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

Summary

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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]

Genomic context

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Location :: 14q11.2

Sequence :: Chromosome: 14; NC_000014.8 (24836145..24848810)

See NFATC4 in Epigenomics, MapViewer

Chromosome 14 - NC_000014.8 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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

Data indicate that NFATc3 undergoes rapid dephosphorylation and nuclear translocation that are essentially complete within 20 min, although NFATc4 remains phosphorylated and localized to the cytosol.
Title: Distinct activation properties of the nuclear factor of activated T-cells (NFAT) isoforms NFATc3 and NFATc4 in neurons.
Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway
Title: Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway.
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.
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.
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.
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].
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.
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.
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.
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.

Submit: New GeneRIF Correction See all (21)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

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

HIV-1 protein interactions

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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, p14	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, p15	vpr	HIV-1 Vpr upregulates NFAT-directed gene expression	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	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:107340	CCNG1	BioGRID	PubMed	Two-hybrid
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:199230	Dlg4	BioGRID	PubMed	Protein-peptide
BioGRID:110849	BioGRID:109104	GPR22	BioGRID	PubMed	Two-hybrid
BioGRID:110849	BioGRID:109931	JUP	BioGRID	PubMed	Two-hybrid
BioGRID:110849	BioGRID:116787	LPIN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110849	BioGRID:111585	MAPK8	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Two-hybrid
BioGRID:110849	BioGRID:111587	MAPK9	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Two-hybrid
BioGRID:110849	BioGRID:114380	NR1I2	BioGRID	PubMed	Two-hybrid
BioGRID:110849	BioGRID:113366	YWHAZ	BioGRID	PubMed	Reconstituted Complex

Pathways from BioSystems

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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...
BDNF signaling pathway, organism-specific biosystem (from WikiPathways)
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...
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...

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

Homology

Homologs of the NFATC4 gene: The NFATC4 gene is conserved in chimpanzee, Rhesus monkey, dog, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding RNA polymerase II transcription factor activity	IEA Inferred from Electronic Annotation more info
transcription coactivator activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
cellular respiration	IEA Inferred from Electronic Annotation more info
cellular response to UV	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
muscle cell development	IEA Inferred from Electronic Annotation more info
patterning of blood vessels	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of transcription from RNA polymerase II promoter	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
cytoplasm	IDA Inferred from Direct Assay more info
cytosol	IEA Inferred from Electronic Annotation more info
intermediate filament cytoskeleton	IDA Inferred from Direct Assay more info
transcription factor complex	IEA Inferred from Electronic Annotation more info

General protein information

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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

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_001136022.1 → 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
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

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
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

ENSP00000396788, OTTHUMP00000246448, ENST00000422617, OTTHUMT00000414144

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
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

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
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: Homo sapiens Annotation Release 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000014.8 Reference GRCh37.p10 Primary Assembly

Range

24836145..24848810

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000146.1 Alternate HuRef

Range

4950950..4963469

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018925.1 Alternate CHM1_1.0

Range

5833503..5846166

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01061342.1 (12678..14377)	None
genomic	ABBA01061343.1	None
genomic	AL096870.5 (10352..21908)	None
genomic	AMYH01005611.1 (136430..149093)	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