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Interleukin-6 receptor, α subunit

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 1708

Nomenclature: Interleukin-6 receptor, α subunit

Abbreviated Name: IL6R

Systematic Nomenclature: interleukin 6 receptor

Family: IL-6 receptor family

Quaternary Structure: Complexes
Interleukin-6 receptor
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 468 1q21.3 IL6R interleukin 6 receptor
Mouse 1 460 3 39.19 cM Il6ra interleukin 6 receptor, alpha
Rat 1 462 2q34 Il6r interleukin 6 receptor
Previous and Unofficial Names Click here for help
CD126 | IL-6R subunit alpha | interleukin 6 receptor
Database Links Click here for help
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of the extra-cellular domains of human Interleukin-6 Receptor alpha chain
PDB Id:  1N26
Resolution:  2.4Å
Species:  Human
References:  7
Natural/Endogenous Ligands Click here for help
IL-6 {Sp: Human}

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Agonists
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Ligand Sp. Action Value Parameter Reference
IL-6 {Sp: Human} Peptide Primary target of this compound Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Agonist 9.4 pKd 5
pKd 9.4 (Kd 4.4x10-10 M) IL6R) expressed stably in murine NIH/3T3 fibroblasts.exhibited a single class of binding sites for 125I-labeled recombinant human interleukin-6 (125I-rhIL-6) (Kd = 440 pM, 20,000 receptors per cell). [5]
Antibodies
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Antibody Sp. Action Value Parameter Reference
sarilumab Peptide Approved drug Primary target of this compound Immunopharmacology Ligand Hs Binding 10.6 – 11.1 pKd 6
pKd 10.6 – 11.1 (Kd 2.3x10-11 – 9x10-12 M) [6]
Description: Dissociation equilibrium constant calculated using two different assay methods (kinetic vs. equilibrium/solution)
Immunopharmacology Comments
IL6R polymorphisms are associated with asthma risk [1].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0002548 monocyte chemotaxis IC
GO:0002690 positive regulation of leukocyte chemotaxis TAS
GO:0006953 acute-phase response TAS
click arrow to show/hide IEA associations
GO:0072540 T-helper 17 cell lineage commitment IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0002690 positive regulation of leukocyte chemotaxis TAS
GO:0002827 positive regulation of T-helper 1 type immune response IBA
GO:0032816 positive regulation of natural killer cell activation IBA
GO:0042104 positive regulation of activated T cell proliferation IBA
GO:0050671 positive regulation of lymphocyte proliferation IBA
GO:0051135 positive regulation of NK T cell activation IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 13 GO processes
GO:0004896 cytokine receptor activity IBA
GO:0004921 interleukin-11 receptor activity IBA
GO:0010573 vascular endothelial growth factor production IDA
GO:0019221 cytokine-mediated signaling pathway IDA
GO:0032717 negative regulation of interleukin-8 production NAS
GO:0032722 positive regulation of chemokine production IDA
GO:0032729 positive regulation of interferon-gamma production IBA
GO:0032755 positive regulation of interleukin-6 production IDA
GO:0034097 response to cytokine IDA
GO:0070102 interleukin-6-mediated signaling pathway IMP
GO:0070120 ciliary neurotrophic factor-mediated signaling pathway IMP
click arrow to show/hide IEA associations
GO:0004897 ciliary neurotrophic factor receptor activity IEA
GO:0004915 interleukin-6 receptor activity IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 5 GO processes
GO:0002548 monocyte chemotaxis IC
GO:0002690 positive regulation of leukocyte chemotaxis TAS
GO:0032722 positive regulation of chemokine production IDA
GO:0042104 positive regulation of activated T cell proliferation IBA
GO:0051135 positive regulation of NK T cell activation IBA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0002827 positive regulation of T-helper 1 type immune response IBA
click arrow to show/hide IEA associations
GO:0072540 T-helper 17 cell lineage commitment IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 5 GO processes
GO:0032816 positive regulation of natural killer cell activation IBA
GO:0042104 positive regulation of activated T cell proliferation IBA
GO:0050671 positive regulation of lymphocyte proliferation IBA
GO:0051135 positive regulation of NK T cell activation IBA
click arrow to show/hide IEA associations
GO:0072540 T-helper 17 cell lineage commitment IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 4 GO processes
GO:0002827 positive regulation of T-helper 1 type immune response IBA
GO:0042104 positive regulation of activated T cell proliferation IBA
GO:0051135 positive regulation of NK T cell activation IBA
click arrow to show/hide IEA associations
GO:0072540 T-helper 17 cell lineage commitment IEA
Clinically-Relevant Mutations and Pathophysiology Click here for help
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Single nucleotide polymorphism Human C>T IL6R locus marker for asthma susceptibility. The rs4129267 SNP significantly affects soluble IL-6R availability in asthma patients, increasing serum levels by 19.7 ng/ml for each copy of the T allele. 1,4
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Asthma susceptibility locus.
Nucleotide change:  C>T
SNP accession: 
References:  4
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A potential modifier of lung function in asthmatic patients associated with more severe asthma. The mutation in the IL-6R's proteolytic cleavage site appears to facilitate enhanced ectodomain shedding, as soluble IL-6R. Free circulating IL-6R promotes IL-6 transsignalling and compromises 'classical' IL-6 signalling..
Amino acid change:  Asp358Ala
SNP accession: 
References:  2-3
General Comments
The IL6 receptor is a protein complex consisting of an IL-6 receptor subunit (IL6R) and interleukin 6 signal transducer glycoprotein 130 (gp130 from the IL6ST gene).

References

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1. Ferreira MA, Matheson MC, Duffy DL, Marks GB, Hui J, Le Souëf P, Danoy P, Baltic S, Nyholt DR, Jenkins M et al.. (2011) Identification of IL6R and chromosome 11q13.5 as risk loci for asthma. Lancet, 378 (9795): 1006-14. [PMID:21907864]

2. Garbers C, Monhasery N, Aparicio-Siegmund S, Lokau J, Baran P, Nowell MA, Jones SA, Rose-John S, Scheller J. (2014) The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases. Biochim Biophys Acta, 1842 (9): 1485-94. [PMID:24878322]

3. Hawkins GA, Robinson MB, Hastie AT, Li X, Li H, Moore WC, Howard TD, Busse WW, Erzurum SC, Wenzel SE et al.. (2012) The IL6R variation Asp(358)Ala is a potential modifier of lung function in subjects with asthma. J Allergy Clin Immunol, 130 (2): 510-5.e1. [PMID:22554704]

4. Revez JA, Bain L, Chapman B, Powell JE, Jansen R, Duffy DL, Tung JY, AAGC Collaborators, Penninx BW, Visscher PM et al.. (2013) A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk. Genes Immun, 14 (7): 441-6. [PMID:23945879]

5. Rose-John S, Hipp E, Lenz D, Legrés LG, Korr H, Hirano T, Kishimoto T, Heinrich PC. (1991) Structural and functional studies on the human interleukin-6 receptor. Binding, cross-linking, internalization, and degradation of interleukin-6 by fibroblasts transfected with human interleukin-6-receptor cDNA. J Biol Chem, 266 (6): 3841-6. [PMID:1995637]

6. Stevens S, Huang TT, Martin JH, Fairhurst JL, Rafique A, Smith E, Pobursky KJ, Papadopoulos NJ, Fandl JP, Chen G et al.. (2009) High affinity antibodies to human IL-6 receptor. Patent number: US7582298. Assignee: Regeneron Pharmaceuticals, Inc.. Priority date: 02/06/2006. Publication date: 01/09/2009.

7. Varghese JN, Moritz RL, Lou MZ, Van Donkelaar A, Ji H, Ivancic N, Branson KM, Hall NE, Simpson RJ. (2002) Structure of the extracellular domains of the human interleukin-6 receptor alpha -chain. Proc Natl Acad Sci USA, 99 (25): 15959-64. [PMID:12461182]

How to cite this page

IL-6 receptor family: Interleukin-6 receptor, α subunit. Last modified on 05/10/2016. Accessed on 19/06/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1708.