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Details on Person UniProt:P40189 IL6ST
| Class:Id | ReferenceGeneProduct:57277 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Sat February 7 2015;chain:23-918 added on Sat February 7 2015 |
| _displayName | UniProt:P40189 IL6ST |
| _timestamp | 2024-11-03 20:01:22 |
| chain | signal peptide:1-22 chain:23-918 |
| checksum | 6510A4409FFCF08C |
| comment | FUNCTION Signal-transducing molecule (PubMed:2261637). The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates the intracellular JAK-MAPK and JAK-STAT3 signaling pathways (PubMed:19915009, PubMed:2261637, PubMed:23294003). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In parallel, the IL6 signaling pathway induces the expression of two cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit JAK and terminate the activity of the IL6 signaling pathway as a negative feedback loop (By similarity). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (By similarity). Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL27RA/WSX1 and CNTFR (PubMed:19386761). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity).FUNCTION Binds to the soluble IL6:sIL6R complex (hyper-IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent acute phase response (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:30279168).SUBUNIT Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; associates with the complex IL6:IL6R but does not interact with IL6 (PubMed:12829785, PubMed:2261637). Forms heterodimers composed of LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM (PubMed:8999038). Also forms heterodimers composed of OSMR and IL6ST (type II receptor) which are activated by OSM but not by LIF (PubMed:8999038). Component of a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR which interacts with the neuroprotective peptide humanin (PubMed:19386761). Interacts with HCK (PubMed:9406996). Interacts with INPP5D/SHIP1 (By similarity). Interacts with SRC and YES (PubMed:25731159). Interacts with ARMH4; this interaction prevents IL6ST protein homodimerization and bridges ARMH4 with IL6R and STAT3 and therefore inhibits phosphorylation of STAT3 at 'Tyr-705' (PubMed:26927669).SUBUNIT (Microbial infection) The homodimer binds two molecules of herpes virus 8/HHV-8 protein vIL-6.INTERACTION Found in all the tissues and cell lines examined (PubMed:2261637). Expression not restricted to IL6 responsive cells (PubMed:2261637).TISSUE SPECIFICITY Expressed in blood serum (at protein level) (PubMed:24629561).INDUCTION LIF and OSM activate the type I OSM receptor while only OSM can activate the type II OSM receptor.DOMAIN The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.DOMAIN The box 1 motif is required for JAK interaction and/or activation.PTM Phosphorylation of Ser-782 down-regulates cell surface expression.PTM Heavily N-glycosylated (PubMed:11098061, PubMed:11251120, PubMed:16335952, PubMed:19139490, PubMed:19159218). Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding (PubMed:19915009).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease may be caused by variants affecting the gene represented in this entry.BIOTECHNOLOGY Two extracellular parts of IL6ST/gp130 linked to the Fc-portions of a human IgG1 antibody (sgp130Fc) inhibit IL6 trans-signaling by the IL6:IL6R complex and has no affinity of IL6 or IL6R alone (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks IL11 cluster signaling through IL11R (PubMed:26876177, PubMed:30279168).SIMILARITY Belongs to the type I cytokine receptor family. Type 2 subfamily. |
| description | recommendedName: fullName evidence="40"Interleukin-6 receptor subunit beta shortName: IL-6 receptor subunit beta shortName: IL-6R subunit beta shortName: IL-6R-beta shortName: IL-6RB alternativeName: CDw130 alternativeName: Interleukin-6 signal transducer alternativeName: Membrane glycoprotein 130 shortName evidence="38"gp130 alternativeName: Oncostatin-M receptor subunit alpha cdAntigenNameCD130/cdAntigenName |
| geneName | IL6ST |
| identifier | P40189 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cell membrane Direct protein sequencing Disease variant Disulfide bond Glycoprotein Host-virus interaction Immunoglobulin domain Membrane Phosphoprotein 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:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | IL6ST |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9004745] ENSEMBL:ENSG00000134352 IL6ST [Homo sapiens] |
| secondaryIdentifier | IL6RB_HUMAN A0N0L4 Q5FC04 Q9UQ41 |
| sequenceLength | 918 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:148796] UniProt:P40189-2 IL6ST [Homo sapiens] [ReferenceIsoform:403937] UniProt:P40189-1 IL6ST [Homo sapiens] [ReferenceIsoform:8967442] UniProt:P40189-3 IL6ST [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:448453] IL6ST [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8950439] p-Y-IL6ST [plasma membrane] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:8950742] O4'-phospho-L-tyrosine at unknown position |
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No pathways have been reviewed or authored by UniProt:P40189 IL6ST (57277)
