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Q9WV30

- NFAT5_MOUSE

UniProt

Q9WV30 - NFAT5_MOUSE

Protein

Nuclear factor of activated T-cells 5

Gene

Nfat5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 2 (16 Oct 2013)
      Previous versions | rss
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    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. 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

    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

    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

    ArrayExpressiQ9WV30.
    BgeeiQ9WV30.
    CleanExiMM_NFAT5.
    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.
    InParanoidiQ91WY0.
    KOiK17335.
    OMAiNNMTLAV.
    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. Align

    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

    MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPP RETSVASMSQ     50
    TSGGEAGSPP PAVVAADASS APSSSSMGGA CSSFTTSSSP TIYSTSVTDS 100
    KAMQVESCSS AVGVSNRGVS EKQLTGNTVQ QHPSTPKRHT VLYISPPPED 150
    LLDNSRMSCQ DEGCGLESEQ SCSMWMEDSP SNFSNMSTSS YNDNTEVPRK 200
    SRKRNPKQRP GVKRRDCEES NMDIFDADSA KAPHYVLSQL TTDNKGNSKA 250
    GNGTLDSQKG TGVKKSPMLC GQYPVKSEGK ELKIVVQPET QHRARYLTEG 300
    SRGSVKDRTQ QGFPTVKLEG HNEPVVLQVF VGNDSGRVKP HGFYQACRVT 350
    GRNTTPCKEV DIEGTTVIEV GLDPSNNMTL AVDCVGILKL RNADVEARIG 400
    IAGSKKKSTR ARLVFRVNIT RKDGSTLTLQ TPSSPILCTQ PAGVPEILKK 450
    SLHSCSVKGE EEVFLIGKNF LKGTKVIFQE NVSDENSWKS EAEIDMELFH 500
    QNHLIVKVPP YHDQHITLPV SVGIYVVTNA GRSHDVQPFT YTPDPAAGAL 550
    NVNVKKEISS PARPCSFEEA MKAMKTTGCN VDKVTILPNA LITPLISSSM 600
    IKTEDVTPME VTSEKRSSPI FQTTKSIGST QQTLETISNI AGGAPFSSPS 650
    SSSHLTPESE NQQQLQPKAY NPETLTTIQT QDISQPGTFP AVSAASQLPS 700
    SDALLQQATQ FQTREAQSRD TIQSDTVVNL SQLTEASQQQ QSPLQEQAQT 750
    LQQQIPSNIF PSPSSVSQLQ STIQQLQAGS FTGSAAGGRS GSVDLVQQVL 800
    EAQQQLSSVL FSTPDGNENV QEQLNADIFQ VSQIQNSVSP GMFSSAESAV 850
    HTRPDNLLPG RADSVHQQTE NTLSNQQQQQ QQQQQVMESS AAMVMEMQQS 900
    ICQAAAQIQS ELFPSAASAS GSLQQSPVYQ QPSHMMSALP TNEDMQMQCE 950
    LFSSPPAASG NETSTTTTPQ VATPGSTMFQ TPSSGDGEET GAQAKQIQNS 1000
    VFQTMVQMQR SGDSQPQVNL FSSTKNIMSV QNNGTQQQGN SLFQQGSEMM 1050
    SLQSGNFLQQ SSHSQAQLFH PQNPIADAQN LSQETQGSIF HSPNPIVHSQ 1100
    TSTASSEQLQ PSMFHSQNTI AVLQGSSVPQ DQQSPNIFLS QSSINNLQTN 1150
    TVAQEEQISF FAAQNSISPL QSTSNTEQQA AFQQQPPISH IQTPILSQEQ 1200
    AQPSQQGLFQ PQVALGSLPP NPMPQNQQGP IFQTQRPIVG MQSNSPSQEQ 1250
    QQQQQQQQQQ QQQQQQQQQS ILFSNQNAMA TMASQKQPPP NMMFSPNQNP 1300
    MASQEQQNQS IFHQQSNMAP MNQEQQPMQF QNQPTVSSLQ NPGPTQSESP 1350
    QTSLFHSSPQ IQLVQGSPSS QDQQVTLFLS PASMSALQTS INQPDMQQSP 1400
    LYSPQNNIPG IQGSTSSPQP QATLFHNTTG GTINQIQNSP GSSQQTSGMF 1450
    LFGIQNNCSQ LLTSGPATLP DQLMAINQQG QPQNEGQSSV TTLLSQQMPE 1500
    TSPLASSVNS SQNMEKIDLL VSLQSQGNNL TGSF 1534

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

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS22648.2. [Q9WV30-2 ]
    CCDS40464.1. [Q9WV30-3 ]
    CCDS72168.1. [Q9WV30-4 ]
    RefSeqi NP_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 ]
    UniGenei Mm.390057.

    3D structure databases

    ProteinModelPortali Q9WV30.
    SMRi Q9WV30. Positions 264-544.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000119370.

    PTM databases

    PhosphoSitei Q9WV30.

    Proteomic databases

    MaxQBi Q9WV30.
    PaxDbi Q9WV30.
    PRIDEi Q9WV30.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000075922 ; ENSMUSP00000075311 ; ENSMUSG00000003847 . [Q9WV30-4 ]
    ENSMUST00000077440 ; ENSMUSP00000076653 ; ENSMUSG00000003847 . [Q9WV30-3 ]
    ENSMUST00000125721 ; ENSMUSP00000116094 ; ENSMUSG00000003847 . [Q9WV30-1 ]
    ENSMUST00000151114 ; ENSMUSP00000119370 ; ENSMUSG00000003847 . [Q9WV30-2 ]
    ENSMUST00000169453 ; ENSMUSP00000127784 ; ENSMUSG00000003847 . [Q9WV30-2 ]
    GeneIDi 54446.
    KEGGi mmu:54446.
    UCSCi uc009nhl.2. mouse.
    uc009nhm.2. mouse. [Q9WV30-1 ]
    uc012gkd.1. mouse.

    Organism-specific databases

    CTDi 10725.
    MGIi MGI:1859333. Nfat5.

    Phylogenomic databases

    eggNOGi NOG85658.
    GeneTreei ENSGT00550000074562.
    HOGENOMi HOG000236245.
    HOVERGENi HBG052612.
    InParanoidi Q91WY0.
    KOi K17335.
    OMAi NNMTLAV.
    OrthoDBi EOG79PJND.
    TreeFami TF326480.

    Miscellaneous databases

    ChiTaRSi NFAT5. mouse.
    NextBioi 311314.
    PROi Q9WV30.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9WV30.
    Bgeei Q9WV30.
    CleanExi MM_NFAT5.
    Genevestigatori Q9WV30.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    2.60.40.340. 1 hit.
    InterProi IPR013783. Ig-like_fold.
    IPR014756. Ig_E-set.
    IPR002909. IPT.
    IPR008366. NFAT.
    IPR015646. NFAT5.
    IPR008967. p53-like_TF_DNA-bd.
    IPR011539. RHD.
    [Graphical view ]
    PANTHERi PTHR12533. PTHR12533. 1 hit.
    PTHR12533:SF7. PTHR12533:SF7. 1 hit.
    Pfami PF00554. RHD. 1 hit.
    [Graphical view ]
    PRINTSi PR01789. NUCFACTORATC.
    SMARTi SM00429. IPT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49417. SSF49417. 1 hit.
    SSF81296. SSF81296. 1 hit.
    PROSITEi PS50254. REL_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 107 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