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 27-MAR-2024, entry version 215.
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/";
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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
//