IFNAR1 - interferon alpha and beta receptor subunit 1

Function

Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:2153461, PubMed:7813427, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:24075985, PubMed:21854986, PubMed:31270247, PubMed:33252644, PubMed:35442418). 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:7665574, PubMed:10049744, PubMed:21854986). 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:7813427, PubMed:7665574, PubMed:21854986, PubMed:32972995). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:7813427, PubMed:7526154, PubMed:7665574, PubMed:21854986, PubMed:32972995). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:7813427, PubMed:7665574, PubMed:9121453, PubMed:19561067, PubMed:21854986, PubMed:32972995). 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).

Gene Regulons