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Identification
HMDB Protein ID HMDBP02087
Secondary Accession Numbers
  • 7569
Name Interleukin-6
Synonyms
  1. B-cell stimulatory factor 2
  2. BSF-2
  3. CDF
  4. CTL differentiation factor
  5. Hybridoma growth factor
  6. IFN-beta-2
  7. IL-6
  8. Interferon beta-2
Gene Name IL6
Protein Type Enzyme
Biological Properties
General Function Involved in cytokine activity
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. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoeitic progenitor cells and cells of the CNS. 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
extracellular region
Function
cytokine activity
binding
cytokine receptor binding
interleukin-6 receptor binding
protein binding
receptor binding
Process
immune system process
immune response
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location Chromosome:7
Locus 7p21
SNPs IL6
Gene Sequence
>639 bp
ATGAACTCCTTCTCCACAAGCGCCTTCGGTCCAGTTGCCTTCTCCCTGGGGCTGCTCCTG
GTGTTGCCTGCTGCCTTCCCTGCCCCAGTACCCCCAGGAGAAGATTCCAAAGATGTAGCC
GCCCCACACAGACAGCCACTCACCTCTTCAGAACGAATTGACAAACAAATTCGGTACATC
CTCGACGGCATCTCAGCCCTGAGAAAGGAGACATGTAACAAGAGTAACATGTGTGAAAGC
AGCAAAGAGGCACTGGCAGAAAACAACCTGAACCTTCCAAAGATGGCTGAAAAAGATGGA
TGCTTCCAATCTGGATTCAATGAGGAGACTTGCCTGGTGAAAATCATCACTGGTCTTTTG
GAGTTTGAGGTATACCTAGAGTACCTCCAGAACAGATTTGAGAGTAGTGAGGAACAAGCC
AGAGCTGTCCAGATGAGTACAAAAGTCCTGATCCAGTTCCTGCAGAAAAAGGCAAAGAAT
CTAGATGCAATAACCACCCCTGACCCAACCACAAATGCCAGCCTGCTGACGAAGCTGCAG
GCACAGAACCAGTGGCTGCAGGACATGACAACTCATCTCATTCTGCGCAGCTTTAAGGAG
TTCCTGCAGTCCAGCCTGAGGGCTCTTCGGCAAATGTAG
Protein Properties
Number of Residues 212
Molecular Weight 23718.0
Theoretical pI 6.52
Pfam Domain Function
Signals
  • 1-29
Transmembrane Regions
  • None
Protein Sequence
>Interleukin-6
MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI
LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL
EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ
AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM
GenBank ID Protein 32674
UniProtKB/Swiss-Prot ID P05231
UniProtKB/Swiss-Prot Entry Name IL6_HUMAN
PDB IDs
GenBank Gene ID X04430
GeneCard ID IL6
GenAtlas ID IL6
HGNC ID HGNC:6018
References
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  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 ]