ID NFAT5_RAT Reviewed; 1548 AA. AC D3ZGB1; DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot. DT 20-APR-2010, sequence version 1. DT 13-SEP-2023, entry version 96. DE RecName: Full=Nuclear factor of activated T-cells 5; DE Short=NF-AT5; DE AltName: Full=T-cell transcription factor NFAT5; GN Name=Nfat5; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP FUNCTION, INTERACTION WITH CIDEC, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND INDUCTION BY OSMOTIC STRESS. RX PubMed=23233732; DOI=10.1194/jlr.m033365; RA Ueno M., Shen W.J., Patel S., Greenberg A.S., Azhar S., Kraemer F.B.; RT "Fat-specific protein 27 modulates nuclear factor of activated T cells 5 RT and the cellular response to stress."; RL J. Lipid Res. 54:734-743(2013). CC -!- FUNCTION: Transcription factor involved, among others, in the CC transcriptional regulation of osmoprotective and inflammatory genes CC (PubMed:23233732). Binds the DNA consensus sequence 5'- CC [ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3'. Mediates CC the transcriptional response to hypertonicity. Positively regulates the CC transcription of LCN2 and S100A4 genes; optimal transactivation of CC these genes requires the presence of DDX5/DDX17. Also involved in the CC DNA damage response by preventing formation of R-loops; R-loops are CC composed of a DNA:RNA hybrid and the associated non-template single- CC stranded DNA (By similarity). {ECO:0000250|UniProtKB:O94916, CC ECO:0000269|PubMed:23233732}. CC -!- SUBUNIT: Homodimer when bound to DNA, completely encircles its DNA CC target (By similarity). Interacts with CIDEC; this interaction is CC direct and retains NFAT5 in the cytoplasm (PubMed:23233732). Does not CC bind with Fos and Jun transcription factors. Interacts with DDX5 and CC DDX17; this interaction leads to DDX5/DDX17 recruitment to LNC2 and CC S100A4 promoters and NFAT5-mediated DDX5/DDX17-enhanced transactivation CC (By similarity). {ECO:0000250|UniProtKB:O94916, CC ECO:0000269|PubMed:23233732}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23233732}. Cytoplasm CC {ECO:0000269|PubMed:23233732}. Chromosome CC {ECO:0000250|UniProtKB:O94916}. Note=Nuclear distribution increases CC under hypertonic conditions (By similarity). Recruited to sites of R- CC loop-associated DNA damage following poly-ADP-ribosylation by PARP1 (By CC similarity). {ECO:0000250|UniProtKB:O94916, CC ECO:0000250|UniProtKB:Q9WV30}. CC -!- INDUCTION: Up-regulated under hypertonic conditions. CC {ECO:0000269|PubMed:23233732}. CC -!- PTM: Phosphorylated. Phosphorylated at Thr-152 by CDK5 in response to CC osmotic stress; this phosphorylation mediates its rapid nuclear CC localization. {ECO:0000250|UniProtKB:O94916}. CC -!- PTM: Poly-ADP-ribosylated by PARP1 in response to DNA damage, promoting CC recruitment to sites of R-loop-associated DNA damage. CC {ECO:0000250|UniProtKB:O94916}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AABR06098525; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR06098526; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AABR06098527; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH473972; EDL92476.1; -; Genomic_DNA. DR RefSeq; NP_001100895.1; NM_001107425.1. DR AlphaFoldDB; D3ZGB1; -. DR SMR; D3ZGB1; -. DR BioGRID; 258819; 1. DR STRING; 10116.ENSRNOP00000017005; -. DR iPTMnet; D3ZGB1; -. DR PhosphoSitePlus; D3ZGB1; -. DR PaxDb; D3ZGB1; -. DR Ensembl; ENSRNOT00000017005; ENSRNOP00000017005; ENSRNOG00000011879. DR GeneID; 307820; -. DR KEGG; rno:307820; -. DR AGR; RGD:1309142; -. DR CTD; 10725; -. DR RGD; 1309142; Nfat5. DR eggNOG; ENOG502QSVE; Eukaryota. DR GeneTree; ENSGT00940000155213; -. DR HOGENOM; CLU_004396_0_0_1; -. DR InParanoid; D3ZGB1; -. DR OMA; PYQNQVI; -. DR OrthoDB; 5405363at2759; -. DR TreeFam; TF326480; -. DR PRO; PR:D3ZGB1; -. DR Proteomes; UP000002494; Chromosome 19. DR Proteomes; UP000234681; Chromosome 19. DR Bgee; ENSRNOG00000011879; Expressed in Ammon's horn and 20 other tissues. DR ExpressionAtlas; D3ZGB1; baseline and differential. DR Genevisible; D3ZGB1; RN. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISO:RGD. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IBA:GO_Central. DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:RGD. DR GO; GO:0006974; P:DNA damage response; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; ISO:RGD. DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0062176; P:R-loop processing; ISS:UniProtKB. DR GO; GO:0070884; P:regulation of calcineurin-NFAT signaling cascade; ISO:RGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR CDD; cd01178; IPT_NFAT; 1. DR CDD; cd07882; RHD-n_TonEBP; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 2.60.40.340; Rel homology domain (RHD), DNA-binding domain; 1. 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_RHD_DNA-bd. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR032397; RHD_dimer. DR InterPro; IPR011539; RHD_DNA_bind_dom. DR InterPro; IPR037059; RHD_DNA_bind_dom_sf. DR PANTHER; PTHR12533; NFAT; 1. DR PANTHER; PTHR12533:SF10; NUCLEAR FACTOR OF ACTIVATED T-CELLS 5; 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; SSF81296; E set domains; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR PROSITE; PS50254; REL_2; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; ADP-ribosylation; Chromosome; Cytoplasm; KW DNA damage; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..1548 FT /note="Nuclear factor of activated T-cells 5" FT /id="PRO_0000423618" FT DOMAIN 281..460 FT /note="RHD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265" FT DNA_BIND 310..317 FT /evidence="ECO:0000250|UniProtKB:O94916" FT REGION 54..106 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 141..180 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 192..237 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 258..282 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 659..682 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 750..777 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 851..892 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 970..1010 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1097..1127 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1257..1388 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 60..74 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 86..106 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 141..155 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 192..212 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 258..278 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 873..892 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94916" FT MOD_RES 139 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9WV30" FT MOD_RES 151 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94916" FT MOD_RES 152 FT /note="Phosphothreonine; by CDK5" FT /evidence="ECO:0000250|UniProtKB:O94916" FT MOD_RES 172 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94916" FT MOD_RES 577 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94916" FT CROSSLNK 572 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000250|UniProtKB:O94916" FT CROSSLNK 572 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0000250|UniProtKB:O94916" FT CROSSLNK 619 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O94916" SQ SEQUENCE 1548 AA; 167207 MW; CE3F4A41532770EF CRC64; MPSDFISLLS ADLDLESPKS LYSRDSLKLH PSQNFHRAGL LEESVYDLLP KELQLPPPRE TSAASMSQTS GGEAGSPPPA VVAADASSAP SSSMGGACSS FTTSSSPTIY STSVTDSKAM QVESCSSAVG VSNRGVSEKQ LTGNTVQQHP STPKRHTVLY ISPPPEDLLD NSRMSCQDEG CGLESEQSCS MWMEDSPSNF SNMSTSSYND NTEVPRKSRK RNPKQRPGVK RRDCEESNMD IFDADSAKAP HYVLSQLTTD NKGNSKAGNG TLDSQKGTGV KKSPMLCGQY PVKSEGKELK IVVQPETQHR ARYLTEGSRG SVKDRTQQGF PTVKLEGHNE PVVLQVFVGN DSGRVKPHGF YQACRVTGRN TTPCKEVDIE GTTVIEVGLD PSSNMTLAVD CVGILKLRNA DVEARIGIAG SKKKSTRARL VFRVNITRKD GSTLTLQTPS SPILCTQPAG VPEILKKSLH SCSVKGEEEV FLIGKNFLKG TKVIFQENVS DENSWKSEAE IDMELFHQNH LIVKVPPYHD QHITLPVSVG IYVVTNAGRS HDVQPFTYTP DPAAGALSVN VKKEISSPAR PCSFEEALKA MKTTGCNVDK VTILPNALIT PLISSSMIKT EDVTPMEVTS EKRSSPIFQT TKTVGSTQQT LETISNIAGN ASFSSPSSSH LSPENENQQQ LQPKAYNPET LTTIQTQDIS QPGTFPAVSA SSQLPSSDAL LQQAAQFQTR DAQSRDTMQS DSVVNLSQLT EAPQQQQSPL QEQAQIPSNI FPSPNSVSQL QSTIQQLQAG SFTGSTASGS NGSVDLVQQV LEAQQQLSSV LFSTPDGNEN VQEQLNADIF QVSQIQNSVS PGMFSSTESA VHTRPDNLLP GRADSVHQQT ENTLSSQQQQ QQQQQQQQQQ QVIESSAAMV MEMQQSICQA AAQIQSELFP SAASANGSLQ QSPVYQQPSH MMSALPTSED MQMQCELFSS PPAVSGNETS TTTTPQVATP GSTMFQPPNS GDGEETGAQA KQIQSSVFQT MVQMQHSGDS QPQVNLFSST KNIMSVQSNG TQQQGNSLFQ QGSEMLSLQS GSFLQQSSHS QAQLFHPQNP IADAQSLSQE TQGPMFHSAN PIVHSQTSTA SSEQLQPSMF HSQSTIAVLQ GSSVPQDQQS PNIYLSQSSI SNLQTNTVAQ EEQISFFSAQ NSISPLQSTS NTEQQAAFQQ QPPISHIQTP LLSQEQAQPS QQGLFQPQVA LGSLPANPMP QNQQGPIFQT QRPIVGMQSN SPSQEQQQQQ QQQQQQQQQQ QQQSILFSNQ NAMATMASQK QPPPNMIFSP NQNPMASQEQ QNQSIFHQQS NMAPMNQEQQ PMQFQNQPTV SSLQNPGPTP SESPQTSLFH SSPQIQLVQG SPSSQEQQVT LFLSPASMSA LQTSINQPDM QQSPLYSPQN NIPGIQGSTS SPQPQAALFH NTTGGTINQL QNSPGSSQQT SGMFLFGIQN NCSQLLTSGP ATLPEQLMAI NQPGQPQNEG QSSVTTLLSQ QMPESAPLAS SVNNSQNMEK IDLLVSLQSQ GNNLTGSF //