ID STAT3_HUMAN Reviewed; 770 AA. AC P40763; A8K7B8; O14916; Q9BW54; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 2. DT 19-MAR-2014, entry version 156. DE RecName: Full=Signal transducer and activator of transcription 3; DE AltName: Full=Acute-phase response factor; GN Name=STAT3; Synonyms=APRF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT revised human STAT3 sequence."; RL Gene 213:119-124(1998). RN [3] 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 [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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] 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 [7] 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 [8] 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 [9] 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., RA Shih H.M., Kung H.J., Chen R.H.; RT "Etk, a Btk family tyrosine kinase, mediates cellular transformation RT by linking Src to STAT3 activation."; RL Mol. Cell. Biol. 20:2043-2054(2000). RN [10] RP FUNCTION IN IL6 SIGNALING, PHOSPHORYLATION, AND DEPHOSPHORYLATION BY RP 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 RT dephosphorylation."; RL Biochem. Biophys. Res. Commun. 297:811-817(2002). RN [11] 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 RT coactivator NcoA/SRC1a."; RL J. Biol. Chem. 277:8004-8011(2002). RN [12] 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 [13] RP INTERACTION WITH IL23R. RX PubMed=12023369; 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- RT 12Rbeta1 and a novel cytokine receptor subunit, IL-23R."; RL J. Immunol. 168:5699-5708(2002). RN [14] 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 RT activator of transcription 3 recruitment sites within the epidermal RT growth factor receptor."; RL Cancer Res. 63:3923-3930(2003). RN [15] 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 RT erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent RT pathway."; RL Exp. Hematol. 31:398-405(2003). RN [16] 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 [17] 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., RA 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 [18] 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- RT induced interleukin-10 gene expression."; RL J. Biol. Chem. 279:51697-51703(2004). RN [19] 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 RT degradation of Stat3."; RL Oncogene 23:8908-8919(2004). RN [20] 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 [21] RP PHOSPHORYLATION AT SER-727 BY ZIPK/DAPK3, INTERACTION WITH ZIPK/DAPK3, RP AND 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 [22] 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., RA Gertler A.; RT "Suppressor of cytokine signaling 7 inhibits prolactin, growth RT hormone, and leptin signaling by interacting with STAT5 or STAT3 and RT attenuating their nuclear translocation."; RL J. Biol. Chem. 280:13817-13823(2005). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705, PHOSPHORYLATION RP [LARGE SCALE ANALYSIS] AT TYR-704 (ISOFORM DEL-701), AND RP IDENTIFICATION BY MASS 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 RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [24] 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 RT kinase."; RL Oncogene 25:4904-4912(2006). RN [25] 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 RT activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and RT regulates its constitutive activation in prostate cancer."; RL Cancer Res. 67:8828-8838(2007). RN [26] 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 [27] 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 RT in human gamma-fibrinogen gene expression."; RL J. Biol. Chem. 282:37091-37102(2007). RN [28] 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 [29] 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., RA Borisch B., Hoessli D.C.; RT "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn RT tyrosine kinase in human B-NHL rafts."; RL Blood 111:2310-2320(2008). RN [30] 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 [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION RP BY 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [33] 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., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [34] 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., RA Aprikian A.G., Chevalier S.; RT "The Fer tyrosine kinase cooperates with interleukin-6 to activate RT signal transducer and activator of transcription 3 and promote human RT prostate cancer cell growth."; RL Mol. Cancer Res. 7:142-155(2009). RN [35] 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 [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [37] 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., RA Buerckstuemmer T., 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 [38] 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 [39] 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., RA Minoux H., Souquere S., Marino G., Lachkar S., Senovilla L., RA Galluzzi L., Kepp O., Pierron G., Maiuri M.C., Hikita H., Kroemer R., RA Kroemer G.; RT "Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity."; RL Mol. Cell 48:667-680(2012). RN [40] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS], AND CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., 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 [41] 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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [42] RP VARIANTS AD-HIES 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 RP AND 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 [43] RP VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; TYR-437 AND VAL-463 DEL, RP AND CHARACTERIZATION OF VARIANTS AD-HIES GLN-382; TRP-382; ILE-389; RP TYR-437 AND 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., RA Karasuyama H.; RT "Dominant-negative mutations in the DNA-binding domain of STAT3 cause RT hyper-IgE syndrome."; RL Nature 448:1058-1062(2007). CC -!- FUNCTION: Signal transducer and transcription activator that CC mediates cellular responses to interleukins, KITLG/SCF and other CC growth factors. May mediate cellular responses to activated FGFR1, CC FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)- CC responsive elements identified in the promoters of various acute- CC phase protein genes. Activated by IL31 through IL31RA. Cytoplasmic CC STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. CC Plays an important role in host defense in methicillin-resistant CC S.aureus lung infection by regulating the expression of the CC antimicrobial lectin REG3G (By similarity). CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member (at least STAT1). Interacts with IL31RA, NCOA1, PELP1, CC SIPAR, SOCS7, STATIP1 and TMF1. Interacts with HCV core protein. CC Interacts with IL23R in presence of IL23. Interacts (via SH2 CC domain) with NLK. Interacts with ARL2BP; the interaction is CC enhanced by LIF and JAK1 expression (By similarity). Interacts CC with KPNA4 and KPNA5; KPNA4 may be the primary mediator of nuclear CC import (By similarity). Interacts with CAV2; the interaction is CC increased on insulin-induced tyrosine phosphorylation of CAV2 and CC leads to STAT3 activation (By similarity). Interacts with ARL2BP; CC interaction is enhanced with ARL2. Interacts with NEK6 (By CC similarity). Binds to CDK9 when activated and nuclear. Interacts CC with BMX. Interacts with ZIPK/DAPK3. Interacts with PIAS3; the CC interaction occurs on stimulation by IL6, CNTF or OSM and inhibits CC the DNA binding activity of STAT3. In prostate cancer cells, CC interacts with STAT3 and promotes DNA binding activity of STAT3. CC Interacts with STMN3, antagonizing its microtubule-destabilizing CC activity. Interacts with the 'Lys-129' acetylated form of CC BIRC5/survivin. Interacts with FER. Interacts (via SH2 domain) CC with EIF2AK2/PKR (via the kinase catalytic domain). CC -!- INTERACTION: CC Q9DUM3:- (xeno); NbExp=4; IntAct=EBI-518675, EBI-7971837; CC O14874:BCKDK; NbExp=2; IntAct=EBI-518675, EBI-1046765; CC Q96G01:BICD1; NbExp=2; IntAct=EBI-518675, EBI-1104509; CC P07384:CAPN1; NbExp=2; IntAct=EBI-518675, EBI-1542113; CC P31146:CORO1A; NbExp=2; IntAct=EBI-518675, EBI-1046676; CC Q99062:CSF3R; NbExp=4; IntAct=EBI-518675, EBI-7331284; CC Q9UER7:DAXX; NbExp=4; IntAct=EBI-518675, EBI-77321; CC O95661:DIRAS3; NbExp=3; IntAct=EBI-518675, EBI-6139214; CC Q13011:ECH1; NbExp=2; IntAct=EBI-518675, EBI-711968; CC P30084:ECHS1; NbExp=3; IntAct=EBI-518675, EBI-719602; CC P00533:EGFR; NbExp=12; IntAct=EBI-518675, EBI-297353; CC P04626:ERBB2; NbExp=9; IntAct=EBI-518675, EBI-641062; CC Q15910:EZH2; NbExp=5; IntAct=EBI-518675, EBI-530054; CC Q8TAE8:GADD45GIP1; NbExp=4; IntAct=EBI-518675, EBI-372506; CC Q9BVP2:GNL3; NbExp=2; IntAct=EBI-518675, EBI-641642; CC Q07666:KHDRBS1; NbExp=2; IntAct=EBI-518675, EBI-1364; CC O43318:MAP3K7; NbExp=4; IntAct=EBI-518675, EBI-358684; CC P45984:MAPK9; NbExp=2; IntAct=EBI-518675, EBI-713568; CC P45984-1:MAPK9; NbExp=3; IntAct=EBI-518675, EBI-713586; CC Q8TE76:MORC4; NbExp=2; IntAct=EBI-518675, EBI-3940432; CC Q92665:MRPS31; NbExp=2; IntAct=EBI-518675, EBI-720602; CC P22736:NR4A1; NbExp=3; IntAct=EBI-518675, EBI-721550; CC Q9ULD0:OGDHL; NbExp=2; IntAct=EBI-518675, EBI-3940481; CC P06401:PGR; NbExp=3; IntAct=EBI-518675, EBI-78539; CC P18031:PTPN1; NbExp=2; IntAct=EBI-518675, EBI-968788; CC Q04206:RELA; NbExp=4; IntAct=EBI-518675, EBI-73886; CC P46781:RPS9; NbExp=2; IntAct=EBI-518675, EBI-351206; CC O00570:SOX1; NbExp=2; IntAct=EBI-518675, EBI-2935583; CC P30626:SRI; NbExp=2; IntAct=EBI-518675, EBI-750459; CC Q06520:SULT2A1; NbExp=2; IntAct=EBI-518675, EBI-3921363; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between CC the nucleus and the cytoplasm. Translocated into the nucleus upon CC tyrosine phosphorylation and dimerization, in response to CC signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive CC nuclear presence is independent of tyrosine phosphorylation. CC Predominantly present in the cytoplasm without stimuli. Upon CC leukemia inhibitory factor (LIF) stimulation, accumulates in the CC nucleus. The complex composed of BART and ARL2 plays an important CC 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=2; CC Name=1; CC IsoId=P40763-1; Sequence=Displayed; CC Name=Del-701; CC IsoId=P40763-2; Sequence=VSP_010474; CC Note=Contains a phosphotyrosine at position 704; CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal CC muscle, kidney and pancreas. CC -!- PTM: Tyrosine phosphorylated upon stimulation with EGF. Tyrosine CC phosphorylated in response to constitutively activated FGFR1, CC FGFR2, FGFR3 and FGFR4 (By similarity). Activated through tyrosine CC phosphorylation by BMX. Tyrosine phosphorylated in response to CC IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha and CC OSM. Activated KIT promotes phosphorylation on tyrosine residues CC and subsequent translocation to the nucleus. Phosphorylated on CC serine upon DNA damage, probably by ATM or ATR. Serine CC phosphorylation is important for the formation of stable DNA- CC binding STAT3 homodimers and maximal transcriptional activity. CC ARL2BP may participate in keeping the phosphorylated state of CC STAT3 within the nucleus. Upon LPS challenge, phosphorylated CC within the nucleus by IRAK1. Upon erythropoietin treatment, CC phosphorylated on Ser-727 by RPS6KA5. Phosphoryation at Tyr-705 by CC PTK6 or FER leads to an increase of its transcriptional activity. CC Dephosphorylation on tyrosine residues by PTPN2 negatively CC regulates IL6/interleukin-6 signaling. CC -!- DISEASE: Hyperimmunoglobulin E recurrent infection syndrome, CC autosomal dominant (AD-HIES) [MIM:147060]: A rare disorder of CC immunity and connective tissue characterized by immunodeficiency, CC chronic eczema, recurrent Staphylococcal infections, increased CC serum IgE, eosinophilia, distinctive coarse facial appearance, CC abnormal dentition, hyperextensibility of the joints, and bone CC fractures. Note=The disease is caused by mutations affecting the CC gene represented in this entry. CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT3 entry; CC URL="http://en.wikipedia.org/wiki/STAT3"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html"; CC -!- WEB RESOURCE: Name=STAT3base; Note=STAT3 mutation db; CC URL="http://bioinf.uta.fi/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; AY572796; AAS66986.1; -; Genomic_DNA. DR EMBL; AK291933; BAF84622.1; -; mRNA. DR EMBL; BC000627; AAH00627.1; -; mRNA. DR EMBL; BC014482; AAH14482.1; -; mRNA. DR EMBL; AF029311; AAB84254.1; -; mRNA. DR PIR; A54444; A54444. DR RefSeq; NP_003141.2; NM_003150.3. DR RefSeq; NP_644805.1; NM_139276.2. DR RefSeq; NP_998827.1; NM_213662.1. DR UniGene; Hs.463059; -. DR ProteinModelPortal; P40763; -. DR SMR; P40763; 2-715. DR BioGrid; 112651; 153. DR DIP; DIP-33584N; -. DR IntAct; P40763; 83. DR MINT; MINT-146801; -. DR STRING; 9606.ENSP00000264657; -. DR BindingDB; P40763; -. DR ChEMBL; CHEMBL4026; -. DR PhosphoSite; P40763; -. DR DMDM; 48429227; -. DR PaxDb; P40763; -. DR PeptideAtlas; P40763; -. DR PRIDE; P40763; -. DR DNASU; 6774; -. DR Ensembl; ENST00000264657; ENSP00000264657; ENSG00000168610. [P40763-1] DR Ensembl; ENST00000404395; ENSP00000384943; ENSG00000168610. [P40763-2] DR Ensembl; ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1] DR GeneID; 6774; -. DR KEGG; hsa:6774; -. DR UCSC; uc002hzk.1; human. [P40763-1] DR UCSC; uc002hzm.1; human. [P40763-2] DR CTD; 6774; -. DR GeneCards; GC17M040465; -. DR HGNC; HGNC:11364; STAT3. DR HPA; CAB003859; -. DR HPA; HPA001671; -. DR MIM; 102582; gene. DR MIM; 147060; phenotype. DR neXtProt; NX_P40763; -. DR Orphanet; 2314; Autosomal dominant hyper-IgE syndrome. DR PharmGKB; PA337; -. DR eggNOG; NOG303257; -. DR HOGENOM; HOG000220792; -. DR HOVERGEN; HBG055669; -. DR InParanoid; P40763; -. DR KO; K04692; -. DR OMA; NKESHAT; -. DR OrthoDB; EOG73JKTT; -. DR TreeFam; TF318648; -. DR Reactome; REACT_111102; Signal Transduction. DR Reactome; REACT_116125; Disease. DR Reactome; REACT_6900; Immune System. DR SignaLink; P40763; -. DR ChiTaRS; STAT3; human. DR GeneWiki; STAT3; -. DR GenomeRNAi; 6774; -. DR NextBio; 26438; -. DR PMAP-CutDB; P40763; -. DR PRO; PR:P40763; -. DR ArrayExpress; P40763; -. DR Bgee; P40763; -. DR CleanEx; HS_STAT3; -. DR Genevestigator; P40763; -. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0004879; F:ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity; IDA:BHF-UCL. DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB. DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl. DR GO; GO:0006928; P:cellular component movement; TAS:ProtInc. DR GO; GO:0042755; P:eating behavior; 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:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; ISS:UniProtKB. DR GO; GO:0060548; P:negative regulation of cell death; IEA:Ensembl. DR GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. 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:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IDA:BHF-UCL. DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl. DR GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB. DR GO; GO:0019827; P:stem cell maintenance; IEA:Ensembl. DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 1.10.238.10; -; 1. DR Gene3D; 1.10.532.10; -; 1. DR Gene3D; 1.20.1050.20; -; 1. DR Gene3D; 2.60.40.630; -; 1. DR Gene3D; 3.30.505.10; -; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR000980; SH2. DR InterPro; IPR001217; STAT. 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_sub. 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; SM00252; SH2; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF47655; SSF47655; 1. DR SUPFAM; SSF48092; SSF48092; 1. DR SUPFAM; SSF49417; SSF49417; 1. DR PROSITE; PS50001; SH2; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative splicing; Complete proteome; KW Cytoplasm; Disease mutation; DNA-binding; Host-virus interaction; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; KW Transcription; Transcription regulation. FT INIT_MET 1 1 Removed. FT CHAIN 2 770 Signal transducer and activator of FT transcription 3. FT /FTId=PRO_0000182417. FT DOMAIN 580 670 SH2. FT MOTIF 150 162 Essential for nuclear import. FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 705 705 Phosphotyrosine; by FER and PTK6. FT MOD_RES 727 727 Phosphoserine; by DYRK2, NLK, NEK6, FT IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE. FT VAR_SEQ 701 701 Missing (in isoform Del-701). FT /FTId=VSP_010474. FT VARIANT 32 32 Q -> K (in dbSNP:rs1803125). FT /FTId=VAR_018683. FT VARIANT 143 143 M -> I (in dbSNP:rs17878478). FT /FTId=VAR_018679. FT VARIANT 382 382 R -> L (in AD-HIES). FT /FTId=VAR_037365. FT VARIANT 382 382 R -> Q (in AD-HIES; loss of function). FT /FTId=VAR_037366. FT VARIANT 382 382 R -> W (in AD-HIES; loss of function). FT /FTId=VAR_037367. FT VARIANT 384 384 F -> L (in AD-HIES). FT /FTId=VAR_037368. FT VARIANT 384 384 F -> S (in AD-HIES). FT /FTId=VAR_037369. FT VARIANT 389 389 T -> I (in AD-HIES; loss of function). FT /FTId=VAR_037370. FT VARIANT 423 423 R -> Q (in AD-HIES). FT /FTId=VAR_037371. FT VARIANT 437 437 H -> Y (in AD-HIES; loss of function). FT /FTId=VAR_037372. FT VARIANT 463 463 Missing (in AD-HIES; loss of function). FT /FTId=VAR_037373. FT VARIANT 561 561 F -> Y (in dbSNP:rs1064116). FT /FTId=VAR_037374. FT VARIANT 611 611 S -> N (in AD-HIES). FT /FTId=VAR_037375. FT VARIANT 621 621 F -> V (in AD-HIES). FT /FTId=VAR_037376. FT VARIANT 622 622 T -> I (in AD-HIES). FT /FTId=VAR_037377. FT VARIANT 637 637 V -> L (in AD-HIES). FT /FTId=VAR_037378. FT VARIANT 637 637 V -> M (in AD-HIES). FT /FTId=VAR_037379. FT VARIANT 644 644 Missing (in AD-HIES). FT /FTId=VAR_037380. FT VARIANT 657 657 Y -> C (in AD-HIES). FT /FTId=VAR_037381. FT CONFLICT 133 133 T -> A (in Ref. 4; BAF84622). FT CONFLICT 288 288 Q -> H (in Ref. 1; AAA58374). FT CONFLICT 460 460 P -> S (in Ref. 1; AAA58374). FT CONFLICT 548 548 K -> N (in Ref. 1; AAA58374). FT CONFLICT 652 652 E -> V (in Ref. 4; BAF84622). FT CONFLICT 667 667 V -> L (in Ref. 1; AAA58374). FT CONFLICT 730 730 T -> A (in Ref. 1; AAA58374). 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 //