ID   INAR2_HUMAN             Reviewed;         515 AA.
AC   P48551; A8KAJ4; D3DSE8; D3DSE9; Q15467; Q6FHD7;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   24-JAN-2024, entry version 214.
DE   RecName: Full=Interferon alpha/beta receptor 2;
DE            Short=IFN-R-2;
DE            Short=IFN-alpha binding protein;
DE            Short=IFN-alpha/beta receptor 2;
DE   AltName: Full=Interferon alpha binding protein;
DE   AltName: Full=Type I interferon receptor 2;
DE   Flags: Precursor;
GN   Name=IFNAR2; Synonyms=IFNABR, IFNARB;
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 2), PARTIAL PROTEIN SEQUENCE,
RP   GLYCOSYLATION AT ASN-87 AND ASN-192, FUNCTION, SUBUNIT, INTERACTION WITH
RP   JAK1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT VAL-10.
RC   TISSUE=Monocyte;
RX   PubMed=8181059; DOI=10.1016/0092-8674(94)90154-6;
RA   Novick D., Cohen B., Rubinstein M.;
RT   "The human interferon alpha/beta receptor: characterization and molecular
RT   cloning.";
RL   Cell 77:391-400(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3), AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Lymphoblastoma;
RX   PubMed=7588638; DOI=10.1002/j.1460-2075.1995.tb00192.x;
RA   Lutfalla G., Holland S.J., Cinato E., Monneron D., Reboul J., Rogers N.C.,
RA   Smith J.M., Stark G.R., Gardiner K., Mogensen K.E., Kerr I.M., Uze G.;
RT   "Mutant U5A cells are complemented by an interferon-alpha beta receptor
RT   subunit generated by alternative processing of a new member of a cytokine
RT   receptor gene cluster.";
RL   EMBO J. 14:5100-5108(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND SUBUNIT.
RC   TISSUE=Myeloma;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP   INTERACTION WITH JAK1, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, PHOSPHORYLATION, AND VARIANT VAL-10.
RC   TISSUE=Blood;
RX   PubMed=7759950; DOI=10.1002/jlb.57.5.712;
RA   Novick D., Cohen B., Tal N., Rubinstein M.;
RT   "Soluble and membrane-anchored forms of the human IFN-alpha/beta
RT   receptor.";
RL   J. Leukoc. Biol. 57:712-718(1995).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-10.
RC   TISSUE=Blood;
RA   Cohen B., Kim S.H., Novick D., Rubinstein M.;
RL   Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-8; VAL-10 AND VAL-196.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Uterus;
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [9]
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   [10]
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   [11]
RP   FUNCTION.
RX   PubMed=8798579; DOI=10.1074/jbc.271.39.23630;
RA   Platanias L.C., Uddin S., Domanski P., Colamonici O.R.;
RT   "Differences in interferon alpha and beta signaling. Interferon beta
RT   selectively induces the interaction of the alpha and betaL subunits of the
RT   type I interferon receptor.";
RL   J. Biol. Chem. 271:23630-23633(1996).
RN   [12]
RP   FUNCTION.
RX   PubMed=8969169; DOI=10.1074/jbc.271.52.33165;
RA   Croze E., Russell-Harde D., Wagner T.C., Pu H., Pfeffer L.M., Perez H.D.;
RT   "The human type I interferon receptor. Identification of the interferon
RT   beta-specific receptor-associated phosphoprotein.";
RL   J. Biol. Chem. 271:33165-33168(1996).
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   INTERACTION WITH IFNAR1, AND FUNCTION.
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.
RX   PubMed=10556041; DOI=10.1006/jmbi.1999.3230;
RA   Piehler J., Schreiber G.;
RT   "Mutational and structural analysis of the binding interface between type I
RT   interferons and their receptor Ifnar2.";
RL   J. Mol. Biol. 294:223-237(1999).
RN   [16]
RP   FUNCTION, PHOSPHORYLATION AT TYR-337 AND TYR-512, AND MUTAGENESIS OF
RP   TYR-269; TYR-306; TYR-316; TYR-318; TYR-337; TYR-411 AND TYR-512.
RX   PubMed=11682488; DOI=10.1074/jbc.m108928200;
RA   Wagner T.C., Velichko S., Vogel D., Rani M.R., Leung S., Ransohoff R.M.,
RA   Stark G.R., Perez H.D., Croze E.;
RT   "Interferon signaling is dependent on specific tyrosines located within the
RT   intracellular domain of IFNAR2c. Expression of IFNAR2c tyrosine mutants in
RT   U5A cells.";
RL   J. Biol. Chem. 277:1493-1499(2002).
RN   [17]
RP   FUNCTION, PHOSPHORYLATION AT TYR-337 AND TYR-512, AND MUTAGENESIS OF
RP   TYR-269; TYR-306; TYR-316; TYR-318; TYR-337; TYR-411 AND TYR-512.
RX   PubMed=12105218; DOI=10.1074/jbc.m204578200;
RA   Velichko S., Wagner T.C., Turkson J., Jove R., Croze E.;
RT   "STAT3 activation by type I interferons is dependent on specific tyrosines
RT   located in the cytoplasmic domain of interferon receptor chain 2c.
RT   Activation of multiple STATS proceeds through the redundant usage of two
RT   tyrosine residues.";
RL   J. Biol. Chem. 277:35635-35641(2002).
RN   [18]
RP   FUNCTION.
RX   PubMed=17517919; DOI=10.1096/fj.07-8585com;
RA   Kumaran J., Wei L., Kotra L.P., Fish E.N.;
RT   "A structural basis for interferon-alpha-receptor interactions.";
RL   FASEB J. 21:3288-3296(2007).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-400, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
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   [20]
RP   STRUCTURE BY NMR OF 28-237, AND DISULFIDE BONDS.
RX   PubMed=12842042; DOI=10.1016/s0969-2126(03)00120-5;
RA   Chill J.H., Quadt S.R., Levy R., Schreiber G., Anglister J.;
RT   "The human type I interferon receptor: NMR structure reveals the molecular
RT   basis of ligand binding.";
RL   Structure 11:791-802(2003).
RN   [21]
RP   INVOLVEMENT IN SUSCEPTIBILITY TO HBV INFECTION, VARIANTS SER-8 AND VAL-10,
RP   AND CHARACTERIZATION OF VARIANT SER-8.
RX   PubMed=16757563; DOI=10.1073/pnas.0602800103;
RA   Frodsham A.J., Zhang L., Dumpis U., Taib N.A.M., Best S., Durham A.,
RA   Hennig B.J.W., Hellier S., Knapp S., Wright M., Chiaramonte M., Bell J.I.,
RA   Graves M., Whittle H.C., Thomas H.C., Thursz M.R., Hill A.V.S.;
RT   "Class II cytokine receptor gene cluster is a major locus for hepatitis B
RT   persistence.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:9148-9153(2006).
RN   [22]
RP   INTERACTION WITH IFNAR1, AND IDENTIFICATION 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   STRUCTURE BY NMR OF 28-239 IN COMPLEX WITH IFNA2, AND DISULFIDE BONDS.
RX   PubMed=17001036; DOI=10.1110/ps.062283006;
RA   Quadt-Akabayov S.R., Chill J.H., Levy R., Kessler N., Anglister J.;
RT   "Determination of the human type I interferon receptor binding site on
RT   human interferon-alpha2 by cross saturation and an NMR-based model of the
RT   complex.";
RL   Protein Sci. 15:2656-2668(2006).
RN   [24]
RP   STRUCTURE BY NMR OF 28-239 IN COMPLEX WITH IFNA2, AND DISULFIDE BONDS.
RX   PubMed=20496919; DOI=10.1021/bi100041f;
RA   Nudelman I., Akabayov S.R., Schnur E., Biron Z., Levy R., Xu Y., Yang D.,
RA   Anglister J.;
RT   "Intermolecular interactions in a 44 kDa interferon-receptor complex
RT   detected by asymmetric reverse-protonation and two-dimensional NOESY.";
RL   Biochemistry 49:5117-5133(2010).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 28-436 IN COMPLEX WITH IFNAR1 AND
RP   IFNW1, FUNCTION, AND DISULFIDE BONDS.
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   [26]
RP   STRUCTURE BY NMR OF 28-237, AND DISULFIDE BONDS.
RX   PubMed=21819146; DOI=10.1021/ja205480v;
RA   Nudelman I., Akabayov S.R., Scherf T., Anglister J.;
RT   "Observation of intermolecular interactions in large protein complexes by
RT   2D-double difference nuclear Overhauser enhancement spectroscopy:
RT   application to the 44 kDa interferon-receptor complex.";
RL   J. Am. Chem. Soc. 133:14755-14764(2011).
RN   [27]
RP   INVOLVEMENT IN IMD45, AND FUNCTION.
RX   PubMed=26424569; DOI=10.1126/scitranslmed.aac4227;
RA   Duncan C.J., Mohamad S.M., Young D.F., Skelton A.J., Leahy T.R.,
RA   Munday D.C., Butler K.M., Morfopoulou S., Brown J.R., Hubank M.,
RA   Connell J., Gavin P.J., McMahon C., Dempsey E., Lynch N.E., Jacques T.S.,
RA   Valappil M., Cant A.J., Breuer J., Engelhardt K.R., Randall R.E.,
RA   Hambleton S.;
RT   "Human IFNAR2 deficiency: Lessons for antiviral immunity.";
RL   Sci. Transl. Med. 7:307RA154-307RA154(2015).
RN   [28]
RP   FUNCTION, INTERACTION WITH STAT2 AND USP18, AND REGION.
RX   PubMed=28165510; DOI=10.1038/nsmb.3378;
RA   Arimoto K.I., Loechte S., Stoner S.A., Burkart C., Zhang Y., Miyauchi S.,
RA   Wilmes S., Fan J.B., Heinisch J.J., Li Z., Yan M., Pellegrini S.,
RA   Colland F., Piehler J., Zhang D.E.;
RT   "STAT2 is an essential adaptor in USP18-mediated suppression of type I
RT   interferon signaling.";
RL   Nat. Struct. Mol. Biol. 24:279-289(2017).
RN   [29]
RP   VARIANTS GLN-37; VAL-73; VAL-138; GLY-215; ARG-283; LEU-295; CYS-318;
RP   ASN-324; SER-346; SER-362; LEU-385 AND LEU-450, CHARACTERIZATION OF
RP   VARIANTS GLN-37; VAL-73; VAL-138; GLY-215; ARG-283; LEU-295; CYS-318;
RP   ASN-324; SER-346; SER-362; LEU-385 AND LEU-450, 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).
CC   -!- FUNCTION: Together with IFNAR1, forms the heterodimeric receptor for
CC       type I interferons (including interferons alpha, beta, epsilon, omega
CC       and kappa) (PubMed:8181059, PubMed:7665574, PubMed:7759950,
CC       PubMed:8798579, PubMed:8969169, PubMed:10049744, PubMed:10556041,
CC       PubMed:21854986, PubMed:26424569, PubMed:28165510, PubMed:32972995).
CC       Type I interferon binding activates the JAK-STAT signaling cascade,
CC       resulting in transcriptional activation or repression of interferon-
CC       regulated genes that encode the effectors of the interferon response
CC       (PubMed:8181059, PubMed:7665574, PubMed:7759950, PubMed:8798579,
CC       PubMed:8969169, PubMed:10049744, PubMed:17517919, PubMed:21854986,
CC       PubMed:26424569, PubMed:28165510, PubMed:32972995). Mechanistically,
CC       type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into
CC       close proximity with one another, driving their associated Janus
CC       kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to
CC       cross-phosphorylate one another (PubMed:10556041, PubMed:11682488,
CC       PubMed:12105218, PubMed:21854986, PubMed:32972995). The activated
CC       kinases phosphorylate specific tyrosine residues on the intracellular
CC       domains of IFNAR1 and IFNAR2, forming docking sites for the STAT
CC       transcription factors (STAT1, STAT2 and STAT) (PubMed:11682488,
CC       PubMed:12105218, 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:9121453, PubMed:12105218, PubMed:28165510).
CC       {ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:10556041,
CC       ECO:0000269|PubMed:11682488, ECO:0000269|PubMed:12105218,
CC       ECO:0000269|PubMed:17517919, ECO:0000269|PubMed:21854986,
CC       ECO:0000269|PubMed:26424569, ECO:0000269|PubMed:28165510,
CC       ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:7665574,
CC       ECO:0000269|PubMed:7759950, ECO:0000269|PubMed:8181059,
CC       ECO:0000269|PubMed:8798579, ECO:0000269|PubMed:8969169,
CC       ECO:0000269|PubMed:9121453}.
CC   -!- FUNCTION: [Isoform 3]: Potent inhibitor of type I IFN receptor
CC       activity. {ECO:0000269|PubMed:7759950}.
CC   -!- SUBUNIT: Heterodimer with IFNAR1; forming the receptor for type I
CC       interferon (PubMed:8181059, PubMed:7665574, PubMed:10049744,
CC       PubMed:24075985, PubMed:21854986). Interacts with JAK1 (PubMed:8181059,
CC       PubMed:7759950). Interacts with the transcriptional factors STAT1 and
CC       STAT2 (PubMed:9121453, PubMed:28165510). Interacts with USP18;
CC       indirectly via STAT2, it negatively regulates the assembly of the
CC       ternary interferon-IFNAR1-IFNAR2 complex and therefore type I
CC       interferon signaling (PubMed:28165510). {ECO:0000269|PubMed:10049744,
CC       ECO:0000269|PubMed:17001036, ECO:0000269|PubMed:20496919,
CC       ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:24075985,
CC       ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:7665574,
CC       ECO:0000269|PubMed:7759950, ECO:0000269|PubMed:8181059,
CC       ECO:0000269|PubMed:9121453}.
CC   -!- INTERACTION:
CC       P48551; Q92793: CREBBP; NbExp=4; IntAct=EBI-958408, EBI-81215;
CC       P48551; P01563: IFNA2; NbExp=2; IntAct=EBI-958408, EBI-4394394;
CC       P48551; Q00978: IRF9; NbExp=6; IntAct=EBI-958408, EBI-626526;
CC       P48551; P23458: JAK1; NbExp=3; IntAct=EBI-958408, EBI-1383438;
CC       P48551; P63244: RACK1; NbExp=4; IntAct=EBI-958408, EBI-296739;
CC       P48551; P42224: STAT1; NbExp=2; IntAct=EBI-958408, EBI-1057697;
CC       P48551; P52630: STAT2; NbExp=4; IntAct=EBI-958408, EBI-1546963;
CC       P48551; Q9UMW8: USP18; NbExp=4; IntAct=EBI-958408, EBI-356206;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC       {ECO:0000269|PubMed:7665574}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:7665574}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC       {ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7759950,
CC       ECO:0000269|PubMed:8181059}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:7665574}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted
CC       {ECO:0000269|PubMed:7759950, ECO:0000269|PubMed:8181059}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=Long form beta {ECO:0000303|PubMed:7665574}, IFNaR2-2,
CC       IFNaR2-1b;
CC         IsoId=P48551-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short form beta {ECO:0000303|PubMed:7665574},
CC       IFNaR2-1, IFNaR2-1a;
CC         IsoId=P48551-2; Sequence=VSP_001738, VSP_001739;
CC       Name=3; Synonyms=IFNaR2-3, IFNaR2-2a, P40 {ECO:0000303|PubMed:8181059};
CC         IsoId=P48551-3; Sequence=VSP_001736, VSP_001737;
CC   -!- TISSUE SPECIFICITY: Isoform 3 is detected in the urine (at protein
CC       level) (PubMed:8181059, PubMed:7759950). Expressed in blood cells.
CC       Expressed in lymphoblastoid and fibrosarcoma cell lines.
CC       {ECO:0000269|PubMed:7588638, ECO:0000269|PubMed:7759950,
CC       ECO:0000269|PubMed:8181059}.
CC   -!- PTM: Phosphorylated on tyrosine residues upon interferon binding.
CC       Phosphorylation at Tyr-337 or Tyr-512 are sufficient to mediate
CC       interferon dependent activation of STAT1, STAT2 and STAT3 leading to
CC       antiproliferative effects on many different cell types.
CC       {ECO:0000269|PubMed:11682488, ECO:0000269|PubMed:12105218,
CC       ECO:0000269|PubMed:7759950}.
CC   -!- PTM: Glycosylated. {ECO:0000269|PubMed:8181059}.
CC   -!- POLYMORPHISM: Genetic variations in IFNAR2 influence susceptibility to
CC       hepatitis B virus (HBV) infection [MIM:610424].
CC   -!- DISEASE: Immunodeficiency 45 (IMD45) [MIM:616669]: An autosomal
CC       recessive disorder characterized by increased susceptibility to viral
CC       infection due to impaired antiviral immunity, resulting in infection-
CC       associated encephalopathy. Affected individuals are at risk for
CC       developing fatal encephalitis after routine measles/mumps/rubella (MMR)
CC       vaccination. {ECO:0000269|PubMed:26424569}. Note=The disease is caused
CC       by variants affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: [Isoform 3]: Soluble receptor. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the type II cytokine receptor family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/ifnar2/";
CC   ---------------------------------------------------------------------------
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DR   EMBL; X77722; CAA54785.1; -; mRNA.
DR   EMBL; L42243; AAB46417.1; -; Genomic_DNA.
DR   EMBL; L42238; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42239; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42240; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42323; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42241; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42242; AAB46417.1; JOINED; Genomic_DNA.
DR   EMBL; L42243; AAB46418.1; -; Genomic_DNA.
DR   EMBL; L42238; AAB46418.1; JOINED; Genomic_DNA.
DR   EMBL; L42239; AAB46418.1; JOINED; Genomic_DNA.
DR   EMBL; L42240; AAB46418.1; JOINED; Genomic_DNA.
DR   EMBL; L42323; AAB46418.1; JOINED; Genomic_DNA.
DR   EMBL; L42241; AAB46418.1; JOINED; Genomic_DNA.
DR   EMBL; L42243; AAB46419.1; -; Genomic_DNA.
DR   EMBL; L42238; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L42239; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L42240; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L42323; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L42241; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L42242; AAB46419.1; JOINED; Genomic_DNA.
DR   EMBL; L41942; AAB46413.1; -; mRNA.
DR   EMBL; L41943; AAB46414.1; -; mRNA.
DR   EMBL; L41944; AAB46415.1; -; mRNA.
DR   EMBL; U29584; AAC50202.1; -; mRNA.
DR   EMBL; X89814; CAA61940.1; -; mRNA.
DR   EMBL; X89772; CAA61914.1; -; mRNA.
DR   EMBL; AY740397; AAU21038.1; -; Genomic_DNA.
DR   EMBL; AK293059; BAF85748.1; -; mRNA.
DR   EMBL; CR541817; CAG46616.1; -; mRNA.
DR   EMBL; AP000292; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP000293; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP000294; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AP000295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471079; EAX09842.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09843.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09844.1; -; Genomic_DNA.
DR   EMBL; CH471079; EAX09846.1; -; Genomic_DNA.
DR   CCDS; CCDS13621.1; -. [P48551-1]
DR   CCDS; CCDS13622.1; -. [P48551-2]
DR   CCDS; CCDS74782.1; -. [P48551-3]
DR   PIR; I39073; I39073.
DR   PIR; S59501; S59501.
DR   RefSeq; NP_000865.2; NM_000874.4. [P48551-2]
DR   RefSeq; NP_001276054.1; NM_001289125.1. [P48551-1]
DR   RefSeq; NP_001276055.1; NM_001289126.1. [P48551-3]
DR   RefSeq; NP_001276057.1; NM_001289128.1. [P48551-3]
DR   RefSeq; NP_997467.1; NM_207584.2. [P48551-2]
DR   RefSeq; NP_997468.1; NM_207585.2. [P48551-1]
DR   PDB; 1N6U; NMR; -; A=28-237.
DR   PDB; 1N6V; NMR; -; A=28-237.
DR   PDB; 2HYM; NMR; -; A=28-237.
DR   PDB; 2KZ1; NMR; -; B=28-237.
DR   PDB; 2LAG; NMR; -; B=28-237.
DR   PDB; 3S8W; X-ray; 2.60 A; A/B/C=131-232.
DR   PDB; 3S9D; X-ray; 2.00 A; B/D=37-232.
DR   PDB; 3SE3; X-ray; 4.00 A; C=34-232.
DR   PDB; 3SE4; X-ray; 3.50 A; C=34-232.
DR   PDBsum; 1N6U; -.
DR   PDBsum; 1N6V; -.
DR   PDBsum; 2HYM; -.
DR   PDBsum; 2KZ1; -.
DR   PDBsum; 2LAG; -.
DR   PDBsum; 3S8W; -.
DR   PDBsum; 3S9D; -.
DR   PDBsum; 3SE3; -.
DR   PDBsum; 3SE4; -.
DR   AlphaFoldDB; P48551; -.
DR   BMRB; P48551; -.
DR   SMR; P48551; -.
DR   BioGRID; 109677; 30.
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; P48551; -.
DR   DIP; DIP-945N; -.
DR   IntAct; P48551; 16.
DR   MINT; P48551; -.
DR   STRING; 9606.ENSP00000343957; -.
DR   ChEMBL; CHEMBL2364170; -.
DR   DrugBank; DB05472; Human interferon omega-1.
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; DB06152; Nylidrin.
DR   DrugBank; DB00008; Peginterferon alfa-2a.
DR   DrugBank; DB00022; Peginterferon alfa-2b.
DR   DrugBank; DB15119; Ropeginterferon alfa-2b.
DR   DrugCentral; P48551; -.
DR   GlyConnect; 2051; 4 N-Linked glycans (1 site).
DR   GlyCosmos; P48551; 5 sites, 8 glycans.
DR   GlyGen; P48551; 6 sites, 8 N-linked glycans (1 site).
DR   iPTMnet; P48551; -.
DR   PhosphoSitePlus; P48551; -.
DR   BioMuta; IFNAR2; -.
DR   DMDM; 1352466; -.
DR   jPOST; P48551; -.
DR   MassIVE; P48551; -.
DR   MaxQB; P48551; -.
DR   PaxDb; 9606-ENSP00000343957; -.
DR   PeptideAtlas; P48551; -.
DR   ProteomicsDB; 55905; -. [P48551-1]
DR   ProteomicsDB; 55906; -. [P48551-2]
DR   ProteomicsDB; 55907; -. [P48551-3]
DR   Antibodypedia; 34938; 485 antibodies from 35 providers.
DR   DNASU; 3455; -.
DR   Ensembl; ENST00000342101.7; ENSP00000343289.3; ENSG00000159110.22. [P48551-3]
DR   Ensembl; ENST00000342136.9; ENSP00000343957.5; ENSG00000159110.22. [P48551-1]
DR   Ensembl; ENST00000382264.7; ENSP00000371699.3; ENSG00000159110.22. [P48551-2]
DR   Ensembl; ENST00000404220.7; ENSP00000384309.2; ENSG00000159110.22. [P48551-2]
DR   Ensembl; ENST00000683941.1; ENSP00000508013.1; ENSG00000159110.22. [P48551-1]
DR   GeneID; 3455; -.
DR   KEGG; hsa:3455; -.
DR   MANE-Select; ENST00000342136.9; ENSP00000343957.5; NM_001289125.3; NP_001276054.1.
DR   UCSC; uc002yrb.5; human. [P48551-1]
DR   AGR; HGNC:5433; -.
DR   CTD; 3455; -.
DR   DisGeNET; 3455; -.
DR   GeneCards; IFNAR2; -.
DR   HGNC; HGNC:5433; IFNAR2.
DR   HPA; ENSG00000159110; Low tissue specificity.
DR   MalaCards; IFNAR2; -.
DR   MIM; 602376; gene.
DR   MIM; 610424; phenotype.
DR   MIM; 616669; phenotype.
DR   neXtProt; NX_P48551; -.
DR   OpenTargets; ENSG00000159110; -.
DR   Orphanet; 431166; Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.
DR   PharmGKB; PA29671; -.
DR   VEuPathDB; HostDB:ENSG00000159110; -.
DR   eggNOG; ENOG502S60E; Eukaryota.
DR   GeneTree; ENSGT00510000049322; -.
DR   HOGENOM; CLU_072607_0_0_1; -.
DR   InParanoid; P48551; -.
DR   OMA; PSAECPW; -.
DR   OrthoDB; 4258084at2759; -.
DR   PhylomeDB; P48551; -.
DR   TreeFam; TF335897; -.
DR   PathwayCommons; P48551; -.
DR   Reactome; R-HSA-909733; Interferon alpha/beta signaling. [P48551-2]
DR   Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling. [P48551-2]
DR   Reactome; R-HSA-9679191; Potential therapeutics for SARS. [P48551-2]
DR   Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. [P48551-2]
DR   SignaLink; P48551; -.
DR   SIGNOR; P48551; -.
DR   BioGRID-ORCS; 3455; 23 hits in 1179 CRISPR screens.
DR   ChiTaRS; IFNAR2; human.
DR   EvolutionaryTrace; P48551; -.
DR   GeneWiki; IFNAR2; -.
DR   GenomeRNAi; 3455; -.
DR   Pharos; P48551; Tclin.
DR   PRO; PR:P48551; -.
DR   Proteomes; UP000005640; Chromosome 21.
DR   RNAct; P48551; Protein.
DR   Bgee; ENSG00000159110; Expressed in blood and 196 other cell types or tissues.
DR   ExpressionAtlas; P48551; baseline and differential.
DR   Genevisible; P48551; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0019955; F:cytokine binding; IPI:UniProtKB.
DR   GO; GO:0042018; F:interleukin-22 receptor activity; IBA:GO_Central.
DR   GO; GO:0008269; F:JAK pathway signal transduction adaptor activity; TAS:UniProt.
DR   GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR   GO; GO:0019962; F:type I interferon binding; IPI:UniProtKB.
DR   GO; GO:0004905; F:type I interferon receptor activity; IDA:UniProtKB.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
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:0051607; P:defense response to virus; IMP:UniProtKB.
DR   GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:UniProtKB.
DR   GO; GO:0035455; P:response to interferon-alpha; IDA:UniProtKB.
DR   GO; GO:0035456; P:response to interferon-beta; IDA: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   Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR015373; Interferon/interleukin_rcp_dom.
DR   PANTHER; PTHR20859:SF84; INTERFERON ALPHA/BETA RECEPTOR 2; 1.
DR   PANTHER; PTHR20859; INTERFERON/INTERLEUKIN RECEPTOR; 1.
DR   Pfam; PF09294; Interfer-bind; 1.
DR   Pfam; PF01108; Tissue_fac; 1.
DR   SUPFAM; SSF49265; Fibronectin type III; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Membrane;
KW   Phosphoprotein; Receptor; Reference proteome; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..26
FT   CHAIN           27..515
FT                   /note="Interferon alpha/beta receptor 2"
FT                   /id="PRO_0000011006"
FT   TOPO_DOM        27..243
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        244..264
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        265..515
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          318..418
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          418..444
FT                   /note="Mediates interaction with STAT2 (and required for
FT                   the recruitment of USP18)"
FT                   /evidence="ECO:0000269|PubMed:28165510"
FT   REGION          455..515
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        466..497
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         337
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MOD_RES         400
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         467
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O35664"
FT   MOD_RES         512
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8181059"
FT   CARBOHYD        116
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8181059"
FT   DISULFID        39..122
FT                   /evidence="ECO:0000269|PubMed:17001036,
FT                   ECO:0000269|PubMed:20496919, ECO:0000269|PubMed:21819146,
FT                   ECO:0000269|PubMed:21854986, ECO:0007744|PDB:1N6U,
FT                   ECO:0007744|PDB:1N6V, ECO:0007744|PDB:2HYM,
FT                   ECO:0007744|PDB:2KZ1, ECO:0007744|PDB:2LAG,
FT                   ECO:0007744|PDB:3S9D, ECO:0007744|PDB:3SE3,
FT                   ECO:0007744|PDB:3SE4"
FT   DISULFID        85..93
FT                   /evidence="ECO:0000269|PubMed:17001036,
FT                   ECO:0000269|PubMed:20496919, ECO:0000269|PubMed:21819146,
FT                   ECO:0000269|PubMed:21854986, ECO:0007744|PDB:1N6U,
FT                   ECO:0007744|PDB:1N6V, ECO:0007744|PDB:2HYM,
FT                   ECO:0007744|PDB:2KZ1, ECO:0007744|PDB:2LAG,
FT                   ECO:0007744|PDB:3S9D, ECO:0007744|PDB:3SE3,
FT                   ECO:0007744|PDB:3SE4"
FT   DISULFID        207..227
FT                   /evidence="ECO:0000269|PubMed:17001036,
FT                   ECO:0000269|PubMed:20496919, ECO:0000269|PubMed:21819146,
FT                   ECO:0000269|PubMed:21854986, ECO:0007744|PDB:1N6U,
FT                   ECO:0007744|PDB:1N6V, ECO:0007744|PDB:2HYM,
FT                   ECO:0007744|PDB:2KZ1, ECO:0007744|PDB:2LAG,
FT                   ECO:0007744|PDB:3S8W, ECO:0007744|PDB:3S9D,
FT                   ECO:0007744|PDB:3SE3, ECO:0007744|PDB:3SE4"
FT   VAR_SEQ         238..239
FT                   /note="SA -> FS (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:7588638,
FT                   ECO:0000303|PubMed:7759950"
FT                   /id="VSP_001736"
FT   VAR_SEQ         240..515
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:7588638,
FT                   ECO:0000303|PubMed:7759950"
FT                   /id="VSP_001737"
FT   VAR_SEQ         281..331
FT                   /note="NFHNFLAWPFPNLPPLEAMDMVEVIYINRKKKVWDYNYDDESDSDTEAAPR
FT                   -> RQGLAKGWNAVAIHRCSHNALQSETPELKQSSCLSFPSSWDYKRASLCPSD (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7588638,
FT                   ECO:0000303|PubMed:8181059, ECO:0000303|Ref.8"
FT                   /id="VSP_001738"
FT   VAR_SEQ         332..515
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:7588638,
FT                   ECO:0000303|PubMed:8181059, ECO:0000303|Ref.8"
FT                   /id="VSP_001739"
FT   VARIANT         8
FT                   /note="F -> S (risk factor for HVB infection; lower cell
FT                   surface levels; lower induction of MHC class 1 expression
FT                   by INF-alpha; dbSNP:rs2229207)"
FT                   /evidence="ECO:0000269|PubMed:16757563, ECO:0000269|Ref.6"
FT                   /id="VAR_020521"
FT   VARIANT         10
FT                   /note="F -> V (in dbSNP:rs1051393)"
FT                   /evidence="ECO:0000269|PubMed:16757563,
FT                   ECO:0000269|PubMed:7759950, ECO:0000269|PubMed:8181059,
FT                   ECO:0000269|Ref.5, ECO:0000269|Ref.6"
FT                   /id="VAR_020522"
FT   VARIANT         37
FT                   /note="E -> Q (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs201003373)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084099"
FT   VARIANT         73
FT                   /note="M -> V (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs142850110)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084100"
FT   VARIANT         138
FT                   /note="E -> V (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084101"
FT   VARIANT         196
FT                   /note="I -> V (in dbSNP:rs17860223)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_020523"
FT   VARIANT         215
FT                   /note="S -> G (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs747605798)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084102"
FT   VARIANT         283
FT                   /note="H -> R (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs763508005)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084103"
FT   VARIANT         295
FT                   /note="P -> L (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs759744926)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084104"
FT   VARIANT         318
FT                   /note="Y -> C (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs756571542)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084105"
FT   VARIANT         324
FT                   /note="S -> N (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs201411274)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084106"
FT   VARIANT         346
FT                   /note="P -> S (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs148519830)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084107"
FT   VARIANT         362
FT                   /note="P -> S (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs1441207963)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084108"
FT   VARIANT         385
FT                   /note="P -> L (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs1231284605)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084109"
FT   VARIANT         450
FT                   /note="S -> L (no effect on activation of STAT1 upon IFNA2
FT                   or IFNG binding; dbSNP:rs866733383)"
FT                   /evidence="ECO:0000269|PubMed:32972995"
FT                   /id="VAR_084110"
FT   MUTAGEN         269
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-306; F-316; F-
FT                   318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-306; F-316;
FT                   F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-306; F-316;
FT                   F-318 and F-337."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         306
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-316; F-
FT                   318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-269; F-316;
FT                   F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-512. Does
FT                   not inhibit STAT1, STAT2 and STAT3 activation by IFN; when
FT                   associated with F-269; F-316; F-318 and F-337."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         316
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-306; F-
FT                   318; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-269; F-306;
FT                   F-318; F-411 and F-512. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-512. Does
FT                   not inhibit STAT1, STAT2 and STAT3 activation by IFN; when
FT                   associated with F-269; F-306; F-318 and F-337."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         318
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-306; F-
FT                   316; F-337; F-411 and F-512. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-269; F-306;
FT                   F-316; F-411 and F-512. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-512. Does
FT                   not inhibit STAT1, STAT2 and STAT3 activation by IFN; when
FT                   associated with F-269; F-306; F-316 and F-337."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         337
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-306; F-
FT                   316; F-318; F-411 and F-512. Does not inhibit STAT1, STAT2
FT                   and STAT3 activation by IFN; when associated with F-512.
FT                   Does not inhibit STAT1, STAT2 and STAT3 activation by IFN;
FT                   when associated with F-269; F-306; F-316 and F-318."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         411
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-306; F-
FT                   316; F-318; F-337 and F-512. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-269; F-306;
FT                   F-316; F-318 and F-512. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-512."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   MUTAGEN         512
FT                   /note="Y->F: Does not inhibit STAT1, STAT2 and STAT3
FT                   activation by IFN. Inhibits STAT1, STAT2 and STAT3
FT                   activation by IFN; when associated with F-269; F-306; F-
FT                   316; F-318; F-337 and F-411. Inhibits STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-269; F-306;
FT                   F-316; F-318 and F-411. Does not inhibit STAT1, STAT2 and
FT                   STAT3 activation by IFN; when associated with F-411."
FT                   /evidence="ECO:0000269|PubMed:11682488,
FT                   ECO:0000269|PubMed:12105218"
FT   CONFLICT        151
FT                   /note="M -> V (in Ref. 3; AAC50202)"
FT                   /evidence="ECO:0000305"
FT   STRAND          40..46
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          49..55
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          59..61
FT                   /evidence="ECO:0007829|PDB:1N6U"
FT   STRAND          65..75
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   HELIX           83..85
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          86..89
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          91..94
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   TURN            96..98
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          102..104
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          106..113
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          119..126
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   HELIX           128..131
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          138..143
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          148..153
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   HELIX           159..161
FT                   /evidence="ECO:0007829|PDB:1N6U"
FT   STRAND          167..174
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          177..181
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          186..188
FT                   /evidence="ECO:0007829|PDB:3S8W"
FT   STRAND          191..197
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          205..213
FT                   /evidence="ECO:0007829|PDB:3S9D"
FT   STRAND          226..229
FT                   /evidence="ECO:0007829|PDB:3S9D"
SQ   SEQUENCE   515 AA;  57759 MW;  4D7730D93AA739F4 CRC64;
     MLLSQNAFIF RSLNLVLMVY ISLVFGISYD SPDYTDESCT FKISLRNFRS ILSWELKNHS
     IVPTHYTLLY TIMSKPEDLK VVKNCANTTR SFCDLTDEWR STHEAYVTVL EGFSGNTTLF
     SCSHNFWLAI DMSFEPPEFE IVGFTNHINV MVKFPSIVEE ELQFDLSLVI EEQSEGIVKK
     HKPEIKGNMS GNFTYIIDKL IPNTNYCVSV YLEHSDEQAV IKSPLKCTLL PPGQESESAE
     SAKIGGIITV FLIALVLTST IVTLKWIGYI CLRNSLPKVL NFHNFLAWPF PNLPPLEAMD
     MVEVIYINRK KKVWDYNYDD ESDSDTEAAP RTSGGGYTMH GLTVRPLGQA SATSTESQLI
     DPESEEEPDL PEVDVELPTM PKDSPQQLEL LSGPCERRKS PLQDPFPEED YSSTEGSGGR
     ITFNVDLNSV FLRVLDDEDS DDLEAPLMLS SHLEEMVDPE DPDNVQSNHL LASGEGTQPT
     FPSPSSEGLW SEDAPSDQSD TSESDVDLGD GYIMR
//