Nfatc4 nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nfatc4provided by MGI
Official Full Name: nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 4provided by MGI
Primary source: MGI:MGI:1920431
See related: Ensembl:ENSMUSG00000023411 AllianceGenome:MGI:1920431
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Nfat3; 3110041H08Rik
Summary: Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including brain-derived neurotrophic factor receptor signaling pathway; long-term memory; and regulation of transcription by RNA polymerase II. Acts upstream of or within several processes, including circulatory system development; intracellular signal transduction; and positive regulation of apoptotic process. Located in cytosol and nucleus. Part of transcription regulator complex. Is expressed in several structures, including branchial arch; central nervous system; genitourinary system; heart; and maxillary process. Human ortholog(s) of this gene implicated in dilated cardiomyopathy. Orthologous to human NFATC4 (nuclear factor of activated T cells 4). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in limb E14.5 (RPKM 41.5), CNS E11.5 (RPKM 14.6) and 14 other tissues See more
Orthologs: human all
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Genomic context

Location:: 14 C3; 14 28.19 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	14	NC_000080.7 (56062252..56071400)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	14	NC_000080.6 (55824795..55833943)

Chromosome 14 - NC_000080.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury.
Title: NFATc4 Knockout Promotes Neuroprotection and Retinal Ganglion Cell Regeneration After Optic Nerve Injury.
The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4.
Title: The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4.
Trypanosoma cruzi down-regulates adiponectin expression in mouse adipocytes via the NFAT signaling pathway.
Title: Trypanosoma cruzi down-regulates adiponectin expression in mouse adipocytes via the NFAT signaling pathway.
Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination.
Title: Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination.
Nfatc4 Deficiency Attenuates Ototoxicity by Suppressing Tnf-Mediated Hair Cell Apoptosis in the Mouse Cochlea.
Title: Nfatc4 Deficiency Attenuates Ototoxicity by Suppressing Tnf-Mediated Hair Cell Apoptosis in the Mouse Cochlea.
BDNF regulates the timing of neurodevelopment via a novel mechanism of extranuclear sequestration of NFATc4 in Golgi. This leads to accelerated derepression of an NFI temporal occupancy gene program in cerebellar granule cells that includes Bdnf itself, revealing an autoregulatory loop within the program driven by BDNF and NFATc4.
Title: BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4.
Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons.
Title: Neuritin Up-regulates Kv4.2 α-Subunit of Potassium Channel Expression and Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway.
Nfatc4 expression was coordinately upregulated by top hypoxia-activated transcription factors, while NFATc4 target genes were enriched in hypoxic neural stem cells.
Title: Transcriptional Profiling of Hypoxic Neural Stem Cells Identifies Calcineurin-NFATc4 Signaling as a Major Regulator of Neural Stem Cell Biology.
results indicate that NFAT is a BACE1 transcription factor. Our study suggests that inhibition of NFAT-mediated BACE1 expression may be a valuable drug target for AD therapy
Title: Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing.
our results suggest that activation of NHE1 induces hypertrophy through the activation of NFAT3/Gata4 and OPN expression
Title: Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4.

Submit: New GeneRIF Correction See all GeneRIFs (41)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW107667 (e-PCR)
- UniSTS:180637

Nfatc4 (e-PCR), detects polymorphism
- UniSTS:499102

PMC135666P1 (e-PCR)
- UniSTS:270770

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
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	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
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 peroxisome proliferator activated receptor binding	IEA Inferred from Electronic Annotation more info
enables peroxisome proliferator activated receptor binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription factor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in brain-derived neurotrophic factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within branching involved in blood vessel morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in calcineurin-NFAT signaling cascade	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within calcineurin-NFAT signaling cascade	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cellular respiration	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to UV	IGI Inferred from Genetic Interaction more info	PubMed
involved_in cellular response to ionomycin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to lithium ion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to DNA damage	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of chromatin binding	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of dendrite morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of miRNA transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of miRNA transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein binding	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of synapse maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within 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	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of synaptic plasticity	ISO Inferred from Sequence Orthology more info
acts_upstream_of synapse maturation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within vascular associated smooth muscle cell development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within vascular associated smooth muscle cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in nuclear speck	IEA Inferred from Electronic Annotation more info
located_in nuclear speck	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of transcription regulator complex	IBA Inferred from Biological aspect of Ancestor more info
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: nuclear factor of activated T-cells, cytoplasmic 4

Names: NF-AT3; NF-ATc4; T-cell transcription factor NFAT3; transcription complex subunit NF-ATc4

NCBI Reference Sequences (RefSeq)

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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)

NM_001168346.1 → NP_001161818.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 2

See identical proteins and their annotated locations for NP_001161818.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) has an additional segment in the 3' region, as compared to variant 1. The resulting isoform (2) is shorter and has a different C-terminus, as compared to isoform 1.

Source sequence(s)

AW493556, CJ067971, EU887657

Consensus CDS

CCDS49500.1

UniProtKB/TrEMBL

A0A2I3BRR0

Related

ENSMUSP00000132763.2, ENSMUST00000172271.9

Conserved Domains (2) summary

cd07881
Location:407 → 580

RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

cd01178
Location:585 → 685

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.
NM_023699.3 → NP_076188.3 nuclear factor of activated T-cells, cytoplasmic 4 isoform 1

See identical proteins and their annotated locations for NP_076188.3

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AK159078, AW493556, CJ067971

Consensus CDS

CCDS27132.1

UniProtKB/Swiss-Prot

B5B2X2, Q3TXW7, Q8K120, Q9EP91

UniProtKB/TrEMBL

A0A2I3BRR0

Related

ENSMUSP00000024179.6, ENSMUST00000024179.6

Conserved Domains (2) summary

cd07881
Location:407 → 580

RHD-n_NFAT; N-terminal sub-domain of the Rel homology domain (RHD) of nuclear factor of activated T-cells (NFAT) proteins

cd01178
Location:585 → 685

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.