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O94916 (NFAT5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear factor of activated T-cells 5

Short name=NF-AT5
Alternative name(s):
T-cell transcription factor NFAT5
Tonicity-responsive enhancer-binding protein
Short name=TonE-binding protein
Short name=TonEBP
Gene names
Name:NFAT5
Synonyms:KIAA0827, TONEBP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1531 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor involved in the transcriptional regulation of osmoprotective and inflammatory genes. Regulates hypertonicity-induced cellular accumulation of osmolytes.

Subunit 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. Ref.13

Subcellular location

Nucleus. Cytoplasm By similarity. Note: Nuclear distribution increases under hypertonic conditions By similarity.

Tissue specificity

Highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes. Also expressed in placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon.

Post-translational modification

Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization. Ref.12

Sequence similarities

Contains 1 RHD (Rel-like) domain.

Sequence caution

The sequence BAA74850.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAB09693.1 differs from that shown. Reason: Frameshift at position 1164.

The sequence CAC42765.1 differs from that shown. Reason: Frameshift at position 20.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DDX17Q928413EBI-308320,EBI-746012
DDX5P178444EBI-308320,EBI-351962

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform C (identifier: O94916-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform A (identifier: O94916-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.
Isoform B (identifier: O94916-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: Missing.
Isoform D (identifier: O94916-4)

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQNFHRAGLLE
     546-546: Missing.
Note: No experimental confirmation available.
Isoform E (identifier: O94916-5)

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQNFHRAGLLE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15311531Nuclear factor of activated T-cells 5
PRO_0000205183

Regions

Domain264 – 443180RHD
DNA binding293 – 3008
Compositional bias69 – 10032Ser-rich
Compositional bias739 – 7435Poly-Gln
Compositional bias879 – 88810Poly-Gln
Compositional bias966 – 9716Poly-Thr
Compositional bias1248 – 126619Poly-Gln

Amino acid modifications

Modified residue1201Phosphoserine Ref.12
Modified residue1221N6-acetyllysine By similarity
Modified residue1341Phosphoserine Ref.12
Modified residue1351Phosphothreonine; by CDK5 Ref.12
Modified residue1551Phosphoserine Ref.12

Natural variations

Alternative sequence1 – 7676Missing in isoform A.
VSP_005605
Alternative sequence1 – 4747Missing in isoform B.
VSP_005606
Alternative sequence241R → RDSLKLHPSQNFHRAGLLE in isoform D and isoform E.
VSP_043840
Alternative sequence5461Missing in isoform D.
VSP_043841

Experimental info

Mutagenesis1201S → A: Normal nuclear localization. Ref.12
Mutagenesis1341S → A: Reduced nuclear localization. Ref.12
Mutagenesis1351T → A: Reduced nuclear localization. Ref.12
Mutagenesis1551S → A: Increased nuclear localization. Ref.12
Sequence conflict666 – 6672QP → HA in AAK91166. Ref.4
Sequence conflict666 – 6672QP → HA in CAC42764. Ref.4
Sequence conflict13691E → D in CAB09693. Ref.9

Secondary structure

................................................. 1531
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform C [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: A68C68088DABF69E

FASTA1,531165,763
        10         20         30         40         50         60 
MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPS RETSVASMSQ TSGGEAGSPP 

        70         80         90        100        110        120 
PAVVAADASS APSSSSMGGA CSSFTTSSSP TIYSTSVTDS KAMQVESCSS AVGVSNRGVS 

       130        140        150        160        170        180 
EKQLTSNTVQ QHPSTPKRHT VLYISPPPED LLDNSRMSCQ DEGCGLESEQ SCSMWMEDSP 

       190        200        210        220        230        240 
SNFSNMSTSS YNDNTEVPRK SRKRNPKQRP GVKRRDCEES NMDIFDADSA KAPHYVLSQL 

       250        260        270        280        290        300 
TTDNKGNSKA GNGTLENQKG TGVKKSPMLC GQYPVKSEGK ELKIVVQPET QHRARYLTEG 

       310        320        330        340        350        360 
SRGSVKDRTQ QGFPTVKLEG HNEPVVLQVF VGNDSGRVKP HGFYQACRVT GRNTTPCKEV 

       370        380        390        400        410        420 
DIEGTTVIEV GLDPSNNMTL AVDCVGILKL RNADVEARIG IAGSKKKSTR ARLVFRVNIM 

       430        440        450        460        470        480 
RKDGSTLTLQ TPSSPILCTQ PAGVPEILKK SLHSCSVKGE EEVFLIGKNF LKGTKVIFQE 

       490        500        510        520        530        540 
NVSDENSWKS EAEIDMELFH QNHLIVKVPP YHDQHITLPV SVGIYVVTNA GRSHDVQPFT 

       550        560        570        580        590        600 
YTPDPAAAGA LNVNVKKEIS SPARPCSFEE AMKAMKTTGC NLDKVNIIPN ALMTPLIPSS 

       610        620        630        640        650        660 
MIKSEDVTPM EVTAEKRSST IFKTTKSVGS TQQTLENISN IAGNGSFSSP SSSHLPSENE 

       670        680        690        700        710        720 
KQQQIQPKAY NPETLTTIQT QDISQPGTFP AVSASSQLPN SDALLQQATQ FQTRETQSRE 

       730        740        750        760        770        780 
ILQSDGTVVN LSQLTEASQQ QQQSPLQEQA QTLQQQISSN IFPSPNSVSQ LQNTIQQLQA 

       790        800        810        820        830        840 
GSFTGSTASG SSGSVDLVQQ VLEAQQQLSS VLFSAPDGNE NVQEQLSADI FQQVSQIQSG 

       850        860        870        880        890        900 
VSPGMFSSTE PTVHTRPDNL LPGRAESVHP QSENTLSNQQ QQQQQQQQVM ESSAAMVMEM 

       910        920        930        940        950        960 
QQSICQAAAQ IQSELFPSTA SANGNLQQSP VYQQTSHMMS ALSTNEDMQM QCELFSSPPA 

       970        980        990       1000       1010       1020 
VSGNETSTTT TQQVATPGTT MFQTSSSGDG EETGTQAKQI QNSVFQTMVQ MQHSGDNQPQ 

      1030       1040       1050       1060       1070       1080 
VNLFSSTKSM MSVQNSGTQQ QGNGLFQQGN EMMSLQSGNF LQQSSHSQAQ LFHPQNPIAD 

      1090       1100       1110       1120       1130       1140 
AQNLSQETQG SLFHSPNPIV HSQTSTTSSE QMQPPMFHSQ STIAVLQGSS VPQDQQSTNI 

      1150       1160       1170       1180       1190       1200 
FLSQSPMNNL QTNTVAQEAF FAAPNSISPL QSTSNSEQQA AFQQQAPISH IQTPMLSQEQ 

      1210       1220       1230       1240       1250       1260 
AQPPQQGLFQ PQVALGSLPP NPMPQSQQGT MFQSQHSIVA MQSNSPSQEQ QQQQQQQQQQ 

      1270       1280       1290       1300       1310       1320 
QQQQQQSILF SNQNTMATMA SPKQPPPNMI FNPNQNPMAN QEQQNQSIFH QQSNMAPMNQ 

      1330       1340       1350       1360       1370       1380 
EQQPMQFQSQ STVSSLQNPG PTQSESSQTP LFHSSPQIQL VQGSPSSQEQ QVTLFLSPAS 

      1390       1400       1410       1420       1430       1440 
MSALQTSINQ QDMQQSPLYS PQNNMPGIQG ATSSPQPQAT LFHNTAGGTM NQLQNSPGSS 

      1450       1460       1470       1480       1490       1500 
QQTSGMFLFG IQNNCSQLLT SGPATLPDQL MAISQPGQPQ NEGQPPVTTL LSQQMPENSP 

      1510       1520       1530 
LASSINTNQN IEKIDLLVSL QNQGNNLTGS F 

« Hide

Isoform A [UniParc].

Checksum: 4FA637348EAC0041
Show »

FASTA1,455157,983
Isoform B [UniParc].

Checksum: F3E61D1947D310D3
Show »

FASTA1,484160,556
Isoform D [UniParc].

Checksum: 48E5072E004F9C09
Show »

FASTA1,548167,737
Isoform E [UniParc].

Checksum: 12DBBD89C630E445
Show »

FASTA1,549167,808

References

« Hide 'large scale' references
[1]"NFAT5: the NF-AT family of transcription factors expands in a new direction."
Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Copeland N.G., Gilbert D.J., Thomas S., Disteche C., Jenkins N.A., Rao A.
Cold Spring Harb. Symp. Quant. Biol. 64:517-526(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Brain.
[2]"Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity."
Miyakawa H., Woo S.K., Dahl S.C., Handler J.S., Kwon H.M.
Proc. Natl. Acad. Sci. U.S.A. 96:2538-2542(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
[3]"NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun."
Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Rao A.
Proc. Natl. Acad. Sci. U.S.A. 96:7214-7219(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
Tissue: Brain.
[4]"Genomic organization of the human NFAT5 gene: exon-intron structure of the 14-kb transcript and CpG-island analysis of the promoter region."
Dalski A., Schwinger E., Zuhlke C.
Cytogenet. Cell Genet. 93:239-241(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND E).
[5]"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
Tissue: Brain.
[6]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS C AND D).
[9]"Isolation and characterization of novel CAG repeat containing genes expressed in human brain."
Zuehlke C., Kiehl R., Johannsmeyer A., Grzeschik K.H., Schwinger E.
DNA Seq. 10:1-6(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 675-1531.
Tissue: Brain.
[10]"Mouse TonEBP-NFAT5: expression in early development and alternative splicing."
Maouyo D., Kim J.Y., Lee S.D., Wu Y., Woo S.K., Kwon H.M.
Am. J. Physiol. 282:F802-F809(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization."
Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B., Ferraris J.D.
Mol. Biol. Cell 22:703-714(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-120; SER-134; THR-135 AND SER-155, MUTAGENESIS OF SER-120; SER-134; THR-135 AND SER-155.
[13]"Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor."
Stroud J.C., Lopez-Rodriguez C., Rao A., Chen L.
Nat. Struct. Biol. 9:90-94(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 264-544 IN COMPLEX WITH DNA, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF163836 mRNA. Translation: AAD48441.1.
AF089824 mRNA. Translation: AAD18136.1.
AF134870 mRNA. Translation: AAD38360.1.
AF346509 mRNA. Translation: AAK91166.1.
AJ243298 mRNA. Translation: CAC42764.1.
AJ243299 mRNA. Translation: CAC42765.1. Frameshift.
AB020634 mRNA. Translation: BAA74850.2. Different initiation.
AC009032 Genomic DNA. No translation available.
AC012321 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83281.1.
BC131509 mRNA. Translation: AAI31510.1.
BC146765 mRNA. Translation: AAI46766.1.
Z97016 mRNA. Translation: CAB09693.1. Frameshift.
RefSeqNP_001106649.1. NM_001113178.2.
NP_006590.1. NM_006599.3.
NP_619727.2. NM_138713.3.
NP_619728.2. NM_138714.3.
NP_775321.1. NM_173214.2.
NP_775322.1. NM_173215.2.
UniGeneHs.371987.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IMHX-ray2.86C/D264-544[»]
ProteinModelPortalO94916.
SMRO94916. Positions 264-544.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115949. 3 interactions.
DIPDIP-58524N.
IntActO94916. 5 interactions.
STRING9606.ENSP00000396538.

PTM databases

PhosphoSiteO94916.

Proteomic databases

PaxDbO94916.
PRIDEO94916.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000349945; ENSP00000338806; ENSG00000102908. [O94916-2]
ENST00000354436; ENSP00000346420; ENSG00000102908. [O94916-1]
ENST00000393742; ENSP00000377343; ENSG00000102908. [O94916-2]
ENST00000432919; ENSP00000396538; ENSG00000102908. [O94916-5]
ENST00000566899; ENSP00000455628; ENSG00000102908. [O94916-2]
ENST00000567239; ENSP00000457593; ENSG00000102908. [O94916-4]
GeneID10725.
KEGGhsa:10725.
UCSCuc002exi.3. human. [O94916-1]
uc002exn.2. human. [O94916-4]

Organism-specific databases

CTD10725.
GeneCardsGC16P069599.
HGNCHGNC:7774. NFAT5.
MIM604708. gene.
neXtProtNX_O94916.
PharmGKBPA31581.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG85658.
HOGENOMHOG000236245.
HOVERGENHBG052612.
InParanoidO94916.
KOK17335.
OMANNMTLAV.
OrthoDBEOG79PJND.
PhylomeDBO94916.
TreeFamTF326480.

Gene expression databases

ArrayExpressO94916.
BgeeO94916.
CleanExHS_NFAT5.
GenevestigatorO94916.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR015646. NFAT5.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
PANTHERPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF1. PTHR12533:SF1. 1 hit.
PfamPF00554. RHD. 1 hit.
[Graphical view]
PRINTSPR01789. NUCFACTORATC.
SMARTSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNFAT5. human.
EvolutionaryTraceO94916.
GeneWikiNFAT5.
GenomeRNAi10725.
NextBio40713.
PROO94916.
SOURCESearch...

Entry information

Entry nameNFAT5_HUMAN
AccessionPrimary (citable) accession number: O94916
Secondary accession number(s): A2RRB4 expand/collapse secondary AC list , A6H8V5, E9PHR7, O95693, Q7LA65, Q969Q8, Q96QH3, Q9UN18
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM