{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P17181","secondaryAccessions":["B2R6L9","B4DNT3","D3DSF0","Q53GW9","Q53H11","Q6PKD7","Q7M4L2","Q8WTZ2"],"uniProtkbId":"INAR1_HUMAN","entryAudit":{"firstPublicDate":"1990-08-01","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2006-03-07","entryVersion":223,"sequenceVersion":3},"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":{"value":"Interferon alpha/beta receptor 1"},"shortNames":[{"value":"IFN-R-1"},{"value":"IFN-alpha/beta receptor 1"}]},"alternativeNames":[{"fullName":{"value":"Cytokine receptor class-II member 1"}},{"fullName":{"value":"Cytokine receptor family 2 member 1"},"shortNames":[{"value":"CRF2-1"}]},{"fullName":{"value":"Type I interferon receptor 1"}}],"flag":"Precursor"},"genes":[{"geneName":{"value":"IFNAR1"},"synonyms":[{"value":"IFNAR"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P33896"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10049744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15337770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19561067"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2153461"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21854986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24075985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31270247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32972995"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33252644"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35442418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7526154"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7665574"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7813427"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9121453"}],"value":"Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2153461, PubMed:21854986, PubMed:24075985, PubMed:31270247, PubMed:33252644, PubMed:35442418, PubMed:7813427). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:21854986, PubMed:7665574). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:21854986, PubMed:32972995, PubMed:7526154, PubMed:7665574, PubMed:7813427). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:19561067, PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427, PubMed:9121453). Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10049744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15337770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21854986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24075985"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24704786"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33811647"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7526154"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7665574"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9121453"}],"value":"Heterodimer with IFNAR2; forming the receptor for type I interferon (PubMed:10049744, PubMed:21854986, PubMed:7665574). Interacts with TYK2 (PubMed:15337770, PubMed:24704786, PubMed:7526154). Interacts with STAT1 and STAT2; the interaction requires its phosphorylation at Tyr-466 (PubMed:9121453). Interacts (serine-phosphorylated form) with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:14532120, PubMed:15337770, PubMed:18056411). Interacts with SHMT2; this promotes interaction with ABRAXAS2 and the BRISC complex (PubMed:24075985). Interacts with TRIM10; this interaction prevents association between IFNAR1 and TYK2 (PubMed:33811647)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P17181","intActId":"EBI-1547250"},"interactantTwo":{"uniProtKBAccession":"Q9UKB1","geneName":"FBXW11","intActId":"EBI-355189"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17181","intActId":"EBI-1547250"},"interactantTwo":{"uniProtKBAccession":"Q86VI4","geneName":"LAPTM4B","intActId":"EBI-3267258"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17181","intActId":"EBI-1547250"},"interactantTwo":{"uniProtKBAccession":"P42224","geneName":"STAT1","intActId":"EBI-1057697"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17181","intActId":"EBI-1547250"},"interactantTwo":{"uniProtKBAccession":"P52630","geneName":"STAT2","intActId":"EBI-1546963"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P17181-1","intActId":"EBI-16099379"},"interactantTwo":{"uniProtKBAccession":"P29597","geneName":"TYK2","intActId":"EBI-1383454"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Isoform 1","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"}],"value":"Interferon binding triggers internalization of the receptor from the cell membrane into endosomes and then into lysosomes"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2153461"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35442418"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"7665574"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Single-pass type I membrane protein","id":"SL-9905"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"14532120"}],"value":"Late endosome","id":"SL-0152"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"14532120"}],"value":"Lysosome","id":"SL-0158"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["P17181-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"Sol-1"},{"value":"Soluble form 1"}],"isoformIds":["P17181-2"],"sequenceIds":["VSP_029930","VSP_029931"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"Sol-2"},{"value":"Soluble form 2"}],"isoformIds":["P17181-3"],"sequenceIds":["VSP_029928","VSP_029929"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["P17181-4"],"sequenceIds":["VSP_055322"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8307198"}],"value":"IFN receptors are present in all tissues and even on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN-alpha resistant myeloma cell line U266R"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15337770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18056411"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24075985"}],"value":"Ubiquitinated, leading to its internalization and degradation (PubMed:14532120, PubMed:15337770). Polyubiquitinated via 'Lys-48'-linked and 'Lys-63'-linked ubiquitin chains, leading to receptor internalization and lysosomal degradation (PubMed:18056411). The 'Lys-63'-linked ubiquitin chains are cleaved off by the BRISC complex (PubMed:24075985)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10049744"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15337770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7526154"}],"value":"Phosphorylated on tyrosine residues in response to interferon-binding: phosphorylation by TYK2 tyrosine kinase creates docking sites for STAT proteins (PubMed:10049744, PubMed:7526154). Phosphorylated on serine residues in response to interferon binding; this promotes interaction with FBXW11 and ubiquitination (PubMed:14532120, PubMed:15337770, PubMed:24075985)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19561067"}],"value":"Palmitoylation at Cys-463 is required for the activation of STAT1 and STAT2"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Immunodeficiency 106, susceptibility to viral infections","diseaseAccession":"DI-06465","acronym":"IMD106","description":"An autosomal recessive immunologic disorder characterized by increased susceptibility to viral infections beginning in infancy or early childhood. IMD106 affected individuals may demonstrate adverse reactions to vaccination with live attenuated viral vaccines, most notably measles, mumps and rubella (MMR) and yellow fever vaccines. A subset of IMD106 patients develop severe reactions, including excessive hyperinflammatory response, encephalopathy, acute respiratory distress syndrome, and multiorgan failure. IMD106 may also predispose to severe respiratory infection with SARS-CoV-2.","diseaseCrossReference":{"database":"MIM","id":"619935"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31270247"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33252644"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35442418"}]},"note":{"texts":[{"value":"Disease susceptibility is associated with variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Incomplete sequence"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 2"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Incomplete sequence"}],"commentType":"MISCELLANEOUS","molecule":"Isoform 3"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the type II cytokine receptor family"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Miscellaneous discrepancy","sequence":"AAH02590.1","note":"Contaminating sequence. Potential poly-A sequence.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":27,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":28,"modifier":"EXACT"},"end":{"value":557,"modifier":"EXACT"}},"description":"Interferon alpha/beta receptor 1","featureId":"PRO_0000011001"},{"type":"Topological domain","location":{"start":{"value":28,"modifier":"EXACT"},"end":{"value":436,"modifier":"EXACT"}},"description":"Extracellular","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Transmembrane","location":{"start":{"value":437,"modifier":"EXACT"},"end":{"value":457,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological 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