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Q9WV30 (NFAT5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
Rel domain-containing transcription factor NFAT5
T-cell transcription factor NFAT5
Gene names
Name:Nfat5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1534 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. Ref.2 Ref.6

Subunit structure

Homodimer when bound to DNA, completely encircles its DNA target. Does not bind with Fos and Jun transcription factors. Interacts with CIDEC; this interaction is direct and retains NFAT5 in the cytoplasm By similarity.

Subcellular location

Nucleus. Cytoplasm. Note: Nuclear distribution increases under hypertonic conditions. Ref.2

Tissue specificity

Detected in white and brown adipose tissue, muscle, heart, liver and kidney. Expressed in lymphocytes (at protein level). Ref.6 Ref.7

Developmental stage

At 10.5 dpc, expressed in brain and developing lens. At 12.5 dpc, the expression is extended to liver. By 17.5 dpc, expressed abundantly in brain, spinal cord, heart end liver and moderately in salivary gland, lung, kidney, gut and bladder (at protein level). Ref.2

Induction

Up-regulated upon hypertonic conditions, this up-regulation in not observed in ES cells. Ref.2 Ref.7

Post-translational modification

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

Disruption phenotype

Embryonic and perinatal lethality with incomplete penetrance. At 17.5 dpc, 50% of the expected Mendelian rate with only 3.4% of the expected number living past 21 days after birth. The few survivors to adulthood fail to thrive and their weight is half compared to the wild-type. At 3 weeks old, kidney hypoplasia and an altered medullary morphology are observed with an increased apoptosis in the kidney inner medulla. Under osmotic stress, the transcriptional regulation of osmoprotective genes is altered in the kidney medulla. Ref.6

Sequence similarities

Contains 1 RHD (Rel-like) domain.

Sequence caution

The sequence AAF31405.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence EDL11405.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9WV30-1)

Also known as: C;

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.
Note: May have longer half-life and is more efficient in stimulation of transcription than isoform 3.
Isoform 2 (identifier: Q9WV30-2)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQTFHRAGLLE
Isoform 3 (identifier: Q9WV30-3)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.
Isoform 4 (identifier: Q9WV30-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1213-1225: VALGSLPPNPMPQ → ESLHSHITPDACK
     1226-1534: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15341534Nuclear factor of activated T-cells 5
PRO_0000205184

Regions

Domain264 – 443180RHD
DNA binding293 – 3008 By similarity
Compositional bias69 – 10032Ser-rich
Compositional bias647 – 6537Poly-Ser
Compositional bias738 – 7414Poly-Gln
Compositional bias876 – 88510Poly-Gln
Compositional bias963 – 9686Poly-Thr

Amino acid modifications

Modified residue1201Phosphoserine By similarity
Modified residue1221N6-acetyllysine Ref.8
Modified residue1341Phosphoserine By similarity
Modified residue1351Phosphothreonine; by CDK5 By similarity
Modified residue1551Phosphoserine By similarity

Natural variations

Alternative sequence1 – 7676Missing in isoform 3.
VSP_053211
Alternative sequence241R → RDSLKLHPSQTFHRAGLLE in isoform 2.
VSP_053212
Alternative sequence1213 – 122513VALGS…NPMPQ → ESLHSHITPDACK in isoform 4.
VSP_053213
Alternative sequence1226 – 1534309Missing in isoform 4.
VSP_053214

Experimental info

Sequence conflict1081C → G in AAK97603. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (C) [UniParc].

Last modified October 16, 2013. Version 2.
Checksum: 996904A84D3A7AFE

FASTA1,534165,800
        10         20         30         40         50         60 
MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPP RETSVASMSQ TSGGEAGSPP 

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

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

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

       250        260        270        280        290        300 
TTDNKGNSKA GNGTLDSQKG 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 ARLVFRVNIT 

       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 
YTPDPAAGAL NVNVKKEISS PARPCSFEEA MKAMKTTGCN VDKVTILPNA LITPLISSSM 

       610        620        630        640        650        660 
IKTEDVTPME VTSEKRSSPI FQTTKSIGST QQTLETISNI AGGAPFSSPS SSSHLTPESE 

       670        680        690        700        710        720 
NQQQLQPKAY NPETLTTIQT QDISQPGTFP AVSAASQLPS SDALLQQATQ FQTREAQSRD 

       730        740        750        760        770        780 
TIQSDTVVNL SQLTEASQQQ QSPLQEQAQT LQQQIPSNIF PSPSSVSQLQ STIQQLQAGS 

       790        800        810        820        830        840 
FTGSAAGGRS GSVDLVQQVL EAQQQLSSVL FSTPDGNENV QEQLNADIFQ VSQIQNSVSP 

       850        860        870        880        890        900 
GMFSSAESAV HTRPDNLLPG RADSVHQQTE NTLSNQQQQQ QQQQQVMESS AAMVMEMQQS 

       910        920        930        940        950        960 
ICQAAAQIQS ELFPSAASAS GSLQQSPVYQ QPSHMMSALP TNEDMQMQCE LFSSPPAASG 

       970        980        990       1000       1010       1020 
NETSTTTTPQ VATPGSTMFQ TPSSGDGEET GAQAKQIQNS VFQTMVQMQR SGDSQPQVNL 

      1030       1040       1050       1060       1070       1080 
FSSTKNIMSV QNNGTQQQGN SLFQQGSEMM SLQSGNFLQQ SSHSQAQLFH PQNPIADAQN 

      1090       1100       1110       1120       1130       1140 
LSQETQGSIF HSPNPIVHSQ TSTASSEQLQ PSMFHSQNTI AVLQGSSVPQ DQQSPNIFLS 

      1150       1160       1170       1180       1190       1200 
QSSINNLQTN TVAQEEQISF FAAQNSISPL QSTSNTEQQA AFQQQPPISH IQTPILSQEQ 

      1210       1220       1230       1240       1250       1260 
AQPSQQGLFQ PQVALGSLPP NPMPQNQQGP IFQTQRPIVG MQSNSPSQEQ QQQQQQQQQQ 

      1270       1280       1290       1300       1310       1320 
QQQQQQQQQS ILFSNQNAMA TMASQKQPPP NMMFSPNQNP MASQEQQNQS IFHQQSNMAP 

      1330       1340       1350       1360       1370       1380 
MNQEQQPMQF QNQPTVSSLQ NPGPTQSESP QTSLFHSSPQ IQLVQGSPSS QDQQVTLFLS 

      1390       1400       1410       1420       1430       1440 
PASMSALQTS INQPDMQQSP LYSPQNNIPG IQGSTSSPQP QATLFHNTTG GTINQIQNSP 

      1450       1460       1470       1480       1490       1500 
GSSQQTSGMF LFGIQNNCSQ LLTSGPATLP DQLMAINQQG QPQNEGQSSV TTLLSQQMPE 

      1510       1520       1530 
TSPLASSVNS SQNMEKIDLL VSLQSQGNNL TGSF 

« Hide

Isoform 2 (D) [UniParc].

Checksum: E387B2F80B28E788
Show »

FASTA1,552167,832
Isoform 3 (A) [UniParc].

Checksum: 108F6CCD85985A12
Show »

FASTA1,458158,010
Isoform 4 [UniParc].

Checksum: 6A91537E7949A527
Show »

FASTA1,225132,192

References

« Hide 'large scale' references
[1]"Identification of NFAT5, a new rel-like transcription factor."
Lu J., Xu H., Olson E.N.
Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
[2]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, FUNCTION, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, INDUCTION.
Tissue: Brain.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] OF 13-1534 (ISOFORM 2).
Tissue: Skeletal muscle.
[6]"Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression."
Lopez-Rodriguez C., Antos C.L., Shelton J.M., Richardson J.A., Lin F., Novobrantseva T.I., Bronson R.T., Igarashi P., Rao A., Olson E.N.
Proc. Natl. Acad. Sci. U.S.A. 101:2392-2397(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RENAL HOMEOSTASIS, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[7]"Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress."
Ueno M., Shen W.J., Patel S., Greenberg A.S., Azhar S., Kraemer F.B.
J. Lipid Res. 54:734-743(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION BY OSMOTIC STRESS.
[8]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-122, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF162853 mRNA. Translation: AAD44343.1.
AF369980 mRNA. Translation: AAK97603.1.
AC125207 Genomic DNA. No translation available.
AC158364 Genomic DNA. No translation available.
CH466525 Genomic DNA. Translation: EDL11404.1.
CH466525 Genomic DNA. Translation: EDL11405.1. Sequence problems.
AF200687 mRNA. Translation: AAF31405.1. Different initiation.
CCDSCCDS22648.2. [Q9WV30-2]
CCDS40464.1. [Q9WV30-3]
CCDS72168.1. [Q9WV30-4]
RefSeqNP_001273189.1. NM_001286260.1. [Q9WV30-4]
NP_061293.2. NM_018823.2. [Q9WV30-2]
NP_598718.2. NM_133957.3. [Q9WV30-3]
XP_006531255.1. XM_006531192.1. [Q9WV30-1]
UniGeneMm.390057.

3D structure databases

ProteinModelPortalQ9WV30.
SMRQ9WV30. Positions 264-544.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000119370.

PTM databases

PhosphoSiteQ9WV30.

Proteomic databases

MaxQBQ9WV30.
PaxDbQ9WV30.
PRIDEQ9WV30.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000075922; ENSMUSP00000075311; ENSMUSG00000003847. [Q9WV30-4]
ENSMUST00000077440; ENSMUSP00000076653; ENSMUSG00000003847. [Q9WV30-3]
ENSMUST00000125721; ENSMUSP00000116094; ENSMUSG00000003847. [Q9WV30-1]
ENSMUST00000151114; ENSMUSP00000119370; ENSMUSG00000003847. [Q9WV30-2]
ENSMUST00000169453; ENSMUSP00000127784; ENSMUSG00000003847. [Q9WV30-2]
GeneID54446.
KEGGmmu:54446.
UCSCuc009nhl.2. mouse.
uc009nhm.2. mouse. [Q9WV30-1]
uc012gkd.1. mouse.

Organism-specific databases

CTD10725.
MGIMGI:1859333. Nfat5.

Phylogenomic databases

eggNOGNOG85658.
GeneTreeENSGT00550000074562.
HOGENOMHOG000236245.
HOVERGENHBG052612.
InParanoidQ91WY0.
KOK17335.
OMANNMTLAV.
OrthoDBEOG79PJND.
TreeFamTF326480.

Gene expression databases

ArrayExpressQ9WV30.
BgeeQ9WV30.
CleanExMM_NFAT5.
GenevestigatorQ9WV30.

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:SF7. PTHR12533:SF7. 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. mouse.
NextBio311314.
PROQ9WV30.
SOURCESearch...

Entry information

Entry nameNFAT5_MOUSE
AccessionPrimary (citable) accession number: Q9WV30
Secondary accession number(s): E9Q0P3 expand/collapse secondary AC list , E9Q6U2, G5E8N9, Q91WY0, Q9JLA1
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 16, 2013
Last modified: July 9, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot