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interleukin-6 receptor

Function: - activation may lead to the regulation of the immune response, acute-phase reactions & hematopoiesis Structure: - hexamer of two molecules each of IL6, IL6R & gp130 - external domain of IL6R interacts with gp130, that functions as a signal transducer Pharmacology: - IL-6 receptor inhibitors sarilumab & tocilizumab indicated for treatment of rheumatoid arthritis - sarilumab more effective than adalimumab (TNF-alpha inhibitor) as monotherapy forheumatoid arthritis [4] - tocilizumab also used for treatment of giant cell arteritis Polymorphism: - IL6 receptor gene SNP(s) associated with risk for aortic aneurysm

Related

interleukin-6; IL-6; B-cell stimulatory factor 2; BSF-2; CTL differentiation factor; CDF; hybridoma growth factor; interferon beta-2; IFN-beta-2 (IL6, IFNB2) sarilumab (Kevzara)

General

interleukin receptor multisubunit protein

Properties

COMPARTMENT: plasma membrane MOTIF: ligand-binding site transmembrane domain cysteine residue box1 motif FOR-BINDING-OF: Janus kinase (JAK) box2 motif FOR-BINDING-OF: Janus kinase (JAK) Tyr phosphorylation site SUBUNITS: interleukin-6 receptor subunit beta MOTIF: signal sequence {1-22} immunoglobulin superfamily domain {26-120} MOTIF: cysteine residue {C28} MODIFICATION: cysteine residue {C54} N-glycosylation site {N43} cysteine residue {C48} MODIFICATION: cysteine residue {C103} cysteine residue {C54} MODIFICATION: cysteine residue {C28} N-glycosylation site {N83} cysteine residue {C103} MODIFICATION: cysteine residue {C48} fibronectin type III domain or F3 module {125-216} MOTIF: N-glycosylation site {N131} cysteine residue {C134} MODIFICATION: cysteine residue {C144} cysteine residue {C144} MODIFICATION: cysteine residue {C134} N-glycosylation site {N157} cysteine residue {C172} MODIFICATION: cysteine residue {C182} cysteine residue {C182} MODIFICATION: cysteine residue {C172} fibronectin type III domain or F3 module {222-321} MOTIF: N-glycosylation site {N227} WSXWS motif {310-314} fibronectin type III domain or F3 module {326-418} MOTIF: N-glycosylation site {N379} N-glycosylation site {N383} fibronectin type III domain or F3 module {423-514} MOTIF: cysteine residue {C458} MODIFICATION: cysteine residue {C466} cysteine residue {C466} MODIFICATION: cysteine residue {C458} fibronectin type III domain or F3 module {518-610} MOTIF: N-glycosylation site {N553} N-glycosylation site {N564} transmembrane domain {620-641} box1 motif SITE: 651-659 FOR-BINDING-OF: Janus kinase (JAK) Ser phosphorylation site {S667} serine-rich region {725-755} MOTIF: serine residue (SEVERAL) Ser phosphorylation site {S782} Ser phosphorylation site {S820} Ser phosphorylation site {S829} IL-6 receptor alpha MOTIF: signal sequence {1-19} cysteine residue {C25} MODIFICATION: cysteine residue {C193} immunoglobulin superfamily domain {26-112} MOTIF: cysteine residue {C47} MODIFICATION: cysteine residue {C96} N-glycosylation site {N55} N-glycosylation site {N93} cysteine residue {C96} MODIFICATION: cysteine residue {C47} cysteine residue {C121} MODIFICATION: cysteine residue {C132} cysteine residue {C132} MODIFICATION: cysteine residue {C121} cysteine residue {C165} MODIFICATION: cysteine residue {C176} cysteine residue {C176} MODIFICATION: cysteine residue {C165} cysteine residue {C193} MODIFICATION: cysteine residue {C25} fibronectin type III domain or F3 module {216-311} MOTIF: N-glycosylation site {N221} asparagine residue {245} WSXWS motif {303-307} transmembrane domain {366-386}

References

  1. Ihle JN et al Signaling by the cytokine receptor superfamily: JAKs and STATs TIBS 19:222 1994 PMID: 8048164
  2. Itoh N, Yonehara S, Schreurs J, Gorman DM, Maruyama K, Ishii A, Yahara I, Arai K, Miyajima A. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Science. 1990 Jan 19;247(4940):324-7. PMID: 2404337
  3. Miyajima A, Hara T, Kitamura T. Common subunits of cytokine receptors and the functional redundancy of cytokines. Trends Biochem Sci. 1992 Oct;17(10):378-82. Review. PMID: 1455505
  4. Burmester GR, Lin Y, Patel R et al Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. Nov 17, 2016 PMID: 27856432 Free full text http://ard.bmj.com/content/early/2016/11/16/annrheumdis-2016-210310.abstract
  5. Cai T, Zhang Y, Ho YL et al Association of Interleukin 6 Receptor Variant With Cardiovascular Disease Effects of Interleukin 6 Receptor Blocking Therapy. A Phenome-Wide Association Study. JAMA Cardiol. Published online August 8, 2018 PMID: 30090940 https://jamanetwork.com/journals/jamacardiology/fullarticle/2696438

Components

CD126; interleukin-6 receptor subunit alpha; IL-6R-alpha; IL-6R 1; membrane glycoprotein 80; gp80 (IL6R) CD130; gp130; interleukin-6 receptor subunit beta; IL-6R-beta; interleukin-6 signal transducer; membrane glycoprotein 130; CDw130; oncostatin-M receptor alpha subunit (IL6ST)