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Interleukin-6 receptor, α subunit

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Target id: 1708

Nomenclature: Interleukin-6 receptor, α subunit

Abbreviated Name: IL6R

Systematic Nomenclature: interleukin 6 receptor

Family: IL-6 receptor family

Contents:

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
Alphafold P08887 (Hs), P22272 (Mm), P22273 (Rn)
CATH/Gene3D 2.60.40.10
ChEMBL Target CHEMBL2364155 (Hs), CHEMBL4289 (Rn)
DrugBank Target P08887 (Hs)
Ensembl Gene ENSG00000160712 (Hs), ENSMUSG00000027947 (Mm), ENSRNOG00000020811 (Rn)
Entrez Gene 3570 (Hs), 16194 (Mm), 24499 (Rn)
Human Protein Atlas ENSG00000160712 (Hs)
KEGG Gene hsa:3570 (Hs), mmu:16194 (Mm), rno:24499 (Rn)
OMIM 147880 (Hs)
Pharos P08887 (Hs)
UniProtKB P08887 (Hs), P22272 (Mm), P22273 (Rn)
Wikipedia IL6R (Hs)
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
Key to terms and symbols Click column headers to sort
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
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Chemotaxis & migration
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
Immuno Process:  T cell (activation)
Clinically-Relevant Mutations and Pathophysiology Click here for help
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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:  rs4129267
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:  rs2228145
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 15/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1708.