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The CNTFR complex indeed consists of the membrane-anchored non-signaling receptor CNTFR and the two signaling receptor subunits IL6ST/gp130 and LIFR that transduce the signal into the cell (PubMed:36930708). Functionally, promotes neuronal survival, supports differentiation of various neuronal and non-neuronal cells, and importantly regulates oligodendrocyte progenitor proliferation (PubMed:1861138, PubMed:1883844, PubMed:31932351). Mechanistically, ligand binding to the CNTFR induces dimerization of the IL6ST/gp130 and LIFR, which activates JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains (PubMed:11294841). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (PubMed:11294841). The tyrosine phosphorylated signaling receptors serve in turn as docking sites for recruitment and activation of signal transducer and activators of transcription (STAT3 and to lesser extent STAT1) (PubMed:11285233, PubMed:11294841). Can also signal via trans-signaling using soluble forms of CNTFR (PubMed:31932351, PubMed:7681218). Seems to prevent the degeneration of motor axons after axotomy (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7796798"}],"value":"Homodimer"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q96MA6","geneName":"AK8","intActId":"EBI-8466265"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"P02649","geneName":"APOE","intActId":"EBI-1222467"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"P05067","geneName":"APP","intActId":"EBI-77613"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"P26992","geneName":"CNTFR","intActId":"EBI-743758"},"numberOfExperiments":15,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"A8MQ03","geneName":"CYSRT1","intActId":"EBI-3867333"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"P40189","geneName":"IL6ST","intActId":"EBI-1030834"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q15323","geneName":"KRT31","intActId":"EBI-948001"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q6A162","geneName":"KRT40","intActId":"EBI-10171697"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"P42702","geneName":"LIFR","intActId":"EBI-7702162"},"numberOfExperiments":11,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"O14561","geneName":"NDUFAB1","intActId":"EBI-1246261"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q8NG50","geneName":"RDM1","intActId":"EBI-10288724"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q99523","geneName":"SORT1","intActId":"EBI-1057058"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q96N21","geneName":"TEPSIN","intActId":"EBI-11139477"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26441","intActId":"EBI-1050897"},"interactantTwo":{"uniProtKBAccession":"Q15654","geneName":"TRIP6","intActId":"EBI-742327"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P20294"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"1915374"}],"value":"The precursor semms to be cytoplasmic (Probable). The lack of a specific hydrophobic segment in the precursor sequence suggests that CNTF is released by damaged cells or is secreted by a mechanism differing from that used for other secretory proteins (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"1915374"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q02011"}],"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36930708"}],"value":"At the structural level composed of a canonical four-helix bundle structure in which four major helices (termed helices A to D) are linked by three loops (termed AB, BC, and CD loops), as well as three conserved receptor binding epitopes (termed sites 1 to 3) (PubMed:36930708). Sites 2 and 3 bind to IL6ST/gp130 and LIFR, respectively, while site 1 is occupied by CNTFR (PubMed:36930708)"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the CNTF family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Wikipedia","resourceUrl":"https://en.wikipedia.org/wiki/Ciliary_neurotrophic_factor","ftp":false,"note":"Ciliary neurotrophic factor entry"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":200,"modifier":"EXACT"}},"description":"Ciliary neurotrophic factor","featureId":"PRO_0000149519"},{"type":"Natural variant","location":{"start":{"value":49,"modifier":"EXACT"},"end":{"value":49,"modifier":"EXACT"}},"description":"in dbSNP:rs17152779","featureCrossReferences":[{"database":"dbSNP","id":"rs17152779"}],"featureId":"VAR_033777","alternativeSequence":{"originalSequence":"N","alternativeSequences":["S"]}},{"type":"Natural variant","location":{"start":{"value":182,"modifier":"EXACT"},"end":{"value":182,"modifier":"EXACT"}},"description":"in dbSNP:rs6266","featureCrossReferences":[{"database":"dbSNP","id":"rs6266"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10391209"}],"featureId":"VAR_013924","alternativeSequence":{"originalSequence":"H","alternativeSequences":["R"]}},{"type":"Helix","location":{"start":{"value":13,"modifier":"EXACT"},"end":{"value":41,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Turn","location":{"start":{"value":64,"modifier":"EXACT"},"end":{"value":66,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"8D74"}]},{"type":"Helix","location":{"start":{"value":69,"modifier":"EXACT"},"end":{"value":93,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Helix","location":{"start":{"value":94,"modifier":"EXACT"},"end":{"value":98,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Beta strand","location":{"start":{"value":99,"modifier":"EXACT"},"end":{"value":101,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Helix","location":{"start":{"value":104,"modifier":"EXACT"},"end":{"value":129,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Helix","location":{"start":{"value":134,"modifier":"EXACT"},"end":{"value":137,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Beta strand","location":{"start":{"value":138,"modifier":"EXACT"},"end":{"value":140,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]},{"type":"Helix","location":{"start":{"value":152,"modifier":"EXACT"},"end":{"value":180,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"1CNT"}]}],"keywords":[{"id":"KW-0002","category":"Technical term","name":"3D-structure"},{"id":"KW-0963","category":"Cellular component","name":"Cytoplasm"},{"id":"KW-0217","category":"Molecular function","name":"Developmental protein"},{"id":"KW-0221","category":"Biological process","name":"Differentiation"},{"id":"KW-0339","category":"Molecular function","name":"Growth factor"},{"id":"KW-0524","category":"Biological process","name":"Neurogenesis"},{"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"}],"references":[{"referenceNumber":1,"citation":{"id":"1861138","citationType":"journal article","authors":["Masiakowski P.","Liu H.","Radziejewski C.","Lottspeich F.","Oberthuer W.","Wong V.","Lindsay R.M.","Furth M.E.","Panayotatos N."],"citationCrossReferences":[{"database":"PubMed","id":"1861138"},{"database":"DOI","id":"10.1111/j.1471-4159.1991.tb08250.x"}],"title":"Recombinant human and rat ciliary neurotrophic factors.","publicationDate":"1991","journal":"J. 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