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    NFATC4 nuclear factor of activated T-cells 4 [ Homo sapiens (human) ]

    Gene ID: 4776, updated on 9-Jul-2017
    Official Symbol
    NFATC4provided by HGNC
    Official Full Name
    nuclear factor of activated T-cells 4provided by HGNC
    Primary source
    HGNC:HGNC:7778
    See related
    Ensembl:ENSG00000100968 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-AT3; NF-ATC4
    Summary
    This gene encodes a member of the nuclear factor of activated T cells (NFAT) protein family. The encoded protein is part of a 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 stimulation and an inducible nuclear component. NFAT proteins are activated by the calmodulin-dependent phosphatase, calcineurin. The encoded protein plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of interleukin-2 and interleukin-4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
    Orthologs
    Location:
    14q12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 14 NC_000014.9 (24366911..24379604)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (24834885..24848810)

    Chromosome 14 - NC_000014.9Genomic 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 KH and NYN domain containing Neighboring gene cerebellin 3 precursor

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
    NHGRI GWA Catalog
    Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    NHGRI GWA Catalog

    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 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 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
    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

    • 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...
    • Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystem (from WikiPathways)
      Brain-Derived Neurotrophic Factor (BDNF) signaling pathway, organism-specific biosystemBrain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, b...
    • 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...
    • Hepatitis B, organism-specific biosystem (from KEGG)
      Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
    • Initiation of transcription and translation elongation at the HIV-1 LTR, organism-specific biosystem (from WikiPathways)
      Initiation of transcription and translation elongation at the HIV-1 LTR, organism-specific biosystemFollowing cellular activation or drug treatment, NFAT and NF-kB translocate to the nucleus and bind sites at the HIV-1 LTR. NFAT and NF-kB recruit p300/CBP to the LTR, resulting in acetylation of his...
    • 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...
    • Oxytocin signaling pathway, organism-specific biosystem (from KEGG)
      Oxytocin signaling pathway, organism-specific biosystemOxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and ...
    • Oxytocin signaling pathway, conserved biosystem (from KEGG)
      Oxytocin signaling pathway, conserved biosystemOxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and ...
    • Physiological and Pathological Hypertrophy of the Heart, organism-specific biosystem (from WikiPathways)
      Physiological and Pathological Hypertrophy of the Heart, organism-specific biosystemPathways in physiological and pathological hypertrophy of the heart. Largely based on the article from Wang Y; ''Signal transduction in cardiac hypertrophy--dissecting compensatory versus pathologica...
    • 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...
    • cGMP-PKG signaling pathway, organism-specific biosystem (from KEGG)
      cGMP-PKG signaling pathway, organism-specific biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...
    • cGMP-PKG signaling pathway, conserved biosystem (from KEGG)
      cGMP-PKG signaling pathway, conserved biosystemCyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated i...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    branching involved in blood vessel morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    calcineurin-NFAT signaling cascade IEA
    Inferred from Electronic Annotation
    more info
     
    cellular respiration IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to UV IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to ionomycin IEA
    Inferred from Electronic Annotation
    more info
     
    cellular response to lithium ion IEA
    Inferred from Electronic Annotation
    more info
     
    heart development IEA
    Inferred from Electronic Annotation
    more info
     
    inflammatory response TAS
    Traceable Author Statement
    more info
    PubMed 
    intrinsic apoptotic signaling pathway in response to DNA damage IEA
    Inferred from Electronic Annotation
    more info
     
    muscle cell development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of dendrite morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of pri-miRNA transcription from RNA polymerase II promoter IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    negative regulation of protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of synapse maturation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of tumor necrosis factor production IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of synaptic plasticity IEA
    Inferred from Electronic Annotation
    more info
     
    smooth muscle cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    nuclear speck IDA
    Inferred from Direct Assay
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    nuclear factor of activated T-cells, cytoplasmic 4
    Names
    T-cell transcription factor NFAT3
    nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4

    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_001136022.2NP_001129494.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 1

      See identical proteins and their annotated locations for NP_001129494.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes isoform (1).
      Source sequence(s)
      BC053855, DC403050, EU887634
      Consensus CDS
      CCDS45089.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000388910.2, OTTHUMP00000246434, ENST00000413692.6, OTTHUMT00000414125
      Conserved Domains (2) summary
      cd07881
      Location:470643
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:648748
      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_001198965.1NP_001185894.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 3

      See identical proteins and their annotated locations for NP_001185894.1

      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
      ENSP00000451151.1, OTTHUMP00000246442, ENST00000554050.5, OTTHUMT00000414136
      Conserved Domains (2) summary
      cd07881
      Location:407580
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:585685
      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_001198966.2NP_001185895.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 4

      See identical proteins and their annotated locations for NP_001185895.1

      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, BG723088, EU887632, EU887634
      Consensus CDS
      CCDS55911.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000452349.1, OTTHUMP00000246444, ENST00000553879.5, OTTHUMT00000414140
      Conserved Domains (2) summary
      cd07881
      Location:337510
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:515615
      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.
    4. NM_001198967.2NP_001185896.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 5

      See identical proteins and their annotated locations for NP_001185896.1

      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, DC403050, EU887633, EU887640
      Consensus CDS
      CCDS55909.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000452039.1, OTTHUMP00000246435, ENST00000554591.5, OTTHUMT00000414127
      Conserved Domains (2) summary
      cd07881
      Location:470643
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:648748
      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.
    5. NM_001288802.1NP_001275731.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 6

      See identical proteins and their annotated locations for NP_001275731.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks part of the 5' coding region, contains an alternate 5'-terminal exon, and initiates translation from an alternate start codon, compared to variant 1. The encoded isoform (6) has a shorter and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AK310433, BC053855, EU887634
      Consensus CDS
      CCDS73625.1
      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000396788.3, OTTHUMP00000246448, ENST00000422617.7, OTTHUMT00000414144
      Conserved Domains (2) summary
      cd07881
      Location:395568
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:573673
      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.
    6. NM_001320043.1NP_001306972.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) is alternatively spliced at the 3' end compared to transcript variant 1. This results in translation termination at a downstream stop codon, and a longer isoform (7) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AL096870, BC008857, BC053855, DC403050, EU887632
      UniProtKB/Swiss-Prot
      Q14934
      Conserved Domains (2) summary
      cd07881
      Location:470643
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:648748
      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.
    7. NM_004554.4NP_004545.2  nuclear factor of activated T-cells, cytoplasmic 4 isoform 2

      See identical proteins and their annotated locations for NP_004545.2

      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
      ENSP00000250373.4, OTTHUMP00000164787, ENST00000250373.8, OTTHUMT00000073206
      Conserved Domains (2) summary
      cd07881
      Location:407580
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:585685
      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: Homo sapiens Annotation Release 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000014.9 Reference GRCh38.p7 Primary Assembly

      Range
      24366911..24379604
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011536798.1XP_011535100.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform X2

      Conserved Domains (2) summary
      cd07881
      Location:384557
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:562662
      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. XM_011536799.2XP_011535101.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform X3

      See identical proteins and their annotated locations for XP_011535101.1

      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000451454.1, OTTHUMP00000246449, ENST00000556169.5, OTTHUMT00000414145
      Conserved Domains (2) summary
      cd07881
      Location:395568
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:573673
      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. XM_011536797.2XP_011535099.1  nuclear factor of activated T-cells, cytoplasmic 4 isoform X1

      See identical proteins and their annotated locations for XP_011535099.1

      UniProtKB/Swiss-Prot
      Q14934
      Related
      ENSP00000450686.1, OTTHUMP00000246450, ENST00000555453.5, OTTHUMT00000414146
      Conserved Domains (2) summary
      cd07881
      Location:395568
      RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins
      cd01178
      Location:573673
      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.

    Alternate CHM1_1.1

    Genomic

    1. NC_018925.2 Alternate CHM1_1.1

      Range
      24834694..24847385
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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