Interleukin-6 receptor

Interleukin 6 receptor
PDB rendering based on 1n26.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1N26​, 1N2Q​, 1P9M​, 2ARW​
Identifiers
Symbols	IL6R ; CD126; IL-6R-1; IL-6RA; IL6Q; IL6RA; IL6RQ; gp80
External IDs	OMIM: 147880 MGI: 105304 HomoloGene: 474 GeneCards: IL6R Gene
Gene ontology Molecular function • ciliary neurotrophic factor receptor activity • interleukin-6 receptor activity • interleukin-6 receptor binding • protein binding • enzyme binding • interleukin-6 binding • protein homodimerization activity • ciliary neurotrophic factor binding Cellular component • extracellular region • extracellular space • plasma membrane • interleukin-6 receptor complex • cell surface • basolateral plasma membrane • apical plasma membrane • neuronal cell body membrane • ciliary neurotrophic factor receptor complex Biological process • hepatic immune response • neutrophil mediated immunity • monocyte chemotaxis • positive regulation of leukocyte chemotaxis • acute-phase response • positive regulation of cell proliferation • response to gamma radiation • positive regulation of activation of Janus kinase activity • cell growth • cytokine-mediated signaling pathway • endocrine pancreas development • response to lipopolysaccharide • negative regulation of interleukin-8 production • positive regulation of chemokine production • positive regulation of interleukin-6 production • negative regulation of collagen biosynthetic process • response to cytokine • positive regulation of tyrosine phosphorylation of Stat3 protein • positive regulation of MAPK cascade • response to peptide hormone • response to ethanol • positive regulation of osteoblast differentiation • positive regulation of smooth muscle cell proliferation • positive regulation of peptidyl-tyrosine phosphorylation • defense response to Gram-negative bacterium • defense response to Gram-positive bacterium • positive regulation of NF-kappaB transcription factor activity • response to glucocorticoid • response to cAMP • interleukin-6-mediated signaling pathway • ciliary neurotrophic factor-mediated signaling pathway • extrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3570	16194
Ensembl	ENSG00000160712	ENSMUSG00000027947
UniProt	P08887	P22272
RefSeq (mRNA)	NM_000565	NM_010559
RefSeq (protein)	NP_000556	NP_034689
Location (UCSC)	Chr 1: 154.41 – 154.47 Mb	Chr 3: 89.86 – 89.91 Mb
PubMed search

Interleukin 6 receptor (IL6R) also known as CD126 (Cluster of Differentiation 126) is a type I cytokine receptor.

Function

Interleukin 6 (IL6) is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in immune response. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer.

In melanocytic cells IL6R gene expression may be regulated by MITF.^[1]

Structure

The IL6 receptor is a protein complex consisting of an IL-6 receptor subunit (IL6R) and interleukin 6 signal transducer Glycoprotein 130. IL6R also denotes the human gene encoding this subunit. Alternatively spliced transcript variants encoding distinct isoforms have been reported.^[2] IL6R subunit is also shared by many other cytokines.

Interactions

Interleukin-6 receptor has been shown to interact with Interleukin 6^[3][4][5] and Ciliary neurotrophic factor.^[4][6]

See also

• Cluster of differentiation
• Tocilizumab, a monoclonal antibody against IL6R

References

1. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
2. "Entrez Gene: IL6R interleukin 6 receptor".
3. Schwantner A, Dingley AJ, Ozbek S, Rose-John S, Grötzinger J (Jan 2004). "Direct determination of the interleukin-6 binding epitope of the interleukin-6 receptor by NMR spectroscopy". J. Biol. Chem. 279 (1): 571–6. doi:10.1074/jbc.M311019200. PMID 14557255.
4. Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, Rose-John S, Kallen KJ (Mar 2003). "Signaling of human ciliary neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF". J. Biol. Chem. 278 (11): 9528–35. doi:10.1074/jbc.M210044200. PMID 12643274.
5. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (Aug 1989). "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130". Cell 58 (3): 573–81. doi:10.1016/0092-8674(89)90438-8. PMID 2788034.
6. Schooltink H, Stoyan T, Roeb E, Heinrich PC, Rose-John S (Dec 1992). "Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes". FEBS Lett. 314 (3): 280–4. doi:10.1016/0014-5793(92)81489-9. PMID 1281789.

Further reading

• Krause E, Wegenka U, Möller C, Horn F, Heinrich PC (1992). "Gene expression of the high molecular weight proteinase inhibitor alpha 2-macroglobulin". Biol. Chem. Hoppe-Seyler 373 (7): 509–15. doi:10.1515/bchm3.1992.373.2.509. PMID 1381187.
• Schooltink H, Stoyan T, Roeb E, Heinrich PC, Rose-John S (1992). "Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes". FEBS Lett. 314 (3): 280–4. doi:10.1016/0014-5793(92)81489-9. PMID 1281789.
• Schooltink H, Stoyan T, Lenz D, Schmitz H, Hirano T, Kishimoto T, Heinrich PC, Rose-John S (1991). "Structural and functional studies on the human hepatic interleukin-6 receptor. Molecular cloning and overexpression in HepG2 cells". Biochem. J. 277 ( Pt 3) (Pt 3): 659–64. PMC 1151293. PMID 1872801.
• Szpirer J, Szpirer C, Rivière M, Houart C, Baumann M, Fey GH, Poli V, Cortese R, Islam MQ, Levan G (1991). "The Interleukin-6-dependent DNA-binding protein gene (transcription factor 5: TCF5) maps to human chromosome 20 and rat chromosome 3, the IL6 receptor locus (IL6R) to human chromosome 1 and rat chromosome 2, and the rat IL6 gene to rat chromosome 4". Genomics 10 (3): 539–46. doi:10.1016/0888-7543(91)90433-F. PMID 1889804.
• Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T, Kishimoto T (1990). "Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis". J. Exp. Med. 171 (6): 2001–9. doi:10.1084/jem.171.6.2001. PMC 2187962. PMID 2112585.
• Snyers L, De Wit L, Content J (1990). "Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells". Proc. Natl. Acad. Sci. U.S.A. 87 (7): 2838–42. doi:10.1073/pnas.87.7.2838. PMC 53786. PMID 2157217.
• Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (1990). "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63 (6): 1149–57. doi:10.1016/0092-8674(90)90411-7. PMID 2261637.
• Novick D, Engelmann H, Wallach D, Rubinstein M (1989). "Soluble cytokine receptors are present in normal human urine". J. Exp. Med. 170 (4): 1409–14. doi:10.1084/jem.170.4.1409. PMC 2189483. PMID 2529343.
• Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (1989). "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130". Cell 58 (3): 573–81. doi:10.1016/0092-8674(89)90438-8. PMID 2788034.
• Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988). "Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor". Science 241 (4867): 825–8. doi:10.1126/science.3136546. PMID 3136546.
• Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M, Matsumoto A, Yamamoto M, Yamamoto N (1994). "Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism". Eur. J. Immunol. 24 (8): 1945–8. doi:10.1002/eji.1830240837. PMID 8056053.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Tamura T, Udagawa N, Takahashi N, Miyaura C, Tanaka S, Yamada Y, Koishihara Y, Ohsugi Y, Kumaki K, Taga T (1993). "Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6". Proc. Natl. Acad. Sci. U.S.A. 90 (24): 11924–8. doi:10.1073/pnas.90.24.11924. PMC 48097. PMID 8265649.
• Kluck PM, Wiegant J, Jansen RP, Bolk MW, Raap AK, Willemze R, Landegent JE (1993). "The human interleukin-6 receptor alpha chain gene is localized on chromosome 1 band q21". Hum. Genet. 90 (5): 542–4. doi:10.1007/BF00217455. PMID 8428753.
• Chirmule N, Kalyanaraman VS, Lederman S, Oyaizu N, Yagura H, Yellin MJ, Chess L, Pahwa S (1993). "HIV-gp 160-induced T cell-dependent B cell differentiation. Role of T cell-B cell activation molecule and IL-6". J. Immunol. 150 (6): 2478–86. PMID 8450224.
• Yawata H, Yasukawa K, Natsuka S, Murakami M, Yamasaki K, Hibi M, Taga T, Kishimoto T (1993). "Structure-function analysis of human IL-6 receptor: dissociation of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130". EMBO J. 12 (4): 1705–12. PMC 413384. PMID 8467812.
• Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM (1997). "Identification of novel human WW domain-containing proteins by cloning of ligand targets". J. Biol. Chem. 272 (23): 14611–6. doi:10.1074/jbc.272.23.14611. PMID 9169421.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, Nishinakamura R, Toyama Y, Yabe Y, Hori M, Takahashi N, Suda T (1999). "Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene". Endocrinology 140 (2): 925–32. doi:10.1210/en.140.2.925. PMID 9927325.

External links

• IL6R protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.