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 exist... See more...

Aliases for NFAT5 Gene

Aliases for NFAT5 Gene

  • Nuclear Factor Of Activated T Cells 5 2 3 5
  • Nuclear Factor Of Activated T-Cells 5 2 3 4
  • Nuclear Factor Of Activated T-Cells 5, Tonicity-Responsive 2 3
  • Tonicity-Responsive Enhancer-Binding Protein 3 4
  • T-Cell Transcription Factor NFAT5 3 4
  • TonE-Binding Protein 3 4
  • NF-AT5 3 4
  • TONEBP 3 4
  • Tonicity-Responsive Enhancer Binding Protein 2
  • Osmotic Response Element-Binding Protein 3
  • Glutamine Rich Protein H65 3
  • NFAT-Like Protein 1 3
  • EC 3.6.3.14 52
  • KIAA0827 4
  • EC 3.6.1 52
  • NFATL1 3
  • TonEBP 4
  • NFATZ 3
  • OREBP 3

External Ids for NFAT5 Gene

Previous GeneCards Identifiers for NFAT5 Gene

  • GC16P060284
  • GC16P069977
  • GC16P069334
  • GC16P069375
  • GC16P068156
  • GC16P069599
  • GC16P055477

Summaries for NFAT5 Gene

Entrez Gene Summary for NFAT5 Gene

  • 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]

GeneCards Summary for NFAT5 Gene

NFAT5 (Nuclear Factor Of Activated T Cells 5) is a Protein Coding gene. Diseases associated with NFAT5 include Inflammatory Bowel Disease-Recurrent Sinopulmonary Infections Syndrome and Spinocerebellar Ataxia 4. Among its related pathways are ICos-ICosL Pathway in T-Helper Cell and RANK Signaling in Osteoclasts. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific. An important paralog of this gene is NFATC3.

UniProtKB/Swiss-Prot Summary for NFAT5 Gene

  • Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394).

Gene Wiki entry for NFAT5 Gene

Additional gene information for NFAT5 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NFAT5 Gene

Genomics for NFAT5 Gene

GeneHancer (GH) Regulatory Elements for NFAT5 Gene

Promoters and enhancers for NFAT5 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NFAT5 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NFAT5

Top Transcription factor binding sites by QIAGEN in the NFAT5 gene promoter:
  • AP-1
  • ATF-2

Genomic Locations for NFAT5 Gene

Genomic Locations for NFAT5 Gene
chr16:69,565,094-69,704,666
(GRCh38/hg38)
Size:
139,573 bases
Orientation:
Plus strand
chr16:69,598,997-69,738,569
(GRCh37/hg19)
Size:
139,573 bases
Orientation:
Plus strand

Genomic View for NFAT5 Gene

Genes around NFAT5 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NFAT5 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NFAT5 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NFAT5 Gene

Proteins for NFAT5 Gene

  • Protein details for NFAT5 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O94916-NFAT5_HUMAN
    Recommended name:
    Nuclear factor of activated T-cells 5
    Protein Accession:
    O94916
    Secondary Accessions:
    • A2RRB4
    • A6H8V5
    • E9PHR7
    • O95693
    • Q7LA65
    • Q969Q8
    • Q96QH3
    • Q9UN18

    Protein attributes for NFAT5 Gene

    Size:
    1531 amino acids
    Molecular mass:
    165763 Da
    Quaternary structure:
    • Homodimer when bound to DNA, completely encircles its DNA target. Interacts with CIDEC; this interaction is direct and retains NFAT5 in the cytoplasm (By similarity). Does not bind with Fos and Jun transcription factors. Interacts with DDX5 and DDX17; this interaction leads to DDX5/DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX5/DDX17-enhanced transactivation (PubMed:22266867).
    Miscellaneous:
    • [Isoform A]: The transcript encoding this isoform contains an alternative coding exon 4 which contains 2 stop codons and could target the transcript to nonsense-mediated mRNA decay after the pioneer round of translation, as suggested by the decreased NFAT5 protein levels when the number of exon 4-containing transcripts increases. The insertion of exon 4 is stimulated in the presence of DDX5 and DDX17. Isoform A sequence described in this entry starts at the first methionine downstream of exon 4 last stop codon. An alternative protein sequence can be predicted from this transcript starting at Met-1. This isoform encodes an 81 amino acid-long protein.
    • [Isoform B]: The transcript encoding this isoform contains an alternative coding exon 4 which contains 2 stop codons and could target the transcript to nonsense-mediated mRNA decay after the pioneer round of translation, as suggested by the decreased NFAT5 protein levels when the number of exon 4-containing transcripts increases. The insertion of exon 4 is stimulated in the presence of DDX5 and DDX17.
    SequenceCaution:
    • Sequence=AAK91166.1; Type=Erroneous translation; Evidence={ECO:0000305}; Sequence=AAK91166.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAA74850.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAB09693.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAC42765.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for NFAT5 Gene

    Alternative splice isoforms for NFAT5 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NFAT5 Gene

Selected DME Specific Peptides for NFAT5 Gene

O94916:
  • NQKGTGV
  • TTVIEVG

Post-translational modifications for NFAT5 Gene

  • Phosphorylated (PubMed:10377394). Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization (PubMed:21209322).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for NFAT5 Gene

Gene Families for NFAT5 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NFAT5 Gene

Blocks:
  • Cell surface receptor IPT/TIG
  • Nuclear factor of activated T cells (NFAT) signature
  • Rel homology
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NFAT5 Gene

GenScript: Design optimal peptide antigens:
  • Tonicity-responsive enhancer-binding protein (NFAT5_HUMAN)
genes like me logo Genes that share domains with NFAT5: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for NFAT5 Gene

Function for NFAT5 Gene

Molecular function for NFAT5 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394).

Enzyme Numbers (IUBMB) for NFAT5 Gene

Phenotypes From GWAS Catalog for NFAT5 Gene

Gene Ontology (GO) - Molecular Function for NFAT5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IEA,IDA 11485737
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific NAS 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 11485737
GO:0003677 DNA binding IEA --
GO:0003682 chromatin binding IBA 21873635
genes like me logo Genes that share ontologies with NFAT5: view
genes like me logo Genes that share phenotypes with NFAT5: view

Animal Models for NFAT5 Gene

MGI Knock Outs for NFAT5:

miRNA for NFAT5 Gene

miRTarBase miRNAs that target NFAT5

Clone Products

  • Addgene plasmids for NFAT5

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NFAT5 Gene

Localization for NFAT5 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NFAT5 Gene

Nucleus. Cytoplasm. Note=Nuclear distribution increases under hypertonic conditions. {ECO:0000250 UniProtKB:Q9WV30}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NFAT5 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NFAT5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IDA,TAS 12370307
GO:0005654 nucleoplasm IDA --
GO:0005667 transcription factor complex IBA 21873635
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with NFAT5: view

Pathways & Interactions for NFAT5 Gene

PathCards logo

SuperPathways for NFAT5 Gene

SuperPathway Contained pathways
1 Activation of cAMP-Dependent PKA
.77
.77
.71
.56
2 TCR Signaling (Qiagen)
.68
.68
.54
.49
3 RANK Signaling in Osteoclasts
.92
.92
.45
4 IL-2 Pathway
.48
.43
.35
5 ICos-ICosL Pathway in T-Helper Cell
.66
.66
genes like me logo Genes that share pathways with NFAT5: view

Pathways by source for NFAT5 Gene

2 GeneGo (Thomson Reuters) pathways for NFAT5 Gene
  • Immune response CD28 signaling
  • Immune response NFAT in immune response
28 Qiagen pathways for NFAT5 Gene
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • APRIL Pathway
  • BAFF in B-Cell Signaling
  • cAMP Pathway

SIGNOR curated interactions for NFAT5 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NFAT5 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001816 cytokine production IBA 21873635
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006366 transcription by RNA polymerase II IEA --
GO:0006970 response to osmotic stress IEA --
GO:0007165 signal transduction NAS 10377394
genes like me logo Genes that share ontologies with NFAT5: view

Drugs & Compounds for NFAT5 Gene

(6) Drugs for NFAT5 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(4) Additional Compounds for NFAT5 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NFAT5: view

Transcripts for NFAT5 Gene

mRNA/cDNA for NFAT5 Gene

7 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids for NFAT5

Alternative Splicing Database (ASD) splice patterns (SP) for NFAT5 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13
SP1: -
SP2:
SP3: - -
SP4: -
SP5:
SP6:
SP7: -
SP8:

Relevant External Links for NFAT5 Gene

GeneLoc Exon Structure for
NFAT5

Expression for NFAT5 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NFAT5 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NFAT5 Gene

This gene is overexpressed in Plasma (27.3), Placenta (22.9), and Retina (11.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NFAT5 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NFAT5

SOURCE GeneReport for Unigene cluster for NFAT5 Gene:

Hs.371987

mRNA Expression by UniProt/SwissProt for NFAT5 Gene:

O94916-NFAT5_HUMAN
Tissue specificity: Widely expressed, with highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes.

Evidence on tissue expression from TISSUES for NFAT5 Gene

  • Nervous system(4.8)
  • Liver(4.4)
  • Kidney(3)
  • Muscle(2.1)
  • Blood(2)
  • Heart(2)
genes like me logo Genes that share expression patterns with NFAT5: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for NFAT5 Gene

Orthologs for NFAT5 Gene

This gene was present in the common ancestor of animals.

Orthologs for NFAT5 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NFAT5 31 30
  • 99.64 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NFAT5 31 30
  • 93.62 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NFAT5 31 30
  • 93.48 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Nfat5 17 31 30
  • 90.81 (n)
rat
(Rattus norvegicus)
Mammalia Nfat5 30
  • 89.45 (n)
oppossum
(Monodelphis domestica)
Mammalia NFAT5 31
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NFAT5 31
  • 85 (a)
OneToOne
chicken
(Gallus gallus)
Aves NFAT5 31 30
  • 80.03 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NFAT5 31
  • 68 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nfat5 30
  • 68.92 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC555802 30
  • 62.94 (n)
NFAT5 (1 of 2) 31
  • 51 (a)
OneToMany
nfat5 31
  • 45 (a)
OneToMany
wufi46f11 30
fruit fly
(Drosophila melanogaster)
Insecta NFAT 31 32
  • 23 (a)
OneToMany
Species where no ortholog for NFAT5 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NFAT5 Gene

ENSEMBL:
Gene Tree for NFAT5 (if available)
TreeFam:
Gene Tree for NFAT5 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NFAT5: view image

Paralogs for NFAT5 Gene

Paralogs for NFAT5 Gene

(1) SIMAP similar genes for NFAT5 Gene using alignment to 5 proteins:

  • NFAT5_HUMAN
  • F6X8W2_HUMAN
  • H3BP21_HUMAN
  • J3KRL6_HUMAN
  • J3QKS5_HUMAN
genes like me logo Genes that share paralogs with NFAT5: view

Variants for NFAT5 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NFAT5 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
639543 Uncertain Significance: Immunodeficiency 69,692,515(+) A/G MISSENSE_VARIANT
640242 Uncertain Significance: Immunodeficiency 69,691,918(+) C/A MISSENSE_VARIANT
640834 Uncertain Significance: Immunodeficiency 69,693,477(+) C/T NONSENSE
641656 Uncertain Significance: Immunodeficiency 69,693,174(+) A/G MISSENSE_VARIANT
641918 Uncertain Significance: Immunodeficiency 69,655,768(+) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for NFAT5 Gene

Structural Variations from Database of Genomic Variants (DGV) for NFAT5 Gene

Variant ID Type Subtype PubMed ID
esv3638928 CNV gain 21293372
esv3892878 CNV gain 25118596
nsv1070771 CNV deletion 25765185
nsv1852 CNV deletion 18451855

Variation tolerance for NFAT5 Gene

Residual Variation Intolerance Score: 1.08% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.88; 35.13% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NFAT5 Gene

Human Gene Mutation Database (HGMD)
NFAT5
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NFAT5

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NFAT5 Gene

Disorders for NFAT5 Gene

MalaCards: The human disease database

(3) MalaCards diseases for NFAT5 Gene - From: Orphanet and DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search NFAT5 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NFAT5

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NFAT5: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NFAT5 Gene

Publications for NFAT5 Gene

  1. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. (PMID: 10377394) Lopez-Rodríguez C … Rao A (Proceedings of the National Academy of Sciences of the United States of America 1999) 2 3 4 23 54
  2. Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor. (PMID: 11780147) Stroud JC … Chen L (Nature structural biology 2002) 3 4 23 54
  3. Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb transcript and CpG-island analysis of the promoter region. (PMID: 11528118) Dalski A … Zühlke C (Cytogenetics and cell genetics 2001) 3 4 23 54
  4. Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity. (PMID: 10051678) Miyakawa H … Kwon HM (Proceedings of the National Academy of Sciences of the United States of America 1999) 3 4 23 54
  5. Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor. (PMID: 22266867) Germann S … Auboeuf D (Oncogene 2012) 3 4 54

Products for NFAT5 Gene