IL6R

This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been reported. A pseudogene of this gene is found on chromosome 9.[provided by RefSeq, May 2011]

Interleukin 6 Receptor

Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003).
Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509).
The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).
Isoform 1
Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity).
Isoform 2
Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364).
The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364).
In complex with IL6, is required for induction of VEGF production (PubMed:12794819).
Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity).
'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity).
Soluble interleukin-6 receptor subunit alpha
Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364).
The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364).
In complex with IL6, is required for induction of VEGF production (PubMed:12794819).
Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity).
'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity).

Acute-phase responseManual Assertion Based On ExperimentTAS:BHF-UCL
Ciliary neurotrophic factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:BHF-UCL
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Defense response to Gram-negative bacteriumManual Assertion Based On ExperimentTAS:BHF-UCL
Defense response to Gram-positive bacteriumNAS:BHF-UCL
Endocrine pancreas developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentTAS:BHF-UCL
Hepatic immune responseManual Assertion Based On ExperimentTAS:BHF-UCL
Interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIDA:ARUK-UCL
Monocyte chemotaxis1 PublicationIC:BHF-UCL
Negative regulation of collagen biosynthetic processIDA:BHF-UCL
Negative regulation of interleukin-8 productionNAS:BHF-UCL
Neutrophil mediated immunityTAS:BHF-UCL
Positive regulation of activation of Janus kinase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of chemokine productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of glomerular mesangial cell proliferationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of leukocyte chemotaxisManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of MAPK cascadeIDA:BHF-UCL
Positive regulation of osteoblast differentiationManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of platelet aggregationIDA:ARUK-UCL
Positive regulation of smooth muscle cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIMP:BHF-UCL
Response to cytokineManual Assertion Based On ExperimentIDA:BHF-UCL
T-helper 17 cell lineage commitmentIEA:Ensembl
Vascular endothelial growth factor productionManual Assertion Based On ExperimentIDA:UniProtKB

Isoform 1: Cell membrane
Isoform 2: Secreted
Soluble interleukin-6 receptor subunit alpha: Secreted

Hyper-IgE recurrent infection syndrome 5, autosomal recessive (HIES5):
An immunologic disorder characterized by recurrent sinopulmonary and deep skin infections, mostly caused by bacteria, including H. influenza and Staphylococcus aureus. Additional features include asthma, atopic dermatitis, and impaired inflammatory responses during infection. Disease onset is in early infancy.

Extracellular: 20-365
Helical: 366-386
Cytoplasmic: 387-468

A short soluble form is released from the membrane by proteolysis (PubMed:26876177).
The sIL6R is formed mostly by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, but is also directly secreted from the cells after alternative mRNA splicing (PubMed:26876177, PubMed:28060820).
mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177, PubMed:28060820).
Glycosylated. Glycosylation is dispensable for transport, signaling, and cell-surface turnover. Glycosylation at Asn-55 is a protease-regulatory exosite. Glycosylation is required for ADAM17-mediated proteolysis.