Interleukin-6

<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

<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

• cytokine activity Source: BHF-UCL <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
  • Ref.4

    "Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines."
    Zilberstein A., Ruggieri R., Korn J.H., Revel M.
    EMBO J. 5:2529-2537(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  • Ref.1

    "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
    Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
    Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
• growth factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF."
    Schuster B., Kovaleva M., Sun Y., Regenhard P., Matthews V., Grotzinger J., Rose-John S., Kallen K.J.
    J. Biol. Chem. 278:9528-9535(2003) [PubMed] [Europe PMC] [Abstract]
  • "Molecular cloning and expression of an IL-6 signal transducer, gp130."
    Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T.
    Cell 63:1149-1157(1990) [PubMed] [Europe PMC] [Abstract]
• interleukin-6 receptor binding Source: BHF-UCL <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
  • "Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex."
    Boulanger M.J., Chow D.-C., Brevnova E.E., Garcia K.C.
    Science 300:2101-2104(2003) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• acute-phase response Source: BHF-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE)."
    Matthews V., Schuster B., Schutze S., Bussmeyer I., Ludwig A., Hundhausen C., Sadowski T., Saftig P., Hartmann D., Kallen K.J., Rose-John S.
    J. Biol. Chem. 278:38829-38839(2003) [PubMed] [Europe PMC] [Abstract]
• cellular protein metabolic process Source: Reactome
• cellular response to hydrogen peroxide Source: BHF-UCLInferred from direct assayⁱ
  • "IL-6 protects against hyperoxia-induced mitochondrial damage via Bcl-2-induced Bak interactions with mitofusins."
    Waxman A.B., Kolliputi N.
    Am. J. Respir. Cell Mol. Biol. 41:385-396(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to lipopolysaccharide Source: MGI <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
  • "SASH1 is a scaffold molecule in endothelial TLR4 signaling."
    Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., Fuller M.E., Blonder J., Veenstra T.D., Karsan A.
    J. Immunol. 191:892-901(2013) [PubMed] [Europe PMC] [Abstract]
• cytokine-mediated signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF."
    Schuster B., Kovaleva M., Sun Y., Regenhard P., Matthews V., Grotzinger J., Rose-John S., Kallen K.J.
    J. Biol. Chem. 278:9528-9535(2003) [PubMed] [Europe PMC] [Abstract]
  • "Molecular cloning and expression of an IL-6 signal transducer, gp130."
    Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T.
    Cell 63:1149-1157(1990) [PubMed] [Europe PMC] [Abstract]
• defense response to Gram-negative bacterium Source: BHF-UCLTraceable author statementⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J. Immunol. 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• defense response to Gram-positive bacterium Source: BHF-UCLTraceable author statementⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J. Immunol. 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• defense response to virus Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines."
    Zilberstein A., Ruggieri R., Korn J.H., Revel M.
    EMBO J. 5:2529-2537(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
• endocrine pancreas development Source: BHF-UCL
• glucagon secretion Source: BHF-UCL
• hepatic immune response Source: BHF-UCLInferred from direct assayⁱ
  • "Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells."
    Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H.
    Proc. Natl. Acad. Sci. U.S.A. 84:7251-7255(1987) [PubMed] [Europe PMC] [Abstract]
• humoral immune response Source: BHF-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • Ref.1

    "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
    Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
    Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
• inflammatory response Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• interleukin-6-mediated signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • "Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2."
    Leung K.C., Doyle N., Ballesteros M., Sjogren K., Watts C.K., Low T.H., Leong G.M., Ross R.J., Ho K.K.
    Proc. Natl. Acad. Sci. U.S.A. 100:1016-1021(2003) [PubMed] [Europe PMC] [Abstract]
  • "STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation."
    Verga Falzacappa M.V., Vujic Spasic M., Kessler R., Stolte J., Hentze M.W., Muckenthaler M.U.
    Blood 109:353-358(2007) [PubMed] [Europe PMC] [Abstract]
• maintenance of permeability of blood-brain barrier Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res. 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• monocyte chemotaxis Source: BHF-UCLInferred by curatorⁱ
  • "Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor."
    Klouche M., Bhakdi S., Hemmes M., Rose-John S.
    J. Immunol. 163:4583-4589(1999) [PubMed] [Europe PMC] [Abstract]
• negative regulation of apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Interleukin-6 suppression of neutrophil apoptosis is neutrophil concentration dependent."
    Biffl W.L., Moore E.E., Moore F.A., Barnett C.C. Jr.
    J. Leukoc. Biol. 58:582-584(1995) [PubMed] [Europe PMC] [Abstract]
• negative regulation of bone resorption Source: BHF-UCL
• negative regulation of cell population proliferation Source: ProtIncTraceable author statementⁱ
  • Ref.4

    "Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines."
    Zilberstein A., Ruggieri R., Korn J.H., Revel M.
    EMBO J. 5:2529-2537(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
• negative regulation of chemokine biosynthetic process Source: UniProtKB
• negative regulation of collagen biosynthetic process Source: BHF-UCLInferred from direct assayⁱ
  • "JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression."
    Legendre F., Dudhia J., Pujol J.P., Bogdanowicz P.
    J. Biol. Chem. 278:2903-2912(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of fat cell differentiation Source: BHF-UCL <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes."
    Gustafson B., Smith U.
    J. Biol. Chem. 281:9507-9516(2006) [PubMed] [Europe PMC] [Abstract]
• negative regulation of interleukin-1-mediated signaling pathway Source: BHF-UCL
• negative regulation of lipid storage Source: BHF-UCLNon-traceable author statementⁱ
  • "Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes."
    Gustafson B., Smith U.
    J. Biol. Chem. 281:9507-9516(2006) [PubMed] [Europe PMC] [Abstract]
• negative regulation of neurogenesis Source: ARUK-UCLTraceable author statementⁱ
  • "Fractalkine and CX 3 CR1 regulate hippocampal neurogenesis in adult and aged rats."
    Bachstetter A.D., Morganti J.M., Jernberg J., Schlunk A., Mitchell S.H., Brewster K.W., Hudson C.E., Cole M.J., Harrison J.K., Bickford P.C., Gemma C.
    Neurobiol. Aging 32:2030-2044(2011) [PubMed] [Europe PMC] [Abstract]
• neuron cellular homeostasis Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res. 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• neuron projection development Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6."
    Satoh T., Nakamura S., Taga T., Matsuda T., Hirano T., Kishimoto T., Kaziro Y.
    Mol. Cell. Biol. 8:3546-3549(1988) [PubMed] [Europe PMC] [Abstract]
• neutrophil apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Interleukin-6 suppression of neutrophil apoptosis is neutrophil concentration dependent."
    Biffl W.L., Moore E.E., Moore F.A., Barnett C.C. Jr.
    J. Leukoc. Biol. 58:582-584(1995) [PubMed] [Europe PMC] [Abstract]
• neutrophil mediated immunity Source: BHF-UCLTraceable author statementⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J. Immunol. 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• platelet activation Source: BHF-UCLTraceable author statementⁱ
  • "Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism."
    Oleksowicz L., Mrowiec Z., Zuckerman D., Isaacs R., Dutcher J., Puszkin E.
    Thromb. Haemost. 72:302-308(1994) [PubMed] [Europe PMC] [Abstract]
• positive regulation of acute inflammatory response Source: BHF-UCLInferred from direct assayⁱ
  • "Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells."
    Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H.
    Proc. Natl. Acad. Sci. U.S.A. 84:7251-7255(1987) [PubMed] [Europe PMC] [Abstract]
• positive regulation of apoptotic DNA fragmentation Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions."
    Ye E.A., Steinle J.J.
    Vision Res. 139:15-22(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of apoptotic process Source: UniProtKBInferred from direct assayⁱ
  • "Both Stat3-activation and Stat3-independent BCL2 downregulation are important for interleukin-6-induced apoptosis of 1A9-M cells."
    Oritani K., Tomiyama Y., Kincade P.W., Aoyama K., Yokota T., Matsumura I., Kanakura Y., Nakajima K., Hirano T., Matsuzawa Y.
    Blood 93:1346-1354(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of B cell activation Source: BHF-UCLInferred from direct assayⁱ
  • Ref.1

    "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
    Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
    Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
• positive regulation of cell population proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Molecular cloning and expression of an IL-6 signal transducer, gp130."
    Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T.
    Cell 63:1149-1157(1990) [PubMed] [Europe PMC] [Abstract]
• positive regulation of chemokine production Source: BHF-UCLInferred from direct assayⁱ
  • "Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor."
    Klouche M., Bhakdi S., Hemmes M., Rose-John S.
    J. Immunol. 163:4583-4589(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of DNA-binding transcription factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells."
    Stuber E., Neurath M., Calderhead D., Fell H.P., Strober W.
    Immunity 2:507-521(1995) [PubMed] [Europe PMC] [Abstract]
• positive regulation of epithelial to mesenchymal transition Source: ARUK-UCLInferred from direct assayⁱ
  • "Epigenetic silencing of microRNA-149 in cancer-associated fibroblasts mediates prostaglandin E2/interleukin-6 signaling in the tumor microenvironment."
    Li P., Shan J.X., Chen X.H., Zhang D., Su L.P., Huang X.Y., Yu B.Q., Zhi Q.M., Li C.L., Wang Y.Q., Tomei S., Cai Q., Ji J., Li J.F., Chouchane L., Yu Y.Y., Sun F.Z., Xu Z.H., Liu B.Y., Zhu Z.G.
    Cell Res. 25:588-603(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of extracellular matrix disassembly Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration."
    Ji M.L., Lu J., Shi P.L., Zhang X.J., Wang S.Z., Chang Q., Chen H., Wang C.
    J. Bone Miner. Res. 31:900-909(2016) [PubMed] [Europe PMC] [Abstract]
• positive regulation of gene expression Source: BHF-UCLInferred from direct assayⁱ
  • "Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway."
    Brock M., Trenkmann M., Gay R.E., Michel B.A., Gay S., Fischler M., Ulrich S., Speich R., Huber L.C.
    Circ. Res. 104:1184-1191(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of glial cell proliferation Source: ARUK-UCLInferred from direct assayⁱ
  • "Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor."
    Selmaj K.W., Farooq M., Norton W.T., Raine C.S., Brosnan C.F.
    J. Immunol. 144:129-135(1990) [PubMed] [Europe PMC] [Abstract]
• positive regulation of immunoglobulin secretion Source: BHF-UCLInferred from direct assayⁱ
  • Ref.1

    "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
    Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
    Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
• positive regulation of interleukin-17 biosynthetic process Source: ARUK-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "miR26a modulates Th17/T reg balance in the EAE model of multiple sclerosis by targeting IL6."
    Zhang R., Tian A., Wang J., Shen X., Qi G., Tang Y.
    Neuromolecular Med. 17:24-34(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-6 production Source: BHF-UCLInferred from direct assayⁱ
  • "Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor."
    Klouche M., Bhakdi S., Hemmes M., Rose-John S.
    J. Immunol. 163:4583-4589(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of leukocyte chemotaxis Source: BHF-UCLTraceable author statementⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J. Immunol. 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of MAPK cascade Source: BHF-UCLInferred from direct assayⁱ
  • "JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression."
    Legendre F., Dudhia J., Pujol J.P., Bogdanowicz P.
    J. Biol. Chem. 278:2903-2912(2003) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuroinflammatory response Source: ARUK-UCLTraceable author statementⁱ
  • "Role of TNF in mast cell neuroinflammation and pain."
    Gu Y., Yang D.K., Spinas E., Kritas S.K., Saggini A., Caraffa A., Antinolfi P., Saggini R., Conti P.
    J. Biol. Regul. Homeost. Agents 29:787-791(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of osteoblast differentiation Source: ARUK-UCLInferred from direct assayⁱ
  • "Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway."
    Wu R., Ruan J., Sun Y., Liu M., Sha Z., Fan C., Wu Q.
    Stem Cell Res Ther 9:348-348(2018) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptidyl-serine phosphorylation Source: MGIInferred from direct assayⁱ
  • "Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells."
    Yin T., Yang Y.C.
    J. Biol. Chem. 269:3731-3738(1994) [PubMed] [Europe PMC] [Abstract]
• positive regulation of peptidyl-tyrosine phosphorylation Source: MGIInferred from direct assayⁱ
  • "Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells."
    Yin T., Yang Y.C.
    J. Biol. Chem. 269:3731-3738(1994) [PubMed] [Europe PMC] [Abstract]
• positive regulation of receptor signaling pathway via JAK-STAT Source: BHF-UCLInferred from direct assayⁱ
  • "JAK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a down-regulation of SOX9 expression."
    Legendre F., Dudhia J., Pujol J.P., Bogdanowicz P.
    J. Biol. Chem. 278:2903-2912(2003) [PubMed] [Europe PMC] [Abstract]
  • "Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2."
    Leung K.C., Doyle N., Ballesteros M., Sjogren K., Watts C.K., Low T.H., Leong G.M., Ross R.J., Ho K.K.
    Proc. Natl. Acad. Sci. U.S.A. 100:1016-1021(2003) [PubMed] [Europe PMC] [Abstract]
  • "Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells."
    Theiss A.L., Obertone T.S., Merlin D., Sitaraman S.V.
    J. Biol. Chem. 282:12804-12812(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of smooth muscle cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor."
    Klouche M., Bhakdi S., Hemmes M., Rose-John S.
    J. Immunol. 163:4583-4589(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of T cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "Synergistic activation of human T cells by interleukin 1 and interleukin 6."
    Houssiau F.A., Coulie P.G., Olive D., Van Snick J.
    Eur. J. Immunol. 18:653-656(1988) [PubMed] [Europe PMC] [Abstract]
• positive regulation of T-helper 2 cell cytokine production Source: BHF-UCL
• positive regulation of transcription, DNA-templated Source: UniProtKBInferred from direct assayⁱ
  • "B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma."
    Kryczek I., Zou L., Rodriguez P., Zhu G., Wei S., Mottram P., Brumlik M., Cheng P., Curiel T., Myers L., Lackner A., Alvarez X., Ochoa A., Chen L., Zou W.
    J. Exp. Med. 203:871-881(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: BHF-UCLInferred from direct assayⁱ
  • "STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation."
    Verga Falzacappa M.V., Vujic Spasic M., Kessler R., Stolte J., Hentze M.W., Muckenthaler M.U.
    Blood 109:353-358(2007) [PubMed] [Europe PMC] [Abstract]
  • "Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells."
    Theiss A.L., Obertone T.S., Merlin D., Sitaraman S.V.
    J. Biol. Chem. 282:12804-12812(2007) [PubMed] [Europe PMC] [Abstract]
• positive regulation of translation Source: UniProtKBInferred from direct assayⁱ
  • "BCL3 is induced by IL-6 via Stat3 binding to intronic enhancer HS4 and represses its own transcription."
    Brocke-Heidrich K., Ge B., Cvijic H., Pfeifer G., Loffler D., Henze C., McKeithan T.W., Horn F.
    Oncogene 25:7297-7304(2006) [PubMed] [Europe PMC] [Abstract]
• positive regulation of type B pancreatic cell apoptotic process Source: BHF-UCLTraceable author statementⁱ
  • "Interleukin-6 regulates pancreatic alpha-cell mass expansion."
    Ellingsgaard H., Ehses J.A., Hammar E.B., Van Lommel L., Quintens R., Martens G., Kerr-Conte J., Pattou F., Berney T., Pipeleers D., Halban P.A., Schuit F.C., Donath M.Y.
    Proc. Natl. Acad. Sci. U.S.A. 105:13163-13168(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCLInferred from direct assayⁱ
  • "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF."
    Schuster B., Kovaleva M., Sun Y., Regenhard P., Matthews V., Grotzinger J., Rose-John S., Kallen K.J.
    J. Biol. Chem. 278:9528-9535(2003) [PubMed] [Europe PMC] [Abstract]
  • "Interleukin-6 modulates the expression of the bone morphogenic protein receptor type II through a novel STAT3-microRNA cluster 17/92 pathway."
    Brock M., Trenkmann M., Gay R.E., Michel B.A., Gay S., Fischler M., Ulrich S., Speich R., Huber L.C.
    Circ. Res. 104:1184-1191(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of vascular endothelial growth factor production Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "miR-146a suppresses STAT3/VEGF pathways and reduces apoptosis through IL-6 signaling in primary human retinal microvascular endothelial cells in high glucose conditions."
    Ye E.A., Steinle J.J.
    Vision Res. 139:15-22(2017) [PubMed] [Europe PMC] [Abstract]
• post-translational protein modification Source: Reactome
• regulation of angiogenesis Source: BHF-UCLInferred by curatorⁱ
  • "Interleukin 6 induces the expression of vascular endothelial growth factor."
    Cohen T., Nahari D., Cerem L.W., Neufeld G., Levi B.Z.
    J. Biol. Chem. 271:736-741(1996) [PubMed] [Europe PMC] [Abstract]
• regulation of astrocyte activation Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res. 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• regulation of microglial cell activation Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res. 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• regulation of neuroinflammatory response Source: ARUK-UCLTraceable author statementⁱ
  • "TNF-alpha-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IkappaB-NFkappaB and JAK-STAT3 pathways."
    Matsumoto J., Dohgu S., Takata F., Machida T., Bolukbasi Hatip F.F., Hatip-Al-Khatib I., Yamauchi A., Kataoka Y.
    Brain Res. 1692:34-44(2018) [PubMed] [Europe PMC] [Abstract]
• regulation of vascular endothelial growth factor production Source: BHF-UCLInferred from direct assayⁱ
  • "Interleukin 6 induces the expression of vascular endothelial growth factor."
    Cohen T., Nahari D., Cerem L.W., Neufeld G., Levi B.Z.
    J. Biol. Chem. 271:736-741(1996) [PubMed] [Europe PMC] [Abstract]
• response to glucocorticoid Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor."
    Franchimont D., Martens H., Hagelstein M.T., Louis E., Dewe W., Chrousos G.P., Belaiche J., Geenen V.
    J. Clin. Endocrinol. Metab. 84:2834-2839(1999) [PubMed] [Europe PMC] [Abstract]
• response to peptidoglycan Source: BHF-UCLNon-traceable author statementⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J. Immunol. 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• T-helper 17 cell lineage commitment Source: UniProtKB

<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

<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 provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Mutagenesis

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation 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

Gene expression databases

Organism-specific 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%27">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

• cytokine activity Source: BHF-UCLInferred from direct assayⁱ
  • Ref.4

    "Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines."
    Zilberstein A., Ruggieri R., Korn J.H., Revel M.
    EMBO J. 5:2529-2537(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  • Ref.1

    "Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin."
    Hirano T., Yasukawa K., Harada H., Taga T., Watanabe Y., Matsuda T., Kashiwamura S., Nakajima K., Koyama K., Iwamatsu A., Tsunasawa S., Sakiyama F., Matsui H., Takahara Y., Taniguchi T., Kishimoto T.
    Nature 324:73-76(1986) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
• growth factor activity Source: BHF-UCLInferred from direct assayⁱ
  • "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF."
    Schuster B., Kovaleva M., Sun Y., Regenhard P., Matthews V., Grotzinger J., Rose-John S., Kallen K.J.
    J. Biol. Chem. 278:9528-9535(2003) [PubMed] [Europe PMC] [Abstract]
  • "Molecular cloning and expression of an IL-6 signal transducer, gp130."
    Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T.
    Cell 63:1149-1157(1990) [PubMed] [Europe PMC] [Abstract]
• interleukin-6 receptor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex."
    Boulanger M.J., Chow D.-C., Brevnova E.E., Garcia K.C.
    Science 300:2101-2104(2003) [PubMed] [Europe PMC] [Abstract]

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

<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>Sequence (1+)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 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MNSFSTSAFG PVAFSLGLLL VLPAAFPAPV PPGEDSKDVA APHRQPLTSS 
        60         70         80         90        100
ERIDKQIRYI LDGISALRKE TCNKSNMCES SKEALAENNL NLPKMAEKDG 
       110        120        130        140        150
CFQSGFNEET CLVKIITGLL EFEVYLEYLQ NRFESSEEQA RAVQMSTKVL 
       160        170        180        190        200
IQFLQKKAKN LDAITTPDPT TNASLLTKLQ AQNQWLQDMT THLILRSFKE 
       210 
FLQSSLRALR QM                                          

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismⁱ

Natural variant

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

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. Human chromosome 7
   Human chromosome 7: entries, gene names and cross-references to MIM
2. SIMILARITY comments
   Index of protein domains and families
3. Human entries with polymorphisms or disease mutations
   List of human entries with polymorphisms or disease mutations
4. Human polymorphisms and disease mutations
   Index of human polymorphisms and disease mutations
5. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
6. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references