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

Summary

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; AllianceGenome:HGNC:7778
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]
Expression: Broad expression in ovary (RPKM 15.2), endometrium (RPKM 13.8) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q12

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (24366911..24379604)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (18565666..18578358)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (24836117..24848810)

Chromosome 14 - NC_000014.9 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: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
NFATC4 promotes quiescence and chemotherapy resistance in ovarian cancer.
Title: NFATC4 promotes quiescence and chemotherapy resistance in ovarian cancer.
NULP1 Alleviates Cardiac Hypertrophy by Suppressing NFAT3 Transcriptional Activity.
Title: NULP1 Alleviates Cardiac Hypertrophy by Suppressing NFAT3 Transcriptional Activity.
NFATc1 knockdown strongly reduced the number and the surface area of myotubes, NFATc4 knockdown increased the surface area of myotubes and reduced the pool of reserve cells.
Title: Distinct roles of NFATc1 and NFATc4 in human primary myoblast differentiation and in the maintenance of reserve cells.
TBX5 deficiency-mediated downregulation of NFAT3 is crucial for the high cytokine-producing activity of T cells
Title: Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial for Cytokine Expression in T Cells.
These results provided evidence supporting the oncogenic potential of NFAT3 and suggested that CDK3-mediated phosphorylation of NFAT3 has an important role in skin tumorigenesis.
Title: Phosphorylation of NFAT3 by CDK3 induces cell transformation and promotes tumor growth in skin cancer.
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.
Data indicate that RNA interference of NFAT isoforms NFATc1, NFATc2, NFATc3 and NFATc4 regulate gene expression differentially in human retinal microvascular endothelial cells (HRMEC).
Title: NFAT isoforms play distinct roles in TNFα-induced retinal leukostasis.
NFAT3 expression plays a role in regulating CXCR4 expression.
Title: Novel role for NFAT3 in ERK-mediated regulation of CXCR4.
Suggest nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-beta1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.
Title: Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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	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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NFATC4_1481 (e-PCR)
- UniSTS:277531

NFATC4_v498 (e-PCR)
- UniSTS:277531

WI-11710 (e-PCR)
- UniSTS:77342

SHGC-57765 (e-PCR)
- UniSTS:14528

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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 peroxisome proliferator activated receptor binding	IEA Inferred from Electronic Annotation more info
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 cis-regulatory region binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in brain-derived neurotrophic factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in branching involved in blood vessel morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in calcineurin-NFAT signaling cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular respiration	IEA Inferred from Electronic Annotation more info
involved_in cellular response to UV	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lithium ion	IEA Inferred from Electronic Annotation more info
involved_in dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in intrinsic apoptotic signaling pathway in response to DNA damage	IEA Inferred from Electronic Annotation more info
involved_in long-term memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of miRNA transcription	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of synapse maturation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor production	IEA Inferred from Electronic Annotation more info
involved_in synapse maturation	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in vascular associated smooth muscle cell development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nuclear speck	IDA Inferred from Direct Assay 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
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 4

Names: T-cell transcription factor NFAT3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4

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_001136022.3 → NP_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

Source sequence(s)

BC053855, DC403050, EU887634

Consensus CDS

CCDS45089.1

UniProtKB/Swiss-Prot

Q14934

Related

ENSP00000388910.2, ENST00000413692.6

Conserved Domains (2) summary

cd07881
Location:470 → 643

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

cd01178
Location:648 → 748

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_001198965.2 → NP_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

Source sequence(s)

BC053855, DC318153, EU887634, EU887642

Consensus CDS

CCDS55910.1

UniProtKB/Swiss-Prot

Q14934

Related

ENSP00000451151.1, ENST00000554050.5

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_001198966.2 → NP_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

Source sequence(s)

AK302271, BC053855, BG723088, EU887632, EU887634

Consensus CDS

CCDS55911.1

UniProtKB/Swiss-Prot

Q14934

Related

ENSP00000452349.1, ENST00000553879.5

Conserved Domains (2) summary

cd07881
Location:337 → 510

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

cd01178
Location:515 → 615

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_001198967.3 → NP_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

Source sequence(s)

BC053855, DC403050, EU887633, EU887640

Consensus CDS

CCDS55909.1

UniProtKB/Swiss-Prot

Q14934

Related

ENSP00000452039.1, ENST00000554591.5

Conserved Domains (2) summary

cd07881
Location:470 → 643

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

cd01178
Location:648 → 748

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_001288802.2 → NP_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

Source sequence(s)

AK310433, AL096870, BC053855, EU887634

Consensus CDS

CCDS73625.1

UniProtKB/Swiss-Prot

Q14934

Related

ENSP00000396788.3, ENST00000422617.7

Conserved Domains (2) summary

cd07881
Location:395 → 568

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

cd01178
Location:573 → 673

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_001320043.2 → NP_001306972.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 7

Status: REVIEWED

Source sequence(s)

AL096870, BC008857, BC053855, DC403050, EU887632

UniProtKB/Swiss-Prot

Q14934

Conserved Domains (2) summary

cd07881
Location:470 → 643

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

cd01178
Location:648 → 748

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_001363681.1 → NP_001350610.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 8

Status: REVIEWED

Source sequence(s)

AL096870, EU887644

Consensus CDS

CCDS86380.1

Related

ENSP00000450686.1, ENST00000555453.5

Conserved Domains (3) summary

cd07881
Location:395 → 568

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

cd01178
Location:573 → 673

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.

cl26464
Location:202 → 401

Atrophin-1; Atrophin-1 family
NM_001363682.1 → NP_001350611.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 9

Status: REVIEWED

Source sequence(s)

AL096870, EU887645

Consensus CDS

CCDS86379.1

Related

ENSP00000451454.1, ENST00000556169.5

Conserved Domains (3) summary

cd07881
Location:395 → 568

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

cd01178
Location:573 → 673

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.

cl26464
Location:202 → 401

Atrophin-1; Atrophin-1 family
NM_004554.5 → NP_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

Source sequence(s)

BC008857, BC053855, DB372155, DC318153

Consensus CDS

CCDS9629.1

UniProtKB/Swiss-Prot

B4DDG5, B4DY55, B5B2U7, B5B2U8, B5B2U9, B5B2V0, B5B2V1, B5B2V2, B5B2V3, B5B2V4, B5B2V5, B5B2V7, B5B2V8, B5B2V9, B5B2W0, B5B2W1, B5B2W2, B5B2W3, B5B2W4, B5B2W5, B5B2W6, B5B2W7, B5B2W8, B5B2W9, B5B2X0, Q14934, Q7Z598, Q96H68

Related

ENSP00000250373.4, ENST00000250373.9

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.