFATX; NF-AT4c; n339260
    Summary
    The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Nov 2010]
    Expression
    Ubiquitous expression in testis (RPKM 17.4), lymph node (RPKM 16.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    16q22.1
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (68085370..68229259)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (73881124..74025006)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (68119273..68263162)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68055836-68056586 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68056587-68057337 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:68078446-68078635 Neighboring gene DEAD-box helicase 28 Neighboring gene dihydrouridine synthase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11003 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11005 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7638 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7639 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11006 Neighboring gene Sharpr-MPRA regulatory region 7518 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7640 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:68197467-68198334 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:68221558-68222058 Neighboring gene small nucleolar RNA SNORA48 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11007 Neighboring gene ribosomal protein S12 pseudogene 27 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11008 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7641 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68270229-68270817 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68270818-68271405 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68271406-68271994 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:68271995-68272581 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:68278082-68278620 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7644 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:68279742-68280242 Neighboring gene microRNA 6773 Neighboring gene epithelial splicing regulatory protein 2 Neighboring gene phospholipase A2 group XV

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Hypoxia-induced NFATc3 deSUMOylation enhances pancreatic carcinoma progression. Tong Y, et al. Cell Death Dis, 2022 Apr 28. PMID 35484132, Free PMC Article
    2. NFATc3 inhibits hepatocarcinogenesis and HBV replication via positively regulating RIG-I-mediated interferon transcription. Zao X, et al. Oncoimmunology, 2021 Jan 11. PMID 33520407, Free PMC Article
    3. NFAT4 is required for JC virus infection of glial cells. Manley K, et al. J Virol, 2006 Dec. PMID 17035332, Free PMC Article
    4. ATP autocrine/paracrine signaling induces calcium oscillations and NFAT activation in human mesenchymal stem cells. Kawano S, et al. Cell Calcium, 2006 Apr. PMID 16445977
    5. A constitutively nuclear form of NFATx shows efficient transactivation activity and induces differentiation of CD4(+)CD8(+) T cells. Amasaki Y, et al. J Biol Chem, 2002 Jul 12. PMID 11997392

    See all (98) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability.
      Title: CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability.
    2. lncRNA NEAT1 promotes hypoxia-induced inflammation and fibrosis of alveolar epithelial cells via targeting miR-29a/NFATc3 axis.
      Title: lncRNA NEAT1 promotes hypoxia-induced inflammation and fibrosis of alveolar epithelial cells via targeting miR-29a/NFATc3 axis.
    3. Hypoxia-induced NFATc3 deSUMOylation enhances pancreatic carcinoma progression.
      Title: Hypoxia-induced NFATc3 deSUMOylation enhances pancreatic carcinoma progression.
    4. Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms.
      Title: Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms.
    5. Fusobacterium nucleatum Promotes Cisplatin-Resistance and Migration of Oral Squamous Carcinoma Cells by Up-Regulating Wnt5a-Mediated NFATc3 Expression.
      Title: Fusobacterium nucleatum Promotes Cisplatin-Resistance and Migration of Oral Squamous Carcinoma Cells by Up-Regulating Wnt5a-Mediated NFATc3 Expression.
    6. Blocking NFATc3 ameliorates azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer in mice via the inhibition of inflammatory responses and epithelial-mesenchymal transition.
      Title: Blocking NFATc3 ameliorates azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer in mice via the inhibition of inflammatory responses and epithelial-mesenchymal transition.
    7. circNFATC3 sponges miR-548I acts as a ceRNA to protect NFATC3 itself and suppressed hepatocellular carcinoma progression.
      Title: circNFATC3 sponges miR-548I acts as a ceRNA to protect NFATC3 itself and suppressed hepatocellular carcinoma progression.
    8. NFATc3 inhibits hepatocarcinogenesis and HBV replication via positively regulating RIG-I-mediated interferon transcription.
      Title: NFATc3 inhibits hepatocarcinogenesis and HBV replication via positively regulating RIG-I-mediated interferon transcription.
    9. data indicated that NRON alleviates atrial fibrosis via promoting NFATc3 phosphorylation.
      Title: LncRNA NRON alleviates atrial fibrosis via promoting NFATc3 phosphorylation.
    10. Expression of the NFATC3-PLA2G15 chimera correlated with aggressive disease biology in murine patient-derived T-ALL xenografts, and poor prognosis in human T-ALL patients.
      Title: Novel Intergenically Spliced Chimera, NFATC3-PLA2G15, Is Associated with Aggressive T-ALL Biology and Outcome.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Biological insights from 108 schizophrenia-associated genetic loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 and anti-CD4 antibodies induce a specific, significant decrease in the binding activity of NF-AT, NF-kappa B and AP-1, which leads to an inhibition of IL-2 production and cell proliferation PubMed
    env Using either anti-CD4 monoclonal antibodies or HIV-1 gp120 binding to CD4 reveals a common epitope-specific activation of both the HIV-1 LTR and of the transcription factors NF-kappa B and NF-AT PubMed
    Nef nef HIV-1 Vpu downregulates NRON levels but HIV-1 Nef upregulates NRON levels in Jurkat cells, leading to reciprocal regulation in NFAT activity through NRON by Vpu and Nef PubMed
    Tat tat The transcription factors NF-KappaB and NF-AT contribute to the Tat-induced activation of the HERV-K (HML-2) gag RNA transcripts in Jurkat T cells and in primary lymphocytes PubMed
    tat HIV-1 Tat expression in Jurkat T cells enhances cooperative NFAT/AP-1- but not AP-1-dependent transcription independent of its ability to transactivate the HIV-1 LTR PubMed
    tat Transcription factors NFAT and AP-1 (c-Jun/c-Fos) are required for HIV-1 Tat-induced upregulation of COX-2 PubMed
    tat Induction of TNF-alpha by HIV-1 Tat is inhibited by cyclosporin A, an inhibitor of calcineurin that acts by preventing the dephosphorylation of NF-AT PubMed
    tat HIV-1 Tat enhances IL-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif PubMed
    Vpr vpr HIV-1 Vpr upregulates NFAT-directed gene expression PubMed
    Vpu vpu HIV-1 Vpu downregulates NRON levels but HIV-1 Nef upregulates NRON levels in Jurkat cells, leading to reciprocal regulation in NFAT activity through NRON by Vpu and Nef PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Potential readthrough

    Included gene: DUS2

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables DNA-binding transcription repressor activity, RNA polymerase II-specific IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables transcription factor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in DN4 thymocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in calcineurin-NFAT signaling cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cytokine production IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of miRNA transcription IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of vascular associated smooth muscle cell differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of artery morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of cardiac muscle hypertrophy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of nitric oxide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive thymic T cell selection ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein import into nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    part_of chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of transcription regulator complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    nuclear factor of activated T-cells, cytoplasmic 3
    Names
    NF-ATc3
    T cell transcription factor NFAT4
    nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029147.2 RefSeqGene

      Range
      5005..148894
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_004555.4 → NP_004546.1  nuclear factor of activated T-cells, cytoplasmic 3 isoform 2

      See identical proteins and their annotated locations for NP_004546.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an additional segment in the coding region, which causes a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC020978, BU849493, CA418693, L41067
      Consensus CDS
      CCDS10862.1
      UniProtKB/TrEMBL
      B5B2S0, B5B2S2
      Related
      ENSP00000331324.4, ENST00000329524.8
      Conserved Domains (2) summary
      cd07881
      Location:421 → 594
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:599 → 699
      IPT_NFAT; IPT domain of the NFAT family of transcription factors. NFAT transcription complexes are a target of calcineurin, a calcium dependent phosphatase, and activate genes mainly involved in cell-cell-interaction.

    2. NM_173163.3 → NP_775186.1  nuclear factor of activated T-cells, cytoplasmic 3 isoform 3

      See identical proteins and their annotated locations for NP_775186.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an additional segment in the coding region, which causes a frameshift, compared to variant 1. The resulting isoform (3) contains a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC020978, BU849493, CA418693, L41067, U85429
      Consensus CDS
      CCDS10861.1
      UniProtKB/TrEMBL
      B5B2S2
      Related
      ENSP00000264008.6, ENST00000349223.9
      Conserved Domains (2) summary
      cd07881
      Location:421 → 594
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:599 → 699
      IPT_NFAT; IPT domain of the NFAT family of transcription factors. NFAT transcription complexes are a target of calcineurin, a calcium dependent phosphatase, and activate genes mainly involved in cell-cell-interaction.

    3. NM_173165.3 → NP_775188.1  nuclear factor of activated T-cells, cytoplasmic 3 isoform 1

      See identical proteins and their annotated locations for NP_775188.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC020978, BC001050, BU849493, CA418693
      Consensus CDS
      CCDS10860.1
      UniProtKB/Swiss-Prot
      O75211, Q12968, Q14516, Q99840, Q99841, Q99842
      UniProtKB/TrEMBL
      A8K2V5, B5B2S1
      Related
      ENSP00000300659.5, ENST00000346183.8
      Conserved Domains (2) summary
      cd07881
      Location:421 → 594
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:599 → 699
      IPT_NFAT; IPT domain of the NFAT family of transcription factors. NFAT transcription complexes are a target of calcineurin, a calcium dependent phosphatase, and activate genes mainly involved in cell-cell-interaction.

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      68085370..68229259
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      73881124..74025006
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_173164.1: Suppressed sequence

      Description
      NM_173164.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q12968.1 GenPept UniProtKB/Swiss-Prot:Q12968

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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