NFAT5 nuclear factor of activated T cells 5 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NFAT5provided by HGNC
Official Full Name: nuclear factor of activated T cells 5provided by HGNC
Primary source: HGNC:HGNC:7774
See related: Ensembl:ENSG00000102908 MIM:604708; AllianceGenome:HGNC:7774
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: NFATZ; OREBP; NF-AT5; NFATL1; TONEBP
Summary: The product of this gene is a member of the nuclear factors of activated T cells family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in skin (RPKM 6.6), placenta (RPKM 5.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (69565966..69704654)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (75368170..75506838)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (69599869..69738557)

Chromosome 16 - NC_000016.10 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
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?

TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.
Title: TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.
TonEBP: A Key Transcription Factor in Microglia Following Intracerebral Hemorrhage Induced-Neuroinflammation.
Title: TonEBP: A Key Transcription Factor in Microglia Following Intracerebral Hemorrhage Induced-Neuroinflammation.
TonEBP expression is essential in the IL-1beta-induced migration and invasion of human A549 lung cancer cells.
Title: TonEBP expression is essential in the IL-1β-induced migration and invasion of human A549 lung cancer cells.
SAFB2 Inhibits the Progression of Breast Cancer by Suppressing the Wnt/beta-Catenin Signaling Pathway via NFAT5.
Title: SAFB2 Inhibits the Progression of Breast Cancer by Suppressing the Wnt/β-Catenin Signaling Pathway via NFAT5.
Associations of the Methylation Levels of NFAT5, PVT1, RPS6KA1, and MIB1 with Steroid-Resistant Asthma.
Title: Associations of the Methylation Levels of NFAT5, PVT1, RPS6KA1, and MIB1 with Steroid-Resistant Asthma.
NFAT5 Controls the Integrity of Epidermis.
Title: NFAT5 Controls the Integrity of Epidermis.
Circular RNA_0037128 aggravates high glucose-induced damage in HK-2 cells via regulation of microRNA-497-5p/nuclear factor of activated T cells 5 axis.
Title: Circular RNA_0037128 aggravates high glucose-induced damage in HK-2 cells via regulation of microRNA-497-5p/nuclear factor of activated T cells 5 axis.
TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.
Title: TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.
The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases.
Title: The TLR-2/TonEBP signaling pathway regulates 29-kDa fibronectin fragment-dependent expression of matrix metalloproteinases.
PARP1-mediated PARylation of TonEBP prevents R-loop-associated DNA damage.
Title: PARP1-mediated PARylation of TonEBP prevents R-loop-associated DNA damage.

Submit: New GeneRIF Correction See all GeneRIFs (114)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide contribution of genotype by environment interaction to variation of diabetes-related traits. EBI GWAS Catalog EBI GWAS CatalogPubMed
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. 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
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
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
retropepsin	gag-pol	HIV-1 PR is identified to have a physical interaction with nuclear factor of activated T-cells 5, tonicity-responsive (NFAT5) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	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

SHGC-32665 (e-PCR)
- UniSTS:45829

NoName (e-PCR)
- UniSTS:9484

RH47171 (e-PCR)
- UniSTS:92441

D11S2560 (e-PCR)
- UniSTS:37928

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

NFAT5_227 (e-PCR)
- UniSTS:468545

RH47172 (e-PCR)
- UniSTS:83016

HUM000S343 (e-PCR)
- UniSTS:29820

SHGC-151 (e-PCR)
- UniSTS:29821

SGC32667 (e-PCR)
- UniSTS:68226

UniSTS:224902 (e-PCR)
- UniSTS:224902

SHGC-60799 (e-PCR)
- UniSTS:40350

SHGC-141495 (e-PCR)
- UniSTS:182952

SHGC-17239 (e-PCR)
- UniSTS:61619

RH123983 (e-PCR)
- UniSTS:136121

D16S2916 (e-PCR)
- UniSTS:153542

STS-W61007 (e-PCR)
- UniSTS:82168

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
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 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 chromatin binding	IDA Inferred from Direct Assay more info	PubMed
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 factor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in R-loop processing	IDA Inferred from Direct Assay more info	PubMed
involved_in calcineurin-NFAT signaling cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular hyperosmotic response	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to cytokine stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytokine production	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of leukocyte adhesion to vascular endothelial cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of calcineurin-NFAT signaling cascade	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed
involved_in transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay 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 5

Names: NFAT-like protein 1; T-cell transcription factor NFAT5; TonE-binding protein; glutamine rich protein H65; nuclear factor of activated T-cells 5, tonicity-responsive; osmotic response element-binding protein; tonicity-responsive enhancer-binding protein

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.

Genomic

NG_029600.1 RefSeqGene

Range

5873..144561

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1332

mRNA and Protein(s)

NM_001113178.3 → NP_001106649.1 nuclear factor of activated T-cells 5 isoform d

See identical proteins and their annotated locations for NP_001106649.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an exon in the 5' region and uses an alternate in-frame splice site in the central coding region, compared to variant 1. These differences result in an isoform (d) with a longer N-terminus and lacking an internal aa, compared to isoform a.

Source sequence(s)

AA291524, AC009032, AC012321, BC131509

Consensus CDS

CCDS45519.1

UniProtKB/Swiss-Prot

O94916

Related

ENSP00000457593.1, ENST00000567239.5

Conserved Domains (3) summary

cd07882
Location:298 → 458

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:462 → 561

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.

pfam03153
Location:1299 → 1460

TFIIA; Transcription factor IIA, alpha/beta subunit
NM_001367709.1 → NP_001354638.1 nuclear factor of activated T-cells 5 isoform e

Status: REVIEWED

Source sequence(s)

AC009032, AC012321
NM_006599.4 → NP_006590.1 nuclear factor of activated T-cells 5 isoform c

See identical proteins and their annotated locations for NP_006590.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two exons in the 5' region, compared to variant 1. This difference causes translation initiation at an upstream start codon and results in an isoform (c) with a longer N-terminus compared to isoform a.

Source sequence(s)

AA291524, AB020634, AC009032, AC012321

Consensus CDS

CCDS10881.1

UniProtKB/Swiss-Prot

A2RRB4, A6H8V5, E9PHR7, O94916, O95693, Q7LA65, Q969Q8, Q96QH3, Q9UN18

Related

ENSP00000346420.2, ENST00000354436.6

Conserved Domains (3) summary

cd07882
Location:280 → 440

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:444 → 543

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.

pfam03153
Location:1282 → 1443

TFIIA; Transcription factor IIA, alpha/beta subunit
NM_138713.4 → NP_619727.2 nuclear factor of activated T-cells 5 isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' region, compared to variant 1. This difference causes translation initiation at an upstream start codon and results in an isoform (b) with a longer N-terminus compared to isoform a.

Source sequence(s)

AA291524, AC009032, AC012321, AJ243299, BC131509

Consensus CDS

CCDS45518.1

UniProtKB/Swiss-Prot

O94916

Related

ENSP00000338806.3, ENST00000349945.7

Conserved Domains (2) summary

cd07882
Location:298 → 458

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:462 → 561

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_138714.4 → NP_619728.2 nuclear factor of activated T-cells 5 isoform a

See identical proteins and their annotated locations for NP_619728.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. This variant and variants 4 and 5 encode the same isoform (a).

Source sequence(s)

AA291524, AB020634, AC012321, AF346509

Conserved Domains (3) summary

cd07882
Location:204 → 364

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:368 → 467

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.

pfam03153
Location:1206 → 1367

TFIIA; Transcription factor IIA, alpha/beta subunit
NM_173214.3 → NP_775321.1 nuclear factor of activated T-cells 5 isoform a

See identical proteins and their annotated locations for NP_775321.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an exon in the 5' UTR, compared to variant 1. Variants 1, 4 and 5 encode the same isoform (a).

Source sequence(s)

AA291524, AC009032, AC012321, AF089824

Conserved Domains (3) summary

cd07882
Location:204 → 364

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:368 → 467

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.

pfam03153
Location:1206 → 1367

TFIIA; Transcription factor IIA, alpha/beta subunit
NM_173215.3 → NP_775322.1 nuclear factor of activated T-cells 5 isoform a

See identical proteins and their annotated locations for NP_775322.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' and 3' UTRs, compared to variant 1. It encodes isoform a, which is also encoded by variants 1 and 4.

Source sequence(s)

AA321843, AC009032, AC012321, AF163836, AJ005683, AJ243298

Conserved Domains (3) summary

cd07882
Location:204 → 364

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:368 → 467

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.

pfam03153
Location:1206 → 1367

TFIIA; Transcription factor IIA, alpha/beta subunit

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

69565966..69704654

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011522817.4 → XP_011521119.1 nuclear factor of activated T-cells 5 isoform X1

Conserved Domains (3) summary

cd07882
Location:280 → 440

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:444 → 543

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.

pfam03153
Location:1281 → 1442

TFIIA; Transcription factor IIA, alpha/beta subunit
XM_011522822.4 → XP_011521124.1 nuclear factor of activated T-cells 5 isoform X5

See identical proteins and their annotated locations for XP_011521124.1

Conserved Domains (3) summary

cd07882
Location:74 → 234

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:238 → 337

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.

pfam03153
Location:1076 → 1237

TFIIA; Transcription factor IIA, alpha/beta subunit
XM_047433511.1 → XP_047289467.1 nuclear factor of activated T-cells 5 isoform X2
XM_011522820.4 → XP_011521122.1 nuclear factor of activated T-cells 5 isoform X5

See identical proteins and their annotated locations for XP_011521122.1

Conserved Domains (3) summary

cd07882
Location:74 → 234

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:238 → 337

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.

pfam03153
Location:1076 → 1237

TFIIA; Transcription factor IIA, alpha/beta subunit
XM_047433510.1 → XP_047289466.1 nuclear factor of activated T-cells 5 isoform X2
XM_047433513.1 → XP_047289469.1 nuclear factor of activated T-cells 5 isoform X4
XM_047433512.1 → XP_047289468.1 nuclear factor of activated T-cells 5 isoform X3
XM_047433514.1 → XP_047289470.1 nuclear factor of activated T-cells 5 isoform X5
XM_047433515.1 → XP_047289471.1 nuclear factor of activated T-cells 5 isoform X6
XM_017022872.3 → XP_016878361.1 nuclear factor of activated T-cells 5 isoform X5

Conserved Domains (3) summary

cd07882
Location:74 → 234

RHD-n_TonEBP; N-terminal sub-domain of the Rel homology domain (RHD) of tonicity-responsive enhancer binding protein (TonEBP)

cd01178
Location:238 → 337

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.

pfam03153
Location:1076 → 1237

TFIIA; Transcription factor IIA, alpha/beta subunit

RNA

XR_007064848.1 RNA Sequence

Related

ENST00000426654.6

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

75368170..75506838

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054379401.1 → XP_054235376.1 nuclear factor of activated T-cells 5 isoform X1
XM_054379409.1 → XP_054235384.1 nuclear factor of activated T-cells 5 isoform X5
XM_054379403.1 → XP_054235378.1 nuclear factor of activated T-cells 5 isoform X2
XM_054379407.1 → XP_054235382.1 nuclear factor of activated T-cells 5 isoform X5
XM_054379402.1 → XP_054235377.1 nuclear factor of activated T-cells 5 isoform X2
XM_054379405.1 → XP_054235380.1 nuclear factor of activated T-cells 5 isoform X4
XM_054379404.1 → XP_054235379.1 nuclear factor of activated T-cells 5 isoform X3
XM_054379406.1 → XP_054235381.1 nuclear factor of activated T-cells 5 isoform X5
XM_054379410.1 → XP_054235385.1 nuclear factor of activated T-cells 5 isoform X6
XM_054379408.1 → XP_054235383.1 nuclear factor of activated T-cells 5 isoform X5