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Details on Person UniProt:P08887 IL6R

Class:Id	ReferenceGeneProduct:57275
_chainChangeLog	signal peptide:1-19 added on Fri February 6 2015;chain:20-468 added on Fri February 6 2015;chain:20-355 for 57275 added on Wed August 26 2020
_displayName	UniProt:P08887 IL6R
_timestamp	2024-11-03 20:01:22
chain	signal peptide:1-19 chain:20-468 chain:20-355
checksum	62AA239FA14F1B8B
comment	FUNCTION 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).FUNCTION 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).FUNCTION 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 pro-inflammatory 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).FUNCTION 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 pro-inflammatory 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).ACTIVITY REGULATION Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling.SUBUNIT Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST (PubMed:12829785, PubMed:28265003). Interacts (via N-terminal ectodomain) with SORL1; this interaction may affect IL6-binding to IL6R, hence decrease IL6 'classic-signaling' (PubMed:28265003).SUBUNIT 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,.SUBUNIT 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,.INTERACTION Expressed in peripheral blood mononuclear cells and weakly found in urine and serum. 1%-20% of the total sIL6R in plasma is generated by alternative splicing (PubMed:28060820).DOMAIN The two fibronectin type-III-like domains, contained in the N-terminal part, form together a cytokine-binding domain.DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.PTM 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).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.POLYMORPHISM Genetic variations in IL6R determine soluble IL6R serum levels [MIM:614689].POLYMORPHISM Genetic variations in IL6R define the IL6 serum level quantitative trait locus [MIM:614752].DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the type I cytokine receptor family. Type 3 subfamily.
description	recommendedName: fullName evidence="25"Interleukin-6 receptor subunit alpha shortName: IL-6 receptor subunit alpha shortName: IL-6R subunit alpha shortName: IL-6R-alpha shortName: IL-6RA alternativeName: IL-6R 1 alternativeName: Membrane glycoprotein 80 shortName: gp80 cdAntigenNameCD126/cdAntigenName component recommendedName: fullName evidence="25"Soluble interleukin-6 receptor subunit alpha shortName evidence="18 22 23"sIL6R /component
geneName	IL6R
identifier	P08887
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Cell membrane Direct protein sequencing Disulfide bond Glycoprotein Immunoglobulin domain Membrane Proteomics identification Receptor Reference proteome Repeat Secreted Signal Transmembrane Transmembrane helix
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	IL6R
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8948439] ENSEMBL:ENSG00000160712 IL6R [Homo sapiens]
secondaryIdentifier	IL6RA_HUMAN A8KAE8 B2R6V4 Q16202 Q53EQ7 Q5FWG2 Q5VZ23
sequenceLength	468
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:148795] UniProt:P08887-2 IL6R [Homo sapiens] [ReferenceIsoform:402630] UniProt:P08887-1 IL6R [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:197824] IL6R [plasma membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P08887 IL6R (57275)