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    NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [ Homo sapiens ]

    Gene ID: 4776, updated on 19-May-2012
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    Summary

    Official Symbol
    NFATC4provided by HGNC
    Official Full Name
    nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4provided by HGNC
    Primary source
    HGNC:7778
    See related
    Ensembl:ENSG00000100968; HPRD:09096; MIM:602699; Vega:OTTHUMG00000029351
    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
    NFAT3; NF-ATc4
    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 of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Oct 2008]
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    Genomic context

    Location :
    14q11.2
    Sequence :
    Chromosome: 14; NC_000014.8 (24836145..24848810)
    See NFATC4 in Epigenomics, MapViewer

    Chromosome 14 - NC_000014.8Genomic Context describing neighboring genes Neighboring gene adenylate cyclase 4 Neighboring gene receptor-interacting serine-threonine kinase 3 Neighboring gene NYN domain and retroviral integrase containing Neighboring gene cerebellin 3 precursor

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Inhibition of the NFAT pathway alleviates amyloid β neurotoxicity in a mouse model of Alzheimer's disease. Hudry E, et al. J Neurosci, 2012 Feb 29. PMID 22378890.
    2. Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Chen Y, et al. Transplantation, 2012 Feb 15. PMID 22234350.
    3. Opposing roles of FoxP1 and Nfat3 in transcriptional control of cardiomyocyte hypertrophy. Bai S, et al. Mol Cell Biol, 2011 Jul. PMID 21606195.
    4. [Expression and significance of COX-2 and its transcription factors NFAT3 and c-Jun in non-small cell lung cancer]. Zhao X, et al. Zhongguo Fei Ai Za Zhi, 2010 Nov. PMID 21081043.
    5. Using genetic and clinical factors to predict tacrolimus dose in renal transplant recipients. Wang P, et al. Pharmacogenomics, 2010 Oct. PMID 21047202.

    See all (46) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Dendritic spine loss and dendritic branching simplification induced by amyloid-beta peptide exposure are mimicked by constitutively active NFATC4, and abolished when NFATC4 activation is blocked by the genetically encoded inhibitor VIVIT.
      Title: Inhibition of the NFAT pathway alleviates amyloid β neurotoxicity in a mouse model of Alzheimer's disease.
    2. Polymorphisms in the NFATc4 gene may confer certain protection or predisposition for new-onset diabetes after transplantation (NODAT).
      Title: Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients.
    3. These data suggest that the opposing transcriptional activities of FoxP1 and Nfat3 maintain cardiomyocyte homeostasis.
      Title: Opposing roles of FoxP1 and Nfat3 in transcriptional control of cardiomyocyte hypertrophy.
    4. The expression of COX-2 was significantly associated with the expressions of transcription factors NFAT3 and c-Fos in nonsmall cell lung cancer.
      Title: [Expression and significance of COX-2 and its transcription factors NFAT3 and c-Jun in non-small cell lung cancer].
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Using genetic and clinical factors to predict tacrolimus dose in renal transplant recipients.
    6. an earlier unknown NFAT3/LCN2 axis that critically controls motility in breast cancer
      Title: NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene.
    7. Data show that inhibition of NFAT3 activation by shNFAT3 significantly downregulated tumor necrosis factor (TNF)-alpha induction, its receptor TNFR1, caspase 10, caspase 3, and poly (ADP-ribose) polymerase.
      Title: Doxorubicin-mediated apoptosis in glioma cells requires NFAT3.
    8. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
      Title: The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes.
    9. estrogen receptor may play a critical role in regulation of NFAT3 transcriptional activity
      Title: Repression of NFAT3 transcriptional activity by estrogen receptors.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    Submit: New GeneRIF Correction See all (19)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Hundreds of variants clustered in genomic loci and biological pathways affect human height.

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    HIV-1 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
    Tat 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 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 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

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q14934 Q92793 CREBBP    HPRD  PubMed  
    Q14934 P43694 GATA4    HPRD  PubMed  
    Q14934 Q16539 MAPK14    HPRD  PubMed  
    Q14934 P27348 YWHAQ    HPRD  PubMed  
    Q14934 P63104 YWHAZ    HPRD  PubMed  
    BioGRID:110849 BioGRID:107479 CEBPA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110849 BioGRID:107777 CREBBP    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110849 BioGRID:116787 LPIN1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110849 BioGRID:113366 YWHAZ    BioGRID  PubMed Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Axon guidance, organism-specific biosystem (from KEGG)
      Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
    • Axon guidance, conserved biosystem (from KEGG)
      Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
    • B cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      B cell receptor signaling pathway, organism-specific biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...
    • B cell receptor signaling pathway, conserved biosystem (from KEGG)
      B cell receptor signaling pathway, conserved biosystemB cells are an important component of adaptive immunity. They produce and secrete millions of different antibody molecules, each of which recognizes a different (foreign) antigen. The B cell receptor...
    • ErbB2/ErbB3 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      ErbB2/ErbB3 signaling events, organism-specific biosystem
      ErbB2/ErbB3 signaling events
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Heart Development, organism-specific biosystem (from WikiPathways)
      Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystem (from WikiPathways)
      MicroRNAs in cardiomyocyte hypertrophy, organism-specific biosystemThis pathway shows the role of microRNAs in the process of cardiac hypertrophy. MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lin...
    • Natural killer cell mediated cytotoxicity, organism-specific biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, organism-specific biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • Natural killer cell mediated cytotoxicity, conserved biosystem (from KEGG)
      Natural killer cell mediated cytotoxicity, conserved biosystemNatural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stre...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • VEGF signaling pathway, organism-specific biosystem (from KEGG)
      VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • VEGF signaling pathway, conserved biosystem (from KEGG)
      VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
    • Wnt signaling pathway, organism-specific biosystem (from KEGG)
      Wnt signaling pathway, organism-specific biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...
    • Wnt signaling pathway, conserved biosystem (from KEGG)
      Wnt signaling pathway, conserved biosystemWnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, i...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    sequence-specific DNA binding transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transcription coactivator activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    intermediate filament cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    nuclear factor of activated T-cells, cytoplasmic 4
    Names
    nuclear factor of activated T-cells, cytoplasmic 4
    NF-AT3
    T cell transcription factor NFAT3
    T-cell transcription factor NFAT3
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    NCBI Reference Sequences (RefSeq)

    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.

    mRNA and Protein(s)

    1. NM_001136022.1 → NP_001129494.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      EU887634
      Consensus CDS
      CCDS45089.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000388910, OTTHUMP00000246434, ENST00000413692, OTTHUMT00000414125
      Conserved Domains (2) summary
      cd01178
      Location:648 – 748
      Blast Score: 406
      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.
      cd07881
      Location:470 – 643
      Blast Score: 929
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

    2. NM_001198965.1 → NP_001185894.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is alternatively spliced at the 5' and 3' ends compared to transcript variant 1. This results in the use of an in-frame downstream AUG, translation termination at a downstream stop codon, and a shorter isoform (3) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC053855, DC318153, EU887634, EU887642
      Consensus CDS
      CCDS55910.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000451151, OTTHUMP00000246442, ENST00000554050, OTTHUMT00000414136
      Conserved Domains (2) summary
      cd01178
      Location:585 – 685
      Blast Score: 407
      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.
      cd07881
      Location:407 – 580
      Blast Score: 930
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

    3. NM_001198966.1 → NP_001185895.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) is alternatively spliced at the 5' and 3' ends compared to transcript variant 1. This results in the use of an in-frame downstream AUG, translation termination at a downstream stop codon, and a shorter isoform (4) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AK302271, BC053855, EU887634, EU887641
      Consensus CDS
      CCDS55911.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000452349, OTTHUMP00000246444, ENST00000553879, OTTHUMT00000414140
      Conserved Domains (2) summary
      cd01178
      Location:515 – 615
      Blast Score: 404
      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.
      cd07881
      Location:337 – 510
      Blast Score: 925
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

    4. NM_001198967.1 → NP_001185896.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) is alternatively spliced at the 3' end compared to transcript variant 1. This results in translation termination at a downstream stop codon, and a shorter isoform (5) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC053855, EU887633, EU887634
      Consensus CDS
      CCDS55909.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000452039, OTTHUMP00000246435, ENST00000554591, OTTHUMT00000414127
      Conserved Domains (2) summary
      cd01178
      Location:648 – 748
      Blast Score: 408
      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.
      cd07881
      Location:470 – 643
      Blast Score: 929
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

    5. NM_004554.4 → NP_004545.2  nuclear factor of activated T-cells, cytoplasmic 4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is alternatively spliced at the 5' and 3' ends compared to transcript variant 1. This results in the use of an in-frame downstream AUG, translation termination at a downstream stop codon, and a shorter isoform (2) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      BC008857, BC053855, DB372155, DC318153
      Consensus CDS
      CCDS9629.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000250373, OTTHUMP00000164787, ENST00000250373, OTTHUMT00000073206
      Conserved Domains (2) summary
      cd01178
      Location:585 – 685
      Blast Score: 406
      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.
      cd07881
      Location:407 – 580
      Blast Score: 929
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000014.8 Reference GRCh37.p5 Primary Assembly

      Range
      24836145..24848810
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000146.1 Alternate HuRef

      Range
      4950950..4963469
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL096870.5 (10351..21907) None
    genomic CH471078.2 EAW66020.1
    mRNA AK293185.1 BAG56726.1
    mRNA AK293873.1 BAG57262.1
    mRNA AK300450.1 BAG62171.1
    mRNA AK302271.1 BAG63617.1
    mRNA AK309339.1 None
    mRNA AK310433.1 None
    mRNA AK310445.1 None
    mRNA AK311078.1 None
    mRNA AK311425.1 None
    mRNA BC008857.2 AAH08857.2
    mRNA BC037735.1 None
    mRNA BC053855.1 AAH53855.1
    mRNA DB372155.1 None
    mRNA DC318153.1 None
    mRNA EU887632.1 ACG55652.1
    mRNA EU887633.1 ACG55653.1
    mRNA EU887634.1 ACG55654.1
    mRNA EU887635.1 ACG55655.1
    mRNA EU887636.1 ACG55656.1
    mRNA EU887637.1 ACG55657.1
    mRNA EU887638.1 ACG55658.1
    mRNA EU887639.1 ACG55659.1
    mRNA EU887640.1 ACG55660.1
    mRNA EU887641.1 ACG55661.1
    mRNA EU887642.1 ACG55662.1
    mRNA EU887643.1 ACG55663.1
    mRNA EU887644.1 ACG55664.1
    mRNA EU887645.1 ACG55665.1
    mRNA EU887646.1 ACG55666.1
    mRNA EU887647.1 ACG55667.1
    mRNA EU887648.1 ACG55668.1
    mRNA EU887649.1 ACG55669.1
    mRNA EU887650.1 ACG55670.1
    mRNA EU887651.1 ACG55671.1
    mRNA EU887652.1 ACG55672.1
    mRNA EU887653.1 ACG55673.1
    mRNA EU887654.1 ACG55674.1
    mRNA EU887655.1 ACG55675.1
    mRNA L41066.1 AAA79175.1
    other-genetic EU446638.1 ABZ92167.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14934.2 GenPept UniProtKB/Swiss-Prot:Q14934
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    Additional Links

    Gene LinkOut

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

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