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. Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory. Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells. Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (By similarity). 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. 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. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling. Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST. Interacts (via N-terminal ectodomain) with SORL1; this interaction may affect IL6-binding to IL6R, hence decrease IL6 'classic-signaling'. Also interacts with SORL1; this interaction leads to soluble IL6R internalization. May form a trimeric complex with the soluble SORL1 ectodomain and circulating IL6 receptor; this interaction might stabilize circulating IL6, hence promote IL6 'trans-signaling'. Expressed in liver. 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. A short soluble form is also released from the membrane by proteolysis. The sIL6R is formed by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding. mIL6R is cleaved by the proteases ADAM10 and ADAM17. 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. Belongs to the type I cytokine receptor family. Type 3 subfamily.