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   29-MAY-2024, entry version 213.
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:10049744, PubMed:14532120, PubMed:15337770,
CC       PubMed:2153461, PubMed:21854986, PubMed:24075985, PubMed:31270247,
CC       PubMed:33252644, PubMed:35442418, PubMed:7813427). 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:10049744,
CC       PubMed:21854986, PubMed:7665574). 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:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427). 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:21854986, PubMed:32972995,
CC       PubMed:7526154, PubMed:7665574, PubMed:7813427). STAT proteins are then
CC       phosphorylated by the JAKs, promoting their translocation into the
CC       nucleus to regulate expression of interferon-regulated genes
CC       (PubMed:19561067, PubMed:21854986, PubMed:32972995, PubMed:7665574,
CC       PubMed:7813427, PubMed:9121453). Can also act independently of IFNAR2:
CC       form an active IFNB1 receptor by itself and activate a signaling
CC       cascade that does not involve activation of the JAK-STAT pathway (By
CC       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:10049744, PubMed:21854986, PubMed:7665574).
CC       Interacts with TYK2 (PubMed:15337770, PubMed:24704786, PubMed:7526154).
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:10049744, PubMed:7526154). 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   ---------------------------------------------------------------------------
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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; 1021 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   Reactome; R-HSA-9833109; Evasion by RSV of host interferon 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.
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
//