NFAT5_HUMAN
ID NFAT5_HUMAN Reviewed; 1531 AA.
AC O94916; A2RRB4; A6H8V5; E9PHR7; O95693; Q7LA65; Q969Q8; Q96QH3; Q9UN18;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Nuclear factor of activated T-cells 5;
DE Short=NF-AT5;
DE AltName: Full=T-cell transcription factor NFAT5;
DE AltName: Full=Tonicity-responsive enhancer-binding protein {ECO:0000303|PubMed:10051678};
DE Short=TonE-binding protein {ECO:0000303|PubMed:10051678};
DE Short=TonEBP {ECO:0000303|PubMed:10051678};
GN Name=NFAT5; Synonyms=KIAA0827, TONEBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10051678; DOI=10.1073/pnas.96.5.2538;
RA Miyakawa H., Woo S.K., Dahl S.C., Handler J.S., Kwon H.M.;
RT "Tonicity-responsive enhancer binding protein, a rel-like protein that
RT stimulates transcription in response to hypertonicity.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2538-2542(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RC TISSUE=Brain;
RX PubMed=10377394; DOI=10.1073/pnas.96.13.7214;
RA Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Rao A.;
RT "NFAT5, a constitutively nuclear NFAT protein that does not cooperate with
RT Fos and Jun.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7214-7219(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND E).
RX PubMed=11528118; DOI=10.1159/000056990;
RA Dalski A., Schwinger E., Zuhlke C.;
RT "Genomic organization of the human NFAT5 gene: exon-intron structure of the
RT 14-kb transcript and CpG-island analysis of the promoter region.";
RL Cytogenet. Cell Genet. 93:239-241(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS C AND D).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-1531.
RC TISSUE=Brain;
RX PubMed=11233530; DOI=10.1101/sqb.1999.64.517;
RA Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Copeland N.G., Gilbert D.J.,
RA Thomas S., Disteche C., Jenkins N.A., Rao A.;
RT "NFAT5: the NF-AT family of transcription factors expands in a new
RT direction.";
RL Cold Spring Harb. Symp. Quant. Biol. 64:517-526(1999).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 675-1531.
RC TISSUE=Brain;
RX PubMed=10565538; DOI=10.3109/10425179909033929;
RA Zuehlke C., Kiehl R., Johannsmeyer A., Grzeschik K.H., Schwinger E.;
RT "Isolation and characterization of novel CAG repeat containing genes
RT expressed in human brain.";
RL DNA Seq. 10:1-6(1999).
RN [10]
RP ALTERNATIVE SPLICING.
RX PubMed=11934689; DOI=10.1152/ajprenal.00123.2001;
RA Maouyo D., Kim J.Y., Lee S.D., Wu Y., Woo S.K., Kwon H.M.;
RT "Mouse TonEBP-NFAT5: expression in early development and alternative
RT splicing.";
RL Am. J. Physiol. 282:F802-F809(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP PHOSPHORYLATION AT SER-120; SER-134; THR-135 AND SER-155, AND MUTAGENESIS
RP OF SER-120; SER-134; THR-135 AND SER-155.
RX PubMed=21209322; DOI=10.1091/mbc.e10-08-0681;
RA Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B., Ferraris J.D.;
RT "High NaCl-induced activation of CDK5 increases phosphorylation of the
RT osmoprotective transcription factor TonEBP/OREBP at threonine 135, which
RT contributes to its rapid nuclear localization.";
RL Mol. Biol. Cell 22:703-714(2011).
RN [13]
RP FUNCTION, INTERACTION WITH DDX5 AND DDX17, AND ALTERNATIVE SPLICING.
RX PubMed=22266867; DOI=10.1038/onc.2011.618;
RA Germann S., Gratadou L., Zonta E., Dardenne E., Gaudineau B., Fougere M.,
RA Samaan S., Dutertre M., Jauliac S., Auboeuf D.;
RT "Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-
RT migratory NFAT5 transcription factor.";
RL Oncogene 31:4536-4549(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-135 AND SER-561, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556, SUMOYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-573 (ISOFORM D), AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556 AND LYS-603, SUMOYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-573 (ISOFORM D), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 264-544 IN COMPLEX WITH DNA, AND
RP SUBUNIT.
RX PubMed=11780147; DOI=10.1038/nsb749;
RA Stroud J.C., Lopez-Rodriguez C., Rao A., Chen L.;
RT "Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription
RT factor.";
RL Nat. Struct. Biol. 9:90-94(2002).
CC -!- FUNCTION: Transcription factor involved, among others, in the
CC transcriptional regulation of osmoprotective and inflammatory genes.
CC Mediates the transcriptional response to hypertonicity
CC (PubMed:10051678). Positively regulates the transcription of LCN2 and
CC S100A4 genes; optimal transactivation of these genes requires the
CC presence of DDX5/DDX17 (PubMed:22266867). Binds the DNA consensus
CC sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3'
CC (PubMed:10377394). {ECO:0000269|PubMed:10051678,
CC ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:22266867}.
CC -!- SUBUNIT: Homodimer when bound to DNA, completely encircles its DNA
CC target. Interacts with CIDEC; this interaction is direct and retains
CC NFAT5 in the cytoplasm (By similarity). Does not bind with Fos and Jun
CC transcription factors. Interacts with DDX5 and DDX17; this interaction
CC leads to DDX5/DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-
CC mediated DDX5/DDX17-enhanced transactivation (PubMed:22266867).
CC {ECO:0000250, ECO:0000269|PubMed:11780147,
CC ECO:0000269|PubMed:22266867}.
CC -!- INTERACTION:
CC O94916; Q92841: DDX17; NbExp=3; IntAct=EBI-308320, EBI-746012;
CC O94916; P17844: DDX5; NbExp=4; IntAct=EBI-308320, EBI-351962;
CC O94916; Q16236: NFE2L2; NbExp=4; IntAct=EBI-308320, EBI-2007911;
CC O94916-1; P29350: PTPN6; NbExp=4; IntAct=EBI-15828651, EBI-78260;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10377394}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9WV30}. Note=Nuclear distribution increases
CC under hypertonic conditions. {ECO:0000250|UniProtKB:Q9WV30}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=C;
CC IsoId=O94916-1; Sequence=Displayed;
CC Name=A;
CC IsoId=O94916-2; Sequence=VSP_058784;
CC Name=B;
CC IsoId=O94916-3; Sequence=VSP_058785, VSP_058786, VSP_058787;
CC Name=D;
CC IsoId=O94916-4; Sequence=VSP_058785, VSP_058788;
CC Name=E;
CC IsoId=O94916-5; Sequence=VSP_058785;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in skeletal
CC muscle, brain, heart and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:10051678, ECO:0000269|PubMed:10377394}.
CC -!- PTM: Phosphorylated (PubMed:10377394). Phosphorylated at Thr-135 by
CC CDK5 in response to osmotic stress; this phosphorylation mediates its
CC rapid nuclear localization (PubMed:21209322).
CC {ECO:0000269|PubMed:10377394, ECO:0000269|PubMed:21209322}.
CC -!- MISCELLANEOUS: [Isoform A]: The transcript encoding this isoform
CC contains an alternative coding exon 4 which contains 2 stop codons and
CC could target the transcript to nonsense-mediated mRNA decay after the
CC pioneer round of translation, as suggested by the decreased NFAT5
CC protein levels when the number of exon 4-containing transcripts
CC increases. The insertion of exon 4 is stimulated in the presence of
CC DDX5 and DDX17. Isoform A sequence described in this entry starts at
CC the first methionine downstream of exon 4 last stop codon. An
CC alternative protein sequence can be predicted from this transcript
CC starting at Met-1. This isoform encodes an 81 amino acid-long protein.
CC {ECO:0000269|PubMed:22266867, ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform B]: The transcript encoding this isoform
CC contains an alternative coding exon 4 which contains 2 stop codons and
CC could target the transcript to nonsense-mediated mRNA decay after the
CC pioneer round of translation, as suggested by the decreased NFAT5
CC protein levels when the number of exon 4-containing transcripts
CC increases. The insertion of exon 4 is stimulated in the presence of
CC DDX5 and DDX17. {ECO:0000269|PubMed:22266867, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK91166.1; Type=Erroneous translation; Evidence={ECO:0000305};
CC Sequence=AAK91166.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA74850.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB09693.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAC42765.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF089824; AAD18136.1; -; mRNA.
DR EMBL; AF134870; AAD38360.1; -; mRNA.
DR EMBL; AF346509; AAK91166.1; ALT_SEQ; mRNA.
DR EMBL; AJ243298; CAC42764.1; -; mRNA.
DR EMBL; AJ243299; CAC42765.1; ALT_FRAME; mRNA.
DR EMBL; AB020634; BAA74850.2; ALT_INIT; mRNA.
DR EMBL; AC009032; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012321; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83281.1; -; Genomic_DNA.
DR EMBL; BC131509; AAI31510.1; -; mRNA.
DR EMBL; BC146765; AAI46766.1; -; mRNA.
DR EMBL; AF163836; AAD48441.1; -; mRNA.
DR EMBL; Z97016; CAB09693.1; ALT_FRAME; mRNA.
DR CCDS; CCDS10881.1; -. [O94916-1]
DR CCDS; CCDS10882.1; -. [O94916-2]
DR CCDS; CCDS45518.1; -. [O94916-5]
DR CCDS; CCDS45519.1; -. [O94916-4]
DR RefSeq; NP_001106649.1; NM_001113178.2. [O94916-4]
DR RefSeq; NP_006590.1; NM_006599.3. [O94916-1]
DR RefSeq; NP_619727.2; NM_138713.3. [O94916-5]
DR RefSeq; NP_619728.2; NM_138714.3. [O94916-2]
DR RefSeq; NP_775321.1; NM_173214.2. [O94916-2]
DR RefSeq; NP_775322.1; NM_173215.2. [O94916-2]
DR RefSeq; XP_006721188.1; XM_006721125.3.
DR RefSeq; XP_011521120.1; XM_011522818.2. [O94916-2]
DR RefSeq; XP_016878359.1; XM_017022870.1. [O94916-2]
DR PDB; 1IMH; X-ray; 2.86 A; C/D=264-544.
DR PDBsum; 1IMH; -.
DR AlphaFoldDB; O94916; -.
DR SMR; O94916; -.
DR BioGRID; 115949; 23.
DR CORUM; O94916; -.
DR DIP; DIP-58524N; -.
DR IntAct; O94916; 10.
DR STRING; 9606.ENSP00000457593; -.
DR GlyGen; O94916; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O94916; -.
DR MetOSite; O94916; -.
DR PhosphoSitePlus; O94916; -.
DR SwissPalm; O94916; -.
DR BioMuta; NFAT5; -.
DR EPD; O94916; -.
DR jPOST; O94916; -.
DR MassIVE; O94916; -.
DR MaxQB; O94916; -.
DR PaxDb; O94916; -.
DR PeptideAtlas; O94916; -.
DR PRIDE; O94916; -.
DR ProteomicsDB; 20588; -.
DR ProteomicsDB; 50551; -. [O94916-1]
DR ProteomicsDB; 50552; -. [O94916-2]
DR ProteomicsDB; 50553; -. [O94916-3]
DR ProteomicsDB; 50554; -. [O94916-4]
DR Antibodypedia; 29866; 317 antibodies from 30 providers.
DR DNASU; 10725; -.
DR Ensembl; ENST00000349945.7; ENSP00000338806.3; ENSG00000102908.22. [O94916-5]
DR Ensembl; ENST00000354436.6; ENSP00000346420.2; ENSG00000102908.22. [O94916-1]
DR Ensembl; ENST00000426654.6; ENSP00000413126.2; ENSG00000102908.22. [O94916-3]
DR Ensembl; ENST00000567239.5; ENSP00000457593.1; ENSG00000102908.22. [O94916-4]
DR GeneID; 10725; -.
DR KEGG; hsa:10725; -.
DR MANE-Select; ENST00000349945.7; ENSP00000338806.3; NM_138713.4; NP_619727.2. [O94916-5]
DR UCSC; uc002exi.4; human. [O94916-1]
DR CTD; 10725; -.
DR DisGeNET; 10725; -.
DR GeneCards; NFAT5; -.
DR HGNC; HGNC:7774; NFAT5.
DR HPA; ENSG00000102908; Low tissue specificity.
DR MalaCards; NFAT5; -.
DR MIM; 604708; gene.
DR neXtProt; NX_O94916; -.
DR OpenTargets; ENSG00000102908; -.
DR Orphanet; 529980; Inflammatory bowel disease-recurrent sinopulmonary infections syndrome.
DR PharmGKB; PA31581; -.
DR VEuPathDB; HostDB:ENSG00000102908; -.
DR eggNOG; ENOG502QSVE; Eukaryota.
DR GeneTree; ENSGT00940000155213; -.
DR HOGENOM; CLU_004396_0_0_1; -.
DR InParanoid; O94916; -.
DR OMA; LMETPGN; -.
DR OrthoDB; 95502at2759; -.
DR PhylomeDB; O94916; -.
DR TreeFam; TF326480; -.
DR PathwayCommons; O94916; -.
DR SignaLink; O94916; -.
DR SIGNOR; O94916; -.
DR BioGRID-ORCS; 10725; 18 hits in 1099 CRISPR screens.
DR ChiTaRS; NFAT5; human.
DR EvolutionaryTrace; O94916; -.
DR GeneWiki; NFAT5; -.
DR GenomeRNAi; 10725; -.
DR Pharos; O94916; Tbio.
DR PRO; PR:O94916; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; O94916; protein.
DR Bgee; ENSG00000102908; Expressed in renal medulla and 188 other tissues.
DR ExpressionAtlas; O94916; baseline and differential.
DR Genevisible; O94916; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IBA:GO_Central.
DR GO; GO:0071474; P:cellular hyperosmotic response; TAS:ProtInc.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; IMP:ARUK-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0070884; P:regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR GO; GO:0006366; P:transcription by RNA polymerase II; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR IDEAL; IID00260; -.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR008366; NFAT.
DR InterPro; IPR015646; NFAT5.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR032397; RHD_dimer.
DR InterPro; IPR011539; RHD_DNA_bind_dom.
DR InterPro; IPR037059; RHD_DNA_bind_dom_sf.
DR PANTHER; PTHR12533; PTHR12533; 1.
DR PANTHER; PTHR12533:SF10; PTHR12533:SF10; 1.
DR Pfam; PF16179; RHD_dimer; 1.
DR Pfam; PF00554; RHD_DNA_bind; 1.
DR PRINTS; PR01789; NUCFACTORATC.
DR SMART; SM00429; IPT; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50254; REL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..1531
FT /note="Nuclear factor of activated T-cells 5"
FT /id="PRO_0000205183"
FT DOMAIN 264..443
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT DNA_BIND 293..300
FT REGION 34..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 114..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 175..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 640..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 841..891
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 958..996
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1211..1304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1316..1371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1473..1502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 40..56
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..89
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 114..138
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 241..261
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 841..855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 868..891
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1219..1282
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 120
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21209322"
FT MOD_RES 122
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WV30"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21209322"
FT MOD_RES 135
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000269|PubMed:21209322,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21209322"
FT MOD_RES 561
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 556
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT CROSSLNK 556
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 603
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:10051678,
FT ECO:0000303|PubMed:10377394, ECO:0000303|PubMed:11528118"
FT /id="VSP_058784"
FT VAR_SEQ 24
FT /note="R -> RDSLKLHPSQNFHRAGLLE (in isoform B, isoform D
FT and isoform E)"
FT /evidence="ECO:0000303|PubMed:11528118,
FT ECO:0000303|PubMed:15489334, ECO:0000305|PubMed:11528118"
FT /id="VSP_058785"
FT VAR_SEQ 67..81
FT /note="DASSAPSSSSMGGAC -> GFASEAGSVCIKNDL (in isoform B)"
FT /evidence="ECO:0000305|PubMed:11528118"
FT /id="VSP_058786"
FT VAR_SEQ 82..1531
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305|PubMed:11528118"
FT /id="VSP_058787"
FT VAR_SEQ 546
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_058788"
FT MUTAGEN 120
FT /note="S->A: Normal nuclear localization."
FT /evidence="ECO:0000269|PubMed:21209322"
FT MUTAGEN 134
FT /note="S->A: Reduced nuclear localization."
FT /evidence="ECO:0000269|PubMed:21209322"
FT MUTAGEN 135
FT /note="T->A: Reduced nuclear localization."
FT /evidence="ECO:0000269|PubMed:21209322"
FT MUTAGEN 155
FT /note="S->A: Increased nuclear localization."
FT /evidence="ECO:0000269|PubMed:21209322"
FT CONFLICT 666..667
FT /note="QP -> HA (in Ref. 3; CAC42764/CAC42765)"
FT /evidence="ECO:0000305"
FT CONFLICT 1369
FT /note="E -> D (in Ref. 9; CAB09693)"
FT /evidence="ECO:0000305"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 325..337
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 342..348
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 358..362
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 365..372
FT /evidence="ECO:0007829|PDB:1IMH"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 384..389
FT /evidence="ECO:0007829|PDB:1IMH"
FT HELIX 392..396
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 410..420
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 426..432
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 446..451
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 462..468
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 475..482
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 489..492
FT /evidence="ECO:0007829|PDB:1IMH"
FT HELIX 496..498
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 501..507
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 520..528
FT /evidence="ECO:0007829|PDB:1IMH"
FT STRAND 537..542
FT /evidence="ECO:0007829|PDB:1IMH"
FT CROSSLNK O94916-4:573
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
SQ SEQUENCE 1531 AA; 165763 MW; A68C68088DABF69E CRC64;
MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPS RETSVASMSQ TSGGEAGSPP
PAVVAADASS APSSSSMGGA CSSFTTSSSP TIYSTSVTDS KAMQVESCSS AVGVSNRGVS
EKQLTSNTVQ QHPSTPKRHT VLYISPPPED LLDNSRMSCQ DEGCGLESEQ SCSMWMEDSP
SNFSNMSTSS YNDNTEVPRK SRKRNPKQRP GVKRRDCEES NMDIFDADSA KAPHYVLSQL
TTDNKGNSKA GNGTLENQKG TGVKKSPMLC GQYPVKSEGK ELKIVVQPET QHRARYLTEG
SRGSVKDRTQ QGFPTVKLEG HNEPVVLQVF VGNDSGRVKP HGFYQACRVT GRNTTPCKEV
DIEGTTVIEV GLDPSNNMTL AVDCVGILKL RNADVEARIG IAGSKKKSTR ARLVFRVNIM
RKDGSTLTLQ TPSSPILCTQ PAGVPEILKK SLHSCSVKGE EEVFLIGKNF LKGTKVIFQE
NVSDENSWKS EAEIDMELFH QNHLIVKVPP YHDQHITLPV SVGIYVVTNA GRSHDVQPFT
YTPDPAAAGA LNVNVKKEIS SPARPCSFEE AMKAMKTTGC NLDKVNIIPN ALMTPLIPSS
MIKSEDVTPM EVTAEKRSST IFKTTKSVGS TQQTLENISN IAGNGSFSSP SSSHLPSENE
KQQQIQPKAY NPETLTTIQT QDISQPGTFP AVSASSQLPN SDALLQQATQ FQTRETQSRE
ILQSDGTVVN LSQLTEASQQ QQQSPLQEQA QTLQQQISSN IFPSPNSVSQ LQNTIQQLQA
GSFTGSTASG SSGSVDLVQQ VLEAQQQLSS VLFSAPDGNE NVQEQLSADI FQQVSQIQSG
VSPGMFSSTE PTVHTRPDNL LPGRAESVHP QSENTLSNQQ QQQQQQQQVM ESSAAMVMEM
QQSICQAAAQ IQSELFPSTA SANGNLQQSP VYQQTSHMMS ALSTNEDMQM QCELFSSPPA
VSGNETSTTT TQQVATPGTT MFQTSSSGDG EETGTQAKQI QNSVFQTMVQ MQHSGDNQPQ
VNLFSSTKSM MSVQNSGTQQ QGNGLFQQGN EMMSLQSGNF LQQSSHSQAQ LFHPQNPIAD
AQNLSQETQG SLFHSPNPIV HSQTSTTSSE QMQPPMFHSQ STIAVLQGSS VPQDQQSTNI
FLSQSPMNNL QTNTVAQEAF FAAPNSISPL QSTSNSEQQA AFQQQAPISH IQTPMLSQEQ
AQPPQQGLFQ PQVALGSLPP NPMPQSQQGT MFQSQHSIVA MQSNSPSQEQ QQQQQQQQQQ
QQQQQQSILF SNQNTMATMA SPKQPPPNMI FNPNQNPMAN QEQQNQSIFH QQSNMAPMNQ
EQQPMQFQSQ STVSSLQNPG PTQSESSQTP LFHSSPQIQL VQGSPSSQEQ QVTLFLSPAS
MSALQTSINQ QDMQQSPLYS PQNNMPGIQG ATSSPQPQAT LFHNTAGGTM NQLQNSPGSS
QQTSGMFLFG IQNNCSQLLT SGPATLPDQL MAISQPGQPQ NEGQPPVTTL LSQQMPENSP
LASSINTNQN IEKIDLLVSL QNQGNNLTGS F
