ID INAR1_HUMAN Reviewed; 557 AA. AC P17181; B2R6L9; B4DNT3; D3DSF0; Q53GW9; Q53H11; Q6PKD7; Q7M4L2; Q8WTZ2; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 3. DT 27-MAR-2024, entry version 212. DE RecName: Full=Interferon alpha/beta receptor 1; DE Short=IFN-R-1; DE Short=IFN-alpha/beta receptor 1; DE AltName: Full=Cytokine receptor class-II member 1; DE AltName: Full=Cytokine receptor family 2 member 1; DE Short=CRF2-1; DE AltName: Full=Type I interferon receptor 1; DE Flags: Precursor; GN Name=IFNAR1; Synonyms=IFNAR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-168, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=2153461; DOI=10.1016/0092-8674(90)90738-z; RA Uze G., Lutfalla G., Gresser I.; RT "Genetic transfer of a functional human interferon alpha receptor into RT mouse cells: cloning and expression of its cDNA."; RL Cell 60:225-234(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-168. RX PubMed=1370833; DOI=10.1016/s0021-9258(18)45950-9; RA Lutfalla G., Gardiner K., Proudhon D., Vielh E., Uze G.; RT "The structure of the human interferon alpha/beta receptor gene."; RL J. Biol. Chem. 267:2802-2809(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Lung; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-168. RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-307 AND MET-359. RG SeattleSNPs variation discovery resource; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, and Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION. RX PubMed=7813427; DOI=10.1002/j.1460-2075.1994.tb06932.x; RA Abramovich C., Shulman L.M., Ratovitski E., Harroch S., Tovey M., Eid P., RA Revel M.; RT "Differential tyrosine phosphorylation of the IFNAR chain of the type I RT interferon receptor and of an associated surface protein in response to RT IFN-alpha and IFN-beta."; RL EMBO J. 13:5871-5877(1994). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 398-514 (ISOFORM 3), NUCLEOTIDE SEQUENCE RP [MRNA] OF 419-557 (ISOFORM 2), TISSUE SPECIFICITY, AND ALTERNATIVE RP SPLICING. RC TISSUE=Myeloma; RX PubMed=8307198; DOI=10.1016/0014-5793(94)80287-4; RA Abramovich C., Ratovitski E., Lundgren E., Revel M.; RT "Identification of mRNAs encoding two different soluble forms of the human RT interferon alpha-receptor."; RL FEBS Lett. 338:295-300(1994). RN [11] RP PHOSPHORYLATION AT TYR-466 AND TYR-481 BY TYK2, INTERACTION WITH TYK2, AND RP FUNCTION. RX PubMed=7526154; DOI=10.1128/mcb.14.12.8133-8142.1994; RA Colamonici O., Yan H., Domanski P., Handa R., Smalley D., Mullersman J., RA Witte M., Krishnan K., Krolewski J.; RT "Direct binding to and tyrosine phosphorylation of the alpha subunit of the RT type I interferon receptor by p135tyk2 tyrosine kinase."; RL Mol. Cell. Biol. 14:8133-8142(1994). RN [12] RP FUNCTION, INTERACTION WITH IFNAR2, AND SUBCELLULAR LOCATION. RX PubMed=7665574; DOI=10.1074/jbc.270.37.21606; RA Domanski P., Witte M., Kellum M., Rubinstein M., Hackett R., Pitha P., RA Colamonici O.R.; RT "Cloning and expression of a long form of the beta subunit of the RT interferon alpha beta receptor that is required for signaling."; RL J. Biol. Chem. 270:21606-21611(1995). RN [13] RP FUNCTION, AND INTERACTION WITH STAT1 AND STAT2. RX PubMed=9121453; DOI=10.1128/mcb.17.4.2048; RA Li X., Leung S., Kerr I.M., Stark G.R.; RT "Functional subdomains of STAT2 required for preassociation with the alpha RT interferon receptor and for signaling."; RL Mol. Cell. Biol. 17:2048-2056(1997). RN [14] RP FUNCTION, INTERACTION WITH IFNAR2, AND PHOSPHORYLATION. RX PubMed=10049744; DOI=10.1006/bbrc.1998.0105; RA Russell-Harde D., Wagner T.C., Perez H.D., Croze E.; RT "Formation of a uniquely stable type I interferon receptor complex by RT interferon beta is dependent upon particular interactions between RT interferon beta and its receptor and independent of tyrosine RT phosphorylation."; RL Biochem. Biophys. Res. Commun. 255:539-544(1999). RN [15] RP FUNCTION, INTERACTION WITH FBXW11, UBIQUITINATION, PHOSPHORYLATION AT RP SER-535, MUTAGENESIS OF SER-535, AND SUBCELLULAR LOCATION. RX PubMed=14532120; DOI=10.1093/emboj/cdg524; RA Kumar K.G., Tang W., Ravindranath A.K., Clark W.A., Croze E., Fuchs S.Y.; RT "SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of RT the interferon-alpha receptor."; RL EMBO J. 22:5480-5490(2003). RN [16] RP FUNCTION, PHOSPHORYLATION AT SER-535, MUTAGENESIS OF LYS-501; RP 525-LYS-LYS-526; SER-535 AND SER-539, UBIQUITINATION, AND INTERACTION WITH RP FBXW11 AND TYK2. RX PubMed=15337770; DOI=10.1074/jbc.m407082200; RA Kumar K.G., Krolewski J.J., Fuchs S.Y.; RT "Phosphorylation and specific ubiquitin acceptor sites are required for RT ubiquitination and degradation of the IFNAR1 subunit of type I interferon RT receptor."; RL J. Biol. Chem. 279:46614-46620(2004). RN [17] RP SUBCELLULAR LOCATION, UBIQUITINATION, PHOSPHORYLATION AT SER-535, RP INTERACTION WITH FBXW11, AND MUTAGENESIS OF TYR-466. RX PubMed=18056411; DOI=10.1083/jcb.200706034; RA Kumar K.G., Barriere H., Carbone C.J., Liu J., Swaminathan G., Xu P., RA Li Y., Baker D.P., Peng J., Lukacs G.L., Fuchs S.Y.; RT "Site-specific ubiquitination exposes a linear motif to promote interferon- RT alpha receptor endocytosis."; RL J. Cell Biol. 179:935-950(2007). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [19] RP FUNCTION, AND PALMITOYLATION AT CYS-463. RX PubMed=19561067; DOI=10.1074/jbc.m109.021915; RA Claudinon J., Gonnord P., Beslard E., Marchetti M., Mitchell K., RA Boularan C., Johannes L., Eid P., Lamaze C.; RT "Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is RT required for the activation of Stat1 and Stat2 by IFN-alpha."; RL J. Biol. Chem. 284:24328-24340(2009). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-58; ASN-110 AND ASN-313. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [22] RP FUNCTION, UBIQUITINATION, MUTAGENESIS OF SER-535, PHOSPHORYLATION AT RP SER-535, INTERACTION WITH SHMT2 AND THE BRISC COMPLEX, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=24075985; DOI=10.1016/j.celrep.2013.08.025; RA Zheng H., Gupta V., Patterson-Fortin J., Bhattacharya S., Katlinski K., RA Wu J., Varghese B., Carbone C.J., Aressy B., Fuchs S.Y., Greenberg R.A.; RT "A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon RT responses."; RL Cell Rep. 5:180-193(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP INVOLVEMENT IN IMD106, VARIANT IMD106 261-TRP--VAL-557 DEL, RP CHARACTERIZATION OF VARIANT IMD106 261-TRP--VAL-557 DEL, AND FUNCTION. RX PubMed=31270247; DOI=10.1084/jem.20182295; RA Hernandez N., Bucciol G., Moens L., Le Pen J., Shahrooei M., Goudouris E., RA Shirkani A., Changi-Ashtiani M., Rokni-Zadeh H., Sayar E.H., Reisli I., RA Lefevre-Utile A., Zijlmans D., Jurado A., Pholien R., Drutman S., RA Belkaya S., Cobat A., Boudewijns R., Jochmans D., Neyts J., Seeleuthner Y., RA Lorenzo-Diaz L., Enemchukwu C., Tietjen I., Hoffmann H.H., Momenilandi M., RA Poeyhoenen L., Siqueira M.M., de Lima S.M.B., de Souza Matos D.C., RA Homma A., Maia M.L.S., da Costa Barros T.A., de Oliveira P.M.N., RA Mesquita E.C., Gijsbers R., Zhang S.Y., Seligman S.J., Abel L., Hertzog P., RA Marr N., Martins R.M., Meyts I., Zhang Q., MacDonald M.R., Rice C.M., RA Casanova J.L., Jouanguy E., Bossuyt X.; RT "Inherited IFNAR1 deficiency in otherwise healthy patients with adverse RT reaction to measles and yellow fever live vaccines."; RL J. Exp. Med. 216:2057-2070(2019). RN [25] RP INTERACTION WITH TRIM10. RX PubMed=33811647; DOI=10.1002/eji.202049073; RA Guo M., Cao W., Chen S., Tian R., Wang L., Liu Q., Zhang L., Wang Z., RA Zhao M., Lu Q., Zhu H.; RT "TRIM10 binds to IFN-alpha/beta receptor 1 to negatively regulate type I RT IFN signal transduction."; RL Eur. J. Immunol. 51:1762-1773(2021). RN [26] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 30-332 IN COMPLEX WITH IFNAR2; RP IFNA2 AND IFNW1, FUNCTION, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT RP ASN-172. RX PubMed=21854986; DOI=10.1016/j.cell.2011.06.048; RA Thomas C., Moraga I., Levin D., Krutzik P.O., Podoplelova Y., Trejo A., RA Lee C., Yarden G., Vleck S.E., Glenn J.S., Nolan G.P., Piehler J., RA Schreiber G., Garcia K.C.; RT "Structural linkage between ligand discrimination and receptor activation RT by type I interferons."; RL Cell 146:621-632(2011). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 478-507 IN COMPLEX WITH TYK2, RP INTERACTION WITH TYK2, AND MUTAGENESIS OF 491-LEU-LEU-492; 496-GLU-GLU-497 RP AND GLU-500. RX PubMed=24704786; DOI=10.1038/nsmb.2807; RA Wallweber H.J., Tam C., Franke Y., Starovasnik M.A., Lupardus P.J.; RT "Structural basis of recognition of interferon-alpha receptor by tyrosine RT kinase 2."; RL Nat. Struct. Mol. Biol. 21:443-448(2014). RN [28] RP VARIANTS VAL-24; ARG-57; CYS-73; HIS-80; ALA-83; SER-88; MET-169; VAL-183; RP CYS-306; ILE-307; PRO-335 DEL; LEU-386; ARG-422; THR-424 AND LYS-515, RP CHARACTERIZATION OF VARIANTS VAL-24; ARG-57; CYS-73; HIS-80; ALA-83; RP SER-88; MET-169; VAL-183; CYS-306; ILE-307; PRO-335 DEL; LEU-386; ARG-422; RP THR-424 AND LYS-515, AND FUNCTION. RX PubMed=32972995; DOI=10.1126/science.abd4570; RG COVID-STORM Clinicians; RG COVID Clinicians; RG Imagine COVID Group; RG French COVID Cohort Study Group; RG CoV-Contact Cohort; RG Amsterdam UMC Covid-19 Biobank; RG COVID Human Genetic Effort; RG NIAID-USUHS/TAGC COVID Immunity Group; RA Zhang Q., Bastard P., Liu Z., Le Pen J., Moncada-Velez M., Chen J., RA Ogishi M., Sabli I.K.D., Hodeib S., Korol C., Rosain J., Bilguvar K., RA Ye J., Bolze A., Bigio B., Yang R., Arias A.A., Zhou Q., Zhang Y., RA Onodi F., Korniotis S., Karpf L., Philippot Q., Chbihi M., Bonnet-Madin L., RA Dorgham K., Smith N., Schneider W.M., Razooky B.S., Hoffmann H.H., RA Michailidis E., Moens L., Han J.E., Lorenzo L., Bizien L., Meade P., RA Neehus A.L., Ugurbil A.C., Corneau A., Kerner G., Zhang P., Rapaport F., RA Seeleuthner Y., Manry J., Masson C., Schmitt Y., Schlueter A., Le Voyer T., RA Khan T., Li J., Fellay J., Roussel L., Shahrooei M., Alosaimi M.F., RA Mansouri D., Al-Saud H., Al-Mulla F., Almourfi F., Al-Muhsen S.Z., RA Alsohime F., Al Turki S., Hasanato R., van de Beek D., Biondi A., RA Bettini L.R., D'Angio' M., Bonfanti P., Imberti L., Sottini A., Paghera S., RA Quiros-Roldan E., Rossi C., Oler A.J., Tompkins M.F., Alba C., RA Vandernoot I., Goffard J.C., Smits G., Migeotte I., Haerynck F., RA Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P.E., Keles S., RA Coelkesen F., Ozcelik T., Yasar K.K., Senoglu S., Karabela S.N., RA Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., RA Duval X., Laouenan C., Snow A.L., Dalgard C.L., Milner J.D., Vinh D.C., RA Mogensen T.H., Marr N., Spaan A.N., Boisson B., Boisson-Dupuis S., RA Bustamante J., Puel A., Ciancanelli M.J., Meyts I., Maniatis T., RA Soumelis V., Amara A., Nussenzweig M., Garcia-Sastre A., Krammer F., RA Pujol A., Duffy D., Lifton R.P., Zhang S.Y., Gorochov G., Beziat V., RA Jouanguy E., Sancho-Shimizu V., Rice C.M., Abel L., Notarangelo L.D., RA Cobat A., Su H.C., Casanova J.L.; RT "Inborn errors of type I IFN immunity in patients with life-threatening RT COVID-19."; RL Science 370:0-0(2020). RN [29] RP VARIANT IMD106 308-GLN--VAL-557 DEL, CHARACTERIZATION OF VARIANT IMD106 RP 308-GLN--VAL-557 DEL, AND FUNCTION. RX PubMed=33252644; DOI=10.1093/cid/ciaa1790; RA Gothe F., Hatton C.F., Truong L., Klimova Z., Kanderova V., Fejtkova M., RA Grainger A., Bigley V., Perthen J., Mitra D., Janda A., Fronkova E., RA Moravcikova D., Hambleton S., Duncan C.J.A.; RT "A Novel Case of Homozygous Interferon Alpha/Beta Receptor Alpha Chain RT (IFNAR1) Deficiency With Hemophagocytic Lymphohistiocytosis."; RL Clin. Infect. Dis. 74:136-139(2022). RN [30] RP VARIANT IMD106 386-GLU--VAL-557 DEL, CHARACTERIZATION OF VARIANT IMD106 RP 386-GLU--VAL-557 DEL, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=35442418; DOI=10.1084/jem.20220028; RA Bastard P., Hsiao K.C., Zhang Q., Choin J., Best E., Chen J., Gervais A., RA Bizien L., Materna M., Harmant C., Roux M., Hawley N.L., Weeks D.E., RA McGarvey S.T., Sandoval K., Barberena-Jonas C., Quinto-Cortes C.D., RA Hagelberg E., Mentzer A.J., Robson K., Coulibaly B., Seeleuthner Y., RA Bigio B., Li Z., Uze G., Pellegrini S., Lorenzo L., Sbihi Z., Latour S., RA Besnard M., Adam de Beaumais T., Jacqz Aigrain E., Beziat V., Deka R., RA Esera Tulifau L., Viali S., Reupena M.S., Naseri T., McNaughton P., RA Sarkozy V., Peake J., Blincoe A., Primhak S., Stables S., Gibson K., RA Woon S.T., Drake K.M., Hill A.V.S., Chan C.Y., King R., Ameratunga R., RA Teiti I., Aubry M., Cao-Lormeau V.M., Tangye S.G., Zhang S.Y., Jouanguy E., RA Gray P., Abel L., Moreno-Estrada A., Minster R.L., Quintana-Murci L., RA Wood A.C., Casanova J.L.; RT "A loss-of-function IFNAR1 allele in Polynesia underlies severe viral RT diseases in homozygotes."; RL J. Exp. Med. 219:0-0(2022). CC -!- FUNCTION: Together with IFNAR2, forms the heterodimeric receptor for CC type I interferons (including interferons alpha, beta, epsilon, omega CC and kappa) (PubMed:2153461, PubMed:7813427, PubMed:10049744, CC PubMed:14532120, PubMed:15337770, PubMed:24075985, PubMed:21854986, CC PubMed:31270247, PubMed:33252644, PubMed:35442418). Type I interferon CC binding activates the JAK-STAT signaling cascade, resulting in CC transcriptional activation or repression of interferon-regulated genes CC that encode the effectors of the interferon response (PubMed:7665574, CC PubMed:10049744, PubMed:21854986). Mechanistically, type I interferon- CC binding brings the IFNAR1 and IFNAR2 subunits into close proximity with CC one another, driving their associated Janus kinases (JAKs) (TYK2 bound CC to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another CC (PubMed:7813427, PubMed:7665574, PubMed:21854986, PubMed:32972995). The CC activated kinases phosphorylate specific tyrosine residues on the CC intracellular domains of IFNAR1 and IFNAR2, forming docking sites for CC the STAT transcription factors (PubMed:7813427, PubMed:7526154, CC PubMed:7665574, PubMed:21854986, PubMed:32972995). STAT proteins are CC then phosphorylated by the JAKs, promoting their translocation into the CC nucleus to regulate expression of interferon-regulated genes CC (PubMed:7813427, PubMed:7665574, PubMed:9121453, PubMed:19561067, CC PubMed:21854986, PubMed:32972995). Can also act independently of CC IFNAR2: form an active IFNB1 receptor by itself and activate a CC signaling cascade that does not involve activation of the JAK-STAT CC pathway (By similarity). {ECO:0000250|UniProtKB:P33896, CC ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, CC ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:19561067, CC ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:21854986, CC ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:31270247, CC ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33252644, CC ECO:0000269|PubMed:35442418, ECO:0000269|PubMed:7526154, CC ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7813427, CC ECO:0000269|PubMed:9121453}. CC -!- SUBUNIT: Heterodimer with IFNAR2; forming the receptor for type I CC interferon (PubMed:7665574, PubMed:10049744, PubMed:21854986). CC Interacts with TYK2 (PubMed:7526154, PubMed:15337770, PubMed:24704786). CC Interacts with STAT1 and STAT2; the interaction requires its CC phosphorylation at Tyr-466 (PubMed:9121453). Interacts (serine- CC phosphorylated form) with FBXW11, the substrate recognition component CC of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex CC (PubMed:14532120, PubMed:15337770, PubMed:18056411). Interacts with CC SHMT2; this promotes interaction with ABRAXAS2 and the BRISC complex CC (PubMed:24075985). Interacts with TRIM10; this interaction prevents CC association between IFNAR1 and TYK2 (PubMed:33811647). CC {ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, CC ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:18056411, CC ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:24075985, CC ECO:0000269|PubMed:24704786, ECO:0000269|PubMed:33811647, CC ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7665574, CC ECO:0000269|PubMed:9121453}. CC -!- INTERACTION: CC P17181; Q9UKB1: FBXW11; NbExp=8; IntAct=EBI-1547250, EBI-355189; CC P17181; Q86VI4: LAPTM4B; NbExp=3; IntAct=EBI-1547250, EBI-3267258; CC P17181; P42224: STAT1; NbExp=2; IntAct=EBI-1547250, EBI-1057697; CC P17181; P52630: STAT2; NbExp=5; IntAct=EBI-1547250, EBI-1546963; CC P17181-1; P29597: TYK2; NbExp=3; IntAct=EBI-16099379, EBI-1383454; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane CC {ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:18056411, CC ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:35442418, CC ECO:0000305|PubMed:7665574}; Single-pass type I membrane protein CC {ECO:0000305}. Late endosome {ECO:0000269|PubMed:18056411, CC ECO:0000305|PubMed:14532120}. Lysosome {ECO:0000269|PubMed:18056411, CC ECO:0000305|PubMed:14532120}. Note=Interferon binding triggers CC internalization of the receptor from the cell membrane into endosomes CC and then into lysosomes. {ECO:0000269|PubMed:14532120, CC ECO:0000269|PubMed:18056411}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P17181-1; Sequence=Displayed; CC Name=2; Synonyms=Sol-1, Soluble form 1; CC IsoId=P17181-2; Sequence=VSP_029930, VSP_029931; CC Name=3; Synonyms=Sol-2, Soluble form 2; CC IsoId=P17181-3; Sequence=VSP_029928, VSP_029929; CC Name=4; CC IsoId=P17181-4; Sequence=VSP_055322; CC -!- TISSUE SPECIFICITY: IFN receptors are present in all tissues and even CC on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and CC isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line CC U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha CC resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN- CC alpha resistant myeloma cell line U266R. {ECO:0000269|PubMed:8307198}. CC -!- PTM: Ubiquitinated, leading to its internalization and degradation CC (PubMed:14532120, PubMed:15337770). Polyubiquitinated via 'Lys-48'- CC linked and 'Lys-63'-linked ubiquitin chains, leading to receptor CC internalization and lysosomal degradation (PubMed:18056411). The 'Lys- CC 63'-linked ubiquitin chains are cleaved off by the BRISC complex CC (PubMed:24075985). {ECO:0000269|PubMed:14532120, CC ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:18056411, CC ECO:0000269|PubMed:24075985}. CC -!- PTM: Phosphorylated on tyrosine residues in response to interferon- CC binding: phosphorylation by TYK2 tyrosine kinase creates docking sites CC for STAT proteins (PubMed:7526154, PubMed:10049744). Phosphorylated on CC serine residues in response to interferon binding; this promotes CC interaction with FBXW11 and ubiquitination (PubMed:14532120, CC PubMed:15337770, PubMed:24075985). {ECO:0000269|PubMed:10049744, CC ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, CC ECO:0000269|PubMed:7526154}. CC -!- PTM: Palmitoylation at Cys-463 is required for the activation of STAT1 CC and STAT2. {ECO:0000269|PubMed:19561067}. CC -!- DISEASE: Immunodeficiency 106, susceptibility to viral infections CC (IMD106) [MIM:619935]: An autosomal recessive immunologic disorder CC characterized by increased susceptibility to viral infections beginning CC in infancy or early childhood. IMD106 affected individuals may CC demonstrate adverse reactions to vaccination with live attenuated viral CC vaccines, most notably measles, mumps and rubella (MMR) and yellow CC fever vaccines. A subset of IMD106 patients develop severe reactions, CC including excessive hyperinflammatory response, encephalopathy, acute CC respiratory distress syndrome, and multiorgan failure. IMD106 may also CC predispose to severe respiratory infection with SARS-CoV-2. CC {ECO:0000269|PubMed:31270247, ECO:0000269|PubMed:33252644, CC ECO:0000269|PubMed:35442418}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: Incomplete sequence. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the type II cytokine receptor family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH02590.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/ifnar1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J03171; AAA52730.1; -; mRNA. DR EMBL; X60459; CAA42992.1; -; Genomic_DNA. DR EMBL; AK298051; BAG60345.1; -; mRNA. DR EMBL; AK312631; BAG35516.1; -; mRNA. DR EMBL; AK222770; BAD96490.1; -; mRNA. DR EMBL; AK222812; BAD96532.1; -; mRNA. DR EMBL; AY654286; AAT49100.1; -; Genomic_DNA. DR EMBL; AF039907; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000296; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000297; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000298; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471079; EAX09837.1; -; Genomic_DNA. DR EMBL; CH471079; EAX09839.1; -; Genomic_DNA. DR EMBL; BC002590; AAH02590.1; ALT_SEQ; mRNA. DR EMBL; BC021825; AAH21825.1; -; mRNA. DR CCDS; CCDS13624.1; -. [P17181-1] DR CCDS; CCDS93089.1; -. [P17181-4] DR PIR; A32694; A32694. DR PIR; S41602; S41602. DR RefSeq; NP_000620.2; NM_000629.2. [P17181-1] DR RefSeq; XP_005261021.1; XM_005260964.2. DR PDB; 3S98; X-ray; 1.90 A; A=30-332. DR PDB; 3SE3; X-ray; 4.00 A; A=28-436. DR PDB; 3SE4; X-ray; 3.50 A; A=28-436. DR PDB; 4PO6; X-ray; 1.99 A; B=478-507. DR PDBsum; 3S98; -. DR PDBsum; 3SE3; -. DR PDBsum; 3SE4; -. DR PDBsum; 4PO6; -. DR AlphaFoldDB; P17181; -. DR SMR; P17181; -. DR BioGRID; 109676; 52. DR ComplexPortal; CPX-5995; Interferon alpha receptor-ligand complex, IFNA2 variant. DR ComplexPortal; CPX-5996; Interferon alpha receptor-ligand complex, IFNA1 variant. DR ComplexPortal; CPX-5997; Interferon alpha receptor-ligand complex, IFNA7 variant. DR ComplexPortal; CPX-5998; Interferon alpha receptor-ligand complex, IFNA4 variant. DR ComplexPortal; CPX-5999; Interferon alpha receptor-ligand complex, IFNA5 variant. DR ComplexPortal; CPX-6000; Interferon alpha receptor-ligand complex, IFNA6 variant. DR ComplexPortal; CPX-6001; Interferon alpha receptor-ligand complex, IFNA8 variant. DR ComplexPortal; CPX-6002; Interferon alpha receptor-ligand complex, IFNA10 variant. DR ComplexPortal; CPX-6003; Interferon alpha receptor-ligand complex, IFNA14 variant. DR ComplexPortal; CPX-6004; Interferon alpha receptor-ligand complex, IFNA16 variant. DR ComplexPortal; CPX-6005; Interferon alpha receptor-ligand complex, IFNA17 variant. DR ComplexPortal; CPX-6006; Interferon alpha receptor-ligand complex, IFNA21 variant. DR ComplexPortal; CPX-6007; Interferon beta receptor-ligand complex. DR ComplexPortal; CPX-6008; Interferon epsilon receptor-ligand complex. DR ComplexPortal; CPX-6009; Interferon kappa receptor-ligand complex. DR ComplexPortal; CPX-6010; Interferon omega receptor-ligand complex. DR CORUM; P17181; -. DR DIP; DIP-57N; -. DR ELM; P17181; -. DR IntAct; P17181; 12. DR MINT; P17181; -. DR STRING; 9606.ENSP00000270139; -. DR BindingDB; P17181; -. DR ChEMBL; CHEMBL1887; -. DR DrugBank; DB11976; Anifrolumab. DR DrugBank; DB14999; Human interferon beta. DR DrugBank; DB05472; Human interferon omega-1. DR DrugBank; DB05258; Interferon alfa. DR DrugBank; DB00034; Interferon alfa-2a. DR DrugBank; DB00105; Interferon alfa-2b. DR DrugBank; DB00011; Interferon alfa-n1. DR DrugBank; DB00018; Interferon alfa-n3. DR DrugBank; DB00069; Interferon alfacon-1. DR DrugBank; DB00060; Interferon beta-1a. DR DrugBank; DB00068; Interferon beta-1b. DR DrugBank; DB00008; Peginterferon alfa-2a. DR DrugBank; DB00022; Peginterferon alfa-2b. DR DrugBank; DB09122; Peginterferon beta-1a. DR DrugBank; DB15119; Ropeginterferon alfa-2b. DR DrugCentral; P17181; -. DR GuidetoPHARMACOLOGY; 1723; -. DR TCDB; 8.A.132.1.1; the interferon/interleukin receptor (iir) family. DR GlyConnect; 1946; 8 N-Linked glycans (6 sites). DR GlyCosmos; P17181; 12 sites, 8 glycans. DR GlyGen; P17181; 12 sites, 8 N-linked glycans (6 sites). DR iPTMnet; P17181; -. DR PhosphoSitePlus; P17181; -. DR SwissPalm; P17181; -. DR BioMuta; IFNAR1; -. DR DMDM; 90110827; -. DR jPOST; P17181; -. DR MassIVE; P17181; -. DR MaxQB; P17181; -. DR PaxDb; 9606-ENSP00000270139; -. DR PeptideAtlas; P17181; -. DR ProteomicsDB; 4722; -. DR ProteomicsDB; 53460; -. [P17181-1] DR ProteomicsDB; 53461; -. [P17181-2] DR ProteomicsDB; 53462; -. [P17181-3] DR ABCD; P17181; 19 sequenced antibodies. DR Antibodypedia; 3016; 1019 antibodies from 46 providers. DR DNASU; 3454; -. DR Ensembl; ENST00000270139.8; ENSP00000270139.3; ENSG00000142166.15. [P17181-1] DR Ensembl; ENST00000652450.2; ENSP00000498654.1; ENSG00000142166.15. [P17181-4] DR Ensembl; ENST00000700080.1; ENSP00000514785.1; ENSG00000142166.15. [P17181-4] DR Ensembl; ENST00000703515.1; ENSP00000515348.1; ENSG00000142166.15. [P17181-1] DR Ensembl; ENST00000703556.1; ENSP00000515372.1; ENSG00000142166.15. [P17181-1] DR GeneID; 3454; -. DR KEGG; hsa:3454; -. DR MANE-Select; ENST00000270139.8; ENSP00000270139.3; NM_000629.3; NP_000620.2. DR UCSC; uc002yrn.4; human. [P17181-1] DR AGR; HGNC:5432; -. DR CTD; 3454; -. DR DisGeNET; 3454; -. DR GeneCards; IFNAR1; -. DR HGNC; HGNC:5432; IFNAR1. DR HPA; ENSG00000142166; Low tissue specificity. DR MalaCards; IFNAR1; -. DR MIM; 107450; gene. DR MIM; 619935; phenotype. DR neXtProt; NX_P17181; -. DR OpenTargets; ENSG00000142166; -. DR PharmGKB; PA29670; -. DR VEuPathDB; HostDB:ENSG00000142166; -. DR eggNOG; ENOG502RISU; Eukaryota. DR GeneTree; ENSGT00940000158406; -. DR HOGENOM; CLU_035134_0_0_1; -. DR InParanoid; P17181; -. DR OMA; YCINTTV; -. DR OrthoDB; 5320327at2759; -. DR PhylomeDB; P17181; -. DR PathwayCommons; P17181; -. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; P17181; -. DR SIGNOR; P17181; -. DR BioGRID-ORCS; 3454; 20 hits in 1168 CRISPR screens. DR ChiTaRS; IFNAR1; human. DR EvolutionaryTrace; P17181; -. DR GeneWiki; IFNAR1; -. DR GenomeRNAi; 3454; -. DR Pharos; P17181; Tclin. DR PRO; PR:P17181; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P17181; Protein. DR Bgee; ENSG00000142166; Expressed in monocyte and 172 other cell types or tissues. DR ExpressionAtlas; P17181; baseline and differential. DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB. DR GO; GO:0008269; F:JAK pathway signal transduction adaptor activity; IDA:UniProt. DR GO; GO:0019962; F:type I interferon binding; ISS:UniProtKB. DR GO; GO:0004905; F:type I interferon receptor activity; IDA:UniProtKB. DR GO; GO:0035457; P:cellular response to interferon-alpha; ISS:UniProtKB. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProt. DR GO; GO:0098586; P:cellular response to virus; NAS:ComplexPortal. DR GO; GO:1901857; P:positive regulation of cellular respiration; IMP:ARUK-UCL. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:UniProt. DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB. DR GO; GO:0009615; P:response to virus; TAS:ProtInc. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IDA:UniProtKB. DR DisProt; DP02458; -. DR Gene3D; 2.60.40.10; Immunoglobulins; 4. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR015373; Interferon/interleukin_rcp_dom. DR InterPro; IPR016669; Interferon_alpha/beta_rcpt-1. DR PANTHER; PTHR20859:SF54; INTERFERON ALPHA_BETA RECEPTOR 1; 1. DR PANTHER; PTHR20859; INTERFERON/INTERLEUKIN RECEPTOR; 1. DR Pfam; PF09294; Interfer-bind; 2. DR Pfam; PF01108; Tissue_fac; 1. DR PIRSF; PIRSF016567; IFN_alpha/beta_recept-1; 1. DR SUPFAM; SSF49265; Fibronectin type III; 4. DR PROSITE; PS50853; FN3; 4. DR Genevisible; P17181; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Endosome; Glycoprotein; Isopeptide bond; Lipoprotein; KW Lysosome; Membrane; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT CHAIN 28..557 FT /note="Interferon alpha/beta receptor 1" FT /id="PRO_0000011001" FT TOPO_DOM 28..436 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 437..457 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 458..557 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 32..126 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 127..227 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 231..329 FT /note="Fibronectin type-III 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 331..432 FT /note="Fibronectin type-III 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT REGION 491..500 FT /note="Important for interaction with TYK2" FT /evidence="ECO:0000269|PubMed:24704786" FT REGION 516..557 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 540..557 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 466 FT /note="Phosphotyrosine; by TYK2" FT /evidence="ECO:0000305|PubMed:7526154" FT MOD_RES 481 FT /note="Phosphotyrosine; by TYK2" FT /evidence="ECO:0000305|PubMed:7526154" FT MOD_RES 495 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 535 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:14532120, FT ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:18056411, FT ECO:0000269|PubMed:24075985" FT LIPID 463 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:19561067" FT CARBOHYD 50 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 58 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 81 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 88 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 172 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21854986, FT ECO:0007744|PDB:3S98" FT CARBOHYD 254 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 313 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT CARBOHYD 314 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 376 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 416 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 433 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 79..87 FT /evidence="ECO:0000269|PubMed:21854986, FT ECO:0007744|PDB:3S98, ECO:0007744|PDB:3SE3, FT ECO:0007744|PDB:3SE4" FT DISULFID 199..220 FT /evidence="ECO:0000269|PubMed:21854986, FT ECO:0007744|PDB:3S98, ECO:0007744|PDB:3SE3, FT ECO:0007744|PDB:3SE4" FT DISULFID 283..291 FT /evidence="ECO:0000269|PubMed:21854986, FT ECO:0007744|PDB:3S98, ECO:0007744|PDB:3SE3, FT ECO:0007744|PDB:3SE4" FT DISULFID 403..426 FT /evidence="ECO:0000250|UniProtKB:P33896" FT CROSSLNK 501 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305|PubMed:15337770" FT CROSSLNK 525 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305|PubMed:15337770" FT CROSSLNK 526 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000305|PubMed:15337770" FT VAR_SEQ 1..69 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055322" FT VAR_SEQ 414..421 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8307198" FT /id="VSP_029928" FT VAR_SEQ 428..480 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8307198" FT /id="VSP_029929" FT VAR_SEQ 428..434 FT /note="KTKPGNT -> NISLNSH (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8307198" FT /id="VSP_029930" FT VAR_SEQ 435..557 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8307198" FT /id="VSP_029931" FT VARIANT 24 FT /note="A -> V (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs779701967)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084085" FT VARIANT 57 FT /note="G -> R (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs201532160)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084086" FT VARIANT 73 FT /note="W -> C (abolished STAT1 activation upon IFNA2 FT binding but no effect upon IFNG binding; FT dbSNP:rs181939581)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084087" FT VARIANT 80 FT /note="Q -> H (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding IFNG binding; dbSNP:rs1333470928)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084088" FT VARIANT 83 FT /note="T -> A (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084089" FT VARIANT 88 FT /note="N -> S (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs577823502)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084090" FT VARIANT 168 FT /note="V -> L (in dbSNP:rs2257167)" FT /evidence="ECO:0000269|PubMed:1370833, FT ECO:0000269|PubMed:2153461, ECO:0000269|Ref.4" FT /id="VAR_002717" FT VARIANT 169 FT /note="I -> M (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs747690835)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084091" FT VARIANT 183 FT /note="I -> V (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs770624214)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084092" FT VARIANT 261..557 FT /note="Missing (in IMD106; decreased protein abundance)" FT /evidence="ECO:0000269|PubMed:31270247" FT /id="VAR_087556" FT VARIANT 306 FT /note="R -> C (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs201281365)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084093" FT VARIANT 307 FT /note="V -> I (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs17875833)" FT /evidence="ECO:0000269|PubMed:32972995, ECO:0000269|Ref.5" FT /id="VAR_020502" FT VARIANT 308..557 FT /note="Missing (in IMD106; no protein detected in FT homozygous patient cells; loss of type I interferon FT receptor activity)" FT /evidence="ECO:0000269|PubMed:33252644" FT /id="VAR_087557" FT VARIANT 335 FT /note="Missing (decreased STAT1 activation upon IFNA2 FT binding but no effect upon IFNG binding)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084094" FT VARIANT 359 FT /note="T -> M (in dbSNP:rs17875834)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_020503" FT VARIANT 386..557 FT /note="Missing (in IMD106; loss of localization at the FT plasma membrane; loss of type I interferon receptor FT activity)" FT /evidence="ECO:0000269|PubMed:35442418" FT /id="VAR_087558" FT VARIANT 386 FT /note="E -> L (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; requires 2 nucleotide substitutions)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084095" FT VARIANT 422 FT /note="S -> R (abolished STAT1 activation upon IFNA2 FT binding but no effect upon IFNG binding; FT dbSNP:rs746291558)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084096" FT VARIANT 424 FT /note="A -> T (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs541858922)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084097" FT VARIANT 515 FT /note="E -> K (no effect on activation of STAT1 upon IFNA2 FT or IFNG binding; dbSNP:rs778182995)" FT /evidence="ECO:0000269|PubMed:32972995" FT /id="VAR_084098" FT MUTAGEN 466 FT /note="Y->F: Impairs internalization in response to FT interferon." FT /evidence="ECO:0000269|PubMed:18056411" FT MUTAGEN 491..492 FT /note="LL->AA: Impairs interaction with TYK2." FT /evidence="ECO:0000269|PubMed:24704786" FT MUTAGEN 496..497 FT /note="EE->AA: Impairs interaction with TYK2." FT /evidence="ECO:0000269|PubMed:24704786" FT MUTAGEN 500 FT /note="E->A: Impairs interaction with TYK2." FT /evidence="ECO:0000269|PubMed:24704786" FT MUTAGEN 501 FT /note="K->R: Mildly reduces ubiquitination. Nearly FT abolishes ubiquitination and subsequent degradation; when FT associated with 525-R-R-526." FT /evidence="ECO:0000269|PubMed:15337770" FT MUTAGEN 525..526 FT /note="KK->RR: Reduces ubiquitination. Nearly abolishes FT ubiquitination and subsequent degradation; when associated FT with R-501." FT /evidence="ECO:0000269|PubMed:15337770" FT MUTAGEN 535 FT /note="S->A: Abolishes interaction with FBXW11 and FT decreases ubiquitination." FT /evidence="ECO:0000269|PubMed:14532120, FT ECO:0000269|PubMed:15337770" FT MUTAGEN 535 FT /note="S->A: Abolishes phosphorylation at this site and FT interaction with SHMT2." FT /evidence="ECO:0000269|PubMed:24075985" FT MUTAGEN 539 FT /note="S->A: Abolishes interaction with FBXW11 and FT decreases ubiquitination." FT /evidence="ECO:0000269|PubMed:15337770" FT CONFLICT 17 FT /note="A -> G (in Ref. 1; AAA52730)" FT /evidence="ECO:0000305" FT CONFLICT 59 FT /note="V -> M (in Ref. 4; BAD96532)" FT /evidence="ECO:0000305" FT CONFLICT 279 FT /note="Q -> R (in Ref. 4; BAD96532)" FT /evidence="ECO:0000305" FT CONFLICT 344 FT /note="D -> G (in Ref. 3; BAG35516)" FT /evidence="ECO:0000305" FT CONFLICT 479 FT /note="D -> N (in Ref. 4; BAD96532)" FT /evidence="ECO:0000305" FT STRAND 37..41 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 44..48 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 60..69 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 80..88 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 100..107 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 112..116 FT /evidence="ECO:0007829|PDB:3S98" FT HELIX 122..125 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 142..147 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 164..171 FT /evidence="ECO:0007829|PDB:3S98" FT TURN 172..174 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 186..189 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 197..206 FT /evidence="ECO:0007829|PDB:3S98" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 219..222 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 233..240 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 243..249 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 251..254 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 256..263 FT /evidence="ECO:0007829|PDB:3S98" FT HELIX 264..267 FT /evidence="ECO:0007829|PDB:3S98" FT HELIX 281..283 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 286..294 FT /evidence="ECO:0007829|PDB:3S98" FT HELIX 295..297 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 300..310 FT /evidence="ECO:0007829|PDB:3S98" FT STRAND 322..325 FT /evidence="ECO:0007829|PDB:3S98" SQ SEQUENCE 557 AA; 63525 MW; 24A01779DB7F356F CRC64; MMVVLLGATT LVLVAVAPWV LSAAAGGKNL KSPQKVEVDI IDDNFILRWN RSDESVGNVT FSFDYQKTGM DNWIKLSGCQ NITSTKCNFS SLKLNVYEEI KLRIRAEKEN TSSWYEVDSF TPFRKAQIGP PEVHLEAEDK AIVIHISPGT KDSVMWALDG LSFTYSLVIW KNSSGVEERI ENIYSRHKIY KLSPETTYCL KVKAALLTSW KIGVYSPVHC IKTTVENELP PPENIEVSVQ NQNYVLKWDY TYANMTFQVQ WLHAFLKRNP GNHLYKWKQI PDCENVKTTQ CVFPQNVFQK GIYLLRVQAS DGNNTSFWSE EIKFDTEIQA FLLPPVFNIR SLSDSFHIYI GAPKQSGNTP VIQDYPLIYE IIFWENTSNA ERKIIEKKTD VTVPNLKPLT VYCVKARAHT MDEKLNKSSV FSDAVCEKTK PGNTSKIWLI VGICIALFAL PFVIYAAKVF LRCINYVFFP SLKPSSSIDE YFSEQPLKNL LLSTSEEQIE KCFIIENIST IATVEETNQT DEDHKKYSSQ TSQDSGNYSN EDESESKTSE ELQQDFV //