{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P26992","secondaryAccessions":["Q5U050"],"uniProtkbId":"CNTFR_HUMAN","entryAudit":{"firstPublicDate":"1992-08-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-02-01","entryVersion":214,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"7774913"}],"value":"Ciliary neurotrophic factor receptor subunit alpha"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"7774913"}],"value":"CNTF receptor subunit alpha"},{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"7774913"}],"value":"CNTFR-alpha"}]},"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7774913"},{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAA35707.1"}],"value":"CNTFR"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10966616"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11285233"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11294841"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19386761"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26858303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932351"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36930708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7681218"}],"value":"Functions either as a membrane-anchored non-signaling receptor via a GPI anchor or, after proteolytic release, as a soluble ligand-binding chaperone, and mediates signaling of CNTF-related cytokines, including ciliary neurotrophic factor (CNTF), cardiotrophin-like cytokine factor 1 (CLCF1), and the heterodimeric cytokine formed by CLCF1 and the cytokine receptor-like factor 1 (CRLF1) (PubMed:10966616, PubMed:11285233, PubMed:11294841, PubMed:26858303, PubMed:31932351, PubMed:36930708, PubMed:7681218). Involved namely in cell survival of motor neurons and regulation of oligodendrocyte progenitor proliferation (PubMed:11285233, PubMed:19386761, PubMed:31932351). Functions within the ciliary neurotrophic factor receptor (CNTFR) complex as a membrane-anchored non-signaling receptor subunit associated with two other signaling receptor subunits IL6ST/gp130 and LIFR (PubMed:10966616, PubMed:11285233, PubMed:11294841, PubMed:26858303, PubMed:31932351, PubMed:36930708, PubMed:7681218). Also, functions within the humanin receptor complex as a membrane-anchored non-signaling receptor subunit associated with IL6ST/GP130 and IL27RA/WSX1 that mediates the MT-RNR2/humanin signaling which induces neuroprotection (PubMed:19386761). Alternatively functions as a soluble ligand-binding chaperone that binds ligand in the extracellular space, forming a cytokine complex which is delivered to the IL6ST/gp130 and LIFR signaling receptor subunits (PubMed:11285233, PubMed:31932351, PubMed:7681218). Mechanistically, ligand binding to the CNTFR induces dimerization of the IL6ST/gp130 and LIFR (or IL27RA/WSX1 in the case of MT-RNR2/humanin), which activate JAK tyrosine kinases (JAK1 or JAK2 and to lesser extent TYK2) bound to their intracellular domains (PubMed:10966616, PubMed:11285233, PubMed:11294841, PubMed:19386761, PubMed:7681218). These kinases subsequently phosphorylate IL6ST/gp130 and LIFR (or IL27RA/WSX1) (PubMed:10966616, PubMed:11285233, PubMed:11294841, PubMed:7681218). 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:10966616, PubMed:11285233, PubMed:11294841, PubMed:19386761, PubMed:7681218)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19386761"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26858303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36930708"}],"value":"Homodimer (PubMed:36930708). Component of the ciliary neurotrophic factor receptor (CNTFR) complex composed of CNTFR, LIFR and IL6ST (PubMed:36930708). Either alone or in complex with the heterodimer CLCF1-CRLF1 interacts with SORL1; this interaction may promote internalization and lysosomal degradation (PubMed:26858303). Component of the humanin (HN) receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR; MT-RNR2, the neuroprotective peptide HN, binds to CNTFR and IL27RA (PubMed:19386761)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P26992","intActId":"EBI-743758"},"interactantTwo":{"uniProtKBAccession":"Q9UBD9","geneName":"CLCF1","chainId":"PRO_0000015616","intActId":"EBI-25298664"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26992","intActId":"EBI-743758"},"interactantTwo":{"uniProtKBAccession":"P26441","geneName":"CNTF","intActId":"EBI-1050897"},"numberOfExperiments":15,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26992","intActId":"EBI-743758"},"interactantTwo":{"uniProtKBAccession":"O75462","geneName":"CRLF1","intActId":"EBI-15587902"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P26992","intActId":"EBI-743758"},"interactantTwo":{"uniProtKBAccession":"Q92673","geneName":"SORL1","intActId":"EBI-1171329"},"numberOfExperiments":7,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26858303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31932351"}],"value":"Localized at cell membrane when associated with SORL1 (PubMed:26858303). 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