Interferon alpha/beta receptor 1
Details
- Name
- Interferon alpha/beta receptor 1
- Kind
- protein
- Synonyms
- CRF2-1
- Cytokine receptor class-II member 1
- Cytokine receptor family 2 member 1
- IFN-alpha/beta receptor 1
- IFN-R-1
- IFNAR
- Type I interferon receptor 1
- Gene Name
- IFNAR1
- UniProtKB Entry
- P17181Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0001318|Interferon alpha/beta receptor 1 MMVVLLGATTLVLVAVAPWVLSAAAGGKNLKSPQKVEVDIIDDNFILRWNRSDESVGNVT FSFDYQKTGMDNWIKLSGCQNITSTKCNFSSLKLNVYEEIKLRIRAEKENTSSWYEVDSF TPFRKAQIGPPEVHLEAEDKAIVIHISPGTKDSVMWALDGLSFTYSLVIWKNSSGVEERI ENIYSRHKIYKLSPETTYCLKVKAALLTSWKIGVYSPVHCIKTTVENELPPPENIEVSVQ NQNYVLKWDYTYANMTFQVQWLHAFLKRNPGNHLYKWKQIPDCENVKTTQCVFPQNVFQK GIYLLRVQASDGNNTSFWSEEIKFDTEIQAFLLPPVFNIRSLSDSFHIYIGAPKQSGNTP VIQDYPLIYEIIFWENTSNAERKIIEKKTDVTVPNLKPLTVYCVKARAHTMDEKLNKSSV FSDAVCEKTKPGNTSKIWLIVGICIALFALPFVIYAAKVFLRCINYVFFPSLKPSSSIDE YFSEQPLKNLLLSTSEEQIEKCFIIENISTIATVEETNQTDEDHKKYSSQTSQDSGNYSN EDESESKTSEELQQDFV
- Number of residues
- 557
- Molecular Weight
- 63524.81
- Theoretical pI
- 5.56
- GO Classification
- Functionscytokine binding / JAK pathway signal transduction adaptor activity / type I interferon bindingProcessescell surface receptor signaling pathway via JAK-STAT / cellular response to interferon-alpha / cellular response to interferon-beta / cellular response to virus / positive regulation of cellular respiration / response to lipopolysaccharide / type I interferon-mediated signaling pathwayComponentslate endosome / lysosome
- General Function
- 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)
- Specific Function
- cytokine binding
- Pfam Domain Function
- Signal Regions
- 1-27
- Transmembrane Regions
- 437-457
- Cellular Location
- Cell membrane
- Gene sequence
>lcl|BSEQ0018987|Interferon alpha/beta receptor 1 (IFNAR1) ATGATGGTCGTCCTCCTGGGCGCGACGACCCTAGTGCTCGTCGCCGTGGCGCCATGGGTG TTGTCCGCAGCCGCAGGTGGAAAAAATCTAAAATCTCCTCAAAAAGTAGAGGTCGACATC ATAGATGACAACTTTATCCTGAGGTGGAACAGGAGCGATGAGTCTGTCGGGAATGTGACT TTTTCATTCGATTATCAAAAAACTGGGATGGATAATTGGATAAAATTGTCTGGGTGTCAG AATATTACTAGTACCAAATGCAACTTTTCTTCACTCAAGCTGAATGTTTATGAAGAAATT AAATTGCGTATAAGAGCAGAAAAAGAAAACACTTCTTCATGGTATGAGGTTGACTCATTT ACACCATTTCGCAAAGCTCAGATTGGTCCTCCAGAAGTACATTTAGAAGCTGAAGATAAG GCAATAGTGATACACATCTCTCCTGGAACAAAAGATAGTGTTATGTGGGCTTTGGATGGT TTAAGCTTTACATATAGCTTAGTTATCTGGAAAAACTCTTCAGGTGTAGAAGAAAGGATT GAAAATATTTATTCCAGACATAAAATTTATAAACTCTCACCAGAGACTACTTATTGTCTA AAAGTTAAAGCAGCACTACTTACGTCATGGAAAATTGGTGTCTATAGTCCAGTACATTGT ATAAAGACCACAGTTGAAAATGAACTACCTCCACCAGAAAATATAGAAGTCAGTGTCCAA AATCAGAACTATGTTCTTAAATGGGATTATACATATGCAAACATGACCTTTCAAGTTCAG TGGCTCCACGCCTTTTTAAAAAGGAATCCTGGAAACCATTTGTATAAATGGAAACAAATA CCTGACTGTGAAAATGTCAAAACTACCCAGTGTGTCTTTCCTCAAAACGTTTTCCAAAAA GGAATTTACCTTCTCCGCGTACAAGCATCTGATGGAAATAACACATCTTTTTGGTCTGAA GAGATAAAGTTTGATACTGAAATACAAGCTTTCCTACTTCCTCCAGTCTTTAACATTAGA TCCCTTAGTGATTCATTCCATATCTATATCGGTGCTCCAAAACAGTCTGGAAACACGCCT GTGATCCAGGATTATCCACTGATTTATGAAATTATTTTTTGGGAAAACACTTCAAATGCT GAGAGAAAAATTATCGAGAAAAAAACTGATGTTACAGTTCCTAATTTGAAACCACTGACT GTATATTGTGTGAAAGCCAGAGCACACACCATGGATGAAAAGCTGAATAAAAGCAGTGTT TTTAGTGACGCTGTATGTGAGAAAACAAAACCAGGAAATACCTCTAAAATTTGGCTTATA GTTGGAATTTGTATTGCATTATTTGCTCTCCCGTTTGTCATTTATGCTGCGAAAGTCTTC TTGAGATGCATCAATTATGTCTTCTTTCCATCACTTAAACCTTCTTCCAGTATAGATGAG TATTTCTCTGAACAGCCATTGAAGAATCTTCTGCTTTCAACTTCTGAGGAACAAATCGAA AAATGTTTCATAATTGAAAATATAAGCACAATTGCTACAGTAGAAGAAACTAATCAAACT GATGAAGATCATAAAAAATACAGTTCCCAAACTAGCCAAGATTCAGGAAATTATTCTAAT GAAGATGAAAGCGAAAGTAAAACAAGTGAAGAACTACAGCAGGACTTTGTATGA
- Chromosome Location
- 21
- Locus
- 21q22.11
- External Identifiers
Resource Link UniProtKB ID P17181 UniProtKB Entry Name INAR1_HUMAN GenBank Protein ID 306914 GenBank Gene ID J03171 GeneCard ID IFNAR1 GenAtlas ID IFNAR1 HGNC ID HGNC:5432 PDB ID(s) 3S98, 3SE3, 3SE4, 4PO6 KEGG ID hsa:3454 IUPHAR/Guide To Pharmacology ID 1723 NCBI Gene ID 3454 - General References
- Uze G, Lutfalla G, Gresser I: Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA. Cell. 1990 Jan 26;60(2):225-34. [Article]
- Lutfalla G, Gardiner K, Proudhon D, Vielh E, Uze G: The structure of the human interferon alpha/beta receptor gene. J Biol Chem. 1992 Feb 5;267(4):2802-9. [Article]
- Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
- Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. [Article]
- Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
- Abramovich C, Ratovitski E, Lundgren E, Revel M: Identification of mRNAs encoding two different soluble forms of the human interferon alpha-receptor. FEBS Lett. 1994 Feb 7;338(3):295-300. [Article]
- Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski J: Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994 Dec;14(12):8133-42. [Article]
- Li X, Leung S, Kerr IM, Stark GR: Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling. Mol Cell Biol. 1997 Apr;17(4):2048-56. [Article]
- Russell-Harde D, Wagner TC, Perez HD, Croze E: Formation of a uniquely stable type I interferon receptor complex by interferon beta is dependent upon particular interactions between interferon beta and its receptor and independent of tyrosine phosphorylation. Biochem Biophys Res Commun. 1999 Feb 16;255(2):539-44. [Article]
- Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
- Claudinon J, Gonnord P, Beslard E, Marchetti M, Mitchell K, Boularan C, Johannes L, Eid P, Lamaze C: Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is required for the activation of Stat1 and Stat2 by IFN-alpha. J Biol Chem. 2009 Sep 4;284(36):24328-40. doi: 10.1074/jbc.M109.021915. Epub 2009 Jun 26. [Article]
- Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. [Article]
- Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
- Thomas C, Moraga I, Levin D, Krutzik PO, Podoplelova Y, Trejo A, Lee C, Yarden G, Vleck SE, Glenn JS, Nolan GP, Piehler J, Schreiber G, Garcia KC: Structural linkage between ligand discrimination and receptor activation by type I interferons. Cell. 2011 Aug 19;146(4):621-32. doi: 10.1016/j.cell.2011.06.048. [Article]
Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Interferon alfa-n3 approved, investigational yes target agonist Details Peginterferon alfa-2b approved yes target agonist Details Interferon alfa-2a approved, investigational yes target Details Interferon alfacon-1 approved, investigational yes target binder Details Peginterferon alfa-2a approved, investigational yes target agonist Details Interferon alfa-n1 approved, investigational yes target agonist Details Interferon alfa-2b approved yes target binder Details Interferon beta-1b approved yes target agonist Details Interferon alfa investigational unknown target Details Human interferon omega-1 investigational unknown target Details Interferon beta-1a approved, investigational yes target agonist Details Human interferon beta approved, investigational yes target binder Details Peginterferon beta-1a approved unknown target activatordownregulator Details Anifrolumab approved, investigational yes target inhibitor Details