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