P22273
uniprot
P22273
canonical
activity_regulation
ACTIVITY REGULATION: Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling. {ECO:0000250|UniProtKB:P08887}.
uniprot
proteins
amino_acid_sequence
MLAVGCTLLVALLAAPAVALVLGSCRALEVANGTVTSLPGATVTLICPGKEAAGNATIHWVYSGSQSREWTTTGNTLVLRAVQVNDTGHYLCFLDDHLVGTVPLLVDVPPEEPKLSCFRKNPLVNAFCEWHPSSTPSPTTKAVMFAKKINTTNGKSDFQVPCQYSQQLKSFSCEVEILEGDKVYHIVSLCVANSVGSRSSHNVVFQSLKMVQPDPPANLVVSAIPGXPRWLKVSWQDPESWDPSYYLLQFELRYRPVWSKXFTVWPLQVAQHQCVIHDALRGVKHVVQVRGKEEFDIGQWSKWSPEVTGTPWLAEPRTTPAGIPGNPTQVSVEDYDNHEDQYGSSTEATSVLAPVQGSSPIPLPTFLVAGGSLAFGLLLCVFIILRLKKKWKSQAEKESKTTSPPPYPLGPLKPTFLLVPLLTPSGSHNSSGTDNTGSHSCLGVRDPQCPNDNSNRDYLFPR
uniprot
proteins
function
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. {ECO:0000250|UniProtKB:P22272}.; FUNCTION: [Interleukin-6 receptor subunit alpha]: 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. {ECO:0000250|UniProtKB:P22272}.; FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: 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). {ECO:0000250|UniProtKB:P08887, ECO:0000250|UniProtKB:P22272}.
uniprot
proteins
mass_dalton
50401
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250|UniProtKB:P22272}.; PTM: 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. {ECO:0000250|UniProtKB:P08887}.
uniprot
proteins
protein_family
Type 3 subfamily
uniprot
proteins
protein_family
Type I cytokine receptor family
uniprot
proteins
pubmed
2174054
uniprot
proteins
sequence_length
462
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Interleukin-6 receptor subunit alpha]: Cell membrane {ECO:0000250|UniProtKB:P22272}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Soluble interleukin-6 receptor subunit alpha]: Secreted {ECO:0000250|UniProtKB:P22272}.
uniprot
proteins
transmembrane_region
TRANSMEM 365..385; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins