Interleukin-6

Details

Name
Interleukin-6
Synonyms
  • B-cell stimulatory factor 2
  • BSF-2
  • CDF
  • CTL differentiation factor
  • Hybridoma growth factor
  • IFN-beta-2
  • IFNB2
  • IL-6
  • Interferon beta-2
Gene Name
IL6
Organism
Humans
Amino acid sequence
>lcl|BSEQ0021838|Interleukin-6
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
Number of residues
212
Molecular Weight
23717.965
Theoretical pI
6.52
GO Classification
Functions
cytokine activity / growth factor activity / interleukin-6 receptor binding
Processes
acute-phase response / aging / bone remodeling / branching involved in salivary gland morphogenesis / cell growth / cell redox homeostasis / cellular response to dexamethasone stimulus / cellular response to hydrogen peroxide / cellular response to interleukin-1 / cellular response to lipopolysaccharide / cellular response to tumor necrosis factor / cytokine-mediated signaling pathway / defense response to Gram-negative bacterium / defense response to Gram-positive bacterium / defense response to protozoan / defense response to virus / endocrine pancreas development / epithelial cell proliferation involved in salivary gland morphogenesis / glucagon secretion / glucose homeostasis / hepatic immune response / humoral immune response / inflammatory response / interleukin-6-mediated signaling pathway / monocyte chemotaxis / muscle cell cellular homeostasis / negative regulation of apoptotic process / negative regulation of cell proliferation / negative regulation of chemokine biosynthetic process / negative regulation of collagen biosynthetic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of cytokine secretion / negative regulation of fat cell differentiation / negative regulation of gluconeogenesis / negative regulation of hormone secretion / negative regulation of lipid storage / negative regulation of muscle organ development / negative regulation of neuron death / negative regulation of protein kinase activity / neuron projection development / neutrophil apoptotic process / neutrophil mediated immunity / platelet activation / positive regulation of acute inflammatory response / positive regulation of apoptotic process / positive regulation of B cell activation / positive regulation of cell proliferation / positive regulation of chemokine production / positive regulation of DNA replication / positive regulation of epithelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of immunoglobulin secretion / positive regulation of interleukin-6 production / positive regulation of JAK-STAT cascade / positive regulation of leukocyte chemotaxis / positive regulation of MAPK cascade / positive regulation of neuron differentiation / positive regulation of nitric oxide biosynthetic process / positive regulation of osteoblast differentiation / positive regulation of peptidyl-serine phosphorylation / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of protein import into nucleus, translocation / positive regulation of protein kinase B signaling / positive regulation of sequence-specific DNA binding transcription factor activity / positive regulation of smooth muscle cell proliferation / positive regulation of STAT protein import into nucleus / positive regulation of T cell proliferation / positive regulation of T-helper 2 cell differentiation / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / positive regulation of translation / positive regulation of transmission of nerve impulse / positive regulation of type B pancreatic cell apoptotic process / positive regulation of tyrosine phosphorylation of Stat3 protein / regulation of angiogenesis / regulation of cell shape / regulation of circadian sleep/wake cycle, non-REM sleep / regulation of vascular endothelial growth factor production / response to amino acid / response to antibiotic / response to auditory stimulus / response to caffeine / response to calcium ion / response to cold / response to drug / response to electrical stimulus / response to glucocorticoid / response to heat / response to insulin / response to nutrient levels / response to peptidoglycan / response to yeast / T-helper 17 cell lineage commitment
Components
cytoplasm / external side of plasma membrane / extracellular region / extracellular space / interleukin-6 receptor complex
General Function
Interleukin-6 receptor binding
Specific Function
Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0021839|Interleukin-6 (IL6)
ATGAACTCCTTCTCCACAAGCGCCTTCGGTCCAGTTGCCTTCTCCCTGGGGCTGCTCCTG
GTGTTGCCTGCTGCCTTCCCTGCCCCAGTACCCCCAGGAGAAGATTCCAAAGATGTAGCC
GCCCCACACAGACAGCCACTCACCTCTTCAGAACGAATTGACAAACAAATTCGGTACATC
CTCGACGGCATCTCAGCCCTGAGAAAGGAGACATGTAACAAGAGTAACATGTGTGAAAGC
AGCAAAGAGGCACTGGCAGAAAACAACCTGAACCTTCCAAAGATGGCTGAAAAAGATGGA
TGCTTCCAATCTGGATTCAATGAGGAGACTTGCCTGGTGAAAATCATCACTGGTCTTTTG
GAGTTTGAGGTATACCTAGAGTACCTCCAGAACAGATTTGAGAGTAGTGAGGAACAAGCC
AGAGCTGTGCAGATGAGTACAAAAGTCCTGATCCAGTTCCTGCAGAAAAAGGCAAAGAAT
CTAGATGCAATAACCACCCCTGACCCAACCACAAATGCCAGCCTGCTGACGAAGCTGCAG
GCACAGAACCAGTGGCTGCAGGACATGACAACTCATCTCATTCTGCGCAGCTTTAAGGAG
TTCCTGCAGTCCAGCCTGAGGGCTCTTCGGCAAATGTAG
Chromosome Location
7
Locus
7p21
External Identifiers
ResourceLink
UniProtKB IDP05231
UniProtKB Entry NameIL6_HUMAN
GenBank Protein ID32674
GenBank Gene IDX04430
GenAtlas IDIL6
HGNC IDHGNC:6018
General References
  1. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S, Nakajima K, Koyama K, Iwamatsu A, et al.: Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature. 1986 Nov 6-12;324(6092):73-6. [PubMed:3491322]
  2. Yasukawa K, Hirano T, Watanabe Y, Muratani K, Matsuda T, Nakai S, Kishimoto T: Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene. EMBO J. 1987 Oct;6(10):2939-45. [PubMed:3500852]
  3. May LT, Helfgott DC, Sehgal PB: Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957-61. [PubMed:3538015]
  4. Zilberstein A, Ruggieri R, Korn JH, Revel M: Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 1986 Oct;5(10):2529-37. [PubMed:3023045]
  5. Brakenhoff JP, de Groot ER, Evers RF, Pannekoek H, Aarden LA: Molecular cloning and expression of hybridoma growth factor in Escherichia coli. J Immunol. 1987 Dec 15;139(12):4116-21. [PubMed:3320204]
  6. Tonouchi N, Miwa K, Karasuyama H, Matsui H: Deletion of 3' untranslated region of human BSF-2 mRNA causes stabilization of the mRNA and high-level expression in mouse NIH3T3 cells. Biochem Biophys Res Commun. 1989 Sep 15;163(2):1056-62. [PubMed:2789513]
  7. Haegeman G, Content J, Volckaert G, Derynck R, Tavernier J, Fiers W: Structural analysis of the sequence coding for an inducible 26-kDa protein in human fibroblasts. Eur J Biochem. 1986 Sep 15;159(3):625-32. [PubMed:3758081]
  8. Wong GG, Witek-Giannotti J, Hewick RM, Clark SC, Ogawa M: Interleukin 6: identification as a hematopoietic colony-stimulating factor. Behring Inst Mitt. 1988 Aug;(83):40-7. [PubMed:3266463]
  9. Chen QY: [Stable and efficient expression of human interleukin-6 cDNA in mammalian cells after gene transfer]. Zhonghua Zhong Liu Za Zhi. 1992 Sep;14(5):340-4. [PubMed:1291290]
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  11. Van Damme J, Van Beeumen J, Decock B, Van Snick J, De Ley M, Billiau A: Separation and comparison of two monokines with lymphocyte-activating factor activity: IL-1 beta and hybridoma growth factor (HGF). Identification of leukocyte-derived HGF as IL-6. J Immunol. 1988 Mar 1;140(5):1534-41. [PubMed:3279116]
  12. Ming JE, Cernetti C, Steinman RM, Granelli-Piperno A: Interleukin 6 is the principal cytolytic T lymphocyte differentiation factor for thymocytes in human leukocyte conditioned medium. J Mol Cell Immunol. 1989;4(4):203-11; discussion 211-2. [PubMed:2610854]
  13. May LT, Shaw JE, Khanna AK, Zabriskie JB, Sehgal PB: Marked cell-type-specific differences in glycosylation of human interleukin-6. Cytokine. 1991 May;3(3):204-11. [PubMed:1883960]
  14. Breton J, La Fiura A, Bertolero F, Orsini G, Valsasina B, Ziliotto R, De Filippis V, Polverino de Laureto P, Fontana A: Structure, stability and biological properties of a N-terminally truncated form of recombinant human interleukin-6 containing a single disulfide bond. Eur J Biochem. 1995 Jan 15;227(1-2):573-81. [PubMed:7851440]
  15. Clogston CL, Boone TC, Crandall BC, Mendiaz EA, Lu HS: Disulfide structures of human interleukin-6 are similar to those of human granulocyte colony stimulating factor. Arch Biochem Biophys. 1989 Jul;272(1):144-51. [PubMed:2472117]
  16. Lutticken C, Kruttgen A, Moller C, Heinrich PC, Rose-John S: Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6. FEBS Lett. 1991 May 6;282(2):265-7. [PubMed:2037043]
  17. Nishimura C, Watanabe A, Gouda H, Shimada I, Arata Y: Folding topologies of human interleukin-6 and its mutants as studied by NMR spectroscopy. Biochemistry. 1996 Jan 9;35(1):273-81. [PubMed:8555185]
  18. Xu GY, Yu HA, Hong J, Stahl M, McDonagh T, Kay LE, Cumming DA: Solution structure of recombinant human interleukin-6. J Mol Biol. 1997 May 2;268(2):468-81. [PubMed:9159484]
  19. Somers W, Stahl M, Seehra JS: 1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling. EMBO J. 1997 Mar 3;16(5):989-97. [PubMed:9118960]
  20. Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P: The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998 Oct 1;102(7):1369-76. [PubMed:9769329]
  21. Foster CB, Lehrnbecher T, Samuels S, Stein S, Mol F, Metcalf JA, Wyvill K, Steinberg SM, Kovacs J, Blauvelt A, Yarchoan R, Chanock SJ: An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus. Blood. 2000 Oct 1;96(7):2562-7. [PubMed:11001912]
  22. Ota N, Nakajima T, Nakazawa I, Suzuki T, Hosoi T, Orimo H, Inoue S, Shirai Y, Emi M: A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density. J Hum Genet. 2001;46(5):267-72. [PubMed:11355017]
  23. Chung HW, Seo JS, Hur SE, Kim HL, Kim JY, Jung JH, Kim LH, Park BL, Shin HD: Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women. J Hum Genet. 2003;48(5):243-8. Epub 2003 Apr 18. [PubMed:12768442]
  24. Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. [PubMed:26091039]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01404Ginsengapproved, investigational, nutraceuticalunknownantagonistDetails
DB05017YSIL6investigationalunknownDetails
DB05470VX-702investigationalunknownDetails
DB05744CRx-139investigationalunknownDetails
DB05767AndrographolideinvestigationalunknownDetails
DB06083TapinarofinvestigationalunknownDetails
DB11967Binimetinibapproved, investigationalunknownDetails
DB05513AtiprimodinvestigationalunknownDetails
DB09036Siltuximabapproved, investigationalyesantagonistantibodyDetails
DB12140DilmapimodinvestigationalunknownDetails
DB09221PolaprezincexperimentalunknowninhibitorDetails
DB10770Foreskin fibroblast (neonatal)approvedunknownagonistDetails
DB10772Foreskin keratinocyte (neonatal)approvedyesagonistDetails