ID STAT3_HUMAN Reviewed; 770 AA. AC P40763; A8K7B8; K7ENL3; O14916; Q9BW54; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 2. DT 12-AUG-2020, entry version 225. DE RecName: Full=Signal transducer and activator of transcription 3 {ECO:0000312|HGNC:HGNC:11364}; DE AltName: Full=Acute-phase response factor; GN Name=STAT3 {ECO:0000312|HGNC:HGNC:11364}; GN Synonyms=APRF {ECO:0000312|HGNC:HGNC:11364}; 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 1), AND VARIANT TYR-561. RC TISSUE=Placenta; 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 1). RX PubMed=9630560; DOI=10.1016/s0378-1119(98)00185-1; RA Della Pietra L., Bressan A., Pezzotti A., Serlupi-Crescenzi O.; RT "Highly conserved amino-acid sequence between murine STAT3 and a revised RT human STAT3 sequence."; RL Gene 213:119-124(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Feinstein E., Adamsky S., Erlich S., Molitoris B.; RT "Methods for treating chronic kidney disease."; RL Patent number EP2440214, 18-APR-2012. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ILE-143. RG SeattleSNPs variation discovery resource; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND DEL-701). RC TISSUE=Kidney, and Pancreas; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 564-704. RC TISSUE=Liver; RA Della Pietra L., Bressan A., Pezzotti A.R., Serlupi-Crescenzi O.; RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases. RN [10] RP PHOSPHORYLATION AT SERINE RESIDUES. RX PubMed=7701321; DOI=10.1126/science.7701321; RA Zhang X., Blenis J., Li H.-C., Schindler C., Chen-Kiang S.; RT "Requirement of serine phosphorylation for formation of STAT-promoter RT complexes."; RL Science 267:1990-1994(1995). RN [11] RP INTERACTION WITH PIAS3. 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 [12] RP PHOSPHORYLATION BY BMX, INTERACTION WITH BMX, AND FUNCTION. RX PubMed=10688651; DOI=10.1128/mcb.20.6.2043-2054.2000; RA Tsai Y.T., Su Y.H., Fang S.S., Huang T.N., Qiu Y., Jou Y.S., Shih H.M., RA Kung H.J., Chen R.H.; RT "Etk, a Btk family tyrosine kinase, mediates cellular transformation by RT linking Src to STAT3 activation."; RL Mol. Cell. Biol. 20:2043-2054(2000). RN [13] RP FUNCTION IN IL6 SIGNALING, PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN2. RX PubMed=12359225; DOI=10.1016/s0006-291x(02)02291-x; RA Yamamoto T., Sekine Y., Kashima K., Kubota A., Sato N., Aoki N., RA Matsuda T.; RT "The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates RT interleukin-6-mediated signaling pathway through STAT3 dephosphorylation."; RL Biochem. Biophys. Res. Commun. 297:811-817(2002). RN [14] RP INTERACTION WITH NCOA1. RX PubMed=11773079; DOI=10.1074/jbc.m111486200; RA Giraud S., Bienvenu F., Avril S., Gascan H., Heery D.M., Coqueret O.; RT "Functional interaction of STAT3 transcription factor with the coactivator RT NcoA/SRC1a."; RL J. Biol. Chem. 277:8004-8011(2002). RN [15] RP INTERACTION WITH HCV CORE PROTEIN. RX PubMed=12208879; DOI=10.1084/jem.20012127; RA Yoshida T., Hanada T., Tokuhisa T., Kosai K., Sata M., Kohara M., RA Yoshimura A.; RT "Activation of STAT3 by the hepatitis C virus core protein leads to RT cellular transformation."; RL J. Exp. Med. 196:641-653(2002). RN [16] RP INTERACTION WITH IL23R. RX PubMed=12023369; DOI=10.4049/jimmunol.168.11.5699; RA Parham C., Chirica M., Timans J., Vaisberg E., Travis M., Cheung J., RA Pflanz S., Zhang R., Singh K.P., Vega F., To W., Wagner J., RA O'Farrell A.-M., McClanahan T.K., Zurawski S., Hannum C., Gorman D., RA Rennick D.M., Kastelein R.A., de Waal Malefyt R., Moore K.W.; RT "A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 RT and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [17] RP FUNCTION IN EGFR SIGNALING, AND INTERACTION WITH EGFR. RX PubMed=12873986; RA Shao H., Cheng H.Y., Cook R.G., Tweardy D.J.; RT "Identification and characterization of signal transducer and activator of RT transcription 3 recruitment sites within the epidermal growth factor RT receptor."; RL Cancer Res. 63:3923-3930(2003). RN [18] RP PHOSPHORYLATION AT TYR-705 AND SER-727. RX PubMed=12763138; DOI=10.1016/s0301-472x(03)00045-6; RA Wierenga A.T., Vogelzang I., Eggen B.J., Vellenga E.; RT "Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid RT cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway."; RL Exp. Hematol. 31:398-405(2003). RN [19] RP REVIEW ON ROLE IN KIT SIGNALING. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [20] RP FUNCTION, AND INTERACTION WITH IL31RA. RX PubMed=15194700; DOI=10.1074/jbc.m401122200; RA Dreuw A., Radtke S., Pflanz S., Lippok B.E., Heinrich P.C., Hermanns H.M.; RT "Characterization of the signaling capacities of the novel gp130-like RT cytokine receptor."; RL J. Biol. Chem. 279:36112-36120(2004). RN [21] RP PHOSPHORYLATION AT SER-727 BY IRAK1. RX PubMed=15465816; DOI=10.1074/jbc.m410369200; RA Huang Y., Li T., Sane D.C., Li L.; RT "IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced RT interleukin-10 gene expression."; RL J. Biol. Chem. 279:51697-51703(2004). RN [22] RP INTERACTION WITH TMF1. RX PubMed=15467733; DOI=10.1038/sj.onc.1208149; RA Perry E., Tsruya R., Levitsky P., Pomp O., Taller M., Weisberg S., RA Parris W., Kulkarni S., Malovani H., Pawson T., Shpungin S., Nir U.; RT "TMF/ARA160 is a BC-box-containing protein that mediates the degradation of RT Stat3."; RL Oncogene 23:8908-8919(2004). RN [23] RP INTERACTION WITH PELP1. RX PubMed=15994929; DOI=10.1158/0008-5472.can-04-4664; RA Manavathi B., Nair S.S., Wang R.-A., Kumar R., Vadlamudi R.K.; RT "Proline-, glutamic acid-, and leucine-rich protein-1 is essential in RT growth factor regulation of signal transducers and activators of RT transcription 3 activation."; RL Cancer Res. 65:5571-5577(2005). RN [24] RP PHOSPHORYLATION AT SER-727 BY ZIPK/DAPK3, INTERACTION WITH ZIPK/DAPK3, AND RP SUBCELLULAR LOCATION. RX PubMed=16219639; DOI=10.1093/intimm/dxh331; RA Sato N., Kawai T., Sugiyama K., Muromoto R., Imoto S., Sekine Y., RA Ishida M., Akira S., Matsuda T.; RT "Physical and functional interactions between STAT3 and ZIP kinase."; RL Int. Immunol. 17:1543-1552(2005). RN [25] RP INTERACTION WITH SOCS7. RX PubMed=15677474; DOI=10.1074/jbc.m411596200; RA Martens N., Uzan G., Wery M., Hooghe R., Hooghe-Peters E.L., Gertler A.; RT "Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and RT leptin signaling by interacting with STAT5 or STAT3 and attenuating their RT nuclear translocation."; RL J. Biol. Chem. 280:13817-13823(2005). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT TYR-704 (ISOFORM DEL-701), AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [27] RP PHOSPHORYLATION AT TYR-705 BY PTK6. RX PubMed=16568091; DOI=10.1038/sj.onc.1209501; RA Liu L., Gao Y., Qiu H., Miller W.T., Poli V., Reich N.C.; RT "Identification of STAT3 as a specific substrate of breast tumor kinase."; RL Oncogene 25:4904-4912(2006). RN [28] RP INTERACTION WITH PRKCE, AND PHOSPHORYLATION AT SER-727. RX PubMed=17875724; DOI=10.1158/0008-5472.can-07-1604; RA Aziz M.H., Manoharan H.T., Church D.R., Dreckschmidt N.E., Zhong W., RA Oberley T.D., Wilding G., Verma A.K.; RT "Protein kinase Cepsilon interacts with signal transducers and activators RT of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its RT constitutive activation in prostate cancer."; RL Cancer Res. 67:8828-8838(2007). RN [29] RP SUBCELLULAR LOCATION, 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 [30] RP FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF 434-GLU-GLU-435 AND TYR-705. RX PubMed=17344214; DOI=10.1074/jbc.m609798200; RA Saxena N.K., Vertino P.M., Anania F.A., Sharma D.; RT "leptin-induced growth stimulation of breast cancer cells involves RT recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 RT promoter via activation of Stat3."; RL J. Biol. Chem. 282:13316-13325(2007). RN [31] RP INTERACTION WITH CDK9. RX PubMed=17956865; DOI=10.1074/jbc.m706458200; RA Hou T., Ray S., Brasier A.R.; RT "The functional role of an interleukin 6-inducible CDK9.STAT3 complex in RT human gamma-fibrinogen gene expression."; RL J. Biol. Chem. 282:37091-37102(2007). RN [32] RP FUNCTION. RX PubMed=18242580; DOI=10.1016/j.bbrc.2007.04.004; RA Jiang H., Yu J., Guo H., Song H., Chen S.; RT "up-regulation of survivin by leptin/STAT3 signaling in MCF-7 cells."; RL Biochem. Biophys. Res. Commun. 368:1-5(2008). RN [33] RP PHOSPHORYLATION AT SER-727 BY DYRK2. RX PubMed=18599021; DOI=10.1016/j.bcp.2008.05.021; RA Yoshida K.; RT "Role for DYRK family kinases on regulation of apoptosis."; RL Biochem. Pharmacol. 76:1389-1394(2008). RN [34] RP IDENTIFICATION IN A COMPLEX WITH LYN AND PAG1. RX PubMed=18070987; DOI=10.1182/blood-2007-05-090985; RA Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D., RA van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U., Borisch B., RA Hoessli D.C.; RT "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine RT kinase in human B-NHL rafts."; RL Blood 111:2310-2320(2008). RN [35] RP INTERACTION WITH ARL2BP, PHOSPHORYLATION AT SERINE RESIDUES, AND RP SUBCELLULAR LOCATION. 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 [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP 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 [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [39] RP INTERACTION WITH FER, AND PHOSPHORYLATION BY FER. RX PubMed=19147545; DOI=10.1158/1541-7786.mcr-08-0117; RA Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G., RA Chevalier S.; RT "The Fer tyrosine kinase cooperates with interleukin-6 to activate signal RT transducer and activator of transcription 3 and promote human prostate RT cancer cell growth."; RL Mol. Cancer Res. 7:142-155(2009). RN [40] RP INTERACTION WITH BIRC5/SURVIVIN. RX PubMed=20826784; DOI=10.1074/jbc.m110.152777; RA Wang H., Holloway M.P., Ma L., Cooper Z.A., Riolo M., Samkari A., RA Elenitoba-Johnson K.S., Chin Y.E., Altura R.A.; RT "Acetylation directs survivin nuclear localization to repress STAT3 RT oncogenic activity."; RL J. Biol. Chem. 285:36129-36137(2010). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [42] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [43] RP PHOSPHORYLATION AT TYR-705 IN RESPONSE TO KIT SIGNALING, AND RP PHOSPHORYLATION AT SER-727. 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 [44] RP FUNCTION, AND INTERACTION WITH EIF2AK2. 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 [45] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705; THR-714 AND SER-727, RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-704 (ISOFORM DEL-701), AND 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 [49] RP INTERACTION WITH INPP5F, AND MUTAGENESIS OF TYR-705. RX PubMed=25476455; DOI=10.1038/srep07330; RA Kim H.S., Li A., Ahn S., Song H., Zhang W.; RT "Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 activity RT and suppresses gliomas tumorigenicity."; RL Sci. Rep. 4:7330-7330(2014). RN [50] RP INTERACTION WITH FGFR4. RX PubMed=26675719; DOI=10.1038/nature16449; RA Ulaganathan V.K., Sperl B., Rapp U.R., Ullrich A.; RT "Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding RT site."; RL Nature 528:570-574(2015). RN [51] RP SUBCELLULAR LOCATION, SUBUNIT, ALLYSINE AT LYS-601; LYS-615; LYS-631 AND RP LYS-685, AND ACETYLATION AT LYS-601; LYS-615; LYS-631; LYS-685 AND LYS-707. RX PubMed=28065600; DOI=10.1016/j.molcel.2016.12.002; RA Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., RA Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., RA Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J., Zhang X., Cheng J., RA Chang Z., Chin Y.E.; RT "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 RT deacetylation and deacetylimination modulation."; RL Mol. Cell 65:296-309(2017). RN [52] RP INTERACTION WITH S.TYPHIMURIUM SARA (MICROBIAL INFECTION), AND RP PHOSPHORYLATION AT TYR-705 (MICROBIAL INFECTION). 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 [53] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ZDHHC19, STEAROYLATION, RP PALMITOYLATION AT CYS-687 AND CYS-712, PHOSPHORYLATION AT TYR-705, RP MUTAGENESIS OF ALA-651; CYS-687; TYR-705 AND CYS-712, AND INDUCTION. RX PubMed=31462771; DOI=10.1038/s41586-019-1511-x; RA Niu J., Sun Y., Chen B., Zheng B., Jarugumilli G.K., Walker S.R., RA Hata A.N., Mino-Kenudson M., Frank D.A., Wu X.; RT "Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through RT S-palmitoylation."; RL Nature 573:139-143(2019). RN [54] RP SUBCELLULAR LOCATION, INTERACTION WITH PHB, PHOSPHORYLATION AT TYR-705 AND RP SER-727, AND TISSUE SPECIFICITY. RX PubMed=31899195; DOI=10.1016/j.imlet.2019.12.008; RA Zhang J., Sun Z., Wu Q., Shen J.; RT "Prohibitin 1 interacts with signal transducer and activator of RT transcription 3 in T-helper 17 cells."; RL Immunol. Lett. 219:8-14(2020). RN [55] RP VARIANTS HIES1 GLN-382; LEU-382; TRP-382; LEU-384; SER-384; GLN-423; RP VAL-463 DEL; ASN-611; VAL-621; ILE-622; LEU-637; MET-637; GLN-644 DEL AND RP CYS-657. RX PubMed=17881745; DOI=10.1056/nejmoa073687; RA Holland S.M., DeLeo F.R., Elloumi H.Z., Hsu A.P., Uzel G., Brodsky N., RA Freeman A.F., Demidowich A., Davis J., Turner M.L., Anderson V.L., RA Darnell D.N., Welch P.A., Kuhns D.B., Frucht D.M., Malech H.L., RA Gallin J.I., Kobayashi S.D., Whitney A.R., Voyich J.M., Musser J.M., RA Woellner C., Schaffer A.A., Puck J.M., Grimbacher B.; RT "STAT3 mutations in the hyper-IgE syndrome."; RL N. Engl. J. Med. 357:1608-1619(2007). RN [56] RP VARIANTS HIES1 GLN-382; TRP-382; ILE-389; TYR-437 AND VAL-463 DEL, AND RP CHARACTERIZATION OF VARIANTS HIES1 GLN-382; TRP-382; ILE-389; TYR-437 AND RP VAL-463 DEL. RX PubMed=17676033; DOI=10.1038/nature06096; RA Minegishi Y., Saito M., Tsuchiya S., Tsuge I., Takada H., Hara T., RA Kawamura N., Ariga T., Pasic S., Stojkovic O., Metin A., Karasuyama H.; RT "Dominant-negative mutations in the DNA-binding domain of STAT3 cause RT hyper-IgE syndrome."; RL Nature 448:1058-1062(2007). RN [57] RP VARIANT HIES1 ILE-389. RX PubMed=23342295; DOI=10.2500/ar.2012.3.0035; RA Crosby K., Swender D., Chernin L., Hafez-Khayyata S., Ochs H., RA Tcheurekdjian H., Hostoffer R.; RT "Signal transducer and activator of transcription 3 mutation with invasive RT eosinophilic disease."; RL Allergy Rhinol. (Providence) 3:E94-E97(2012). RN [58] RP VARIANTS ADMIO1 ARG-392; LYS-646; ASN-658 AND MET-716, AND INVOLVEMENT IN RP ADMIO1. RX PubMed=25038750; DOI=10.1038/ng.3040; RA Flanagan S.E., Haapaniemi E., Russell M.A., Caswell R., Lango Allen H., RA De Franco E., McDonald T.J., Rajala H., Ramelius A., Barton J., RA Heiskanen K., Heiskanen-Kosma T., Kajosaari M., Murphy N.P., Milenkovic T., RA Seppaenen M., Lernmark A., Mustjoki S., Otonkoski T., Kere J., Morgan N.G., RA Ellard S., Hattersley A.T.; RT "Activating germline mutations in STAT3 cause early-onset multi-organ RT autoimmune disease."; RL Nat. Genet. 46:812-814(2014). RN [59] RP VARIANTS HIES1 TRP-382; TYR-395; TYR-425; MET-637 AND CYS-657, RP CHARACTERIZATION OF VARIANTS HIES1 TRP-382; TYR-395; TYR-425; MET-637 AND RP CYS-657, AND PHOSPHORYLATION AT TYR-705 AND SER-727. RX PubMed=26293184; DOI=10.1111/cge.12658; RA Alcantara-Montiel J.C., Staines-Boone T., Lopez-Herrera G., RA Espinosa-Rosales F., Espinosa-Padilla S.E., Hernandez-Rivas R., RA Santos-Argumedo L.; RT "Functional characterization of two new STAT3 mutations associated with RT hyper-IgE syndrome in a Mexican cohort."; RL Clin. Genet. 89:217-221(2016). RN [60] RP VARIANT ADMIO1 SER-330, AND CHARACTERIZATION OF VARIANT ADMIO1 SER-330. RX PubMed=28073828; DOI=10.2337/db16-0867; RA Velayos T., Martinez R., Alonso M., Garcia-Etxebarria K., Aguayo A., RA Camarero C., Urrutia I., Martinez de LaPiscina I., Barrio R., Santin I., RA Castano L.; RT "An activating mutation in STAT3 results in neonatal diabetes through RT reduced insulin synthesis."; RL Diabetes 66:1022-1029(2017). CC -!- FUNCTION: Signal transducer and transcription activator that mediates CC cellular responses to interleukins, KITLG/SCF, LEP and other growth CC factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, CC PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:23084476, CC PubMed:31462771). Once activated, recruits coactivators, such as NCOA1 CC or MED1, to the promoter region of the target gene (PubMed:17344214). CC May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and CC FGFR4 (PubMed:12873986). Upon activation of IL6ST/gp130 signaling by CC interleukin-6 (IL6), binds to the IL6-responsive elements identified in CC the promoters of various acute-phase protein genes (PubMed:12359225). CC Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator CC of inflammatory response by regulating differentiation of naive CD4(+) CC T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation CC and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 CC dimerization and inhibit its transcription activity (PubMed:28065600). CC Involved in cell cycle regulation by inducing the expression of key CC genes for the progression from G1 to S phase, such as CCND1 CC (PubMed:17344214). Mediates the effects of LEP on melanocortin CC production, body energy homeostasis and lactation (By similarity). May CC play an apoptotic role by transctivating BIRC5 expression under LEP CC activation (PubMed:18242580). Cytoplasmic STAT3 represses CC macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). CC Plays a crucial role in basal beta cell functions, such as regulation CC of insulin secretion (By similarity). {ECO:0000250|UniProtKB:P42227, CC ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, CC ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, CC ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580, CC ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:28065600}. CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member (at least STAT1) (PubMed:28065600). Interacts with IL31RA, CC NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1 (PubMed:15994929, CC PubMed:15194700, PubMed:17344214, PubMed:15677474, PubMed:15467733) (By CC similarity). Interacts with IL23R in presence of IL23 CC (PubMed:12023369). Interacts (via SH2 domain) with NLK. Interacts with CC ARL2BP; the interaction is enhanced by LIF and JAK1 expression (By CC similarity). Interacts with KPNA4 and KPNA5; KPNA4 may be the primary CC mediator of nuclear import (By similarity). Interacts with CAV2; the CC interaction is increased on insulin-induced tyrosine phosphorylation of CC CAV2 and leads to STAT3 activation (By similarity). Interacts with CC ARL2BP; interaction is enhanced with ARL2 (PubMed:18234692). Interacts CC with NEK6 (By similarity). Binds to CDK9 when activated and nuclear CC (PubMed:17956865). Interacts with BMX (PubMed:10688651). Interacts with CC ZIPK/DAPK3 (PubMed:16219639). Interacts with PIAS3; the interaction CC occurs on stimulation by IL6, CNTF or OSM and inhibits the DNA binding CC activity of STAT3 (PubMed:9388184). In prostate cancer cells, interacts CC with STAT3 and promotes DNA binding activity of STAT3. Interacts with CC STMN3, antagonizing its microtubule-destabilizing activity. Interacts CC with the 'Lys-129' acetylated form of BIRC5/survivin (PubMed:20826784). CC Interacts with FER (PubMed:19147545). Interacts (via SH2 domain) with CC EIF2AK2/PKR (via the kinase catalytic domain) (PubMed:23084476). CC Interacts with STAT3; the interaction is independent of STAT3 Tyr-705 CC phosphorylation status (PubMed:25476455). Interacts with FGFR4 CC (PubMed:26675719). Interacts with OCAD1 (By similarity). Interacts with CC ZDHHC19, leading to palmitoylation which promotes homodimerization and CC activation (PubMed:31462771). Interacts (unphosphorylated or CC phosphorylated at Ser-727) with PHB (PubMed:31899195). CC {ECO:0000250|UniProtKB:P42227, ECO:0000250|UniProtKB:P52631, CC ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:11773079, CC ECO:0000269|PubMed:12023369, ECO:0000269|PubMed:12873986, CC ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:15467733, CC ECO:0000269|PubMed:15677474, ECO:0000269|PubMed:15994929, CC ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17344214, CC ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:17956865, CC ECO:0000269|PubMed:18070987, ECO:0000269|PubMed:18234692, CC ECO:0000269|PubMed:19147545, ECO:0000269|PubMed:20826784, CC ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:25476455, CC ECO:0000269|PubMed:26675719, ECO:0000269|PubMed:28065600, CC ECO:0000269|PubMed:31462771, ECO:0000269|PubMed:31899195, CC ECO:0000269|PubMed:9388184}. CC -!- SUBUNIT: (Microbial infection) Interacts with HCV core protein. CC {ECO:0000269|PubMed:12208879}. CC -!- SUBUNIT: (Microbial infection) Interacts with S.typhimurium SarA. CC {ECO:0000269|PubMed:29924996}. CC -!- INTERACTION: CC P40763; O14874: BCKDK; NbExp=2; IntAct=EBI-518675, EBI-1046765; CC P40763; Q96G01: BICD1; NbExp=2; IntAct=EBI-518675, EBI-1104509; CC P40763; P51451: BLK; NbExp=9; IntAct=EBI-518675, EBI-2105445; CC P40763; P51813: BMX; NbExp=8; IntAct=EBI-518675, EBI-696657; CC P40763; P07384: CAPN1; NbExp=2; IntAct=EBI-518675, EBI-1542113; CC P40763; P50750: CDK9; NbExp=2; IntAct=EBI-518675, EBI-1383449; CC P40763; P31146: CORO1A; NbExp=2; IntAct=EBI-518675, EBI-1046676; CC P40763; Q99062: CSF3R; NbExp=4; IntAct=EBI-518675, EBI-7331284; CC P40763; Q9UER7: DAXX; NbExp=4; IntAct=EBI-518675, EBI-77321; CC P40763; O95661: DIRAS3; NbExp=3; IntAct=EBI-518675, EBI-6139214; CC P40763; Q13011: ECH1; NbExp=2; IntAct=EBI-518675, EBI-711968; CC P40763; P30084: ECHS1; NbExp=3; IntAct=EBI-518675, EBI-719602; CC P40763; P00533: EGFR; NbExp=15; IntAct=EBI-518675, EBI-297353; CC P40763; P04626: ERBB2; NbExp=9; IntAct=EBI-518675, EBI-641062; CC P40763; Q15910: EZH2; NbExp=5; IntAct=EBI-518675, EBI-530054; CC P40763; Q8TAE8: GADD45GIP1; NbExp=4; IntAct=EBI-518675, EBI-372506; CC P40763; Q9BVP2: GNL3; NbExp=2; IntAct=EBI-518675, EBI-641642; CC P40763; P12268: IMPDH2; NbExp=3; IntAct=EBI-518675, EBI-353389; CC P40763; P23458: JAK1; NbExp=2; IntAct=EBI-518675, EBI-1383438; CC P40763; Q07666: KHDRBS1; NbExp=2; IntAct=EBI-518675, EBI-1364; CC P40763; P25791: LMO2; NbExp=3; IntAct=EBI-518675, EBI-739696; CC P40763; O43318: MAP3K7; NbExp=4; IntAct=EBI-518675, EBI-358684; CC P40763; P45984: MAPK9; NbExp=2; IntAct=EBI-518675, EBI-713568; CC P40763; P45984-1: MAPK9; NbExp=3; IntAct=EBI-518675, EBI-713586; CC P40763; Q8TE76: MORC4; NbExp=2; IntAct=EBI-518675, EBI-3940432; CC P40763; Q92665: MRPS31; NbExp=2; IntAct=EBI-518675, EBI-720602; CC P40763; Q14938-3: NFIX; NbExp=3; IntAct=EBI-518675, EBI-20559045; CC P40763; Q14938-4: NFIX; NbExp=3; IntAct=EBI-518675, EBI-20558886; CC P40763; P22736: NR4A1; NbExp=3; IntAct=EBI-518675, EBI-721550; CC P40763; Q9ULD0: OGDHL; NbExp=2; IntAct=EBI-518675, EBI-3940481; CC P40763; P06401: PGR; NbExp=3; IntAct=EBI-518675, EBI-78539; CC P40763; Q96HA1-2: POM121; NbExp=3; IntAct=EBI-518675, EBI-11956563; CC P40763; P32119: PRDX2; NbExp=4; IntAct=EBI-518675, EBI-1266300; CC P40763; P18031: PTPN1; NbExp=2; IntAct=EBI-518675, EBI-968788; CC P40763; Q04206: RELA; NbExp=4; IntAct=EBI-518675, EBI-73886; CC P40763; P07949: RET; NbExp=3; IntAct=EBI-518675, EBI-2480756; CC P40763; O75116: ROCK2; NbExp=3; IntAct=EBI-518675, EBI-366288; CC P40763; P46781: RPS9; NbExp=2; IntAct=EBI-518675, EBI-351206; CC P40763; O00570: SOX1; NbExp=2; IntAct=EBI-518675, EBI-2935583; CC P40763; P08047: SP1; NbExp=4; IntAct=EBI-518675, EBI-298336; CC P40763; P30626: SRI; NbExp=3; IntAct=EBI-518675, EBI-750459; CC P40763; P42224: STAT1; NbExp=5; IntAct=EBI-518675, EBI-1057697; CC P40763; P40763: STAT3; NbExp=8; IntAct=EBI-518675, EBI-518675; CC P40763; Q06520: SULT2A1; NbExp=2; IntAct=EBI-518675, EBI-3921363; CC P40763; P43405: SYK; NbExp=10; IntAct=EBI-518675, EBI-78302; CC P40763; Q810M5: Zdhhc19; Xeno; NbExp=4; IntAct=EBI-518675, EBI-22225085; CC P40763; Q9DUM3; Xeno; NbExp=4; IntAct=EBI-518675, EBI-7971837; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28065600, CC ECO:0000269|PubMed:31462771, ECO:0000269|PubMed:31899195}. Nucleus CC {ECO:0000269|PubMed:28065600, ECO:0000269|PubMed:31462771, CC ECO:0000269|PubMed:31899195}. Note=Shuttles between the nucleus and the CC cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation CC and dimerization, in response to signaling by activated FGFR1, FGFR2, CC FGFR3 or FGFR4. Constitutive nuclear presence is independent of CC tyrosine phosphorylation. Predominantly present in the cytoplasm CC without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, CC accumulates in the nucleus. The complex composed of BART and ARL2 plays CC an important role in the nuclear translocation and retention of STAT3. CC Identified in a complex with LYN and PAG1. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P40763-1; Sequence=Displayed; CC Name=Del-701; CC IsoId=P40763-2; Sequence=VSP_010474; CC Name=3; CC IsoId=P40763-3; Sequence=VSP_055918, VSP_055919; CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal CC muscle, kidney and pancreas. Expressed in naive CD4(+) T cells as well CC as T-helper Th17, Th1 and Th2 cells (PubMed:31899195). CC {ECO:0000269|PubMed:31899195}. CC -!- INDUCTION: Positive feedback loop through phosphorylation and CC palmitoylation in response to stimulation with palmitic acid and CC cytokines. {ECO:0000269|PubMed:31462771}. CC -!- PTM: Tyrosine phosphorylated upon stimulation with EGF. Tyrosine CC phosphorylated in response to constitutively activated FGFR1, FGFR2, CC FGFR3 and FGFR4 (By similarity). Activated through tyrosine CC phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, CC IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. CC Activated KIT promotes phosphorylation on tyrosine residues and CC subsequent translocation to the nucleus. 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. Upon LPS challenge, CC phosphorylated within the nucleus by IRAK1. Upon erythropoietin CC treatment, phosphorylated on Ser-727 by RPS6KA5. Phosphorylation at CC Tyr-705 by PTK6 or FER leads to an increase of its transcriptional CC activity (PubMed:12763138, PubMed:16568091, PubMed:21135090, CC PubMed:31462771). Dephosphorylation on tyrosine residues by PTPN2 CC negatively regulates IL6/interleukin-6 signaling. CC {ECO:0000250|UniProtKB:P42227, ECO:0000269|PubMed:10688651, CC ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12763138, CC ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:16219639, CC ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:17344214, CC ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:18234692, CC ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19147545, CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:31462771, CC ECO:0000269|PubMed:7701321}. CC -!- PTM: Acetylated on lysine residues by CREBBP. Deacetylation by LOXL3 CC leads to disrupt STAT3 dimerization and inhibit STAT3 transcription CC activity (PubMed:28065600). Oxidation of lysine residues to allysine on CC STAT3 preferentially takes place on lysine residues that are acetylated CC (PubMed:28065600). {ECO:0000269|PubMed:28065600}. CC -!- PTM: Some lysine residues are oxidized to allysine by LOXL3, leading to CC disrupt STAT3 dimerization and inhibit STAT3 transcription activity CC (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 CC preferentially takes place on lysine residues that are acetylated CC (PubMed:28065600). {ECO:0000269|PubMed:28065600}. CC -!- PTM: (Microbial infection) Phosphorylated on Tyr-705 in the presence of CC S.typhimurium SarA. {ECO:0000269|PubMed:29924996}. CC -!- PTM: S-palmitoylated by ZDHHC19 in SH2 putative lipid-binding pockets, CC leading to homodimerization (PubMed:31462771). Nuclear STAT3 is highly CC palmitoylated (about 75%) compared with cytoplasmic STAT3 (about 20%) CC (PubMed:31462771). {ECO:0000269|PubMed:31462771}. CC -!- PTM: S-stearoylated, probably by ZDHHC19. {ECO:0000269|PubMed:31462771, CC ECO:0000305|PubMed:31462771}. CC -!- DISEASE: Hyper-IgE recurrent infection syndrome 1, autosomal dominant CC (HIES1) [MIM:147060]: A rare disorder of immunity and connective tissue CC characterized by immunodeficiency, chronic eosinophilia, distinctive CC coarse facial appearance, abnormal dentition, hyperextensibility of the CC joints, and bone fractures. {ECO:0000269|PubMed:17676033, CC ECO:0000269|PubMed:17881745, ECO:0000269|PubMed:23342295, CC ECO:0000269|PubMed:26293184}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- DISEASE: Autoimmune disease, multisystem, infantile-onset, 1 (ADMIO1) CC [MIM:615952]: A disorder characterized by early childhood onset of a CC spectrum of autoimmune manifestations affecting multiple organs, CC including insulin-dependent diabetes mellitus and autoimmune CC enteropathy or celiac disease. Other features include short stature, CC non-specific dermatitis, hypothyroidism, autoimmune arthritis, and CC delayed puberty. {ECO:0000269|PubMed:25038750, CC ECO:0000269|PubMed:28073828}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT3 entry; CC URL="https://en.wikipedia.org/wiki/STAT3"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html"; CC -!- WEB RESOURCE: Name=STAT3base; Note=STAT3 mutation db; CC URL="http://structure.bmc.lu.se/idbase/STAT3base/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/stat3/"; 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; L29277; AAA58374.1; -; mRNA. DR EMBL; AJ012463; CAA10032.1; -; mRNA. DR EMBL; JB252046; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK291933; BAF84622.1; -; mRNA. DR EMBL; AY572796; AAS66986.1; -; Genomic_DNA. DR EMBL; AC087691; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471152; EAW60822.1; -; Genomic_DNA. DR EMBL; BC000627; AAH00627.1; -; mRNA. DR EMBL; BC014482; AAH14482.1; -; mRNA. DR EMBL; AF029311; AAB84254.1; -; mRNA. DR CCDS; CCDS32656.1; -. [P40763-1] DR CCDS; CCDS32657.1; -. [P40763-2] DR CCDS; CCDS59288.1; -. [P40763-3] DR PIR; A54444; A54444. DR RefSeq; NP_003141.2; NM_003150.3. [P40763-2] DR RefSeq; NP_644805.1; NM_139276.2. [P40763-1] DR RefSeq; NP_998827.1; NM_213662.1. [P40763-3] DR RefSeq; XP_005257673.2; XM_005257616.3. DR RefSeq; XP_005257674.2; XM_005257617.3. DR RefSeq; XP_011523447.1; XM_011525145.2. DR RefSeq; XP_011523448.1; XM_011525146.2. DR RefSeq; XP_016880461.1; XM_017024972.1. DR RefSeq; XP_016880464.1; XM_017024975.1. DR PDB; 5AX3; X-ray; 2.98 A; B=571-582. DR PDB; 5U5S; NMR; -; B=81-92. DR PDB; 6NJS; X-ray; 2.70 A; A=127-688. DR PDB; 6NUQ; X-ray; 3.15 A; A=127-688. DR PDB; 6QHD; X-ray; 2.85 A; A/B=127-715. DR PDBsum; 5AX3; -. DR PDBsum; 5U5S; -. DR PDBsum; 6NJS; -. DR PDBsum; 6NUQ; -. DR PDBsum; 6QHD; -. DR SMR; P40763; -. DR BioGRID; 112651; 282. DR CORUM; P40763; -. DR DIP; DIP-33584N; -. DR ELM; P40763; -. DR IntAct; P40763; 208. DR MINT; P40763; -. DR STRING; 9606.ENSP00000264657; -. DR BindingDB; P40763; -. DR ChEMBL; CHEMBL4026; -. DR DrugBank; DB05959; ENMD-1198. DR DrugCentral; P40763; -. DR GuidetoPHARMACOLOGY; 2994; -. DR MoonDB; P40763; Predicted. DR GlyGen; P40763; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P40763; -. DR MetOSite; P40763; -. DR PhosphoSitePlus; P40763; -. DR SwissPalm; P40763; -. DR BioMuta; STAT3; -. DR DMDM; 48429227; -. DR CPTAC; CPTAC-1275; -. DR CPTAC; CPTAC-1276; -. DR CPTAC; CPTAC-1751; -. DR EPD; P40763; -. DR jPOST; P40763; -. DR MassIVE; P40763; -. DR MaxQB; P40763; -. DR PaxDb; P40763; -. DR PeptideAtlas; P40763; -. DR PRIDE; P40763; -. DR ProteomicsDB; 55378; -. [P40763-1] DR ProteomicsDB; 55379; -. [P40763-2] DR Antibodypedia; 660; 2383 antibodies. DR DNASU; 6774; -. DR Ensembl; ENST00000264657; ENSP00000264657; ENSG00000168610. [P40763-1] DR Ensembl; ENST00000404395; ENSP00000384943; ENSG00000168610. [P40763-2] DR Ensembl; ENST00000585517; ENSP00000467000; ENSG00000168610. [P40763-3] DR Ensembl; ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1] DR GeneID; 6774; -. DR KEGG; hsa:6774; -. DR UCSC; uc002hzl.2; human. [P40763-1] DR CTD; 6774; -. DR DisGeNET; 6774; -. DR EuPathDB; HostDB:ENSG00000168610.14; -. DR GeneCards; STAT3; -. DR GeneReviews; STAT3; -. DR HGNC; HGNC:11364; STAT3. DR HPA; ENSG00000168610; Low tissue specificity. DR MalaCards; STAT3; -. DR MIM; 102582; gene. DR MIM; 147060; phenotype. DR MIM; 615952; phenotype. DR neXtProt; NX_P40763; -. DR OpenTargets; ENSG00000168610; -. DR Orphanet; 520; Acute promyelocytic leukemia. DR Orphanet; 2314; Autosomal dominant hyper-IgE syndrome. DR Orphanet; 512017; Chronic lymphoproliferative disorder of natural killer cells. DR Orphanet; 99885; Permanent neonatal diabetes mellitus. DR Orphanet; 438159; STAT3-related early-onset multisystem autoimmune disease. DR Orphanet; 86872; T-cell large granular lymphocyte leukemia. DR PharmGKB; PA337; -. DR eggNOG; KOG3667; Eukaryota. DR GeneTree; ENSGT00990000203599; -. DR HOGENOM; CLU_014189_3_0_1; -. DR InParanoid; P40763; -. DR KO; K04692; -. DR OMA; GKYCRSE; -. DR OrthoDB; 327469at2759; -. DR PhylomeDB; P40763; -. DR TreeFam; TF318648; -. DR PathwayCommons; P40763; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-111453; BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members. DR Reactome; R-HSA-1266695; Interleukin-7 signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-198745; Signalling to STAT3. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2586552; Signaling by Leptin. DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation. DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis. DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-8849474; PTK6 Activates STAT3. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8875791; MET activates STAT3. DR Reactome; R-HSA-8983432; Interleukin-15 signaling. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-8985947; Interleukin-9 signaling. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR Reactome; R-HSA-9020933; Interleukin-23 signaling. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR Reactome; R-HSA-9020958; Interleukin-21 signaling. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants. DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR SignaLink; P40763; -. DR SIGNOR; P40763; -. DR BioGRID-ORCS; 6774; 20 hits in 906 CRISPR screens. DR ChiTaRS; STAT3; human. DR GeneWiki; STAT3; -. DR GenomeRNAi; 6774; -. DR Pharos; P40763; Tchem. DR PRO; PR:P40763; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P40763; protein. DR Bgee; ENSG00000168610; Expressed in upper lobe of lung and 250 other tissues. DR ExpressionAtlas; P40763; baseline and differential. DR Genevisible; P40763; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IMP:BHF-UCL. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl. DR GO; GO:0005667; C:transcription regulator complex; IDA:ARUK-UCL. DR GO; GO:0031730; F:CCR5 chemokine receptor binding; IEA:Ensembl. DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0035259; F:glucocorticoid receptor binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004879; F:nuclear receptor activity; IDA:BHF-UCL. DR GO; GO:0070878; F:primary miRNA binding; IGI:ARUK-UCL. DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl. DR GO; GO:0071345; P:cellular response to cytokine stimulus; TAS:Reactome. DR GO; GO:0032870; P:cellular response to hormone stimulus; IDA:BHF-UCL. DR GO; GO:0044320; P:cellular response to leptin stimulus; IDA:UniProtKB. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0006952; P:defense response; IBA:GO_Central. DR GO; GO:0042755; P:eating behavior; ISS:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB. DR GO; GO:0001754; P:eye photoreceptor cell differentiation; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0060396; P:growth hormone receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB. DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038114; P:interleukin-21-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038155; P:interleukin-23-mediated signaling pathway; TAS:Reactome. DR GO; GO:0070106; P:interleukin-27-mediated signaling pathway; TAS:Reactome. DR GO; GO:0070757; P:interleukin-35-mediated signaling pathway; TAS:Reactome. DR GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0038111; P:interleukin-7-mediated signaling pathway; TAS:Reactome. DR GO; GO:0038113; P:interleukin-9-mediated signaling pathway; TAS:Reactome. DR GO; GO:0030522; P:intracellular receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0033210; P:leptin-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0035278; P:miRNA mediated inhibition of translation; IDA:BHF-UCL. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0010507; P:negative regulation of autophagy; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0045820; P:negative regulation of glycolytic process; IEA:Ensembl. DR GO; GO:0010730; P:negative regulation of hydrogen peroxide biosynthetic process; IEA:Ensembl. DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl. DR GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl. DR GO; GO:2000635; P:negative regulation of primary miRNA processing; IMP:ARUK-UCL. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:ProtInc. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL. DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IGI:ARUK-UCL. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:2000637; P:positive regulation of gene silencing by miRNA; IDA:BHF-UCL. DR GO; GO:1902728; P:positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; IEA:Ensembl. DR GO; GO:0045410; P:positive regulation of interleukin-6 biosynthetic process; ISS:ARUK-UCL. DR GO; GO:1904685; P:positive regulation of metalloendopeptidase activity; IGI:BHF-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:ARUK-UCL. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB. DR GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; TAS:Reactome. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0099527; P:postsynapse to nucleus signaling pathway; IEA:Ensembl. DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB. DR GO; GO:0060019; P:radial glial cell differentiation; ISS:UniProtKB. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IBA:GO_Central. 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:0060259; P:regulation of feeding behavior; ISS:UniProtKB. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. 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:0019953; P:sexual reproduction; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035019; P:somatic stem cell population maintenance; TAS:Reactome. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB. DR GO; GO:0072538; P:T-helper 17 type immune response; IDA:UniProtKB. DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR CDD; cd10374; SH2_STAT3; 1. DR Gene3D; 1.10.532.10; -; 1. DR Gene3D; 2.60.40.630; -; 1. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR035855; STAT3_SH2. 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; PTHR11801; 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 SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF47655; SSF47655; 1. DR SUPFAM; SSF48092; SSF48092; 1. DR SUPFAM; SSF49417; SSF49417; 1. DR SUPFAM; SSF55550; SSF55550; 1. DR PROSITE; PS50001; SH2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm; KW Diabetes mellitus; Disease mutation; DNA-binding; Dwarfism; KW Host-virus interaction; Lipoprotein; Nucleus; Palmitate; Phosphoprotein; KW Polymorphism; Reference proteome; SH2 domain; Transcription; KW Transcription regulation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000244|PubMed:22223895" FT CHAIN 2..770 FT /note="Signal transducer and activator of transcription 3" FT /id="PRO_0000182417" 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:0000244|PubMed:22223895" FT MOD_RES 601 FT /note="Allysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 601 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 615 FT /note="Allysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 615 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 631 FT /note="Allysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 631 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 685 FT /note="Allysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 685 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 705 FT /note="Phosphotyrosine; by FER and PTK6" FT /evidence="ECO:0000244|PubMed:15592455, FT ECO:0000244|PubMed:24275569, ECO:0000269|PubMed:12763138, FT ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:26293184, ECO:0000269|PubMed:31462771, FT ECO:0000269|PubMed:31899195" FT MOD_RES 707 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:28065600" FT MOD_RES 714 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:24275569" FT MOD_RES 727 FT /note="Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5, FT ZIPK/DAPK3 and PKC/PRKCE" FT /evidence="ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163, ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:12763138, ECO:0000269|PubMed:15465816, FT ECO:0000269|PubMed:16219639, ECO:0000269|PubMed:17875724, FT ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:26293184, ECO:0000269|PubMed:31899195" FT LIPID 687 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:31462771" FT LIPID 712 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:31462771" FT VAR_SEQ 701 FT /note="Missing (in isoform Del-701)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_010474" FT VAR_SEQ 716..722 FT /note="TTCSNTI -> FIDAVWK (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_055918" FT VAR_SEQ 723..770 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_055919" FT VARIANT 32 FT /note="Q -> K (in dbSNP:rs1803125)" FT /id="VAR_018683" FT VARIANT 143 FT /note="M -> I (in dbSNP:rs17878478)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_018679" FT VARIANT 330 FT /note="P -> S (in ADMIO1; increases transcriptional FT activity; increases binding to ISL1 promoter region; FT decreases glucose stimulated insulin secretion)" FT /evidence="ECO:0000269|PubMed:28073828" FT /id="VAR_078445" FT VARIANT 382 FT /note="R -> L (in HIES1; dbSNP:rs113994136)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037365" FT VARIANT 382 FT /note="R -> Q (in HIES1; loss of function; FT dbSNP:rs113994136)" FT /evidence="ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745" FT /id="VAR_037366" FT VARIANT 382 FT /note="R -> W (in HIES1; loss of function; reduced DNA- FT binding ability; dbSNP:rs113994135)" FT /evidence="ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745, ECO:0000269|PubMed:26293184" FT /id="VAR_037367" FT VARIANT 384 FT /note="F -> L (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037368" FT VARIANT 384 FT /note="F -> S (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037369" FT VARIANT 389 FT /note="T -> I (in HIES1; loss of function; FT dbSNP:rs397514766)" FT /evidence="ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:23342295" FT /id="VAR_037370" FT VARIANT 392 FT /note="K -> R (in ADMIO1; dbSNP:rs587777648)" FT /evidence="ECO:0000269|PubMed:25038750" FT /id="VAR_071885" FT VARIANT 395 FT /note="N -> Y (in HIES1; unknown pathological significance; FT reduced DNA-binding ability)" FT /evidence="ECO:0000269|PubMed:26293184" FT /id="VAR_075414" FT VARIANT 423 FT /note="R -> Q (in HIES1; dbSNP:rs113994137)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037371" FT VARIANT 425 FT /note="N -> Y (in HIES1; unknown pathological significance; FT reduced DNA-binding ability)" FT /evidence="ECO:0000269|PubMed:26293184" FT /id="VAR_075415" FT VARIANT 437 FT /note="H -> Y (in HIES1; loss of function)" FT /evidence="ECO:0000269|PubMed:17676033" FT /id="VAR_037372" FT VARIANT 463 FT /note="Missing (in HIES1; loss of function)" FT /evidence="ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745" FT /id="VAR_037373" FT VARIANT 561 FT /note="F -> Y (in dbSNP:rs1064116)" FT /evidence="ECO:0000269|PubMed:7512451" FT /id="VAR_037374" FT VARIANT 611 FT /note="S -> N (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037375" FT VARIANT 621 FT /note="F -> V (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037376" FT VARIANT 622 FT /note="T -> I (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037377" FT VARIANT 637 FT /note="V -> L (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037378" FT VARIANT 637 FT /note="V -> M (in HIES1; reduced DNA-binding ability; FT dbSNP:rs113994139)" FT /evidence="ECO:0000269|PubMed:17881745, FT ECO:0000269|PubMed:26293184" FT /id="VAR_037379" FT VARIANT 644 FT /note="Missing (in HIES1)" FT /evidence="ECO:0000269|PubMed:17881745" FT /id="VAR_037380" FT VARIANT 646 FT /note="N -> K (in ADMIO1; dbSNP:rs587777649)" FT /evidence="ECO:0000269|PubMed:25038750" FT /id="VAR_071886" FT VARIANT 657 FT /note="Y -> C (in HIES1; reduced DNA-binding ability; FT dbSNP:rs193922721)" FT /evidence="ECO:0000269|PubMed:17881745, FT ECO:0000269|PubMed:26293184" FT /id="VAR_037381" FT VARIANT 658 FT /note="K -> N (in ADMIO1; dbSNP:rs587777650)" FT /evidence="ECO:0000269|PubMed:25038750" FT /id="VAR_071887" FT VARIANT 716 FT /note="T -> M (in ADMIO1; dbSNP:rs869312892)" FT /evidence="ECO:0000269|PubMed:25038750" FT /id="VAR_071888" FT MUTAGEN 434..435 FT /note="EE->AA: Inhibits leptin-mediated transactivation of FT CCND1 promoter. No effect on interaction with INPP5F." FT /evidence="ECO:0000269|PubMed:17344214, FT ECO:0000269|PubMed:25476455" FT MUTAGEN 651 FT /note="A->V: Modifies the lipid-binding pocket leading to FT reduction of palmitoylation levels and homodimerization." FT /evidence="ECO:0000269|PubMed:31462771" FT MUTAGEN 687 FT /note="C->S: Inhibits palmitoylation." FT /evidence="ECO:0000269|PubMed:31462771" FT MUTAGEN 705 FT /note="Y->F: Inhibits leptin-mediated transactivation of FT CCND1 promoter. Inhibits Phosphorylation." FT /evidence="ECO:0000269|PubMed:17344214, FT ECO:0000269|PubMed:31462771" FT MUTAGEN 712 FT /note="C->S: Inhibits palmitoylation." FT /evidence="ECO:0000269|PubMed:31462771" FT CONFLICT 133 FT /note="T -> A (in Ref. 4; BAF84622)" FT /evidence="ECO:0000305" FT CONFLICT 288 FT /note="Q -> H (in Ref. 1; AAA58374)" FT /evidence="ECO:0000305" FT CONFLICT 460 FT /note="P -> S (in Ref. 1; AAA58374)" FT /evidence="ECO:0000305" FT CONFLICT 548 FT /note="K -> N (in Ref. 1; AAA58374)" FT /evidence="ECO:0000305" FT CONFLICT 652 FT /note="E -> V (in Ref. 4; BAF84622)" FT /evidence="ECO:0000305" FT CONFLICT 667 FT /note="V -> L (in Ref. 1; AAA58374)" FT /evidence="ECO:0000305" FT CONFLICT 730 FT /note="T -> A (in Ref. 1; AAA58374)" FT /evidence="ECO:0000305" FT HELIX 139..177 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 194..237 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 239..251 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 261..290 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 297..320 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 321..328 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 338..340 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 345..353 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 356..358 FT /evidence="ECO:0000244|PDB:6NJS" FT TURN 359..361 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 363..368 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 373..376 FT /evidence="ECO:0000244|PDB:6QHD" FT STRAND 384..388 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 391..393 FT /evidence="ECO:0000244|PDB:6NJS" FT TURN 398..401 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 404..415 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 432..434 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 439..447 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 450..457 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 461..466 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 467..469 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 470..483 FT /evidence="ECO:0000244|PDB:6NJS" FT TURN 490..494 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 501..513 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 522..533 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 546..549 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 557..559 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 561..574 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 577..582 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 591..600 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 605..610 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 619..626 FT /evidence="ECO:0000244|PDB:6NJS" FT STRAND 632..636 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 642..645 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 650..656 FT /evidence="ECO:0000244|PDB:6NJS" FT TURN 674..676 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 679..683 FT /evidence="ECO:0000244|PDB:6NJS" FT HELIX 684..686 FT /evidence="ECO:0000244|PDB:6NJS" FT MOD_RES P40763-2:704 FT /note="Phosphotyrosine" FT /evidence="ECO:0000244|PubMed:15592455, FT ECO:0000244|PubMed:24275569" SQ SEQUENCE 770 AA; 88068 MW; 6C00632211C8012D 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 QFESLTFDME LTSECATSPM //