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Details on Person UniProt:Q00560 Il6st
| Class:Id | ReferenceGeneProduct:93067 |
|---|---|
| _chainChangeLog | signal peptide:1-22 added on Fri February 6 2015;chain:23-917 added on Fri February 6 2015 |
| _displayName | UniProt:Q00560 Il6st |
| _timestamp | 2024-08-09 18:34:03 |
| chain | signal peptide:1-22 chain:23-917 |
| checksum | EDA69AB865E5A6E8 |
| comment | FUNCTION Signal-transducing molecule (PubMed:1602143). 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:10661409, PubMed:1602143). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:10661409). 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 (PubMed:9202125). Also activates the yes-associated protein 1 (YAP) and NOTCH pathways to control inflammation-induced epithelial regeneration, independently of STAT3 (PubMed:25731159). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (PubMed:10661409, PubMed:25057188, PubMed:26255596, PubMed:8552649). Has a role in embryonic development (PubMed:10661409). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (PubMed:10377352). Required for expression of TRPA1 in nociceptive neurons (PubMed:25057188). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (PubMed:25228504). Required for normal trabecular bone mass and cortical bone composition (PubMed:24339143, PubMed:26255596, PubMed:9348227).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 (By similarity). Forms heterodimers composed of LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM. Also forms heterodimers composed of OSMR and IL6ST (type II receptor) which are activated by OSM but not by LIF. Interacts with HCK (By similarity). Interacts with INPP5D/SHIP1 (PubMed:17105399). Interacts with SRC and YES (By similarity). 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' (By similarity).INTERACTION Expression not restricted to IL6-responsive cells. Found in tissues such as brain, heart, thymus, spleen, kidney, lung and liver. Found in all the cell lines tested except BaF-B03. Expressed paraventricular nucleus of the hypothalamus (PubMed:28402851).DEVELOPMENTAL STAGE In embryonic stem cells it is found from day 6 of gestation. It reaches a peak on day 8 and gradually declines during the rest of embryogenesis.INDUCTION In paraventricular nucleus of the hypothalamus, expression is enhanced by obesity.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-780 down-regulates cell surface expression.PTM Heavily N-glycosylated. Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding.DISRUPTION PHENOTYPE Progressively lethal between 12.5 dpc and birth (PubMed:8552649). Embryos show hypoplastic ventricular myocardium without septal and trabecular defect, reduced numbers of pluripotential and committed hematopoietic progenitors in liver and reduced differentiated lineages in thymus (PubMed:8552649). Impaired differentiation of astrocytes and decreased number of dorsal root ganglion and motor neurons at 18.5 dpc (PubMed:10377352). Decreased volume of mineralized trabecular bones, while number of osteoclasts is increased (PubMed:26255596, PubMed:9348227). Conditional knockout from the entire osteoblast lineage or specifically in osteocytes causes no significant skeletal or morphological defects but mice show 30% lower trabecular bone formation rate and larger cortical diameter compared to wild type (PubMed:24339143, PubMed:26255596). Conditional knockout in primary nociceptive afferents causes reduced sensitivity to mechanical stimulation due to reduced sensitivity of nociceptive neurons and reduces TRPA1 mRNA expression in dorsal root ganglion neurons (PubMed:25057188).SIMILARITY Belongs to the type I cytokine receptor family. Type 2 subfamily. |
| description | recommendedName: fullName evidence="21"Interleukin-6 receptor subunit beta shortName: IL-6 receptor subunit beta shortName: IL-6R subunit beta shortName: IL-6R-beta shortName: IL-6RB alternativeName: Interleukin-6 signal transducer alternativeName: Membrane glycoprotein 130 shortName evidence="20"gp130 alternativeName: Oncostatin-M receptor subunit alpha cdAntigenNameCD130/cdAntigenName |
| geneName | Il6st |
| identifier | Q00560 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cell membrane Disulfide bond Glycoprotein Immunoglobulin domain Membrane Phosphoprotein Receptor Reference proteome Repeat Signal Transmembrane Transmembrane helix |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8856987] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9767224] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 |
| name | Il6st |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | IL6RB_MOUSE G5E8D2 |
| sequenceLength | 917 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:8950308] p-Y-Il6st [plasma membrane] [Mus musculus] [EntityWithAccessionedSequence:9968620] Il6st [plasma membrane] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:8950539] O4'-phospho-L-tyrosine at unknown position |
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No pathways have been reviewed or authored by UniProt:Q00560 Il6st (93067)
