STAT3_HUMAN
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 03-AUG-2022, entry version 234.
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 PHOSPHORYLATION AT TYR-705.
RX PubMed=22306293; DOI=10.1016/j.molcel.2012.01.001;
RA Gao X., Wang H., Yang J.J., Liu X., Liu Z.R.;
RT "Pyruvate kinase M2 regulates gene transcription by acting as a protein
RT kinase.";
RL Mol. Cell 45:598-609(2012).
RN [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
RP INTERACTION WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION).
RX PubMed=27387064; DOI=10.1371/journal.ppat.1005748;
RA Harwardt T., Lukas S., Zenger M., Reitberger T., Danzer D., Uebner T.,
RA Munday D.C., Nevels M., Paulus C.;
RT "Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to
RT Downstream STAT1 Signaling Switching an IL6-Type to an IFNgamma-Like
RT Response.";
RL PLoS Pathog. 12:e1005748-e1005748(2016).
RN [53]
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 [54]
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 [55]
RP RETRACTED PAPER.
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 [56]
RP RETRACTION NOTICE OF PUBMED:31462771.
RX PubMed=32555452; DOI=10.1038/s41586-020-2414-6;
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.;
RL Nature 583:154-154(2020).
RN [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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:22306293,
CC PubMed:23084476). 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:22306293, ECO:0000269|PubMed:23084476,
CC 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 PRKCE and promotes DNA binding activity of STAT3
CC (PubMed:17875724). Interacts with STMN3, antagonizing its microtubule-
CC destabilizing activity (By similarity). Interacts with the 'Lys-129'
CC acetylated form of BIRC5/survivin (PubMed:20826784). Interacts with FER
CC (PubMed:19147545). Interacts (via SH2 domain) with EIF2AK2/PKR (via the
CC kinase catalytic domain) (PubMed:23084476). Interacts with INPP5F; the
CC interaction is independent of STAT3 Tyr-705 phosphorylation status
CC (PubMed:25476455). Interacts with FGFR4 (PubMed:26675719). Interacts
CC with OCAD1 (By similarity). Interacts (unphosphorylated or
CC phosphorylated at Ser-727) with PHB1 (PubMed:31899195). Interacts and
CC may form heterodimers with NHLH1 (By similarity).
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:31899195, 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 -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC (HHV-5) immediate early protein IE1; this interaction leads to STAT3
CC nuclear accumulation and disruption of IL6-induced STAT3
CC phosphorylation. {ECO:0000269|PubMed:27387064}.
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; O15264: MAPK13; NbExp=2; IntAct=EBI-518675, EBI-2116951;
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; Q16236: NFE2L2; NbExp=5; IntAct=EBI-518675, EBI-2007911;
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=8; 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 P40763-2; P05067: APP; NbExp=3; IntAct=EBI-10692009, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:28065600,
CC ECO:0000269|PubMed:31899195}. Nucleus {ECO:0000269|PubMed:28065600,
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 -!- 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, isoform M2 of PKM (PKM2) or FER leads to an increase
CC of its transcriptional activity (PubMed:12763138, PubMed:16568091,
CC PubMed:21135090, PubMed:22306293). Dephosphorylation on tyrosine
CC residues by PTPN2 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:22306293,
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 -!- 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 variants
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 variants
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 -!- CAUTION: Was shown to be S-palmitoylated by ZDHHC19, leading to STAT3
CC homodimerization. However, this study was later retracted.
CC {ECO:0000305|PubMed:31462771, ECO:0000305|PubMed:32555452}.
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 ---------------------------------------------------------------------------
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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 PDB; 6TLC; X-ray; 2.90 A; A/B=127-722.
DR PDBsum; 5AX3; -.
DR PDBsum; 5U5S; -.
DR PDBsum; 6NJS; -.
DR PDBsum; 6NUQ; -.
DR PDBsum; 6QHD; -.
DR PDBsum; 6TLC; -.
DR AlphaFoldDB; P40763; -.
DR SMR; P40763; -.
DR BioGRID; 112651; 392.
DR ComplexPortal; CPX-6041; STAT1/STAT3 complex.
DR ComplexPortal; CPX-6043; STAT3/STAT5A complex.
DR ComplexPortal; CPX-6044; STAT3/STAT5B complex.
DR ComplexPortal; CPX-6046; STAT3/STAT4 complex.
DR ComplexPortal; CPX-6049; STAT3 homodimer.
DR CORUM; P40763; -.
DR DIP; DIP-33584N; -.
DR ELM; P40763; -.
DR IntAct; P40763; 246.
DR MINT; P40763; -.
DR STRING; 9606.ENSP00000264657; -.
DR BindingDB; P40763; -.
DR ChEMBL; CHEMBL4026; -.
DR DrugBank; DB05959; ENMD-1198.
DR DrugBank; DB16630; OPB-111077.
DR DrugCentral; P40763; -.
DR GuidetoPHARMACOLOGY; 2994; -.
DR MoonDB; P40763; Predicted.
DR GlyGen; P40763; 6 sites, 2 O-linked glycans (6 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 ABCD; P40763; 1 sequenced antibody.
DR Antibodypedia; 660; 2538 antibodies from 56 providers.
DR CPTC; P40763; 1 antibody.
DR DNASU; 6774; -.
DR Ensembl; ENST00000264657.10; ENSP00000264657.4; ENSG00000168610.16. [P40763-1]
DR Ensembl; ENST00000404395.3; ENSP00000384943.3; ENSG00000168610.16. [P40763-2]
DR Ensembl; ENST00000585517.5; ENSP00000467000.1; ENSG00000168610.16. [P40763-3]
DR Ensembl; ENST00000588969.5; ENSP00000467985.1; ENSG00000168610.16. [P40763-1]
DR Ensembl; ENST00000677030.1; ENSP00000503662.1; ENSG00000168610.16. [P40763-3]
DR Ensembl; ENST00000677723.1; ENSP00000503574.1; ENSG00000168610.16. [P40763-2]
DR Ensembl; ENST00000678044.1; ENSP00000503102.1; ENSG00000168610.16. [P40763-1]
DR Ensembl; ENST00000678827.1; ENSP00000503634.1; ENSG00000168610.16. [P40763-3]
DR Ensembl; ENST00000678906.1; ENSP00000504184.1; ENSG00000168610.16. [P40763-1]
DR Ensembl; ENST00000678960.1; ENSP00000503181.1; ENSG00000168610.16. [P40763-1]
DR Ensembl; ENST00000679014.1; ENSP00000503237.1; ENSG00000168610.16. [P40763-2]
DR GeneID; 6774; -.
DR KEGG; hsa:6774; -.
DR MANE-Select; ENST00000264657.10; ENSP00000264657.4; NM_139276.3; NP_644805.1.
DR UCSC; uc002hzl.2; human. [P40763-1]
DR CTD; 6774; -.
DR DisGeNET; 6774; -.
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; Isolated 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 VEuPathDB; HostDB:ENSG00000168610; -.
DR eggNOG; KOG3667; Eukaryota.
DR GeneTree; ENSGT01050000244905; -.
DR HOGENOM; CLU_014189_3_0_1; -.
DR InParanoid; P40763; -.
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-201556; Signaling by ALK.
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-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants.
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-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SignaLink; P40763; -.
DR SIGNOR; P40763; -.
DR BioGRID-ORCS; 6774; 38 hits in 1117 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 type B pancreatic cell and 209 other tissues.
DR ExpressionAtlas; P40763; baseline and differential.
DR Genevisible; P40763; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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:0090575; C:RNA polymerase II transcription regulator complex; IMP:BHF-UCL.
DR GO; GO:0005667; C:transcription regulator complex; IDA:ARUK-UCL.
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:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
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; ISS: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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0035591; F:signaling adaptor activity; IPI:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0032870; P:cellular response to hormone stimulus; IDA:BHF-UCL.
DR GO; GO:0097398; P:cellular response to interleukin-17; IEA:Ensembl.
DR GO; GO:0044320; P:cellular response to leptin stimulus; IDA:UniProtKB.
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:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB.
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: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:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0045820; P:negative regulation of glycolytic process; 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: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:0032731; P:positive regulation of interleukin-1 beta production; IGI:ARUK-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IGI:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:ARUK-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IGI:ARUK-UCL.
DR GO; GO:1904685; P:positive regulation of metalloendopeptidase activity; IGI:BHF-UCL.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IDA: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:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IGI:ARUK-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; 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: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:0044321; P:response to leptin; IDA:UniProtKB.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR GO; GO:0060221; P:retinal rod cell differentiation; IEA:Ensembl.
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; IEA:Ensembl.
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:0007179; P:transforming growth factor beta receptor signaling pathway; IGI:ARUK-UCL.
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 variant; DNA-binding; Dwarfism;
KW Host-virus interaction; Nucleus; Phosphoprotein; Reference proteome;
KW SH2 domain; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|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:0007744|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:0000269|PubMed:12763138,
FT ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:21135090,
FT ECO:0000269|PubMed:22306293, ECO:0000269|PubMed:26293184,
FT ECO:0000269|PubMed:31899195, ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 707
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:28065600"
FT MOD_RES 714
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 727
FT /note="Phosphoserine; by DYRK2, NLK, NEK6, IRAK1, RPS6KA5,
FT ZIPK/DAPK3 and PKC/PRKCE"
FT /evidence="ECO:0000269|PubMed:12763138,
FT ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:16219639,
FT ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:18599021,
FT ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:26293184,
FT ECO:0000269|PubMed:31899195, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
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 705
FT /note="Y->F: Inhibits leptin-mediated transactivation of
FT CCND1 promoter. Abolished phosphorylation by isoform M2 of
FT PKM (PKM2)."
FT /evidence="ECO:0000269|PubMed:17344214,
FT ECO:0000269|PubMed:22306293"
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:0007829|PDB:6NJS"
FT HELIX 194..237
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 239..251
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 261..290
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 297..320
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 321..328
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 345..353
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:6NJS"
FT TURN 359..361
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 363..368
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 373..376
FT /evidence="ECO:0007829|PDB:6QHD"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:6NJS"
FT TURN 398..401
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 404..415
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 439..447
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 450..457
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 461..466
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 470..483
FT /evidence="ECO:0007829|PDB:6NJS"
FT TURN 490..494
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 501..513
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 514..517
FT /evidence="ECO:0007829|PDB:6TLC"
FT HELIX 522..533
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 546..549
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 561..574
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 577..582
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 591..600
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 605..610
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 619..626
FT /evidence="ECO:0007829|PDB:6NJS"
FT STRAND 632..636
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 642..645
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 650..656
FT /evidence="ECO:0007829|PDB:6NJS"
FT TURN 674..676
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 679..683
FT /evidence="ECO:0007829|PDB:6NJS"
FT HELIX 684..686
FT /evidence="ECO:0007829|PDB:6NJS"
FT MOD_RES P40763-2:704
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|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
