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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)DescriptionActionsGraphical viewLength
DNA bindingi293 – 300By similarity8

GO - Molecular functioni

GO - Biological processi

  • cytokine production Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of calcineurin-NFAT signaling cascade Source: MGI
  • response to osmotic stress Source: Ensembl
  • transcription, DNA-templated Source: MGI

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1859333. Nfat5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI

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)DescriptionActionsGraphical viewLength
ChainiPRO_00002051841 – 1534Nuclear factor of activated T-cells 5Add BLAST1534

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei120PhosphoserineBy similarity1
Modified residuei122N6-acetyllysineCombined sources1
Modified residuei134PhosphoserineBy similarity1
Modified residuei135Phosphothreonine; by CDK5By similarity1
Modified residuei155PhosphoserineBy similarity1
Cross-linki555Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki555Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei560PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9WV30.
PRIDEiQ9WV30.

PTM databases

iPTMnetiQ9WV30.
PhosphoSitePlusiQ9WV30.

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

BgeeiENSMUSG00000003847.
CleanExiMM_NFAT5.
ExpressionAtlasiQ9WV30. baseline and differential.
GenevisibleiQ9WV30. MM.

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.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini264 – 443RHDPROSITE-ProRule annotationAdd BLAST180

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi69 – 100Ser-richAdd BLAST32
Compositional biasi647 – 653Poly-Ser7
Compositional biasi738 – 741Poly-Gln4
Compositional biasi876 – 885Poly-Gln10
Compositional biasi963 – 968Poly-Thr6

Phylogenomic databases

eggNOGiENOG410IGY4. Eukaryota.
ENOG41118Z9. LUCA.
GeneTreeiENSGT00550000074562.
HOGENOMiHOG000236245.
HOVERGENiHBG052612.
InParanoidiQ9WV30.
KOiK17335.
OMAiFLFGIQN.
OrthoDBiEOG091G01QP.
TreeFamiTF326480.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiView protein in InterPro
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR015646. NFAT5.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF16. PTHR12533:SF16. 1 hit.
PfamiView protein in Pfam
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
PRINTSiPR01789. NUCFACTORATC.
SMARTiView protein in SMART
SM00429. IPT. 1 hit.
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiView protein in PROSITE
PS50254. REL_2. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

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

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: B

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQTFHRAGLLE
     67-81: DASSAPSSSSMGGAC → GFASEAGSVCIKNDL
     82-1534: Missing.

Note: 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 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 DDX17.1 Publication
Show »
Length:99
Mass (Da):10,456
Checksum:i3E3DBF7679A27EE8
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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAK97603 differs from that shown. Reason: Erroneous translation.Curated
The sequence EDL11405 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108C → G in AAK97603 (PubMed:11934689).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05879024R → RDSLKLHPSQTFHRAGLLE in isoform 2 and isoform 3. 1 Publication1 Publication1
Alternative sequenceiVSP_05879167 – 81DASSA…MGGAC → GFASEAGSVCIKNDL in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_05878982 – 1534Missing in isoform 3. 1 PublicationAdd BLAST1453
Alternative sequenceiVSP_0587921213 – 1225VALGS…NPMPQ → ESLHSHITPDACK in isoform 4. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_0587931226 – 1534Missing in isoform 4. 1 PublicationAdd BLAST309

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF162853 mRNA. Translation: AAD44343.1.
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.
AF369980 mRNA. Translation: AAK97603.1. Sequence problems.
AF200687 mRNA. Translation: AAF31405.1. Different initiation.
CCDSiCCDS22648.2. [Q9WV30-2]
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.
XP_006531255.1. XM_006531192.3. [Q9WV30-1]
XP_017168393.1. XM_017312904.1.
UniGeneiMm.390057.

Genome annotation databases

EnsembliENSMUST00000075922; ENSMUSP00000075311; ENSMUSG00000003847. [Q9WV30-4]
ENSMUST00000125721; ENSMUSP00000116094; ENSMUSG00000003847. [Q9WV30-1]
ENSMUST00000133026; ENSMUSP00000116631; ENSMUSG00000003847. [Q9WV30-3]
ENSMUST00000151114; ENSMUSP00000119370; ENSMUSG00000003847. [Q9WV30-2]
ENSMUST00000169453; ENSMUSP00000127784; ENSMUSG00000003847. [Q9WV30-2]
GeneIDi54446.
KEGGimmu:54446.
UCSCiuc009nhl.2. mouse. [Q9WV30-2]
uc009nhm.3. mouse. [Q9WV30-4]
uc009nhp.1. mouse. [Q9WV30-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF162853 mRNA. Translation: AAD44343.1.
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.
AF369980 mRNA. Translation: AAK97603.1. Sequence problems.
AF200687 mRNA. Translation: AAF31405.1. Different initiation.
CCDSiCCDS22648.2. [Q9WV30-2]
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.
XP_006531255.1. XM_006531192.3. [Q9WV30-1]
XP_017168393.1. XM_017312904.1.
UniGeneiMm.390057.

3D structure databases

ProteinModelPortaliQ9WV30.
SMRiQ9WV30.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000119370.

PTM databases

iPTMnetiQ9WV30.
PhosphoSitePlusiQ9WV30.

Proteomic databases

PaxDbiQ9WV30.
PRIDEiQ9WV30.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075922; ENSMUSP00000075311; ENSMUSG00000003847. [Q9WV30-4]
ENSMUST00000125721; ENSMUSP00000116094; ENSMUSG00000003847. [Q9WV30-1]
ENSMUST00000133026; ENSMUSP00000116631; ENSMUSG00000003847. [Q9WV30-3]
ENSMUST00000151114; ENSMUSP00000119370; ENSMUSG00000003847. [Q9WV30-2]
ENSMUST00000169453; ENSMUSP00000127784; ENSMUSG00000003847. [Q9WV30-2]
GeneIDi54446.
KEGGimmu:54446.
UCSCiuc009nhl.2. mouse. [Q9WV30-2]
uc009nhm.3. mouse. [Q9WV30-4]
uc009nhp.1. mouse. [Q9WV30-1]

Organism-specific databases

CTDi10725.
MGIiMGI:1859333. Nfat5.

Phylogenomic databases

eggNOGiENOG410IGY4. Eukaryota.
ENOG41118Z9. LUCA.
GeneTreeiENSGT00550000074562.
HOGENOMiHOG000236245.
HOVERGENiHBG052612.
InParanoidiQ9WV30.
KOiK17335.
OMAiFLFGIQN.
OrthoDBiEOG091G01QP.
TreeFamiTF326480.

Miscellaneous databases

ChiTaRSiNfat5. mouse.
PROiPR:Q9WV30.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003847.
CleanExiMM_NFAT5.
ExpressionAtlasiQ9WV30. baseline and differential.
GenevisibleiQ9WV30. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiView protein in InterPro
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR015646. NFAT5.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF16. PTHR12533:SF16. 1 hit.
PfamiView protein in Pfam
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
PRINTSiPR01789. NUCFACTORATC.
SMARTiView protein in SMART
SM00429. IPT. 1 hit.
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiView protein in PROSITE
PS50254. REL_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNFAT5_MOUSE
AccessioniPrimary (citable) accession number: Q9WV30
Secondary accession number(s): E9Q0P3
, E9Q6U2, G5E8N9, Q91WY0, Q9JLA1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: October 16, 2013
Last modified: June 7, 2017
This is version 129 of the entry and version 2 of the sequence. See 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

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 one 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.