ID NFAC2_MOUSE Reviewed; 927 AA. AC Q60591; A2APK2; A2APK3; A2AQC5; A2AQC6; A2AQC7; B5B2Q3; Q60984; Q60985; AC Q91Y65; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 211. DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 2; DE Short=NF-ATc2; DE Short=NFATc2; DE AltName: Full=NFAT pre-existing subunit; DE Short=NF-ATp; DE AltName: Full=T-cell transcription factor NFAT1; GN Name=Nfatc2; Synonyms=Nfat1, Nfatp; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE (ISOFORM A). RX PubMed=8235597; DOI=10.1126/science.8235597; RA McCaffrey P.G., Luo C., Kerpolla T.K., Jain J., Badalian T.M., Ho A.M., RA Burgeon E., Lane W.S., Lambert J.N., Curran T., Verdine G.L., Rao A., RA Hogan P.G.; RT "Isolation of the cyclosporin-sensitive T cell transcription factor RT NFATp."; RL Science 262:750-754(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C). RX PubMed=8668213; DOI=10.1128/mcb.16.7.3955; RA Luo C., Burgeon E., Carew J.A., McCaffrey P.G., Badalian T.M., Lane W.S., RA Hogan P.G., Rao A.; RT "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and RT mediates transcription of several cytokine genes."; RL Mol. Cell. Biol. 16:3955-3966(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=11278367; DOI=10.1074/jbc.m007854200; RA Plyte S., Boncristiano M., Fattori E., Galvagni F., Paccani S.R., RA Majolini M.B., Oliviero S., Ciliberto G., Telford J.L., Baldari C.T.; RT "Identification and characterization of a novel nuclear factor of activated RT T-cells-1 isoform expressed in mouse brain."; RL J. Biol. Chem. 276:14350-14358(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RC STRAIN=C57BL/6J; RX PubMed=18675896; DOI=10.1016/j.ygeno.2008.06.011; RA Vihma H., Pruunsild P., Timmusk T.; RT "Alternative splicing and expression of human and mouse NFAT genes."; RL Genomics 92:279-291(2008). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP MUTAGENESIS OF ARG-423; HIS-425; TYR-426; THR-428 AND GLU-429. RX PubMed=7876165; DOI=10.1074/jbc.270.28.16854; RA Jain J., Burgeon E., Badalian T.M., Hogan P.G., Rao A.; RT "A similar DNA-binding motif in NFAT family proteins and the Rel homology RT region."; RL J. Biol. Chem. 270:4138-4145(1995). RN [7] RP INTERACTION WITH NFATC2IP. RX PubMed=8943202; DOI=10.1126/science.274.5294.1903; RA Hodge M.R., Chun H.J., Rengarajan J., Alt A., Lieberson R., Glimcher L.H.; RT "NF-AT-driven interleukin-4 transcription potentiated by NIP45."; RL Science 274:1903-1905(1996). RN [8] RP MUTAGENESIS OF ARG-112; GLU-114 AND THR-116. RX PubMed=9660947; DOI=10.1016/s1097-2765(00)80063-5; RA Aramburu J., Garcia-Cozar F., Raghavan A., Okamura H., Rao A., Hogan P.G.; RT "Selective inhibition of NFAT activation by a peptide spanning the RT calcineurin targeting site of NFAT."; RL Mol. Cell 1:627-637(1998). RN [9] RP REVIEW. RX PubMed=10089876; DOI=10.1016/s0092-8674(00)80571-1; RA Crabtree G.R.; RT "Generic signals and specific outcomes: signaling through Ca2+, RT calcineurin, and NF-AT."; RL Cell 96:611-614(1999). RN [10] RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL RP STAGE. RX PubMed=10620601; DOI=10.1084/jem.191.1.9; RA Ranger A.M., Gerstenfeld L.C., Wang J., Kon T., Bae H., Gravallese E.M., RA Glimcher M.J., Glimcher L.H.; RT "The nuclear factor of activated T cells (NFAT) transcription factor NFATp RT (NFATc2) is a repressor of chondrogenesis."; RL J. Exp. Med. 191:9-22(2000). RN [11] RP PHOSPHORYLATION AT SER-99; SER-136; SER-170; SER-173; SER-174; SER-176; RP SER-177; SER-179; SER-182; SER-215; SER-219; SER-223; SER-238; SER-245; RP SER-270; SER-276; SER-278; SER-282; SER-328 AND SER-365, SUBCELLULAR RP LOCATION, INTERACTION WITH XPO1, MUTAGENESIS OF ARG-164, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=11030334; DOI=10.1016/s1097-2765(00)00053-8; RA Okamura H., Aramburu J., Garcia-Rodriguez C., Viola J.P.B., Raghavan A., RA Tahiliani M., Zhang X., Qin J., Hogan P.G., Rao A.; RT "Concerted dephosphorylation of the transcription factor NFAT1 induces a RT conformational switch that regulates transcriptional activity."; RL Mol. Cell 6:539-550(2000). RN [12] RP DEVELOPMENTAL STAGE. RX PubMed=17198697; DOI=10.1016/j.ydbio.2006.11.036; RA Yang X.Y., Yang T.T.C., Schubert W., Factor S.M., Chow C.-W.; RT "Dosage-dependent transcriptional regulation by the calcineurin/NFAT RT signaling in developing myocardium transition."; RL Dev. Biol. 303:825-837(2007). RN [13] RP TISSUE SPECIFICITY. RX PubMed=17579027; DOI=10.4049/jimmunol.179.1.103; RA Cante-Barrett K., Winslow M.M., Crabtree G.R.; RT "Selective role of NFATc3 in positive selection of thymocytes."; RL J. Immunol. 179:103-110(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136; SER-257 AND SER-365, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, Lung, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [15] RP INTERACTION WITH TBX21. RX PubMed=23616576; DOI=10.4049/jimmunol.1203403; RA Jang E.J., Park H.R., Hong J.H., Hwang E.S.; RT "Lysine 313 of T-box is crucial for modulation of protein stability, DNA RT binding, and threonine phosphorylation of T-bet."; RL J. Immunol. 190:5764-5770(2013). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=24970700; DOI=10.1159/000362647; RA Ranjan R., Deng J., Chung S., Lee Y.G., Park G.Y., Xiao L., Joo M., RA Christman J.W., Karpurapu M.; RT "The transcription factor nuclear factor of activated T cells c3 modulates RT the function of macrophages in sepsis."; RL J. Innate Immun. 6:754-764(2014). RN [17] RP INTERACTION WITH KAT2A. RX PubMed=28424240; DOI=10.4049/jimmunol.1600312; RA Gao B., Kong Q., Zhang Y., Yun C., Dent S.Y.R., Song J., Zhang D.D., RA Wang Y., Li X., Fang D.; RT "The histone acetyltransferase Gcn5 positively regulates T cell RT activation."; RL J. Immunol. 198:3927-3938(2017). CC -!- FUNCTION: Plays a role in the inducible expression of cytokine genes in CC T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha CC or GM-CSF. Promotes invasive migration through the activation of GPC6 CC expression and WNT5A signaling pathway (By similarity). Is involved in CC the negative regulation of chondrogenesis (PubMed:10620601). CC {ECO:0000250|UniProtKB:Q13469, ECO:0000269|PubMed:10620601}. CC -!- SUBUNIT: Member of the multicomponent NFATC transcription complex that CC consists of at least two components, a pre-existing cytoplasmic CC component NFATC2 and an inducible nuclear component NFATC1. Other CC members such as NFATC4, NFATC3 or members of the activating protein-1 CC family, MAF, GATA4 and Cbp/p300 can also bind the complex. The CC phosphorylated form specifically interacts with XPO1; which mediates CC nuclear export. NFATC proteins bind to DNA as monomers. Interacts with CC NFATC2IP. Interacts with FOXP3 (By similarity). Interacts with TBX21 CC ('Thr-302' phosphorylated form) (PubMed:23616576). Interacts with KAT2A CC (PubMed:28424240). Interacts with HOMER2 and HOMER3; this interaction CC competes with calcineurin/PPP3CA-binding and hence prevents NFATC2 CC dephosphorylation and activation (By similarity). Interacts with CC protein phosphatase PPP3CA/calcineurin A (By similarity). CC {ECO:0000250|UniProtKB:Q13469, ECO:0000269|PubMed:11030334, CC ECO:0000269|PubMed:23616576, ECO:0000269|PubMed:28424240, CC ECO:0000269|PubMed:8943202}. CC -!- INTERACTION: CC Q60591; Q86Y07-1: VRK2; Xeno; NbExp=2; IntAct=EBI-643104, EBI-1207633; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11030334, CC ECO:0000269|PubMed:24970700}. Nucleus {ECO:0000269|PubMed:11030334, CC ECO:0000269|PubMed:24970700}. Note=Cytoplasmic for the phosphorylated CC form and nuclear after activation that is controlled by calcineurin- CC mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to CC be one mechanism by which cells distinguish between sustained and CC transient calcium signals. The subcellular localization of NFATC plays CC a key role in the regulation of gene transcription. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=C; CC IsoId=Q60591-3; Sequence=Displayed; CC Name=B; CC IsoId=Q60591-2; Sequence=VSP_005596; CC Name=D; CC IsoId=Q60591-4; Sequence=VSP_005597; CC Name=A; CC IsoId=Q60591-1; Sequence=Not described; CC -!- TISSUE SPECIFICITY: Expressed in spleen, heart, testis, brain, CC placenta, muscle and pancreas (PubMed:18675896). Expressed in the CC thymus (PubMed:18675896, PubMed:17579027). Expressed in the lung CC (PubMed:17579027). Expressed in cartilage (PubMed:10620601). CC {ECO:0000269|PubMed:10620601, ECO:0000269|PubMed:17579027, CC ECO:0000269|PubMed:18675896}. CC -!- DEVELOPMENTAL STAGE: Expressed in the developing heart at 13.5 and 16.5 CC dpc, during the transition from spongy to compact myocardium CC (PubMed:17198697). Not detected in the skeletal system at 11 and 13.5 CC dpc (PubMed:10620601). {ECO:0000269|PubMed:10620601, CC ECO:0000269|PubMed:17198697}. CC -!- DOMAIN: Rel Similarity Domain (RSD) allows DNA-binding and cooperative CC interactions with AP1 factors. {ECO:0000250}. CC -!- PTM: In resting cells, phosphorylated by NFATC-kinase on at least 18 CC sites in the 99-365 region. Upon cell stimulation, all these sites CC except Ser-245 are dephosphorylated by calcineurin. Dephosphorylation CC induces a conformational change that simultaneously exposes an NLS and CC masks an NES, which results in nuclear localization. Simultaneously, CC one site among Ser-53; Ser-54 and Ser-56 is phosphorylated; which is CC required for full transcriptional activity. CC {ECO:0000269|PubMed:11030334}. CC -!- PTM: Ubiquitinated in endothelial cells by RNF213 downstream of the CC non-canonical Wnt signaling pathway, leading to its degradation by the CC proteasome. {ECO:0000250|UniProtKB:Q13469}. CC -!- DISRUPTION PHENOTYPE: NFATC2-knocked down adult animals develop CC progressive difficulty in ambulation, fixed joint contractures and CC reduced joint motion, associated with joint destruction and the CC formation of ectopic cartilage and bone masses. Skeletal morphogenesis CC is normal during embryonic development. Cartilage cells from NFATC2- CC knocked down mice display uncontrolled growth consistent with malignant CC transformation. {ECO:0000269|PubMed:10620601}. CC -!- MISCELLANEOUS: [Isoform A]: PubMed:8668213 (AAC52929) sequence is a CC chimeric cDNA. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC52929.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA fused with Phyhd1 (Lrrc8a).; Evidence={ECO:0000305}; 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; U02079; AAC52929.1; ALT_SEQ; mRNA. DR EMBL; U36575; AAC52930.1; -; mRNA. DR EMBL; U36576; AAC52931.1; -; mRNA. DR EMBL; AF289078; AAK49895.1; -; mRNA. DR EMBL; EU887588; ACG55608.1; -; mRNA. DR EMBL; AL840639; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL844575; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS17112.1; -. [Q60591-3] DR CCDS; CCDS50803.1; -. [Q60591-2] DR PIR; A48753; A48753. DR RefSeq; NP_035029.2; NM_010899.3. [Q60591-3] DR AlphaFoldDB; Q60591; -. DR SMR; Q60591; -. DR BioGRID; 201739; 3. DR ComplexPortal; CPX-610; AP-1 transcription factor complex FOS-JUN-NFATC2. DR CORUM; Q60591; -. DR DIP; DIP-49476N; -. DR ELM; Q60591; -. DR IntAct; Q60591; 11. DR STRING; 10090.ENSMUSP00000074198; -. DR MoonDB; Q60591; Predicted. DR iPTMnet; Q60591; -. DR PhosphoSitePlus; Q60591; -. DR EPD; Q60591; -. DR jPOST; Q60591; -. DR MaxQB; Q60591; -. DR PaxDb; 10090-ENSMUSP00000074198; -. DR PeptideAtlas; Q60591; -. DR ProteomicsDB; 287400; -. [Q60591-3] DR ProteomicsDB; 287401; -. [Q60591-2] DR ProteomicsDB; 287402; -. [Q60591-4] DR Antibodypedia; 1758; 653 antibodies from 46 providers. DR DNASU; 18019; -. DR Ensembl; ENSMUST00000074618.10; ENSMUSP00000074198.4; ENSMUSG00000027544.17. [Q60591-3] DR Ensembl; ENSMUST00000109184.8; ENSMUSP00000104812.2; ENSMUSG00000027544.17. [Q60591-2] DR GeneID; 18019; -. DR KEGG; mmu:18019; -. DR UCSC; uc008oau.2; mouse. [Q60591-3] DR AGR; MGI:102463; -. DR CTD; 4773; -. DR MGI; MGI:102463; Nfatc2. DR VEuPathDB; HostDB:ENSMUSG00000027544; -. DR eggNOG; ENOG502QTJI; Eukaryota. DR GeneTree; ENSGT00940000156230; -. DR HOGENOM; CLU_010185_1_0_1; -. DR InParanoid; Q60591; -. DR OMA; PAIPICX; -. DR OrthoDB; 5405363at2759; -. DR PhylomeDB; Q60591; -. DR TreeFam; TF326480; -. DR Reactome; R-MMU-2025928; Calcineurin activates NFAT. DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-MMU-5607763; CLEC7A (Dectin-1) induces NFAT activation. DR BioGRID-ORCS; 18019; 6 hits in 80 CRISPR screens. DR ChiTaRS; Nfatc2; mouse. DR PRO; PR:Q60591; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q60591; Protein. DR Bgee; ENSMUSG00000027544; Expressed in lumbar subsegment of spinal cord and 209 other cell types or tissues. DR ExpressionAtlas; Q60591; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0035976; C:transcription factor AP-1 complex; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI. DR GO; GO:0003682; F:chromatin binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI. DR GO; GO:0019902; F:phosphatase binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISO:MGI. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IGI:MGI. DR GO; GO:0051216; P:cartilage development; IMP:UniProtKB. DR GO; GO:0016477; P:cell migration; ISS:UniProtKB. DR GO; GO:0071277; P:cellular response to calcium ion; IDA:MGI. DR GO; GO:0006974; P:DNA damage response; ISO:MGI. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0014904; P:myotube cell development; IMP:MGI. DR GO; GO:0098781; P:ncRNA transcription; IMP:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:1905064; P:negative regulation of vascular associated smooth muscle cell differentiation; ISO:MGI. DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:1901741; P:positive regulation of myoblast fusion; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI. DR CDD; cd01178; IPT_NFAT; 1. DR CDD; cd07881; RHD-n_NFAT; 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; 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:SF4; NUCLEAR FACTOR OF ACTIVATED T-CELLS, CYTOPLASMIC 2; 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. DR Genevisible; Q60591; MM. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cytoplasm; Direct protein sequencing; KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..927 FT /note="Nuclear factor of activated T-cells, cytoplasmic 2" FT /id="PRO_0000205179" FT REPEAT 186..202 FT /note="1" FT REPEAT 215..231 FT /note="2" FT REPEAT 274..290 FT /note="3; approximate" FT DOMAIN 394..576 FT /note="RHD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265" FT DNA_BIND 423..430 FT REGION 1..29 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..116 FT /note="Calcineurin-binding" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT REGION 119..201 FT /note="Transactivation domain A (TAD-A)" FT REGION 163..177 FT /note="Required for cytoplasmic retention of the FT phosphorylated form" FT REGION 186..292 FT /note="3 X approximate SP repeats" FT REGION 203..299 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 322..341 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 790..812 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 841..903 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 253..255 FT /note="Nuclear localization signal" FT COMPBIAS 211..226 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 859..882 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 23 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 53 FT /note="Phosphoserine" FT /evidence="ECO:0000305" FT MOD_RES 54 FT /note="Phosphoserine" FT /evidence="ECO:0000305" FT MOD_RES 56 FT /note="Phosphoserine" FT /evidence="ECO:0000305" FT MOD_RES 99 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 107 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 110 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 136 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334, FT ECO:0007744|PubMed:21183079" FT MOD_RES 150 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 170 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 173 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 174 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 176 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 177 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 179 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 182 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11030334" FT MOD_RES 215 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 219 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 223 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 238 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 245 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 257 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 270 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 276 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 278 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 282 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 328 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11030334, FT ECO:0007744|PubMed:21183079" FT MOD_RES 757 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 759 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 761 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT MOD_RES 860 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13469" FT VAR_SEQ 619..806 FT /note="DGQQIWEMEATVDKDKSQPNMLFVEIPEYRNKHIRVPVKVNFYVINGKRKRS FT QPQHFTYHPVPAIKTEPSDEYEPSLICSPAHGGLGSQPYYPQHPMLAESPSCLVATMAP FT CQQFRSGLSSPDARYQQQSPAAALYQRSKSLSPGLLGYQQPSLLAAPLGLADAHRSVLV FT HAGSQGQGQGSTLPHTSS -> GPAGTCETRPLPISLISADRLSPWLSRLQRNPPGSVF FT RCSVLLPAPGSSLVLLAL (in isoform D)" FT /evidence="ECO:0000303|PubMed:11278367" FT /id="VSP_005597" FT VAR_SEQ 910..927 FT /note="VNEIIRKEFSGPPSRNQT -> ELIDTHLSWIQNIL (in isoform B)" FT /evidence="ECO:0000303|PubMed:8668213" FT /id="VSP_005596" FT MUTAGEN 112 FT /note="R->A: Lowers dephosphorylation." FT /evidence="ECO:0000269|PubMed:9660947" FT MUTAGEN 114 FT /note="E->A: Lowers dephosphorylation." FT /evidence="ECO:0000269|PubMed:9660947" FT MUTAGEN 116 FT /note="T->A: No dephosphorylation." FT /evidence="ECO:0000269|PubMed:9660947" FT MUTAGEN 164 FT /note="R->A: Induces aberrant nuclear localization of the FT phosphorylated form." FT /evidence="ECO:0000269|PubMed:11030334" FT MUTAGEN 423 FT /note="R->A: Decrease in binding to DNA." FT /evidence="ECO:0000269|PubMed:7876165" FT MUTAGEN 425 FT /note="H->A: No change in binding to DNA." FT /evidence="ECO:0000269|PubMed:7876165" FT MUTAGEN 426 FT /note="Y->A: Decrease in binding to DNA." FT /evidence="ECO:0000269|PubMed:7876165" FT MUTAGEN 428 FT /note="T->A: No change in binding to DNA." FT /evidence="ECO:0000269|PubMed:7876165" FT MUTAGEN 428 FT /note="T->C: No change in binding to DNA and confers FT DNA-binding sensitivity to sulfhydryl modifications." FT /evidence="ECO:0000269|PubMed:7876165" FT MUTAGEN 429 FT /note="E->A: Decrease in binding to DNA." FT /evidence="ECO:0000269|PubMed:7876165" FT CONFLICT 78 FT /note="L -> P (in Ref. 3; AAK49895)" FT /evidence="ECO:0000305" FT CONFLICT 287 FT /note="L -> P (in Ref. 2; AAC52929/AAC52930/AAC52931)" FT /evidence="ECO:0000305" FT CONFLICT 802 FT /note="P -> R (in Ref. 2; AAC52929/AAC52930/AAC52931)" FT /evidence="ECO:0000305" SQ SEQUENCE 927 AA; 100020 MW; F21E7BABE7DBB40F CRC64; MDVPEPQPDP DGGDGPGHEP GGSPQDELDF SILFDYDYLN PIEEEPIAHK AISSPSGLAY PDDVLDYGLK PCNPLASLSG EPPGRFGEPD SIGFQNFLSP VKPAGASGPS PRIEITPSHE LMQAGGALRG RDAGLSPEQP ALALAGVAAS PRFTLPVPGY EGYREPLCLS PASSGSSASF ISDTFSPYTS PCVSPNNAGP DDLCPQFQNI PAHYSPRTSP IMSPRTSLAE DSCLGRHSPV PRPASRSSSP GAKRRHSCAE ALVAPLPAAS PQRSRSPSPQ PSPHVALQDD SIPAGYPPTA GSAVLMDALN TLATDSPCGI PSKIWKTSPD PTPVSTAPSK AGLARHIYPT VEFLGPCEQE ERRNSAPESI LLVPPTWPKQ LVPAIPICSI PVTASLPPLE WPLSNQSGSY ELRIEVQPKP HHRAHYETEG SRGAVKAPTG GHPVVQLHGY MENKPLGLQI FIGTADERIL KPHAFYQVHR ITGKTVTTTS YEKIVGNTKV LEIPLEPKNN MRATIDCAGI LKLRNADIEL RKGETDIGRK NTRVRLVFRV HVPEPSGRIV SLQAASNPIE CSQRSAHELP MVERQDMDSC LVYGGQQMIL TGQNFTAESK VVFMEKTTDG QQIWEMEATV DKDKSQPNML FVEIPEYRNK HIRVPVKVNF YVINGKRKRS QPQHFTYHPV PAIKTEPSDE YEPSLICSPA HGGLGSQPYY PQHPMLAESP SCLVATMAPC QQFRSGLSSP DARYQQQSPA AALYQRSKSL SPGLLGYQQP SLLAAPLGLA DAHRSVLVHA GSQGQGQGST LPHTSSASQQ ASPVIHYSPT NQQLRGGGHQ EFQHIMYCEN FGPSSARPGP PPINQGQRLS PGAYPTVIQQ QTAPSQRAAK NGPSDQKEAL PTGVTVKQEQ NLDQTYLDDV NEIIRKEFSG PPSRNQT //