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Protein

Nuclear factor of activated T-cells 5

Gene

Nfat5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor involved in the transcriptional regulation of osmoprotective and inflammatory genes. Regulates hypertonicity-induced cellular accumulation of osmolytes.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi293 – 3008By similarity

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
  4. sequence-specific DNA binding transcription factor activity Source: MGI

GO - Biological processi

  1. cytokine production Source: MGI
  2. positive regulation of gene expression Source: MGI
  3. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  4. regulation of calcineurin-NFAT signaling cascade Source: MGI
  5. transcription, DNA-templated Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Nfat5
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 8

Organism-specific databases

MGIiMGI:1859333. Nfat5.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication
Note: Nuclear distribution increases under hypertonic conditions.

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15341534Nuclear factor of activated T-cells 5PRO_0000205184Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei120 – 1201PhosphoserineBy similarity
Modified residuei122 – 1221N6-acetyllysine1 Publication
Modified residuei134 – 1341PhosphoserineBy similarity
Modified residuei135 – 1351Phosphothreonine; by CDK5By similarity
Modified residuei155 – 1551PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9WV30.
PaxDbiQ9WV30.
PRIDEiQ9WV30.

PTM databases

PhosphoSiteiQ9WV30.

Expressioni

Tissue specificityi

Detected in white and brown adipose tissue, muscle, heart, liver and kidney. Expressed in lymphocytes (at protein level).2 Publications

Developmental stagei

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).1 Publication

Inductioni

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

Gene expression databases

BgeeiQ9WV30.
CleanExiMM_NFAT5.
ExpressionAtlasiQ9WV30. baseline and differential.
GenevestigatoriQ9WV30.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000119370.

Structurei

3D structure databases

ProteinModelPortaliQ9WV30.
SMRiQ9WV30. Positions 264-544.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini264 – 443180RHDPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi69 – 10032Ser-richAdd
BLAST
Compositional biasi647 – 6537Poly-Ser
Compositional biasi738 – 7414Poly-Gln
Compositional biasi876 – 88510Poly-Gln
Compositional biasi963 – 9686Poly-Thr

Sequence similaritiesi

Contains 1 RHD (Rel-like) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG85658.
GeneTreeiENSGT00550000074562.
HOGENOMiHOG000236245.
HOVERGENiHBG052612.
InParanoidiQ9WV30.
KOiK17335.
OMAiFGIQNNC.
OrthoDBiEOG79PJND.
TreeFamiTF326480.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR015646. NFAT5.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF7. PTHR12533:SF7. 1 hit.
PfamiPF00554. RHD. 1 hit.
[Graphical view]
PRINTSiPR01789. NUCFACTORATC.
SMARTiSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50254. REL_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist. Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q9WV30-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPP RETSVASMSQ
60 70 80 90 100
TSGGEAGSPP PAVVAADASS APSSSSMGGA CSSFTTSSSP TIYSTSVTDS
110 120 130 140 150
KAMQVESCSS AVGVSNRGVS EKQLTGNTVQ QHPSTPKRHT VLYISPPPED
160 170 180 190 200
LLDNSRMSCQ DEGCGLESEQ SCSMWMEDSP SNFSNMSTSS YNDNTEVPRK
210 220 230 240 250
SRKRNPKQRP GVKRRDCEES NMDIFDADSA KAPHYVLSQL TTDNKGNSKA
260 270 280 290 300
GNGTLDSQKG TGVKKSPMLC GQYPVKSEGK ELKIVVQPET QHRARYLTEG
310 320 330 340 350
SRGSVKDRTQ QGFPTVKLEG HNEPVVLQVF VGNDSGRVKP HGFYQACRVT
360 370 380 390 400
GRNTTPCKEV DIEGTTVIEV GLDPSNNMTL AVDCVGILKL RNADVEARIG
410 420 430 440 450
IAGSKKKSTR ARLVFRVNIT RKDGSTLTLQ TPSSPILCTQ PAGVPEILKK
460 470 480 490 500
SLHSCSVKGE EEVFLIGKNF LKGTKVIFQE NVSDENSWKS EAEIDMELFH
510 520 530 540 550
QNHLIVKVPP YHDQHITLPV SVGIYVVTNA GRSHDVQPFT YTPDPAAGAL
560 570 580 590 600
NVNVKKEISS PARPCSFEEA MKAMKTTGCN VDKVTILPNA LITPLISSSM
610 620 630 640 650
IKTEDVTPME VTSEKRSSPI FQTTKSIGST QQTLETISNI AGGAPFSSPS
660 670 680 690 700
SSSHLTPESE NQQQLQPKAY NPETLTTIQT QDISQPGTFP AVSAASQLPS
710 720 730 740 750
SDALLQQATQ FQTREAQSRD TIQSDTVVNL SQLTEASQQQ QSPLQEQAQT
760 770 780 790 800
LQQQIPSNIF PSPSSVSQLQ STIQQLQAGS FTGSAAGGRS GSVDLVQQVL
810 820 830 840 850
EAQQQLSSVL FSTPDGNENV QEQLNADIFQ VSQIQNSVSP GMFSSAESAV
860 870 880 890 900
HTRPDNLLPG RADSVHQQTE NTLSNQQQQQ QQQQQVMESS AAMVMEMQQS
910 920 930 940 950
ICQAAAQIQS ELFPSAASAS GSLQQSPVYQ QPSHMMSALP TNEDMQMQCE
960 970 980 990 1000
LFSSPPAASG NETSTTTTPQ VATPGSTMFQ TPSSGDGEET GAQAKQIQNS
1010 1020 1030 1040 1050
VFQTMVQMQR SGDSQPQVNL FSSTKNIMSV QNNGTQQQGN SLFQQGSEMM
1060 1070 1080 1090 1100
SLQSGNFLQQ SSHSQAQLFH PQNPIADAQN LSQETQGSIF HSPNPIVHSQ
1110 1120 1130 1140 1150
TSTASSEQLQ PSMFHSQNTI AVLQGSSVPQ DQQSPNIFLS QSSINNLQTN
1160 1170 1180 1190 1200
TVAQEEQISF FAAQNSISPL QSTSNTEQQA AFQQQPPISH IQTPILSQEQ
1210 1220 1230 1240 1250
AQPSQQGLFQ PQVALGSLPP NPMPQNQQGP IFQTQRPIVG MQSNSPSQEQ
1260 1270 1280 1290 1300
QQQQQQQQQQ QQQQQQQQQS ILFSNQNAMA TMASQKQPPP NMMFSPNQNP
1310 1320 1330 1340 1350
MASQEQQNQS IFHQQSNMAP MNQEQQPMQF QNQPTVSSLQ NPGPTQSESP
1360 1370 1380 1390 1400
QTSLFHSSPQ IQLVQGSPSS QDQQVTLFLS PASMSALQTS INQPDMQQSP
1410 1420 1430 1440 1450
LYSPQNNIPG IQGSTSSPQP QATLFHNTTG GTINQIQNSP GSSQQTSGMF
1460 1470 1480 1490 1500
LFGIQNNCSQ LLTSGPATLP DQLMAINQQG QPQNEGQSSV TTLLSQQMPE
1510 1520 1530
TSPLASSVNS SQNMEKIDLL VSLQSQGNNL TGSF

Note: May have longer half-life and is more efficient in stimulation of transcription than isoform 3.

Length:1,534
Mass (Da):165,800
Last modified:October 16, 2013 - v2
Checksum:i996904A84D3A7AFE
GO
Isoform 2 (identifier: Q9WV30-2) [UniParc]FASTAAdd to basket

Also known as: D

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

Show »
Length:1,552
Mass (Da):167,832
Checksum:iE387B2F80B28E788
GO
Isoform 3 (identifier: Q9WV30-3) [UniParc]FASTAAdd to basket

Also known as: A

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.

Show »
Length:1,458
Mass (Da):158,010
Checksum:i108F6CCD85985A12
GO
Isoform 4 (identifier: Q9WV30-4) [UniParc]FASTAAdd to basket

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

Show »
Length:1,225
Mass (Da):132,192
Checksum:i6A91537E7949A527
GO

Sequence cautioni

The sequence AAF31405.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EDL11405.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti108 – 1081C → G in AAK97603 (PubMed:11934689).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7676Missing in isoform 3. 1 PublicationVSP_053211Add
BLAST
Alternative sequencei24 – 241R → RDSLKLHPSQTFHRAGLLE in isoform 2. 1 PublicationVSP_053212
Alternative sequencei1213 – 122513VALGS…NPMPQ → ESLHSHITPDACK in isoform 4. 1 PublicationVSP_053213Add
BLAST
Alternative sequencei1226 – 1534309Missing in isoform 4. 1 PublicationVSP_053214Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS22648.2. [Q9WV30-2]
CCDS40464.1. [Q9WV30-3]
CCDS72168.1. [Q9WV30-4]
RefSeqiNP_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]
UniGeneiMm.390057.

Genome annotation databases

EnsembliENSMUST00000075922; ENSMUSP00000075311; ENSMUSG00000003847. [Q9WV30-4]
ENSMUST00000077440; ENSMUSP00000076653; ENSMUSG00000003847. [Q9WV30-3]
ENSMUST00000125721; ENSMUSP00000116094; ENSMUSG00000003847. [Q9WV30-1]
ENSMUST00000151114; ENSMUSP00000119370; ENSMUSG00000003847. [Q9WV30-2]
ENSMUST00000169453; ENSMUSP00000127784; ENSMUSG00000003847. [Q9WV30-2]
GeneIDi54446.
KEGGimmu:54446.
UCSCiuc009nhl.2. mouse.
uc009nhm.2. mouse. [Q9WV30-1]
uc012gkd.1. mouse.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS22648.2. [Q9WV30-2]
CCDS40464.1. [Q9WV30-3]
CCDS72168.1. [Q9WV30-4]
RefSeqiNP_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]
UniGeneiMm.390057.

3D structure databases

ProteinModelPortaliQ9WV30.
SMRiQ9WV30. Positions 264-544.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000119370.

PTM databases

PhosphoSiteiQ9WV30.

Proteomic databases

MaxQBiQ9WV30.
PaxDbiQ9WV30.
PRIDEiQ9WV30.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075922; ENSMUSP00000075311; ENSMUSG00000003847. [Q9WV30-4]
ENSMUST00000077440; ENSMUSP00000076653; ENSMUSG00000003847. [Q9WV30-3]
ENSMUST00000125721; ENSMUSP00000116094; ENSMUSG00000003847. [Q9WV30-1]
ENSMUST00000151114; ENSMUSP00000119370; ENSMUSG00000003847. [Q9WV30-2]
ENSMUST00000169453; ENSMUSP00000127784; ENSMUSG00000003847. [Q9WV30-2]
GeneIDi54446.
KEGGimmu:54446.
UCSCiuc009nhl.2. mouse.
uc009nhm.2. mouse. [Q9WV30-1]
uc012gkd.1. mouse.

Organism-specific databases

CTDi10725.
MGIiMGI:1859333. Nfat5.

Phylogenomic databases

eggNOGiNOG85658.
GeneTreeiENSGT00550000074562.
HOGENOMiHOG000236245.
HOVERGENiHBG052612.
InParanoidiQ9WV30.
KOiK17335.
OMAiFGIQNNC.
OrthoDBiEOG79PJND.
TreeFamiTF326480.

Miscellaneous databases

ChiTaRSiNfat5. mouse.
NextBioi311314.
PROiQ9WV30.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WV30.
CleanExiMM_NFAT5.
ExpressionAtlasiQ9WV30. baseline and differential.
GenevestigatoriQ9WV30.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR015646. NFAT5.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF7. PTHR12533:SF7. 1 hit.
PfamiPF00554. RHD. 1 hit.
[Graphical view]
PRINTSiPR01789. NUCFACTORATC.
SMARTiSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-1534 (ISOFORM 2).
    Tissue: Skeletal muscle.
  6. 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.

Entry informationi

Entry nameiNFAT5_MOUSE
AccessioniPrimary (citable) accession number: Q9WV30
Secondary accession number(s): E9Q0P3
, E9Q6U2, G5E8N9, Q91WY0, Q9JLA1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 16, 2013
Last modified: March 4, 2015
This is version 111 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.