Interleukin-6 receptor, α subunit

Target id: 1708

Nomenclature: Interleukin-6 receptor, α subunit

Abbreviated Name: IL6R

Systematic Nomenclature: interleukin 6 receptor

Family: IL-6 receptor family

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

   GtoImmuPdb view: OFF :     Interleukin-6 receptor, α subunit has curated GtoImmuPdb data

Quaternary Structure: Complexes
Interleukin-6 receptor
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 468 1q21 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
CD126 | IL-6R subunit alpha | interleukin 6 receptor
Database Links
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Selected 3D Structures
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
IL-6 {Sp: Human}

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
IL-6 {Sp: Human} 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 Affinity Units Reference
sarilumab 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 3 GO processes
GO:0002548 monocyte chemotaxis IC
GO:0002690 positive regulation of leukocyte chemotaxis TAS
GO:0006953 acute-phase response TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 1 GO processes
GO:0002690 positive regulation of leukocyte chemotaxis TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 9 GO processes
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: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
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GO:0004896 cytokine receptor activity IEA
GO:0004915 interleukin-6 receptor activity IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes
GO:0002548 monocyte chemotaxis IC
GO:0002690 positive regulation of leukocyte chemotaxis TAS
GO:0032722 positive regulation of chemokine production IDA
Clinically-Relevant Mutations and Pathophysiology
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
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. U.S.A., 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 19/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1708.