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
Rat 1 462 2q34 Il6r interleukin 6 receptor
Previous and Unofficial Names
CD126 | IL-6R subunit alpha
Database Links
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
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
Key to terms and symbols Click column headers to sort
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
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  monocyte chemotaxis (GO:0002548) IC
positive regulation of leukocyte chemotaxis (GO:0002690) TAS
acute-phase response (GO:0006953) TAS
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of leukocyte chemotaxis (GO:0002690) TAS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  interleukin-6 receptor activity (GO:0004915) IEA
cytokine-mediated signaling pathway (GO:0019221) IDA
negative regulation of interleukin-8 production (GO:0032717) NAS
positive regulation of chemokine production (GO:0032722) IDA
positive regulation of interleukin-6 production (GO:0032755) IDA
response to cytokine (GO:0034097) IDA
interleukin-6-mediated signaling pathway (GO:0070102) IMP
ciliary neurotrophic factor-mediated signaling pathway (GO:0070120) IMP
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  monocyte chemotaxis (GO:0002548) IC
positive regulation of leukocyte chemotaxis (GO:0002690) TAS
positive regulation of chemokine production (GO:0032722) IDA
References: 
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. Lancet378 (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. Acta1842 (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 11/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1708.