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 10-MAY-2017, entry version 192. 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; 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 [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., 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 [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., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA 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 RT the 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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., 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 [13] 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 [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 RT coactivator 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- RT 12Rbeta1 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 RT activator of transcription 3 recruitment sites within the epidermal RT growth factor 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 RT erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent RT 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., 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 [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- RT induced 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 RT degradation of 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, 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 [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., 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 [26] 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 [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 RT 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 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 [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 RP 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 RT CYCLIN D1 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 RT in 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., 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 [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 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 [37] 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 [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., 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 [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., 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 [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 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 [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., 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 [43] RP PHOSPHORYLATION AT TYR-705 IN RESPONSE TO KIT SIGNALING, AND RP PHOSPHORYLATION AT SER-727. RX PubMed=21135090; DOI=10.1074/jbc.M110.182642; RA Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.; RT "Mechanisms of STAT protein activation by oncogenic KIT mutants in RT neoplastic mast cells."; RL J. Biol. Chem. 286:5956-5966(2011). RN [44] RP FUNCTION, AND INTERACTION WITH EIF2AK2. RX PubMed=23084476; DOI=10.1016/j.molcel.2012.09.013; RA Shen S., Niso-Santano M., Adjemian S., Takehara T., Malik S.A., 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 [45] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [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 [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., 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 [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-705; THR-714 AND RP SER-727, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-704 (ISOFORM RP DEL-701), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [49] RP INTERACTION WITH INPP5F, AND MUTAGENESIS OF TYR-705. RX PubMed=25476455; DOI=10.1038/srep07330; RA Kim H.S., Li A., Ahn S., Song H., Zhang W.; RT "Inositol Polyphosphate-5-Phosphatase F (INPP5F) inhibits STAT3 RT activity and suppresses gliomas tumorigenicity."; RL Sci. Rep. 4:7330-7330(2014). RN [50] RP INTERACTION WITH FGFR4. RX PubMed=26675719; DOI=10.1038/nature16449; RA Ulaganathan V.K., Sperl B., Rapp U.R., Ullrich A.; RT "Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 RT binding site."; RL Nature 528:570-574(2015). RN [51] RP SUBCELLULAR LOCATION, SUBUNIT, ALLYSINE AT LYS-601; LYS-615; LYS-631 RP AND LYS-685, AND ACETYLATION AT LYS-601; LYS-615; LYS-631; LYS-685 AND RP LYS-707. RX PubMed=28065600; DOI=10.1016/j.molcel.2016.12.002; RA Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., RA Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., RA Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J., Zhang X., Cheng J., RA Chang Z., Chin Y.E.; RT "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 RT deacetylation and deacetylimination modulation."; RL Mol. Cell 65:296-309(2017). RN [52] RP 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 [53] 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). RN [54] RP VARIANT AD-HIES 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 RT invasive eosinophilic disease."; RL Allergy Rhinol. (Providence) 3:E94-E97(2012). RN [55] RP VARIANTS ADMIO1 ARG-392; LYS-646; ASN-658 AND MET-716, AND INVOLVEMENT RP IN ADMIO1. RX PubMed=25038750; DOI=10.1038/ng.3040; RA Flanagan S.E., Haapaniemi E., Russell M.A., Caswell R., RA Lango Allen H., De Franco E., McDonald T.J., Rajala H., Ramelius A., RA Barton J., Heiskanen K., Heiskanen-Kosma T., Kajosaari M., RA Murphy N.P., Milenkovic T., Seppaenen M., Lernmark A., Mustjoki S., RA Otonkoski T., Kere J., Morgan N.G., 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 [56] RP VARIANTS AD-HIES TRP-382; TYR-395; TYR-425; MET-637 AND CYS-657, RP CHARACTERIZATION OF VARIANTS AD-HIES TRP-382; TYR-395; TYR-425; RP MET-637 AND 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 RT with hyper-IgE syndrome in a Mexican cohort."; RL Clin. Genet. 89:217-221(2016). RN [57] RP VARIANT ADMIO1 SER-330, AND CHARACTERIZATION OF VARIANT ADMIO1 RP 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., RA Santin I., Castano L.; RT "An activating mutation in STAT3 results in neonatal diabetes through RT reduced insulin synthesis."; RL Diabetes 0:0-0(2017). CC -!- FUNCTION: Signal transducer and transcription activator that CC mediates cellular responses to interleukins, KITLG/SCF, LEP and CC other growth factors (PubMed:10688651, PubMed:12359225, CC PubMed:12873986, PubMed:15194700, PubMed:17344214, CC PubMed:18242580, PubMed:23084476). Once activated, recruits CC coactivators, such as NCOA1 or MED1, to the promoter region of the CC target gene (PubMed:17344214). May mediate cellular responses to CC activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds CC to the interleukin-6 (IL-6)-responsive elements identified in the CC promoters of various acute-phase protein genes (PubMed:12359225). CC Activated by IL31 through IL31RA (PubMed:15194700). Acts as a CC regulator of inflammatory response by regulating differentiation CC of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells CC (Treg): deacetylation and oxidation of lysine residues by LOXL3, CC leads to disrupt STAT3 dimerization and inhibit its transcription CC activity (PubMed:28065600). Involved in cell cycle regulation by CC inducing the expression of key genes for the progression from G1 CC to S phase, such as CCND1 (PubMed:17344214). Mediates the effects CC of LEP on melanocortin production, body energy homeostasis and CC lactation (By similarity). May play an apoptotic role by CC transctivating BIRC5 expression under LEP activation CC (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by CC inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial CC role in basal beta cell functions, such as regulation of insulin CC secretion (By similarity). {ECO:0000250|UniProtKB:P42227, CC ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, CC ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, CC ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580, CC ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:28065600}. CC -!- SUBUNIT: Forms a homodimer or a heterodimer with a related family CC member (at least STAT1) (PubMed:28065600). Interacts with IL31RA, CC NCOA1, PELP1, SIPAR, SOCS7, STATIP1 and TMF1. Interacts with IL23R CC in presence of IL23. Interacts (via SH2 domain) with NLK. CC Interacts with ARL2BP; the interaction is enhanced by LIF and JAK1 CC expression (By similarity). Interacts with KPNA4 and KPNA5; KPNA4 CC may be the primary mediator of nuclear import (By similarity). CC Interacts with CAV2; the interaction is increased on insulin- CC induced tyrosine phosphorylation of CAV2 and leads to STAT3 CC activation (By similarity). Interacts with ARL2BP; interaction is CC enhanced with ARL2. Interacts with NEK6 (By similarity). Binds to CC CDK9 when activated and nuclear. Interacts with BMX. Interacts CC with ZIPK/DAPK3. Interacts with PIAS3; the interaction occurs on CC stimulation by IL6, CNTF or OSM and inhibits the DNA binding CC activity of STAT3. In prostate cancer cells, interacts with STAT3 CC and promotes DNA binding activity of STAT3. Interacts with STMN3, CC antagonizing its microtubule-destabilizing activity. Interacts CC with the 'Lys-129' acetylated form of BIRC5/survivin. Interacts CC with FER. Interacts (via SH2 domain) with EIF2AK2/PKR (via the CC kinase catalytic domain). Interacts with STAT3; the interaction is CC independent of STAT3 TYR-705 phosphorylation status CC (PubMed:25476455). Interacts with FGFR4 (PubMed:26675719). 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:17875724, CC ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18070987, CC ECO:0000269|PubMed:18234692, ECO:0000269|PubMed:19147545, CC ECO:0000269|PubMed:20826784, ECO:0000269|PubMed:23084476, CC ECO:0000269|PubMed:25476455, ECO:0000269|PubMed:26675719, CC ECO:0000269|PubMed:28065600, ECO:0000269|PubMed:9388184}. CC -!- SUBUNIT: (Microbial infection) Interacts with HCV core protein. CC {ECO:0000269|PubMed:12208879}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-518675, EBI-518675; 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 P51451:BLK; NbExp=5; IntAct=EBI-518675, EBI-2105445; CC P51813:BMX; NbExp=6; IntAct=EBI-518675, EBI-696657; 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=14; 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 P25791:LMO2; NbExp=3; IntAct=EBI-518675, EBI-739696; 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 P07949:RET; NbExp=3; IntAct=EBI-518675, EBI-2480756; CC P46781:RPS9; NbExp=2; IntAct=EBI-518675, EBI-351206; CC O00570:SOX1; NbExp=2; IntAct=EBI-518675, EBI-2935583; CC P08047:SP1; NbExp=4; IntAct=EBI-518675, EBI-298336; CC P30626:SRI; NbExp=2; IntAct=EBI-518675, EBI-750459; CC P42224:STAT1; NbExp=3; IntAct=EBI-518675, EBI-1057697; CC Q06520:SULT2A1; NbExp=2; IntAct=EBI-518675, EBI-3921363; CC P43405:SYK; NbExp=6; IntAct=EBI-518675, EBI-78302; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus CC {ECO:0000269|PubMed:28065600}. Note=Shuttles between the nucleus CC and the cytoplasm. Translocated into the nucleus upon tyrosine CC phosphorylation and dimerization, in response to signaling by CC activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear CC presence is independent of tyrosine phosphorylation. Predominantly CC present in the cytoplasm without stimuli. Upon leukemia inhibitory CC factor (LIF) stimulation, accumulates in the nucleus. The complex CC composed of BART and ARL2 plays an important role in the nuclear CC translocation and retention of STAT3. Identified in a complex with CC 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 Note=Contains a phosphotyrosine at position 704. CC {ECO:0000244|PubMed:15592455, ECO:0000244|PubMed:24275569}; 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. 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, LEP CC and OSM. Activated KIT promotes phosphorylation on tyrosine CC residues and subsequent translocation to the nucleus. CC Phosphorylated on serine upon DNA damage, probably by ATM or ATR. CC Serine phosphorylation is important for the formation of stable CC DNA-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. Phosphorylation at Tyr-705 CC by PTK6 or FER leads to an increase of its transcriptional CC activity. Dephosphorylation on tyrosine residues by PTPN2 CC negatively regulates IL6/interleukin-6 signaling. CC {ECO:0000250|UniProtKB:P42227, ECO:0000269|PubMed:10688651, CC ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12763138, CC ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:16219639, CC ECO:0000269|PubMed:16568091, ECO:0000269|PubMed:17344214, CC ECO:0000269|PubMed:17875724, ECO:0000269|PubMed:18234692, CC ECO:0000269|PubMed:18599021, ECO:0000269|PubMed:19147545, CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:7701321}. CC -!- PTM: Acetylated on lysine residues by CREBBP. Deacetylation by CC LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 CC transcription activity (PubMed:28065600). Oxidation of lysine CC residues to allysine on STAT3 preferentially takes place on lysine CC residues that are acetylated (PubMed:28065600). CC {ECO:0000269|PubMed:28065600}. CC -!- PTM: Some lysine residues are oxidized to allysine by LOXL3, CC leading to disrupt STAT3 dimerization and inhibit STAT3 CC transcription activity (PubMed:28065600). Oxidation of lysine CC residues to allysine on STAT3 preferentially takes place on lysine CC residues that are acetylated (PubMed:28065600). CC {ECO:0000269|PubMed:28065600}. 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. {ECO:0000269|PubMed:17676033, CC ECO:0000269|PubMed:17881745, ECO:0000269|PubMed:23342295, CC ECO:0000269|PubMed:26293184}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Autoimmune disease, multisystem, infantile-onset, 1 CC (ADMIO1) [MIM:615952]: A disorder characterized by early childhood CC onset of a spectrum of autoimmune manifestations affecting CC multiple organs, including insulin-dependent diabetes mellitus and CC autoimmune enteropathy or celiac disease. Other features include CC short stature, non-specific dermatitis, hypothyroidism, autoimmune CC arthritis, and delayed puberty. {ECO:0000269|PubMed:25038750, CC ECO:0000269|PubMed:28073828}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Involved in the gp130-mediated signaling pathway. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT3 entry; CC URL="https://en.wikipedia.org/wiki/STAT3"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/STAT3ID444.html"; CC -!- WEB RESOURCE: Name=STAT3base; Note=STAT3 mutation db; CC URL="http://structure.bmc.lu.se/idbase/STAT3base/"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/stat3/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L29277; AAA58374.1; -; mRNA. DR EMBL; AJ012463; CAA10032.1; -; mRNA. DR EMBL; JB252046; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK291933; BAF84622.1; -; mRNA. DR EMBL; AY572796; AAS66986.1; -; Genomic_DNA. DR EMBL; AC087691; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471152; EAW60822.1; -; Genomic_DNA. DR EMBL; BC000627; AAH00627.1; -; mRNA. DR EMBL; BC014482; AAH14482.1; -; mRNA. DR EMBL; AF029311; AAB84254.1; -; mRNA. DR CCDS; CCDS32656.1; -. [P40763-1] DR CCDS; CCDS32657.1; -. [P40763-2] DR CCDS; CCDS59288.1; -. [P40763-3] DR PIR; A54444; A54444. DR RefSeq; NP_003141.2; NM_003150.3. [P40763-2] DR RefSeq; NP_644805.1; NM_139276.2. [P40763-1] DR RefSeq; NP_998827.1; NM_213662.1. [P40763-3] DR RefSeq; XP_005257673.2; XM_005257616.3. [P40763-2] DR RefSeq; XP_005257674.2; XM_005257617.3. [P40763-1] DR RefSeq; XP_011523447.1; XM_011525145.2. [P40763-1] DR RefSeq; XP_011523448.1; XM_011525146.2. [P40763-3] DR RefSeq; XP_016880461.1; XM_017024972.1. [P40763-3] DR RefSeq; XP_016880464.1; XM_017024975.1. [P40763-2] DR UniGene; Hs.463059; -. DR PDB; 5AX3; X-ray; 2.98 A; B=571-582. DR PDBsum; 5AX3; -. DR ProteinModelPortal; P40763; -. DR SMR; P40763; -. DR BioGrid; 112651; 238. DR DIP; DIP-33584N; -. DR IntAct; P40763; 159. DR MINT; MINT-146801; -. DR STRING; 9606.ENSP00000264657; -. DR BindingDB; P40763; -. DR ChEMBL; CHEMBL4026; -. DR iPTMnet; P40763; -. DR PhosphoSitePlus; P40763; -. DR BioMuta; STAT3; -. DR DMDM; 48429227; -. DR EPD; P40763; -. DR MaxQB; P40763; -. 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; ENST00000585517; ENSP00000467000; ENSG00000168610. [P40763-3] DR Ensembl; ENST00000588969; ENSP00000467985; ENSG00000168610. [P40763-1] DR GeneID; 6774; -. DR KEGG; hsa:6774; -. DR UCSC; uc002hzl.2; human. [P40763-1] DR CTD; 6774; -. DR DisGeNET; 6774; -. DR GeneCards; STAT3; -. DR GeneReviews; STAT3; -. DR HGNC; HGNC:11364; STAT3. DR HPA; CAB003859; -. DR HPA; CAB068241; -. DR HPA; CAB068242; -. DR HPA; HPA001671; -. DR HPA; HPA058603; -. DR MalaCards; STAT3; -. DR MIM; 102582; gene. DR MIM; 147060; phenotype. DR MIM; 615952; phenotype. DR neXtProt; NX_P40763; -. DR OpenTargets; ENSG00000168610; -. DR Orphanet; 2314; Autosomal dominant hyper-IgE syndrome. DR PharmGKB; PA337; -. DR eggNOG; KOG3667; Eukaryota. DR eggNOG; ENOG410XPN8; LUCA. DR GeneTree; ENSGT00760000119236; -. DR HOGENOM; HOG000220792; -. DR HOVERGEN; HBG055669; -. DR InParanoid; P40763; -. DR KO; K04692; -. DR OMA; NSMSFAE; -. DR OrthoDB; EOG091G03O3; -. DR PhylomeDB; P40763; -. DR TreeFam; TF318648; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-198745; Signalling to STAT3. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2586552; Signaling by Leptin. DR Reactome; R-HSA-2892247; POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation. DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis. DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR Reactome; R-HSA-6785807; Interleukin-4 and 13 signaling. DR Reactome; R-HSA-8849474; PTK6 Activates STAT3. DR Reactome; R-HSA-8875791; MET activates STAT3. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR SignaLink; P40763; -. DR SIGNOR; P40763; -. DR ChiTaRS; STAT3; human. DR GeneWiki; STAT3; -. DR GenomeRNAi; 6774; -. DR PMAP-CutDB; P40763; -. DR PRO; PR:P40763; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000168610; -. DR CleanEx; HS_STAT3; -. DR ExpressionAtlas; P40763; baseline and differential. DR Genevisible; P40763; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription factor complex; IMP:BHF-UCL. DR GO; GO:0031730; F:CCR5 chemokine receptor binding; IEA:Ensembl. DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0035259; F:glucocorticoid receptor binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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 core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0004879; F:RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IMP:BHF-UCL. DR GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:BHF-UCL. DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0048708; P:astrocyte differentiation; ISS:UniProtKB. DR GO; GO:0008283; P:cell proliferation; IEA:Ensembl. DR GO; GO:0032870; P:cellular response to hormone stimulus; IDA:BHF-UCL. DR GO; GO:0044320; P:cellular response to leptin stimulus; IDA:UniProtKB. DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; NAS:UniProtKB. 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: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:0007259; P:JAK-STAT cascade; TAS:UniProtKB. DR GO; GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; IDA:BHF-UCL. DR GO; GO:0033210; P:leptin-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0035278; P:miRNA mediated inhibition of translation; IDA:BHF-UCL. DR GO; GO:0006928; P:movement of cell or subcellular component; TAS:ProtInc. DR GO; GO:0042789; P:mRNA transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:CACAO. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0045820; P:negative regulation of glycolytic process; IEA:Ensembl. DR GO; GO:0010730; P:negative regulation of hydrogen peroxide biosynthetic process; IEA:Ensembl. DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl. DR GO; GO:2001223; P:negative regulation of neuron migration; IEA:Ensembl. DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:2000637; P:positive regulation of gene silencing by miRNA; IDA:BHF-UCL. DR GO; GO:1902728; P:positive regulation of growth factor dependent skeletal muscle satellite cell proliferation; IEA:Ensembl. DR GO; GO:1904685; P:positive regulation of metalloendopeptidase activity; IGI:BHF-UCL. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB. DR GO; GO:1902895; P:positive regulation of pri-miRNA transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; TAS:Reactome. 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:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0060259; P:regulation of feeding behavior; ISS:UniProtKB. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Ensembl. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB. 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:0044321; P:response to leptin; IDA:UniProtKB. DR GO; GO:0019953; P:sexual reproduction; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035019; P:somatic stem cell population maintenance; TAS:Reactome. DR GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProtKB. DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. 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; 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; 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; KW Complete proteome; Cytoplasm; Diabetes mellitus; Disease mutation; KW DNA-binding; Dwarfism; Host-virus interaction; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; KW Transcription; Transcription regulation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:22223895}. FT CHAIN 2 770 Signal transducer and activator of FT transcription 3. FT /FTId=PRO_0000182417. FT DOMAIN 580 670 SH2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT MOTIF 150 162 Essential for nuclear import. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:22223895}. FT MOD_RES 601 601 Allysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 601 601 N6-acetyllysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 615 615 Allysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 615 615 N6-acetyllysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 631 631 Allysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 631 631 N6-acetyllysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 685 685 Allysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 685 685 N6-acetyllysine; alternate. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 705 705 Phosphotyrosine; by FER and PTK6. FT {ECO:0000244|PubMed:15592455, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:12763138, FT ECO:0000269|PubMed:16568091, FT ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:26293184}. FT MOD_RES 707 707 N6-acetyllysine. FT {ECO:0000269|PubMed:28065600}. FT MOD_RES 714 714 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 727 727 Phosphoserine; by DYRK2, NLK, NEK6, FT IRAK1, RPS6KA5, ZIPK/DAPK3 and PKC/PRKCE. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:12763138, FT ECO:0000269|PubMed:15465816, FT ECO:0000269|PubMed:16219639, FT ECO:0000269|PubMed:17875724, FT ECO:0000269|PubMed:18599021, FT ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:26293184}. FT VAR_SEQ 701 701 Missing (in isoform Del-701). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_010474. FT VAR_SEQ 716 722 TTCSNTI -> FIDAVWK (in isoform 3). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_055918. FT VAR_SEQ 723 770 Missing (in isoform 3). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_055919. FT VARIANT 32 32 Q -> K (in dbSNP:rs1803125). FT /FTId=VAR_018683. FT VARIANT 143 143 M -> I (in dbSNP:rs17878478). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_018679. FT VARIANT 330 330 P -> S (in ADMIO1; increases FT transcriptional activity; increases FT binding to ISL1 promoter region; FT decreases glucose stimulated insulin FT secretion). FT {ECO:0000269|PubMed:28073828}. FT /FTId=VAR_078445. FT VARIANT 382 382 R -> L (in AD-HIES; dbSNP:rs113994136). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037365. FT VARIANT 382 382 R -> Q (in AD-HIES; loss of function; FT dbSNP:rs113994136). FT {ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037366. FT VARIANT 382 382 R -> W (in AD-HIES; loss of function; FT reduced DNA-binding ability; FT dbSNP:rs113994135). FT {ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745, FT ECO:0000269|PubMed:26293184}. FT /FTId=VAR_037367. FT VARIANT 384 384 F -> L (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037368. FT VARIANT 384 384 F -> S (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037369. FT VARIANT 389 389 T -> I (in AD-HIES; loss of function; FT dbSNP:rs397514766). FT {ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:23342295}. FT /FTId=VAR_037370. FT VARIANT 392 392 K -> R (in ADMIO1; dbSNP:rs587777648). FT {ECO:0000269|PubMed:25038750}. FT /FTId=VAR_071885. FT VARIANT 395 395 N -> Y (in AD-HIES; unknown pathological FT significance; reduced DNA-binding FT ability). {ECO:0000269|PubMed:26293184}. FT /FTId=VAR_075414. FT VARIANT 423 423 R -> Q (in AD-HIES; dbSNP:rs113994137). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037371. FT VARIANT 425 425 N -> Y (in AD-HIES; unknown pathological FT significance; reduced DNA-binding FT ability). {ECO:0000269|PubMed:26293184}. FT /FTId=VAR_075415. FT VARIANT 437 437 H -> Y (in AD-HIES; loss of function). FT {ECO:0000269|PubMed:17676033}. FT /FTId=VAR_037372. FT VARIANT 463 463 Missing (in AD-HIES; loss of function). FT {ECO:0000269|PubMed:17676033, FT ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037373. FT VARIANT 561 561 F -> Y (in dbSNP:rs1064116). FT {ECO:0000269|PubMed:7512451}. FT /FTId=VAR_037374. FT VARIANT 611 611 S -> N (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037375. FT VARIANT 621 621 F -> V (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037376. FT VARIANT 622 622 T -> I (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037377. FT VARIANT 637 637 V -> L (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037378. FT VARIANT 637 637 V -> M (in AD-HIES; reduced DNA-binding FT ability; dbSNP:rs113994139). FT {ECO:0000269|PubMed:17881745, FT ECO:0000269|PubMed:26293184}. FT /FTId=VAR_037379. FT VARIANT 644 644 Missing (in AD-HIES). FT {ECO:0000269|PubMed:17881745}. FT /FTId=VAR_037380. FT VARIANT 646 646 N -> K (in ADMIO1; dbSNP:rs587777649). FT {ECO:0000269|PubMed:25038750}. FT /FTId=VAR_071886. FT VARIANT 657 657 Y -> C (in AD-HIES; reduced DNA-binding FT ability; dbSNP:rs193922721). FT {ECO:0000269|PubMed:17881745, FT ECO:0000269|PubMed:26293184}. FT /FTId=VAR_037381. FT VARIANT 658 658 K -> N (in ADMIO1; dbSNP:rs587777650). FT {ECO:0000269|PubMed:25038750}. FT /FTId=VAR_071887. FT VARIANT 716 716 T -> M (in ADMIO1). FT {ECO:0000269|PubMed:25038750}. FT /FTId=VAR_071888. FT MUTAGEN 434 435 EE->AA: Inhibits leptin-mediated FT transactivation of CCND1 promoter. No FT effect on interaction with INPP5F. FT {ECO:0000269|PubMed:17344214, FT ECO:0000269|PubMed:25476455}. FT MUTAGEN 705 705 Y->F: Inhibits leptin-mediated FT transactivation of CCND1 promoter. FT {ECO:0000269|PubMed:17344214}. FT CONFLICT 133 133 T -> A (in Ref. 4; BAF84622). FT {ECO:0000305}. FT CONFLICT 288 288 Q -> H (in Ref. 1; AAA58374). FT {ECO:0000305}. FT CONFLICT 460 460 P -> S (in Ref. 1; AAA58374). FT {ECO:0000305}. FT CONFLICT 548 548 K -> N (in Ref. 1; AAA58374). FT {ECO:0000305}. FT CONFLICT 652 652 E -> V (in Ref. 4; BAF84622). FT {ECO:0000305}. FT CONFLICT 667 667 V -> L (in Ref. 1; AAA58374). FT {ECO:0000305}. FT CONFLICT 730 730 T -> A (in Ref. 1; AAA58374). FT {ECO:0000305}. 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 //