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Il6ra

Domain

The two fibronectin type-III-like domains contained in the C-terminal part form together a cytokine-binding domain.

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.

Function

Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis. 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.

Interleukin-6 receptor subunit alpha

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 (PubMed:27893700).

Soluble interleukin-6 receptor subunit alpha

Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:11113088). 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 pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (By similarity). In complex with IL6, is required for induction of VEGF production (By similarity). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (PubMed:11113088). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (PubMed:28402851).

Post-translational modifications

A short soluble form is also released from the membrane by proteolysis (PubMed:26876177). The sIL6R is formed by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding (PubMed:26876177). mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177).

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.

Sequence Similarities

Belongs to the type I cytokine receptor family. Type 3 subfamily.

Tissue Specificity

Expressed by dendritic cells.

Soluble interleukin-6 receptor subunit alpha

Detected in the cerebrospinal fluid.

Cellular localization

Alternative names

CD126, Il6r, Il6ra, Interleukin-6 receptor subunit alpha, IL-6 receptor subunit alpha, IL-6R subunit alpha, IL-6R-alpha, IL-6RA, IL-6R 1

swissprot:P22272 entrezGene:16194

Other research areas