ID STAT3_MOUSE Reviewed; 770 AA. AC P42227; A2A5D1; B7ZC17; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 27-MAR-2024, entry version 243. DE RecName: Full=Signal transducer and activator of transcription 3 {ECO:0000312|MGI:MGI:103038}; DE AltName: Full=Acute-phase response factor {ECO:0000303|PubMed:7512451, ECO:0000303|PubMed:7523373}; GN Name=Stat3 {ECO:0000312|MGI:MGI:103038}; GN Synonyms=Aprf {ECO:0000303|PubMed:7512451, GN ECO:0000303|PubMed:7523373}; 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] (ISOFORM STAT3A), PROTEIN SEQUENCE OF 154-158; RP 181-185 AND 632-640, AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Liver; RX PubMed=7512451; DOI=10.1016/0092-8674(94)90235-6; RA Akira S., Nishio Y., Inoue M., Wang X.-J., Wei S., Matsusaka T., RA Yoshida K., Sudo T., Naruto M., Kishimoto T.; RT "Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91- RT related transcription factor involved in the gp130-mediated signaling RT pathway."; RL Cell 77:63-71(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DEL-701). RC TISSUE=Brain; RX PubMed=7523373; DOI=10.1016/s0021-9258(19)51096-1; RA Raz R., Durbin J.E., Levy D.E.; RT "Acute phase response factor and additional members of the interferon- RT stimulated gene factor 3 family integrate diverse signals from cytokines, RT interferons, and growth factors."; RL J. Biol. Chem. 269:24391-24395(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM STAT3A). RC TISSUE=Thymus; RX PubMed=8140422; DOI=10.1126/science.8140422; RA Zhong Z., Wen Z., Darnell J.E. Jr.; RT "Stat3: a STAT family member activated by tyrosine phosphorylation in RT response to epidermal growth factor and interleukin-6."; RL Science 264:95-98(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM STAT3B), AND TISSUE SPECIFICITY RP (ISOFORM STAT3B). RC STRAIN=BALB/cJ, and C57BL/6J; TISSUE=Liver; RX PubMed=7568080; DOI=10.1073/pnas.92.20.9097; RA Schaefer T.S., Sanders L.K., Nathans D.; RT "Cooperative transcriptional activity of Jun and Stat3 beta, a short form RT of Stat3."; RL Proc. Natl. Acad. Sci. U.S.A. 92:9097-9101(1995). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM STAT3A). RC STRAIN=129/SvJ; RX PubMed=11161808; DOI=10.1006/geno.2000.6433; RA Miyoshi K., Cui Y., Riedlinger G., Robinson P., Lehoczky J., Zon L., RA Oka T., Dewar K., Hennighausen L.; RT "Structure of the mouse Stat 3/5 locus: evolution from Drosophila to RT zebrafish to mouse."; RL Genomics 71:150-155(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM STAT3A). RC STRAIN=C57BL/6J, and NOD/LtJ; RA Davoodi-Semiromi A., She J.-X.; RT "A mutant Stat5b with weaker DNA binding defines a key defective pathway in RT non-obese diabetic (NOD) mice."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM STAT3A). RC STRAIN=FVB/N; TISSUE=Mammary gland; 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 [9] RP PHOSPHORYLATION AT SER-727, AND MUTAGENESIS. RX PubMed=7543024; DOI=10.1016/0092-8674(95)90311-9; RA Wen Z., Zhong Z., Darnell J.E. Jr.; RT "Maximal activation of transcription by Stat1 and Stat3 requires both RT tyrosine and serine phosphorylation."; RL Cell 82:241-250(1995). RN [10] RP INTERACTION WITH PIAS3. RC TISSUE=Thymus; RX PubMed=9388184; DOI=10.1126/science.278.5344.1803; RA Chung C.D., Liao J., Liu B., Rao X., Jay P., Berta P., Shuai K.; RT "Specific inhibition of Stat3 signal transduction by PIAS3."; RL Science 278:1803-1805(1997). RN [11] RP PHOSPHORYLATION BY FER, AND INTERACTION WITH FER. RX PubMed=10878010; DOI=10.1074/jbc.m003402200; RA Priel-Halachmi S., Ben-Dor I., Shpungin S., Tennenbaum T., Molavani H., RA Bachrach M., Salzberg S., Nir U.; RT "FER kinase activation of Stat3 is determined by the N-terminal sequence."; RL J. Biol. Chem. 275:28902-28910(2000). RN [12] RP INTERACTION WITH STATIP1. RX PubMed=10954736; DOI=10.1073/pnas.170192197; RA Collum R.G., Brutsaert S., Lee G., Schindler C.; RT "A Stat3-interacting protein (StIP1) regulates cytokine signal RT transduction."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10120-10125(2000). RN [13] RP PHOSPHORYLATION AT TYR-705 AND SER-727. RX PubMed=11553624; DOI=10.1074/jbc.m106044200; RA Zhang Y., Liu G., Dong Z.; RT "MSK1 and JNKs mediate phosphorylation of STAT3 in UVA-irradiated mouse RT epidermal JB6 cells."; RL J. Biol. Chem. 276:42534-42542(2001). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-705. RX PubMed=11294897; DOI=10.1091/mbc.12.4.931; RA Hart K.C., Robertson S.C., Donoghue D.J.; RT "Identification of tyrosine residues in constitutively activated fibroblast RT growth factor receptor 3 involved in mitogenesis, Stat activation, and RT phosphatidylinositol 3-kinase activation."; RL Mol. Biol. Cell 12:931-942(2001). RN [15] RP FUNCTION. RX PubMed=12594516; DOI=10.1038/nature01388; RA Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., RA Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., RA Schwartz M.W., Myers M.G. Jr.; RT "STAT3 signalling is required for leptin regulation of energy balance but RT not reproduction."; RL Nature 421:856-859(2003). RN [16] RP INTERACTION WITH NLK, PHOSPHORYLATION AT SER-727, AND MUTAGENESIS OF RP SER-727. RX PubMed=15004007; DOI=10.1101/gad.1166904; RA Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N., RA Matsumoto K., Shibuya H.; RT "Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm RT induction."; RL Genes Dev. 18:381-386(2004). RN [17] RP SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-77; LEU-78; PHE-174; ARG-609 AND RP TYR-705, INTERACTION WITH KPNA4 AND KPNA5, AND NUCLEAR IMPORT MOTIF. RX PubMed=15919823; DOI=10.1073/pnas.0501643102; RA Liu L., McBride K.M., Reich N.C.; RT "STAT3 nuclear import is independent of tyrosine phosphorylation and RT mediated by importin-alpha3."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8150-8155(2005). RN [18] RP INTERACTION WITH SIPAR. RC STRAIN=Swiss Webster / NIH; RA Ning H., Rong Y., Zhang Y., Chang Z.; RT "SIPAR interacts with STAT3 to regulate its signal pathway."; RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 32:173-179(2005). RN [19] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=16825198; DOI=10.1074/jbc.m601991200; RA Gonzalez R.R., Cherfils S., Escobar M., Yoo J.H., Carino C., Styer A.K., RA Sullivan B.T., Sakamoto H., Olawaiye A., Serikawa T., Lynch M.P., RA Rueda B.R.; RT "Leptin signaling promotes the growth of mammary tumors and increases the RT expression of vascular endothelial growth factor (VEGF) and its receptor RT type two (VEGF-R2)."; RL J. Biol. Chem. 281:26320-26328(2006). RN [20] RP INTERACTION WITH STMN3. RX PubMed=16401721; DOI=10.1083/jcb.200503021; RA Ng D.C., Lin B.H., Lim C.P., Huang G., Zhang T., Poli V., Cao X.; RT "Stat3 regulates microtubules by antagonizing the depolymerization activity RT of stathmin."; RL J. Cell Biol. 172:245-257(2006). RN [21] RP INTERACTION WITH ARL2BP. RX PubMed=18234692; DOI=10.1093/intimm/dxm154; RA Muromoto R., Sekine Y., Imoto S., Ikeda O., Okayama T., Sato N., RA Matsuda T.; RT "BART is essential for nuclear retention of STAT3."; RL Int. Immunol. 20:395-403(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain; RX PubMed=18034455; DOI=10.1021/pr0701254; RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.; RT "Large-scale identification and evolution indexing of tyrosine RT phosphorylation sites from murine brain."; RL J. Proteome Res. 7:311-318(2008). RN [23] RP INTERACTION WITH NHLH1. RX PubMed=18356286; DOI=10.1210/me.2008-0010; RA Fox D.L., Good D.J.; RT "Nescient helix-loop-helix 2 interacts with signal transducer and activator RT of transcription 3 to regulate transcription of prohormone convertase RT 1/3."; RL Mol. Endocrinol. 22:1438-1448(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-714 AND SER-727, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; 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 [25] RP PHOSPHORYLATION AT SER-727, AND INTERACTION WITH NEK6. RX PubMed=20595392; DOI=10.1074/jbc.m110.137190; RA Jeon Y.J., Lee K.Y., Cho Y.Y., Pugliese A., Kim H.G., Jeong C.H., RA Bode A.M., Dong Z.; RT "Role of NEK6 in tumor promoter-induced transformation in JB6 C141 mouse RT skin epidermal cells."; RL J. Biol. Chem. 285:28126-28133(2010). RN [26] RP FUNCTION, IDENTIFICATION IN COMPLEX WITH NFATC3 AND NFATC4, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION AT TYR-705. RX PubMed=19538478; DOI=10.1111/j.1582-4934.2009.00804.x; RA Manukyan I., Galatioto J., Mascareno E., Bhaduri S., Siddiqui M.A.; RT "Cross-talk between calcineurin/NFAT and Jak/STAT signalling induces RT cardioprotective alphaB-crystallin gene expression in response to RT hypertrophic stimuli."; RL J. Cell. Mol. Med. 14:1707-1716(2010). RN [27] RP PHOSPHORYLATION IN RESPONSE TO KIT SIGNALING. RX PubMed=21135090; DOI=10.1074/jbc.m110.182642; RA Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.; RT "Mechanisms of STAT protein activation by oncogenic KIT mutants in RT neoplastic mast cells."; RL J. Biol. Chem. 286:5956-5966(2011). RN [28] RP FUNCTION. RX PubMed=23084476; DOI=10.1016/j.molcel.2012.09.013; RA Shen S., Niso-Santano M., Adjemian S., Takehara T., Malik S.A., Minoux H., RA Souquere S., Marino G., Lachkar S., Senovilla L., Galluzzi L., Kepp O., RA Pierron G., Maiuri M.C., Hikita H., Kroemer R., Kroemer G.; RT "Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity."; RL Mol. Cell 48:667-680(2012). RN [29] RP INTERACTION WITH OCAD1, AND SUBUNIT. RX PubMed=23972987; DOI=10.1016/j.celrep.2013.07.029; RA Sinha A., Khadilkar R.J., Vinay K.S., Roychowdhury Sinha A., Inamdar M.S.; RT "Conserved regulation of the Jak/STAT pathway by the endosomal protein RT asrij maintains stem cell potency."; RL Cell Rep. 4:649-658(2013). RN [30] RP FUNCTION, TISSUE SPECIFICITY, INDUCTION BY S.AUREUS INFECTION, AND RP PHOSPHORYLATION. RX PubMed=23401489; DOI=10.1084/jem.20120260; RA Choi S.M., McAleer J.P., Zheng M., Pociask D.A., Kaplan M.H., Qin S., RA Reinhart T.A., Kolls J.K.; RT "Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is RT required for host defense against MRSA pneumonia."; RL J. Exp. Med. 210:551-561(2013). RN [31] RP PHOSPHORYLATION AT TYR-705 (MICROBIAL INFECTION). RC STRAIN=C57BL/6J; RX PubMed=29924996; DOI=10.1016/j.celrep.2018.05.072; RA Jaslow S.L., Gibbs K.D., Fricke W.F., Wang L., Pittman K.J., Mammel M.K., RA Thaden J.T., Fowler V.G. Jr., Hammer G.E., Elfenbein J.R., Ko D.C.; RT "Salmonella Activation of STAT3 Signaling by SarA Effector Promotes RT Intracellular Replication and Production of IL-10."; RL Cell Rep. 23:3525-3536(2018). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 136-716. RX PubMed=9671298; DOI=10.1038/28101; RA Becker S., Groner B., Mueller C.W.; RT "Three-dimensional structure of the Stat3beta homodimer bound to DNA."; RL Nature 394:145-151(1998). RN [33] RP DISRUPTION PHENOTYPE. RX PubMed=9108058; DOI=10.1073/pnas.94.8.3801; RA Takeda K., Noguchi K., Shi W., Tanaka T., Matsumoto M., Yoshida N., RA Kishimoto T., Akira S.; RT "Targeted disruption of the mouse Stat3 gene leads to early embryonic RT lethality."; RL Proc. Natl. Acad. Sci. U.S.A. 94:3801-3804(1997). RN [34] RP FUNCTION. RX PubMed=20215569; DOI=10.1210/en.2009-1199; RA Kostromina E., Gustavsson N., Wang X., Lim C.Y., Radda G.K., Li C., Han W.; RT "Glucose intolerance and impaired insulin secretion in pancreas-specific RT signal transducer and activator of transcription-3 knockout mice are RT associated with microvascular alterations in the pancreas."; RL Endocrinology 151:2050-2059(2010). CC -!- FUNCTION: Signal transducer and transcription activator that mediates CC cellular responses to interleukins, KITLG/SCF, LEP and other growth CC factors (By similarity). Once activated, recruits coactivators, such as CC NCOA1 or MED1, to the promoter region of the target gene (By CC similarity). May mediate cellular responses to activated FGFR1, FGFR2, CC FGFR3 and FGFR4 (By similarity). Upon activation of IL6ST/gp130 CC signaling by interleukin-6 (IL6), binds to the IL6-responsive elements CC identified in the promoters of various acute-phase protein genes (By CC similarity). Activated by IL31 through IL31RA (By similarity). Acts as CC a regulator of inflammatory response by regulating differentiation of CC naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): CC acetylation promotes its transcription activity and cell CC differentiation while deacetylation and oxidation of lysine residues by CC LOXL3 inhibits differentiation (By similarity). Involved in cell cycle CC regulation by inducing the expression of key genes for the progression CC from G1 to S phase, such as CCND1 (By similarity). Mediates the effects CC of LEP on melanocortin production, body energy homeostasis and CC lactation (PubMed:12594516). May play an apoptotic role by CC transctivating BIRC5 expression under LEP activation (PubMed:16825198). CC Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR CC activity (By similarity). Plays a crucial role in basal beta cell CC functions, such as regulation of insulin secretion (PubMed:20215569). CC Following JAK/STAT signaling activation and as part of a complex with CC NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB CC and activates transcription in cardiomyocytes (PubMed:19538478). Plays CC an important role in host defense in methicillin-resistant S.aureus CC lung infection by regulating the expression of the antimicrobial lectin CC REG3G (PubMed:23401489). {ECO:0000250|UniProtKB:P40763, CC ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:12594516, CC ECO:0000269|PubMed:16825198, ECO:0000269|PubMed:19538478, CC ECO:0000269|PubMed:20215569, ECO:0000269|PubMed:23084476, CC ECO:0000269|PubMed:23401489}. CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member (at least STAT1). Component of a promoter-binding complex CC composed of STAT3, NFATC3 and NFATC4; complex formation is enhanced by CC calcineurin (PubMed:19538478). Interacts with IL31RA, NCOA1, PELP1, CC SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R in presence of CC IL23. Interacts (via SH2 domain) with NLK. Interacts with ARL2BP; the CC interaction is enhanced by LIF and JAK1 expression (By similarity). CC Interacts with KPNA4 and KPNA5; KPNA4 may be the primary mediator of CC nuclear import (By similarity). Interacts with CAV2; the interaction is CC increased on insulin-induced tyrosine phosphorylation of CAV2 and leads CC to STAT3 activation (By similarity). Interacts with ARL2BP; interaction CC is enhanced with ARL2. Interacts with NEK6 (By similarity). Binds to CC CDK9 when activated and nuclear. Interacts with BMX. Interacts with CC ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on stimulation CC by IL6, CNTF or OSM and inhibits the DNA binding activity of STAT3. In CC prostate cancer cells, interacts with PRKCE and promotes DNA binding CC activity of STAT3. Interacts with STMN3, antagonizing its microtubule- CC destabilizing activity. Interacts with the 'Lys-129' acetylated form of CC BIRC5/survivin. Interacts with FER. Interacts (via SH2 domain) with CC EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). CC Interacts with FGFR4 (By similarity). Interacts with INPP5F; the CC interaction is independent of STAT3 Tyr-705 phosphorylation status (By CC similarity). Interacts with OCAD1 (PubMed:23972987). Interacts CC (unphosphorylated or phosphorylated at Ser-727) with PHB1 (By CC similarity). Interacts and may form heterodimers with NHLH1 CC (PubMed:18356286). Found in a complex with SLC39A6, SLC39A10 and with CC the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (By CC similarity). Interacts (when acetylated) with EP300 (via bromo domain); CC interaction takes place following STAT3 acetylation by EP300 and CC promotes enhanceosome assembly (By similarity). Interacts (when CC acetylated) with BRD2 (via bromo domain); interaction promotes STAT3 CC recruitment to chromatin and T-helper Th17 cell differentiation (By CC similarity). {ECO:0000250|UniProtKB:P40763, CC ECO:0000250|UniProtKB:P52631, ECO:0000269|PubMed:10878010, CC ECO:0000269|PubMed:10954736, ECO:0000269|PubMed:11553624, CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15919823, CC ECO:0000269|PubMed:16401721, ECO:0000269|PubMed:18234692, CC ECO:0000269|PubMed:18356286, ECO:0000269|PubMed:19538478, CC ECO:0000269|PubMed:20595392, ECO:0000269|PubMed:23972987, CC ECO:0000269|PubMed:9388184, ECO:0000269|Ref.18}. CC -!- INTERACTION: CC P42227; Q80VH0: Bank1; NbExp=4; IntAct=EBI-602878, EBI-646949; CC P42227; Q64261: Cdk6; NbExp=3; IntAct=EBI-602878, EBI-847380; CC P42227; P23927: Cryab; NbExp=3; IntAct=EBI-602878, EBI-299046; CC P42227; O54784: Dapk3; NbExp=8; IntAct=EBI-602878, EBI-77359; CC P42227; P70424: Erbb2; NbExp=4; IntAct=EBI-602878, EBI-2945468; CC P42227; O35387: Hax1; NbExp=11; IntAct=EBI-602878, EBI-642449; CC P42227; Q00175: Pgr; NbExp=4; IntAct=EBI-602878, EBI-346821; CC P42227; P42227: Stat3; NbExp=3; IntAct=EBI-602878, EBI-602878; CC P42227; P48025: Syk; NbExp=5; IntAct=EBI-602878, EBI-300116; CC P42227; P30084: ECHS1; Xeno; NbExp=3; IntAct=EBI-602878, EBI-719602; CC P42227; Q8TAE8: GADD45GIP1; Xeno; NbExp=3; IntAct=EBI-602878, EBI-372506; CC P42227; P40189: IL6ST; Xeno; NbExp=4; IntAct=EBI-602878, EBI-1030834; CC P42227; Q9NRF2: SH2B1; Xeno; NbExp=5; IntAct=EBI-602878, EBI-310491; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P40763}. Nucleus CC {ECO:0000269|PubMed:19538478}. Note=Predominantly present in the CC cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) CC stimulation, accumulates in the nucleus. The complex composed of BART CC and ARL2 plays an important role in the nuclear translocation and CC retention of STAT3 (By similarity). Shuttles between the nucleus and CC the cytoplasm. Translocated into the nucleus upon tyrosine CC phosphorylation and dimerization, in response to signaling by activated CC FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is CC independent of tyrosine phosphorylation. Translocates to the nucleus in CC the presence of EDN1 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P52631}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Stat3A; CC IsoId=P42227-1; Sequence=Displayed; CC Name=Stat3B; CC IsoId=P42227-2; Sequence=VSP_006287; CC Name=Del-701; CC IsoId=P42227-3; Sequence=VSP_010475; CC -!- TISSUE SPECIFICITY: Expressed in ventricular cardiomyocytes (at protein CC level) (PubMed:19538478). Expressed in the lung (at protein level) CC (PubMed:23401489). Expressed in the liver, spleen and kidney CC (PubMed:7512451). {ECO:0000269|PubMed:19538478, CC ECO:0000269|PubMed:23401489, ECO:0000269|PubMed:7512451}. CC -!- TISSUE SPECIFICITY: [Isoform Stat3B]: Expressed in the liver. CC {ECO:0000269|PubMed:7568080}. CC -!- INDUCTION: Induced by methicillin-resistant S.aureus infection in the CC lung. {ECO:0000269|PubMed:23401489}. CC -!- PTM: Activated through tyrosine phosphorylation by BMX. Tyrosine CC phosphorylated in response to IL6, IL11, CNTF, LIF, KITLG/SCF, CSF1, CC EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes CC phosphorylation on tyrosine residues and subsequent translocation to CC the nucleus. Tyrosine phosphorylated in response to constitutively CC activated FGFR1, FGFR2, FGFR3 and FGFR4. Phosphorylated on serine upon CC DNA damage, probably by ATM or ATR. Serine phosphorylation is important CC for the formation of stable DNA-binding STAT3 homodimers and maximal CC transcriptional activity. ARL2BP may participate in keeping the CC phosphorylated state of STAT3 within the nucleus. Tyrosine CC phosphorylated upon stimulation with EGF. Upon LPS challenge, CC phosphorylated within the nucleus by IRAK1 (By similarity). Upon UV-A CC treatment, phosphorylated on Ser-727 by RPS6KA5 (By similarity). CC Dephosphorylation on tyrosine residues by PTPN2 negatively regulates CC IL6/interleukin-6 signaling (By similarity). Phosphorylation at Tyr-705 CC by PTK6, isoform M2 of PKM (PKM2) or FER leads to an increase of its CC transcriptional activity (By similarity). Phosphorylation at Tyr-705 is CC increased in the presence of calcineurin (PubMed:19538478). CC {ECO:0000250|UniProtKB:P40763, ECO:0000269|PubMed:10878010, CC ECO:0000269|PubMed:11294897, ECO:0000269|PubMed:11553624, CC ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:16825198, CC ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:20595392, CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:23401489, CC ECO:0000269|PubMed:7543024}. CC -!- PTM: Acetylated on lysine residues by EP300/p300, promoting its CC activation (By similarity). Acetylation at Lys-49 and Lys-87 by CC EP300/p300 promotes its activation (By similarity). Acetylation at Lys- CC 87 by EP300/p300 promotes its association with BRD2 and recruitment to CC chromatin (By similarity). Deacetylated at Lys-49 and Lys-87 by HDAC1 CC (By similarity). Acetylation at Lys-685 by EP300/p300 promotes its CC homodimerization and activation (By similarity). Deacetylated at Lys- CC 685 by HDAC3 (By similarity). Acetylated on lysine residues by CREBBP CC (By similarity). Deacetylation by LOXL3 leads to disrupt STAT3 CC dimerization and inhibit STAT3 transcription activity (By similarity). CC Oxidation of lysine residues to allysine on STAT3 preferentially takes CC place on lysine residues that are acetylated (By similarity). CC {ECO:0000250|UniProtKB:P40763}. CC -!- PTM: Some lysine residues are oxidized to allysine by LOXL3, leading to CC disrupt STAT3 dimerization and inhibit STAT3 transcription activity. CC Oxidation of lysine residues to allysine on STAT3 preferentially takes CC place on lysine residues that are acetylated. CC {ECO:0000250|UniProtKB:P40763}. CC -!- PTM: (Microbial infection) Phosphorylated on Tyr-705 in the presence of CC S.typhimurium SarA. {ECO:0000269|PubMed:29924996}. CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality, day 6.5-7.5. CC Conditional, tissue specific mutants are variably viable and show CC diverse defects including obesity, diabetes, thermal dysregulation and CC infertility. {ECO:0000269|PubMed:20215569, ECO:0000269|PubMed:9108058}. CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {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; L29278; AAA37254.1; -; mRNA. DR EMBL; U08378; AAA56668.1; -; mRNA. DR EMBL; U06922; AAA19452.1; -; mRNA. DR EMBL; U30709; AAC52612.1; -; mRNA. DR EMBL; AF246978; AAL59017.1; -; Genomic_DNA. DR EMBL; AY299489; AAQ75418.1; -; mRNA. DR EMBL; AY299490; AAQ75419.1; -; mRNA. DR EMBL; AL591466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003806; AAH03806.1; -; mRNA. DR CCDS; CCDS25440.1; -. [P42227-1] DR CCDS; CCDS25441.1; -. [P42227-2] DR CCDS; CCDS48934.1; -. [P42227-3] DR PIR; I49508; I49508. DR RefSeq; NP_998824.1; NM_213659.3. [P42227-1] DR RefSeq; NP_998825.1; NM_213660.3. [P42227-3] DR PDB; 1BG1; X-ray; 2.25 A; A=127-715. DR PDB; 3CWG; X-ray; 3.05 A; A/B=127-688. DR PDB; 4E68; X-ray; 2.58 A; A=127-715. DR PDB; 4ZIA; X-ray; 2.70 A; A/B/C/D/E=3-127. DR PDBsum; 1BG1; -. DR PDBsum; 3CWG; -. DR PDBsum; 4E68; -. DR PDBsum; 4ZIA; -. DR AlphaFoldDB; P42227; -. DR SMR; P42227; -. DR BioGRID; 203523; 34. DR CORUM; P42227; -. DR DIP; DIP-442N; -. DR IntAct; P42227; 31. DR MINT; P42227; -. DR STRING; 10090.ENSMUSP00000120152; -. DR BindingDB; P42227; -. DR ChEMBL; CHEMBL5402; -. DR MoonDB; P42227; Predicted. DR MoonProt; P42227; -. DR GlyGen; P42227; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; P42227; -. DR PhosphoSitePlus; P42227; -. DR SwissPalm; P42227; -. DR EPD; P42227; -. DR jPOST; P42227; -. DR MaxQB; P42227; -. DR PaxDb; 10090-ENSMUSP00000120152; -. DR PeptideAtlas; P42227; -. DR ProteomicsDB; 258659; -. [P42227-1] DR ProteomicsDB; 258660; -. [P42227-2] DR ProteomicsDB; 258661; -. [P42227-3] DR Pumba; P42227; -. DR ABCD; P42227; 1 sequenced antibody. DR Antibodypedia; 660; 2987 antibodies from 56 providers. DR DNASU; 20848; -. DR Ensembl; ENSMUST00000092671.12; ENSMUSP00000090342.6; ENSMUSG00000004040.17. [P42227-3] DR Ensembl; ENSMUST00000103114.8; ENSMUSP00000099403.2; ENSMUSG00000004040.17. [P42227-2] DR Ensembl; ENSMUST00000127638.8; ENSMUSP00000120152.2; ENSMUSG00000004040.17. [P42227-1] DR GeneID; 20848; -. DR KEGG; mmu:20848; -. DR UCSC; uc007lmp.1; mouse. [P42227-1] DR UCSC; uc007lmq.1; mouse. [P42227-3] DR AGR; MGI:103038; -. DR CTD; 6774; -. DR MGI; MGI:103038; Stat3. DR VEuPathDB; HostDB:ENSMUSG00000004040; -. DR eggNOG; KOG3667; Eukaryota. DR GeneTree; ENSGT01050000244905; -. DR HOGENOM; CLU_014189_3_0_1; -. DR InParanoid; P42227; -. DR OMA; RCLWEEN; -. DR OrthoDB; 7823at2759; -. DR PhylomeDB; P42227; -. DR TreeFam; TF318648; -. DR Reactome; R-MMU-1059683; Interleukin-6 signaling. DR Reactome; R-MMU-1266695; Interleukin-7 signaling. DR Reactome; R-MMU-1433557; Signaling by SCF-KIT. DR Reactome; R-MMU-186763; Downstream signal transduction. DR Reactome; R-MMU-201556; Signaling by ALK. DR Reactome; R-MMU-6783783; Interleukin-10 signaling. DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-MMU-8849474; PTK6 Activates STAT3. DR Reactome; R-MMU-8854691; Interleukin-20 family signaling. DR Reactome; R-MMU-8875791; MET activates STAT3. DR Reactome; R-MMU-8983432; Interleukin-15 signaling. DR Reactome; R-MMU-8984722; Interleukin-35 Signalling. DR Reactome; R-MMU-8985947; Interleukin-9 signaling. DR Reactome; R-MMU-9008059; Interleukin-37 signaling. DR Reactome; R-MMU-9020933; Interleukin-23 signaling. DR Reactome; R-MMU-9020956; Interleukin-27 signaling. DR Reactome; R-MMU-9020958; Interleukin-21 signaling. DR Reactome; R-MMU-9701898; STAT3 nuclear events downstream of ALK signaling. DR Reactome; R-MMU-9833482; PKR-mediated signaling. DR BioGRID-ORCS; 20848; 4 hits in 87 CRISPR screens. DR ChiTaRS; Stat3; mouse. DR EvolutionaryTrace; P42227; -. DR PRO; PR:P42227; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; P42227; Protein. DR Bgee; ENSMUSG00000004040; Expressed in right lung lobe and 293 other cell types or tissues. DR ExpressionAtlas; P42227; baseline and differential. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI. DR GO; GO:0005743; C:mitochondrial inner membrane; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0014069; C:postsynaptic density; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0140033; F:acetylation-dependent protein binding; ISS:UniProtKB. DR GO; GO:0031730; F:CCR5 chemokine receptor binding; ISO:MGI. DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:MGI. DR GO; GO:0004879; F:nuclear receptor activity; ISO:MGI. DR GO; GO:0070878; F:primary miRNA binding; ISO:MGI. DR GO; GO:0046983; F:protein dimerization activity; IPI:MGI. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0140610; F:RNA sequestering activity; ISO:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:0035591; F:signaling adaptor activity; ISO:MGI. DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW. DR GO; GO:0048708; P:astrocyte differentiation; IMP:UniProtKB. DR GO; GO:0030154; P:cell differentiation; ISO:MGI. DR GO; GO:0008283; P:cell population proliferation; IDA:MGI. DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI. DR GO; GO:0032870; P:cellular response to hormone stimulus; ISO:MGI. DR GO; GO:0097398; P:cellular response to interleukin-17; IDA:MGI. DR GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB. DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0006952; P:defense response; IBA:GO_Central. DR GO; GO:0042755; P:eating behavior; IMP:MGI. DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; ISO:MGI. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IMP:UniProtKB. DR GO; GO:0038154; P:interleukin-11-mediated signaling pathway; ISO:MGI. DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; ISO:MGI. DR GO; GO:0038110; P:interleukin-2-mediated signaling pathway; ISO:MGI. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0038113; P:interleukin-9-mediated signaling pathway; ISO:MGI. DR GO; GO:0030522; P:intracellular receptor signaling pathway; ISO:MGI. DR GO; GO:0033210; P:leptin-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:MGI. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0010507; P:negative regulation of autophagy; ISO:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0045820; P:negative regulation of glycolytic process; IMP:MGI. DR GO; GO:0010730; P:negative regulation of hydrogen peroxide biosynthetic process; ISO:MGI. DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProt. DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; IDA:UniProt. DR GO; GO:2001223; P:negative regulation of neuron migration; IGI:MGI. DR GO; GO:2000635; P:negative regulation of primary miRNA processing; ISO:MGI. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:MGI. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProt. DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IGI:BHF-UCL. DR GO; GO:1902728; P:positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; ISO:MGI. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:MGI. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI. DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; ISO:MGI. DR GO; GO:0006606; P:protein import into nucleus; ISS:UniProtKB. DR GO; GO:0060019; P:radial glial cell differentiation; IMP:UniProtKB. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISO:MGI. DR GO; GO:0097696; P:receptor signaling pathway via STAT; ISO:MGI. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:1900037; P:regulation of cellular response to hypoxia; ISO:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:0060259; P:regulation of feeding behavior; IMP:UniProtKB. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISO:MGI. DR GO; GO:0040014; P:regulation of multicellular organism growth; IMP:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0034097; P:response to cytokine; ISO:MGI. DR GO; GO:0032355; P:response to estradiol; ISO:MGI. DR GO; GO:0002931; P:response to ischemia; ISO:MGI. DR GO; GO:0044321; P:response to leptin; IDA:UniProtKB. DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central. DR GO; GO:0060221; P:retinal rod cell differentiation; IMP:MGI. DR GO; GO:0019953; P:sexual reproduction; IMP:MGI. DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; IMP:UniProtKB. DR GO; GO:0072538; P:T-helper 17 type immune response; ISS:UniProtKB. DR GO; GO:0001659; P:temperature homeostasis; IMP:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI. DR CDD; cd10374; SH2_STAT3; 1. DR CDD; cd16853; STAT3_CCD; 1. DR CDD; cd16847; STAT3_DBD; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.20.1050.20; STAT transcription factor, all-alpha domain; 1. DR Gene3D; 2.60.40.630; STAT transcription factor, DNA-binding domain; 1. DR Gene3D; 1.10.532.10; STAT transcription factor, N-terminal domain; 1. DR IDEAL; IID50277; -. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR035855; STAT3_SH2. DR InterPro; IPR048988; STAT_linker. DR InterPro; IPR036535; STAT_N_sf. DR InterPro; IPR013800; STAT_TF_alpha. DR InterPro; IPR015988; STAT_TF_coiled-coil. DR InterPro; IPR013801; STAT_TF_DNA-bd. DR InterPro; IPR012345; STAT_TF_DNA-bd_N. DR InterPro; IPR013799; STAT_TF_prot_interaction. DR PANTHER; PTHR11801; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; 1. DR PANTHER; PTHR11801:SF2; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF01017; STAT_alpha; 1. DR Pfam; PF02864; STAT_bind; 1. DR Pfam; PF02865; STAT_int; 1. DR Pfam; PF21354; STAT_linker; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF47655; STAT; 1. DR SUPFAM; SSF48092; Transcription factor STAT-4 N-domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; P42227; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Acute phase; Alternative splicing; KW Cytoplasm; Direct protein sequencing; DNA-binding; Nucleus; Phosphoprotein; KW Reference proteome; SH2 domain; Transcription; Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P40763" FT CHAIN 2..770 FT /note="Signal transducer and activator of transcription 3" FT /id="PRO_0000182418" FT DOMAIN 580..670 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT MOTIF 150..162 FT /note="Essential for nuclear import" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 49 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 87 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 601 FT /note="Allysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 601 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 615 FT /note="Allysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 615 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 631 FT /note="Allysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 631 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 685 FT /note="Allysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 685 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 705 FT /note="Phosphotyrosine; by FER and PTK6" FT /evidence="ECO:0000269|PubMed:11294897, FT ECO:0000269|PubMed:11553624, ECO:0000269|PubMed:19538478, FT ECO:0007744|PubMed:18034455" FT MOD_RES 707 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40763" FT MOD_RES 714 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 727 FT /note="Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, FT ZIPK/DAPK3 and PKC/PRKCE" FT /evidence="ECO:0000305|PubMed:11553624, FT ECO:0000305|PubMed:15004007, ECO:0000305|PubMed:20595392, FT ECO:0000305|PubMed:7543024, ECO:0007744|PubMed:21183079" FT VAR_SEQ 701 FT /note="Missing (in isoform Del-701)" FT /evidence="ECO:0000303|PubMed:7523373" FT /id="VSP_010475" FT VAR_SEQ 716..770 FT /note="TTCSNTIDLPMSPRTLDSLMQFGNNGEGAEPSAGGQFESLTFDMDLTSECAT FT SPM -> FIDAVWK (in isoform Stat3B)" FT /evidence="ECO:0000303|PubMed:7568080" FT /id="VSP_006287" FT MUTAGEN 77 FT /note="V->A: No effect on nuclear import; when associated FT with A-78 and W-174." FT /evidence="ECO:0000269|PubMed:15919823" FT MUTAGEN 78 FT /note="L->A: No effect on nuclear import; when associated FT with A-77 and W-174." FT /evidence="ECO:0000269|PubMed:15919823" FT MUTAGEN 174 FT /note="F->W: No effect on nuclear import; when associated FT with A-77 and A-78." FT /evidence="ECO:0000269|PubMed:15919823" FT MUTAGEN 609 FT /note="R->A: Nuclear localization to the same extent as FT wild-type; when associated with F-705." FT /evidence="ECO:0000269|PubMed:15919823" FT MUTAGEN 705 FT /note="Y->F: Nuclear localization to the same extent as FT wild-type; when associated with A-609." FT /evidence="ECO:0000269|PubMed:15919823" FT MUTAGEN 727 FT /note="S->A: Decreased transcriptional activation." FT /evidence="ECO:0000269|PubMed:15004007" FT CONFLICT 16 FT /note="E -> K (in Ref. 2; AAA19452)" FT /evidence="ECO:0000305" FT CONFLICT 25 FT /note="S -> T (in Ref. 2; AAA19452 and 4; AAC52612)" FT /evidence="ECO:0000305" FT CONFLICT 394 FT /note="M -> I (in Ref. 1; AAA37254)" FT /evidence="ECO:0000305" FT HELIX 3..8 FT /evidence="ECO:0007829|PDB:4ZIA" FT TURN 12..14 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 15..20 FT /evidence="ECO:0007829|PDB:4ZIA" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 28..33 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 35..40 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 43..46 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 50..73 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 77..94 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 98..120 FT /evidence="ECO:0007829|PDB:4ZIA" FT HELIX 139..180 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 199..237 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 239..251 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 261..290 FT /evidence="ECO:0007829|PDB:1BG1" FT TURN 297..301 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 302..320 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 321..328 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 345..353 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 356..358 FT /evidence="ECO:0007829|PDB:1BG1" FT TURN 359..361 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 363..369 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 371..373 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 375..377 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 384..388 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 391..393 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 400..402 FT /evidence="ECO:0007829|PDB:4E68" FT STRAND 404..415 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 418..420 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 426..428 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 439..447 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 450..457 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 461..466 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 467..469 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 470..483 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 492..494 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 501..515 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 522..533 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 546..549 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 557..559 FT /evidence="ECO:0007829|PDB:4E68" FT HELIX 561..574 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 575..577 FT /evidence="ECO:0007829|PDB:3CWG" FT HELIX 578..581 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 593..595 FT /evidence="ECO:0007829|PDB:1BG1" FT TURN 596..600 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 608..610 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 619..621 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 626..628 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 642..645 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 650..653 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 664..666 FT /evidence="ECO:0007829|PDB:1BG1" FT STRAND 671..673 FT /evidence="ECO:0007829|PDB:1BG1" FT TURN 674..676 FT /evidence="ECO:0007829|PDB:1BG1" FT TURN 679..683 FT /evidence="ECO:0007829|PDB:1BG1" FT HELIX 684..686 FT /evidence="ECO:0007829|PDB:1BG1" SQ SEQUENCE 770 AA; 88054 MW; 6C00626711C8012D CRC64; MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG QFESLTFDMD LTSECATSPM //