Signal transducer and activator of transcription 3

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• CCR5 chemokine receptor binding Source: MGI
• chromatin DNA binding Source: UniProtKB
• DNA binding Source: MGI <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation."
    Turkson J., Ryan D., Kim J.S., Zhang Y., Chen Z., Haura E., Laudano A., Sebti S., Hamilton A.D., Jove R.
    J Biol Chem 276:45443-45455(2001) [PubMed] [Europe PMC] [Abstract]
  • "A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation."
    Ma J., Zhang T., Novotny-Diermayr V., Tan A.L., Cao X.
    J Biol Chem 278:29252-29260(2003) [PubMed] [Europe PMC] [Abstract]
  • "Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity."
    Fu A.K., Fu W.Y., Ng A.K., Chien W.W., Ng Y.P., Wang J.H., Ip N.Y.
    Proc Natl Acad Sci U S A 101:6728-6733(2004) [PubMed] [Europe PMC] [Abstract]
  • "The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities."
    Hao A., Novotny-Diermayr V., Bian W., Lin B., Lim C.P., Jing N., Cao X.
    Mol Biol Cell 16:1569-1583(2005) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
• DNA-binding transcription factor activity Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 deacetylation and deacetylimination modulation."
    Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J.

    , Zhang X., Cheng J., Chang Z., Chin Y.E.
    Mol. Cell 65:296-309(2017) [PubMed] [Europe PMC] [Abstract]
• DNA-binding transcription factor activity, RNA polymerase II-specific Source: MGIInferred from direct assayⁱ
  • "Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity."
    Fu A.K., Fu W.Y., Ng A.K., Chien W.W., Ng Y.P., Wang J.H., Ip N.Y.
    Proc Natl Acad Sci U S A 101:6728-6733(2004) [PubMed] [Europe PMC] [Abstract]
  • "Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP."
    Ren F., Geng Y., Minami T., Qiu Y., Feng Y., Liu C., Zhao J., Wang Y., Fan X., Wang Y., Li M., Li J., Chang Z.
    FEBS Lett 589:1890-1896(2015) [PubMed] [Europe PMC] [Abstract]
• glucocorticoid receptor binding Source: MGI
• identical protein binding Source: IntAct <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity."
    Siddiquee K., Zhang S., Guida W.C., Blaskovich M.A., Greedy B., Lawrence H.R., Yip M.L., Jove R., McLaughlin M.M., Lawrence N.J., Sebti S.M., Turkson J.
    Proc Natl Acad Sci U S A 104:7391-7396(2007) [PubMed] [Europe PMC] [Abstract]
  • "Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography."
    Nkansah E., Shah R., Collie G.W., Parkinson G.N., Palmer J., Rahman K.M., Bui T.T., Drake A.F., Husby J., Neidle S., Zinzalla G., Thurston D.E., Wilderspin A.F.
    FEBS Lett 587:833-839(2013) [PubMed] [Europe PMC] [Abstract]
• nuclear receptor activity Source: MGI
• primary miRNA binding Source: MGI
• protein dimerization activity Source: MGIInferred from physical interactionⁱ
  • "Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation."
    Turkson J., Ryan D., Kim J.S., Zhang Y., Chen Z., Haura E., Laudano A., Sebti S., Hamilton A.D., Jove R.
    J Biol Chem 276:45443-45455(2001) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: UniProtKBInferred from direct assayⁱ
  • "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 deacetylation and deacetylimination modulation."
    Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J.

    , Zhang X., Cheng J., Chang Z., Chin Y.E.
    Mol. Cell 65:296-309(2017) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.16

    "Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction."
    Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N., Matsumoto K., Shibuya H.
    Genes Dev. 18:381-386(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH NLK, PHOSPHORYLATION AT SER-727, MUTAGENESIS OF SER-727.
• protein phosphatase binding Source: MGI
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: MGI
• RNA polymerase II repressing transcription factor binding Source: MGI
• sequence-specific DNA binding Source: MGIInferred from direct assayⁱ
  • "Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells."
    Suzuki A., Raya A., Kawakami Y., Morita M., Matsui T., Nakashima K., Gage F.H., Rodriguez-Esteban C., Izpisua Belmonte J.C.
    Proc. Natl. Acad. Sci. U.S.A. 103:10294-10299(2006) [PubMed] [Europe PMC] [Abstract]
• transcription factor binding Source: UniProtKB
• transcription regulatory region sequence-specific DNA binding Source: MGI

GO - Biological processⁱ

• acute-phase response Source: UniProtKB-KW
• aging Source: Ensembl
• astrocyte differentiation Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling."
    Kamakura S., Oishi K., Yoshimatsu T., Nakafuku M., Masuyama N., Gotoh Y.
    Nat Cell Biol 6:547-554(2004) [PubMed] [Europe PMC] [Abstract]
• cell population proliferation Source: MGIInferred from direct assayⁱ
  • "The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities."
    Hao A., Novotny-Diermayr V., Bian W., Lin B., Lim C.P., Jing N., Cao X.
    Mol Biol Cell 16:1569-1583(2005) [PubMed] [Europe PMC] [Abstract]
• cellular response to cytokine stimulus Source: MGIInferred from sequence orthologyⁱ
  • "JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway."
    Lv N., Kim E.K., Song M.Y., Choi H.N., Moon W.S., Park S.J., Park J.W., Kwon K.B., Park B.H.
    Exp Cell Res 315:2064-2071(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to hormone stimulus Source: MGI
• cellular response to leptin stimulus Source: UniProtKB
• cellular response to organic cyclic compound Source: MGIInferred from sequence orthologyⁱ
  • "JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway."
    Lv N., Kim E.K., Song M.Y., Choi H.N., Moon W.S., Park S.J., Park J.W., Kwon K.B., Park B.H.
    Exp Cell Res 315:2064-2071(2009) [PubMed] [Europe PMC] [Abstract]
• cytokine-mediated signaling pathway Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• defense response Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• eating behavior Source: MGIInferred from mutant phenotypeⁱ
  • "Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation."
    Gao Q., Wolfgang M.J., Neschen S., Morino K., Horvath T.L., Shulman G.I., Fu X.Y.
    Proc Natl Acad Sci U S A 101:4661-4666(2004) [PubMed] [Europe PMC] [Abstract]
• energy homeostasis Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.15

    "STAT3 signalling is required for leptin regulation of energy balance but not reproduction."
    Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., Schwartz M.W., Myers M.G. Jr.
    Nature 421:856-859(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• eye photoreceptor cell differentiation Source: MGIInferred from mutant phenotypeⁱ
  • "Downregulation of STAT3 activation is required for presumptive rod photoreceptor cells to differentiate in the postnatal retina."
    Ozawa Y., Nakao K., Shimazaki T., Takeda J., Akira S., Ishihara K., Hirano T., Oguchi Y., Okano H.
    Mol Cell Neurosci 26:258-270(2004) [PubMed] [Europe PMC] [Abstract]
• glucose homeostasis Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.15

    "STAT3 signalling is required for leptin regulation of energy balance but not reproduction."
    Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., Schwartz M.W., Myers M.G. Jr.
    Nature 421:856-859(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• growth hormone receptor signaling pathway Source: MGI
• growth hormone receptor signaling pathway via JAK-STAT Source: BHF-UCLInferred from direct assayⁱ
  • "Growth hormone receptor cytoplasmic domain differentially promotes tyrosine phosphorylation of signal transducers and activators of transcription 5b and 3 by activated JAK2 kinase."
    Yi W., Kim S.O., Jiang J., Park S.H., Kraft A.S., Waxman D.J., Frank S.J.
    Mol Endocrinol 10:1425-1443(1996) [PubMed] [Europe PMC] [Abstract]
• inflammatory response Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 deacetylation and deacetylimination modulation."
    Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J.

    , Zhang X., Cheng J., Chang Z., Chin Y.E.
    Mol. Cell 65:296-309(2017) [PubMed] [Europe PMC] [Abstract]
• interleukin-6-mediated signaling pathway Source: UniProtKB
• intracellular receptor signaling pathway Source: MGI
• leptin-mediated signaling pathway Source: UniProtKBInferred from direct assayⁱ
  • Ref.19

    "Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2)."
    Gonzalez R.R., Cherfils S., Escobar M., Yoo J.H., Carino C., Styer A.K., Sullivan B.T., Sakamoto H., Olawaiye A., Serikawa T., Lynch M.P., Rueda B.R.
    J. Biol. Chem. 281:26320-26328(2006) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION.
• modulation of chemical synaptic transmission Source: Ensembl
• mRNA transcription by RNA polymerase II Source: MGIInferred from direct assayⁱ
  • "Nuclear termination of STAT3 signaling through SIPAR (STAT3-Interacting Protein As a Repressor)-dependent recruitment of T cell tyrosine phosphatase TC-PTP."
    Ren F., Geng Y., Minami T., Qiu Y., Feng Y., Liu C., Zhao J., Wang Y., Fan X., Wang Y., Li M., Li J., Chang Z.
    FEBS Lett 589:1890-1896(2015) [PubMed] [Europe PMC] [Abstract]
• negative regulation of autophagy Source: MGI
• negative regulation of cell death Source: MGI
• negative regulation of cell population proliferation Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "STAT3 negatively regulates thyroid tumorigenesis."
    Couto J.P., Daly L., Almeida A., Knauf J.A., Fagin J.A., Sobrinho-Simoes M., Lima J., Maximo V., Soares P., Lyden D., Bromberg J.F.
    Proc Natl Acad Sci U S A 109:E2361-70(2012) [PubMed] [Europe PMC] [Abstract]
• negative regulation of glycolytic process Source: MGIInferred from mutant phenotypeⁱ
  • "STAT3 negatively regulates thyroid tumorigenesis."
    Couto J.P., Daly L., Almeida A., Knauf J.A., Fagin J.A., Sobrinho-Simoes M., Lima J., Maximo V., Soares P., Lyden D., Bromberg J.F.
    Proc Natl Acad Sci U S A 109:E2361-70(2012) [PubMed] [Europe PMC] [Abstract]
• negative regulation of hydrogen peroxide biosynthetic process Source: MGI
• negative regulation of neuron death Source: MGI
• negative regulation of neuron migration Source: MGIInferred from genetic interactionⁱ
  • "The metabolite GnRH-(1-5) inhibits the migration of immortalized GnRH neurons."
    Larco D.O., Cho-Clark M., Mani S.K., Wu T.J.
    Endocrinology 154:783-795(2013) [PubMed] [Europe PMC] [Abstract]
• negative regulation of primary miRNA processing Source: MGI
• negative regulation of stem cell differentiation Source: MGIInferred from mutant phenotypeⁱ
  • "Pwp1 is required for the differentiation potential of mouse embryonic stem cells through regulating Stat3 signaling."
    Shen J., Jia W., Yu Y., Chen J., Cao X., Du Y., Zhang X., Zhu S., Chen W., Xi J., Wei T., Wang G., Yuan D., Duan T., Jiang C., Kang J.
    Stem Cells 33:661-673(2015) [PubMed] [Europe PMC] [Abstract]
• phosphorylation Source: UniProtKBInferred from direct assayⁱ
  • Ref.29

    "Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia."
    Choi S.M., McAleer J.P., Zheng M., Pociask D.A., Kaplan M.H., Qin S., Reinhart T.A., Kolls J.K.
    J. Exp. Med. 210:551-561(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION.
• positive regulation of angiogenesis Source: BHF-UCLInferred from direct assayⁱ
  • "Mmu-miR-351 attenuates the survival of cardiac arterial endothelial cells through targeting STAT3 in the atherosclerotic mice."
    Zhang Y., Liu Y., Zhang H., Wang M., Zhang J.
    Biochem Biophys Res Commun 468:300-305(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of ATP biosynthetic process Source: MGI
• positive regulation of cell migration Source: MGI
• positive regulation of cell population proliferation Source: MGI
• positive regulation of cytokine production involved in inflammatory response Source: MGI
• positive regulation of erythrocyte differentiation Source: UniProtKB
• positive regulation of gene expression Source: BHF-UCLInferred from genetic interactionⁱ
  • "Inhibition of microRNA-92a prevents endothelial dysfunction and atherosclerosis in mice."
    Loyer X., Potteaux S., Vion A.C., Guerin C.L., Boulkroun S., Rautou P.E., Ramkhelawon B., Esposito B., Dalloz M., Paul J.L., Julia P., Maccario J., Boulanger C.M., Mallat Z., Tedgui A.
    Circ Res 114:434-443(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene silencing by miRNA Source: MGI
• positive regulation of growth factor dependent skeletal muscle satellite cell proliferation Source: MGI
• positive regulation of interleukin-10 production Source: MGI
• positive regulation of interleukin-1 beta production Source: MGI
• positive regulation of interleukin-6 production Source: MGI
• positive regulation of interleukin-8 production Source: MGI
• positive regulation of metalloendopeptidase activity Source: MGI
• positive regulation of miRNA mediated inhibition of translation Source: MGI
• positive regulation of NF-kappaB transcription factor activity Source: MGI
• positive regulation of Notch signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling."
    Kamakura S., Oishi K., Yoshimatsu T., Nakafuku M., Masuyama N., Gotoh Y.
    Nat Cell Biol 6:547-554(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of pri-miRNA transcription by RNA polymerase II Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-kappaB-complex-dependent gene expression in human heart failure."
    Choy M.K., Movassagh M., Siggens L., Vujic A., Goddard M., Sanchez A., Perkins N., Figg N., Bennett M., Carroll J., Foo R.
    Genome Med 2:37-37(2010) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • Ref.29

    "Innate Stat3-mediated induction of the antimicrobial protein Reg3gamma is required for host defense against MRSA pneumonia."
    Choi S.M., McAleer J.P., Zheng M., Pociask D.A., Kaplan M.H., Qin S., Reinhart T.A., Kolls J.K.
    J. Exp. Med. 210:551-561(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION.
• positive regulation of transcription by RNA polymerase II Source: MGIInferred from direct assayⁱ
  • "Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity."
    Fu A.K., Fu W.Y., Ng A.K., Chien W.W., Ng Y.P., Wang J.H., Ip N.Y.
    Proc Natl Acad Sci U S A 101:6728-6733(2004) [PubMed] [Europe PMC] [Abstract]
  • "The LIM/homeodomain protein Islet1 recruits Janus tyrosine kinases and signal transducer and activator of transcription 3 and stimulates their activities."
    Hao A., Novotny-Diermayr V., Bian W., Lin B., Lim C.P., Jing N., Cao X.
    Mol Biol Cell 16:1569-1583(2005) [PubMed] [Europe PMC] [Abstract]
  • "IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells."
    Guo L., Wei G., Zhu J., Liao W., Leonard W.J., Zhao K., Paul W.
    Proc Natl Acad Sci U S A 106:13463-13468(2009) [PubMed] [Europe PMC] [Abstract]
  • "Loss of the tyrosine phosphatase PTPRD leads to aberrant STAT3 activation and promotes gliomagenesis."
    Ortiz B., Fabius A.W., Wu W.H., Pedraza A., Brennan C.W., Schultz N., Pitter K.L., Bromberg J.F., Huse J.T., Holland E.C., Chan T.A.
    Proc Natl Acad Sci U S A 111:8149-8154(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of tumor necrosis factor production Source: MGI
• positive regulation of vascular endothelial cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Mmu-miR-351 attenuates the survival of cardiac arterial endothelial cells through targeting STAT3 in the atherosclerotic mice."
    Zhang Y., Liu Y., Zhang H., Wang M., Zhang J.
    Biochem Biophys Res Commun 468:300-305(2015) [PubMed] [Europe PMC] [Abstract]
• postsynapse to nucleus signaling pathway Source: MGI
• protein import into nucleus Source: UniProtKB
• radial glial cell differentiation Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling."
    Kamakura S., Oishi K., Yoshimatsu T., Nakafuku M., Masuyama N., Gotoh Y.
    Nat Cell Biol 6:547-554(2004) [PubMed] [Europe PMC] [Abstract]
• receptor signaling pathway via JAK-STAT Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• regulation of cell cycle Source: UniProtKBInferred from direct assayⁱ
  • Ref.19

    "Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2)."
    Gonzalez R.R., Cherfils S., Escobar M., Yoo J.H., Carino C., Styer A.K., Sullivan B.T., Sakamoto H., Olawaiye A., Serikawa T., Lynch M.P., Rueda B.R.
    J. Biol. Chem. 281:26320-26328(2006) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION.
• regulation of cell population proliferation Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• regulation of feeding behavior Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.15

    "STAT3 signalling is required for leptin regulation of energy balance but not reproduction."
    Bates S.H., Stearns W.H., Dundon T.A., Schubert M., Tso A.W., Wang Y., Banks A.S., Lavery H.J., Haq A.K., Maratos-Flier E., Neel B.G., Schwartz M.W., Myers M.G. Jr.
    Nature 421:856-859(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• regulation of mitochondrial membrane permeability Source: MGI
• regulation of multicellular organism growth Source: MGIInferred from mutant phenotypeⁱ
  • "Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation."
    Gao Q., Wolfgang M.J., Neschen S., Morino K., Horvath T.L., Shulman G.I., Fu X.Y.
    Proc Natl Acad Sci U S A 101:4661-4666(2004) [PubMed] [Europe PMC] [Abstract]
• regulation of transcription, DNA-templated Source: MGI
• response to cytokine Source: MGI
• response to drug Source: Ensembl
• response to estradiol Source: MGI
• response to ethanol Source: Ensembl
• response to leptin Source: UniProtKBInferred from direct assayⁱ
  • Ref.19

    "Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2)."
    Gonzalez R.R., Cherfils S., Escobar M., Yoo J.H., Carino C., Styer A.K., Sullivan B.T., Sakamoto H., Olawaiye A., Serikawa T., Lynch M.P., Rueda B.R.
    J. Biol. Chem. 281:26320-26328(2006) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, PHOSPHORYLATION.
• response to peptide hormone Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• sexual reproduction Source: MGIInferred from mutant phenotypeⁱ
  • "Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation."
    Gao Q., Wolfgang M.J., Neschen S., Morino K., Horvath T.L., Shulman G.I., Fu X.Y.
    Proc Natl Acad Sci U S A 101:4661-4666(2004) [PubMed] [Europe PMC] [Abstract]
• stem cell population maintenance Source: MGIInferred from mutant phenotypeⁱ
  • "Mediator and cohesin connect gene expression and chromatin architecture."
    Kagey M.H., Newman J.J., Bilodeau S., Zhan Y., Orlando D.A., van Berkum N.L., Ebmeier C.C., Goossens J., Rahl P.B., Levine S.S., Taatjes D.J., Dekker J., Young R.A.
    Nature 467:430-435(2010) [PubMed] [Europe PMC] [Abstract]
• temperature homeostasis Source: MGIInferred from mutant phenotypeⁱ
  • "Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation."
    Gao Q., Wolfgang M.J., Neschen S., Morino K., Horvath T.L., Shulman G.I., Fu X.Y.
    Proc Natl Acad Sci U S A 101:4661-4666(2004) [PubMed] [Europe PMC] [Abstract]
• T-helper 17 cell lineage commitment Source: UniProtKBInferred from mutant phenotypeⁱ
  • "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 deacetylation and deacetylimination modulation."
    Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J.

    , Zhang X., Cheng J., Chang Z., Chin Y.E.
    Mol. Cell 65:296-309(2017) [PubMed] [Europe PMC] [Abstract]
• T-helper 17 type immune response Source: UniProtKB
• transcription by RNA polymerase II Source: MGIInferred from direct assayⁱ
  • "Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation."
    Turkson J., Ryan D., Kim J.S., Zhang Y., Chen Z., Haura E., Laudano A., Sebti S., Hamilton A.D., Jove R.
    J Biol Chem 276:45443-45455(2001) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypeⁱ

Mutagenesis

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• CCR5 chemokine receptor binding Source: MGI
• glucocorticoid receptor binding Source: MGI
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • "Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity."
    Siddiquee K., Zhang S., Guida W.C., Blaskovich M.A., Greedy B., Lawrence H.R., Yip M.L., Jove R., McLaughlin M.M., Lawrence N.J., Sebti S.M., Turkson J.
    Proc Natl Acad Sci U S A 104:7391-7396(2007) [PubMed] [Europe PMC] [Abstract]
  • "Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography."
    Nkansah E., Shah R., Collie G.W., Parkinson G.N., Palmer J., Rahman K.M., Bui T.T., Drake A.F., Husby J., Neidle S., Zinzalla G., Thurston D.E., Wilderspin A.F.
    FEBS Lett 587:833-839(2013) [PubMed] [Europe PMC] [Abstract]
• protein dimerization activity Source: MGIInferred from physical interactionⁱ
  • "Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation."
    Turkson J., Ryan D., Kim J.S., Zhang Y., Chen Z., Haura E., Laudano A., Sebti S., Hamilton A.D., Jove R.
    J Biol Chem 276:45443-45455(2001) [PubMed] [Europe PMC] [Abstract]
• protein homodimerization activity Source: UniProtKBInferred from direct assayⁱ
  • "Lysyl oxidase 3 is a dual-specificity enzyme involved in STAT3 deacetylation and deacetylimination modulation."
    Ma L., Huang C., Wang X.J., Xin D.E., Wang L.S., Zou Q.C., Zhang Y.S., Tan M.D., Wang Y.M., Zhao T.C., Chatterjee D., Altura R.A., Wang C., Xu Y.S., Yang J.H., Fan Y.S., Han B.H., Si J.

    , Zhang X., Cheng J., Chang Z., Chin Y.E.
    Mol. Cell 65:296-309(2017) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.16

    "Role of the TAK1-NLK-STAT3 pathway in TGF-beta-mediated mesoderm induction."
    Ohkawara B., Shirakabe K., Hyodo-Miura J., Matsuo R., Ueno N., Matsumoto K., Shibuya H.
    Genes Dev. 18:381-386(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH NLK, PHOSPHORYLATION AT SER-727, MUTAGENESIS OF SER-727.
• protein phosphatase binding Source: MGI
• RNA polymerase II repressing transcription factor binding Source: MGI
• transcription factor binding Source: UniProtKB

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Motif

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE 
        60         70         80         90        100
SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME 
       110        120        130        140        150
IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD 
       160        170        180        190        200
VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM 
       210        220        230        240        250
QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA 
       260        270        280        290        300
CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 
       310        320        330        340        350
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR 
       360        370        380        390        400
LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN 
       410        420        430        440        450
NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL 
       460        470        480        490        500
KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT 
       510        520        530        540        550
WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC 
       560        570        580        590        600
KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 
       610        620        630        640        650
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF 
       660        670        680        690        700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG 
       710        720        730        740        750
SAAPYLKTKF ICVTPTTCSN TIDLPMSPRT LDSLMQFGNN GEGAEPSAGG 
       760        770
QFESLTFDMD LTSECATSPM                                  

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE 
        60         70         80         90        100
SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME 
       110        120        130        140        150
IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD 
       160        170        180        190        200
VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM 
       210        220        230        240        250
QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA 
       260        270        280        290        300
CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 
       310        320        330        340        350
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR 
       360        370        380        390        400
LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN 
       410        420        430        440        450
NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL 
       460        470        480        490        500
KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT 
       510        520        530        540        550
WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC 
       560        570        580        590        600
KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 
       610        620        630        640        650
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF 
       660        670        680        690        700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG 
       710        720 
SAAPYLKTKF ICVTPFIDAV WK                               

        10         20         30         40         50
MAQWNQLQQL DTRYLEQLHQ LYSDSFPMEL RQFLAPWIES QDWAYAASKE 
        60         70         80         90        100
SHATLVFHNL LGEIDQQYSR FLQESNVLYQ HNLRRIKQFL QSRYLEKPME 
       110        120        130        140        150
IARIVARCLW EESRLLQTAA TAAQQGGQAN HPTAAVVTEK QQMLEQHLQD 
       160        170        180        190        200
VRKRVQDLEQ KMKVVENLQD DFDFNYKTLK SQGDMQDLNG NNQSVTRQKM 
       210        220        230        240        250
QQLEQMLTAL DQMRRSIVSE LAGLLSAMEY VQKTLTDEEL ADWKRRQQIA 
       260        270        280        290        300
CIGGPPNICL DRLENWITSL AESQLQTRQQ IKKLEELQQK VSYKGDPIVQ 
       310        320        330        340        350
HRPMLEERIV ELFRNLMKSA FVVERQPCMP MHPDRPLVIK TGVQFTTKVR 
       360        370        380        390        400
LLVKFPELNY QLKIKVCIDK DSGDVAALRG SRKFNILGTN TKVMNMEESN 
       410        420        430        440        450
NGSLSAEFKH LTLREQRCGN GGRANCDASL IVTEELHLIT FETEVYHQGL 
       460        470        480        490        500
KIDLETHSLP VVVISNICQM PNAWASILWY NMLTNNPKNV NFFTKPPIGT 
       510        520        530        540        550
WDQVAEVLSW QFSSTTKRGL SIEQLTTLAE KLLGPGVNYS GCQITWAKFC 
       560        570        580        590        600
KENMAGKGFS FWVWLDNIID LVKKYILALW NEGYIMGFIS KERERAILST 
       610        620        630        640        650
KPPGTFLLRF SESSKEGGVT FTWVEKDISG KTQIQSVEPY TKQQLNNMSF 
       660        670        680        690        700
AEIIMGYKIM DATNILVSPL VYLYPDIPKE EAFGKYCRPE SQEHPEADPG 
       710        720        730        740        750
AAPYLKTKFI CVTPTTCSNT IDLPMSPRTL DSLMQFGNNG EGAEPSAGGQ 
       760 
FESLTFDMDL TSECATSPM                                   

Experimental Info

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases