ID STAT2_HUMAN Reviewed; 851 AA. AC P52630; B4DLC7; G3V2M6; Q16430; Q16431; Q9UDL4; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 24-JAN-2024, entry version 219. DE RecName: Full=Signal transducer and activator of transcription 2; DE AltName: Full=p113; GN Name=STAT2; 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), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=1502204; DOI=10.1073/pnas.89.16.7840; RA Fu X.-Y., Schindler C., Improta T., Aebersold R., Darnell J.E. Jr.; RT "The proteins of ISGF-3, the interferon alpha-induced transcriptional RT activator, define a gene family involved in signal transduction."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7840-7843(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7885841; DOI=10.1093/nar/23.3.459; RA Yan R., Qureshi S., Zhong Z., Wen Z., Darnell J.E. Jr.; RT "The genomic structure of the STAT genes: multiple exons in coincident RT sites in Stat1 and Stat2."; RL Nucleic Acids Res. 23:459-463(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-448; VAL-464; ILE-594 RP AND HIS-826. RG NIEHS SNPs program; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Tongue; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [7] RP PHOSPHORYLATION IN RESPONSE TO IFN-ALPHA. RX PubMed=1638633; DOI=10.1016/0092-8674(92)90106-m; RA Fu X.Y.; RT "A transcription factor with SH2 and SH3 domains is directly activated by RT an interferon alpha-induced cytoplasmic protein tyrosine kinase(s)."; RL Cell 70:323-335(1992). RN [8] RP PHOSPHORYLATION AT TYR-690, AND MUTAGENESIS OF TYR-690. RX PubMed=7532278; DOI=10.1128/mcb.15.3.1312; RA Leung S., Qureshi S.A., Kerr I.M., Darnell J.E. Jr., Stark G.R.; RT "Role of STAT2 in the alpha interferon signaling pathway."; RL Mol. Cell. Biol. 15:1312-1317(1995). RN [9] RP POTENTIAL ALTERNATIVE SPLICING. RX PubMed=8601453; DOI=10.1016/0014-5793(96)00121-4; RA Sugiyama T., Nishio Y., Kishimoto T., Akira S.; RT "Identification of alternative splicing form of Stat2."; RL FEBS Lett. 381:191-194(1996). RN [10] RP FUNCTION, AND SUBUNIT. RX PubMed=9020188; DOI=10.1074/jbc.272.7.4600; RA Bluyssen H.A., Levy D.E.; RT "Stat2 is a transcriptional activator that requires sequence-specific RT contacts provided by stat1 and p48 for stable interaction with DNA."; RL J. Biol. Chem. 272:4600-4605(1997). RN [11] RP INTERACTION WITH IFNAR1 AND IFNAR2, AND PHOSPHORYLATION AT TYR-690. 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 [12] RP REVIEW. RX PubMed=10702714; DOI=10.1159/000053968; RA Cebulla C.M., Miller D.M., Sedmak D.D.; RT "Viral inhibition of interferon signal transduction."; RL Intervirology 42:325-330(1999). RN [13] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-374; LYS-375; ARG-409 AND RP LYS-415. RX PubMed=11150296; DOI=10.1074/jbc.m008821200; RA Melen K., Kinnunen L., Julkunen I.; RT "Arginine/lysine-rich structural element is involved in interferon-induced RT nuclear import of STATs."; RL J. Biol. Chem. 276:16447-16455(2001). RN [14] RP INTERACTION WITH CRSP2 AND CRSP6. RX PubMed=12509459; DOI=10.1128/mcb.23.2.620-628.2003; RA Lau J.F., Nusinzon I., Burakov D., Freedman L.P., Horvath C.M.; RT "Role of metazoan mediator proteins in interferon-responsive RT transcription."; RL Mol. Cell. Biol. 23:620-628(2003). RN [15] RP INTERACTION WITH SIMIAN VIRUS 5 PROTEIN V (MICROBIAL INFECTION). RX PubMed=16227264; DOI=10.1128/jvi.79.21.13434-13441.2005; RA Precious B., Childs K., Fitzpatrick-Swallow V., Goodbourn S., Randall R.E.; RT "Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to RT facilitate the ubiquitination of STAT1."; RL J. Virol. 79:13434-13441(2005). RN [16] RP INTERACTION WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=18701593; DOI=10.1128/jvi.00833-08; RA Huh Y.H., Kim Y.E., Kim E.T., Park J.J., Song M.J., Zhu H., Hayward G.S., RA Ahn J.H.; RT "Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes RT viral growth and is negatively regulated by SUMO."; RL J. Virol. 82:10444-10454(2008). RN [17] RP INTERACTION WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=19812155; DOI=10.1128/jvi.01164-09; RA Krauss S., Kaps J., Czech N., Paulus C., Nevels M.; RT "Physical requirements and functional consequences of complex formation RT between the cytomegalovirus IE1 protein and human STAT2."; RL J. Virol. 83:12854-12870(2009). RN [18] RP INTERACTION WITH DENGUE VIRUS NS5 (MICROBIAL INFECTION). RX PubMed=19279106; DOI=10.1128/jvi.02188-08; RA Ashour J., Laurent-Rolle M., Shi P.Y., Garcia-Sastre A.; RT "NS5 of dengue virus mediates STAT2 binding and degradation."; RL J. Virol. 83:5408-5418(2009). RN [19] RP INTERACTION WITH DENGUE VIRUS NS5 (MICROBIAL INFECTION). RX PubMed=19754307; DOI=10.1086/605847; RA Mazzon M., Jones M., Davidson A., Chain B., Jacobs M.; RT "Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal RT transducer and activator of transcription 2 phosphorylation."; RL J. Infect. Dis. 200:1261-1270(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP INTERACTION WITH VACCINIA VIRUS PROTEIN C6 (MICROBIAL INFECTION). RX PubMed=21931555; DOI=10.1371/journal.ppat.1002247; RA Unterholzner L., Sumner R.P., Baran M., Ren H., Mansur D.S., Bourke N.M., RA Randow F., Smith G.L., Bowie A.G.; RT "Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor RT proteins and inhibits activation of IRF3 and IRF7."; RL PLoS Pathog. 7:E1002247-E1002247(2011). RN [22] RP PHOSPHORYLATION AT SER-283; SER-287 AND THR-294, AND SUBCELLULAR LOCATION. RX PubMed=23139419; DOI=10.1074/jbc.m112.402529; RA Steen H.C., Nogusa S., Thapa R.J., Basagoudanavar S.H., Gill A.L., RA Merali S., Barrero C.A., Balachandran S., Gamero A.M.; RT "Identification of STAT2 serine 287 as a novel regulatory phosphorylation RT site in type I interferon-induced cellular responses."; RL J. Biol. Chem. 288:747-758(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-800, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 IMD44, AND FUNCTION. RX PubMed=23391734; DOI=10.1073/pnas.1220098110; RA Hambleton S., Goodbourn S., Young D.F., Dickinson P., Mohamad S.M., RA Valappil M., McGovern N., Cant A.J., Hackett S.J., Ghazal P., Morgan N.V., RA Randall R.E.; RT "STAT2 deficiency and susceptibility to viral illness in humans."; RL Proc. Natl. Acad. Sci. U.S.A. 110:3053-3058(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-753 AND THR-800, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP INVOLVEMENT IN IMD44, AND FUNCTION. RX PubMed=26122121; DOI=10.1093/brain/awv182; RA Shahni R., Cale C.M., Anderson G., Osellame L.D., Hambleton S., RA Jacques T.S., Wedatilake Y., Taanman J.W., Chan E., Qasim W., Plagnol V., RA Chalasani A., Duchen M.R., Gilmour K.C., Rahman S.; RT "Signal transducer and activator of transcription 2 deficiency is a novel RT disorder of mitochondrial fission."; RL Brain 138:2834-2846(2015). RN [27] RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION). RX PubMed=25631085; DOI=10.1128/jvi.00154-15; RA Ning Y.J., Feng K., Min Y.Q., Cao W.C., Wang M., Deng F., Hu Z., Wang H.; RT "Disruption of type I interferon signaling by the nonstructural protein of RT severe fever with thrombocytopenia syndrome virus via the hijacking of RT STAT2 and STAT1 into inclusion bodies."; RL J. Virol. 89:4227-4236(2015). RN [28] RP INTERACTION WITH DCST1, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=27782195; DOI=10.1038/srep36179; RA Nair S., Bist P., Dikshit N., Krishnan M.N.; RT "Global functional profiling of human ubiquitome identifies E3 ubiquitin RT ligase DCST1 as a novel negative regulator of Type-I interferon RT signaling."; RL Sci. Rep. 6:36179-36179(2016). RN [29] RP INTERACTION WITH ZIKA VIRUS PROTEIN NS5 (MICROBIAL INFECTION). RX PubMed=27797853; DOI=10.15252/embr.201642627; RA Kumar A., Hou S., Airo A.M., Limonta D., Mancinelli V., Branton W., RA Power C., Hobman T.C.; RT "Zika virus inhibits type-I interferon production and downstream RT signaling."; RL EMBO Rep. 17:1766-1775(2016). RN [30] RP INTERACTION WITH ZIKA VIRUS PROTEIN NS5 (MICROBIAL INFECTION). RX PubMed=27212660; DOI=10.1016/j.chom.2016.05.009; RA Grant A., Ponia S.S., Tripathi S., Balasubramaniam V., Miorin L., RA Sourisseau M., Schwarz M.C., Sanchez-Seco M.P., Evans M.J., Best S.M., RA Garcia-Sastre A.; RT "Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling."; RL Cell Host Microbe 19:882-890(2016). RN [31] RP FUNCTION, INTERACTION WITH IFNAR2 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 [32] RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION). RX PubMed=29886262; DOI=10.1016/j.micinf.2018.05.007; RA Kitagawa Y., Sakai M., Shimojima M., Saijo M., Itoh M., Gotoh B.; RT "Nonstructural protein of severe fever with thrombocytopenia syndrome RT phlebovirus targets STAT2 and not STAT1 to inhibit type I interferon- RT stimulated JAK-STAT signaling."; RL Microbes Infect. 20:360-368(2018). RN [33] RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION). RX PubMed=30814285; DOI=10.1128/jvi.02226-18; RA Yoshikawa R., Sakabe S., Urata S., Yasuda J.; RT "Species-Specific Pathogenicity of Severe Fever with Thrombocytopenia RT Syndrome Virus Is Determined by Anti-STAT2 Activity of NSs."; RL J. Virol. 93:0-0(2019). RN [34] RP INTERACTION WITH HEARTLAND VIRUS NSS (MICROBIAL INFECTION). RX PubMed=31040183; DOI=10.1074/jbc.ra118.006563; RA Feng K., Deng F., Hu Z., Wang H., Ning Y.J.; RT "Heartland virus antagonizes type I and III interferon antiviral signaling RT by inhibiting phosphorylation and nuclear translocation of STAT2 and RT STAT1."; RL J. Biol. Chem. 294:9503-9517(2019). RN [35] RP UBIQUITINATION BY HERPES SIMPLEX VIRUS 2 PROTEIN ICP22 (MICROBIAL RP INFECTION). RX PubMed=32699158; DOI=10.4049/jimmunol.2000418; RA Zhang M., Fu M., Li M., Hu H., Gong S., Hu Q.; RT "Herpes Simplex Virus Type 2 Inhibits Type I IFN Signaling Mediated by the RT Novel E3 Ubiquitin Protein Ligase Activity of Viral Protein ICP22."; RL J. Immunol. 205:1281-1292(2020). RN [36] RP INTERACTION WITH EPSTEIN-BARR VIRUS TEGUMENT PROTEIN BGLF2 (MICROBIAL RP INFECTION). RX PubMed=34319780; DOI=10.1128/jvi.01027-21; RA Jangra S., Bharti A., Lui W.Y., Chaudhary V., Botelho M.G., Yuen K.S., RA Jin D.Y.; RT "Suppression of JAK-STAT Signaling by Epstein-Barr Virus Tegument Protein RT BGLF2 through Recruitment of SHP1 Phosphatase and Promotion of STAT2 RT Degradation."; RL J. Virol. 95:e0102721-e0102721(2021). RN [37] RP INVOLVEMENT IN PTORCH3, VARIANT PTORCH3 TRP-148, CHARACTERIZATION OF RP VARIANT PTORCH3 TRP-148, FUNCTION, AND INTERACTION WITH USP18. RX PubMed=31836668; DOI=10.1126/sciimmunol.aav7501; RA Duncan C.J.A., Thompson B.J., Chen R., Rice G.I., Gothe F., Young D.F., RA Lovell S.C., Shuttleworth V.G., Brocklebank V., Corner B., Skelton A.J., RA Bondet V., Coxhead J., Duffy D., Fourrage C., Livingston J.H., Pavaine J., RA Cheesman E., Bitetti S., Grainger A., Acres M., Innes B.A., Mikulasova A., RA Sun R., Hussain R., Wright R., Wynn R., Zarhrate M., Zeef L.A.H., Wood K., RA Hughes S.M., Harris C.L., Engelhardt K.R., Crow Y.J., Randall R.E., RA Kavanagh D., Hambleton S., Briggs T.A.; RT "Severe type I interferonopathy and unrestrained interferon signaling due RT to a homozygous germline mutation in STAT2."; RL Sci. Immunol. 4:0-0(2019). RN [38] RP VARIANT PTORCH3 GLN-148, CHARACTERIZATION OF VARIANT PTORCH3 GLN-148, RP FUNCTION, AND INTERACTION WITH USP18. RX PubMed=32092142; DOI=10.1084/jem.20192319; RA Gruber C., Martin-Fernandez M., Ailal F., Qiu X., Taft J., Altman J., RA Rosain J., Buta S., Bousfiha A., Casanova J.L., Bustamante J., RA Bogunovic D.; RT "Homozygous STAT2 gain-of-function mutation by loss of USP18 activity in a RT patient with type I interferonopathy."; RL J. Exp. Med. 217:0-0(2020). CC -!- FUNCTION: Signal transducer and activator of transcription that CC mediates signaling by type I interferons (IFN-alpha and IFN-beta). CC Following type I IFN binding to cell surface receptors, Jak kinases CC (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of CC STAT1 and STAT2. The phosphorylated STATs dimerize, associate with CC IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that CC enters the nucleus. ISGF3 binds to the IFN stimulated response element CC (ISRE) to activate the transcription of interferon stimulated genes, CC which drive the cell in an antiviral state (PubMed:9020188, CC PubMed:23391734). In addition, has also a negative feedback regulatory CC role in the type I interferon signaling by recruiting USP18 to the type CC I IFN receptor subunit IFNAR2 thereby mitigating the response to type I CC IFNs (PubMed:28165510). Acts as a regulator of mitochondrial fission by CC modulating the phosphorylation of DNM1L at 'Ser-616' and 'Ser-637' CC which activate and inactivate the GTPase activity of DNM1L respectively CC (PubMed:26122121, PubMed:23391734, PubMed:9020188). CC {ECO:0000269|PubMed:23391734, ECO:0000269|PubMed:26122121, CC ECO:0000269|PubMed:28165510, ECO:0000269|PubMed:31836668, CC ECO:0000269|PubMed:32092142, ECO:0000269|PubMed:9020188}. CC -!- SUBUNIT: Heterodimer with STAT1 upon IFN-alpha/beta induced CC phosphorylation (By similarity). The heterodimer STAT1:STAT2 forms the CC interferon-stimulated gene factor 3 complex (ISGF3) with IRF9; CC interacts with IRF9 in the cytoplasm (By similarity). Interacts with CC CRSP2 and CRSP6 (PubMed:12509459). Can form a homodimer upon IFN-alpha CC induced phosphorylation (PubMed:9020188). Interacts with IFNAR1; the CC interaction requires the phosphorylation of IFNAR1 at 'Tyr-466' CC (PubMed:9121453). Interacts with IFNAR2; the interaction is direct CC (PubMed:9121453, PubMed:28165510, PubMed:31836668, PubMed:32092142). CC Interacts with ARL2BP (By similarity). Interacts with E3 ubiquitin CC ligase DCST1; the interaction results in STAT2 ubiquitin-mediated CC proteasomal degradation (PubMed:27782195). Interacts with USP18; the CC interaction is direct and allows the recruitment of USP18 to IFNAR2. CC {ECO:0000250|UniProtKB:Q9WVL2, ECO:0000269|PubMed:12509459, CC ECO:0000269|PubMed:27782195, ECO:0000269|PubMed:28165510, CC ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142, CC ECO:0000269|PubMed:9020188, ECO:0000269|PubMed:9121453}. CC -!- SUBUNIT: (Microbial infection) Interacts with vaccinia virus protein CC C6. {ECO:0000269|PubMed:21931555}. CC -!- SUBUNIT: (Microbial infection) Interacts with Simian virus 5 protein V. CC {ECO:0000269|PubMed:16227264}. CC -!- SUBUNIT: (Microbial infection) Interacts with Rabies virus CC phosphoprotein. {ECO:0000269|PubMed:16227264}. CC -!- SUBUNIT: (Microbial infection) Interacts with Human CC cytomegalovirus/HHV-5 protein UL123; this interaction promotes viral CC growth. {ECO:0000269|PubMed:18701593}. CC -!- SUBUNIT: (Microbial infection) Interacts with Dengue virus NS5; this CC interaction inhibits the phosphorylation of STAT2, and, when all viral CC proteins are present (polyprotein), targets STAT2 for degradation. CC {ECO:0000269|PubMed:19279106, ECO:0000269|PubMed:19754307}. CC -!- SUBUNIT: (Microbial infection) Interacts with Zika virus NS5; this CC interaction targets STAT2 for degradation. CC {ECO:0000269|PubMed:27212660, ECO:0000269|PubMed:27797853}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC (HHV-5) immediate early protein IE1; this interaction promotes viral CC growth and counteracts the antiviral interferon response. CC {ECO:0000269|PubMed:18701593, ECO:0000269|PubMed:19812155}. CC -!- SUBUNIT: (Microbial infection) Interacts with heartland virus NSs; this CC interaction blocks the nuclear translocation and activation of STAT2. CC {ECO:0000269|PubMed:31040183}. CC -!- SUBUNIT: (Microbial infection) Interacts with severe fever with CC thrombocytopenia syndrome virus (SFTSV) NSs; this interaction leads to CC STAT2 sequestration into viral inclusion bodies and inhibition of STAT2 CC phosphorylation thereby suppressing type I IFN-induced nuclear CC translocation of the transcription factor. CC {ECO:0000269|PubMed:25631085, ECO:0000269|PubMed:29886262, CC ECO:0000269|PubMed:30814285}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein Barr virus (EBV) CC tegument protein BGLF2; this interaction leads to STAT2 degradation. CC {ECO:0000269|PubMed:34319780}. CC -!- INTERACTION: CC P52630; P17181: IFNAR1; NbExp=5; IntAct=EBI-1546963, EBI-1547250; CC P52630; P48551: IFNAR2; NbExp=4; IntAct=EBI-1546963, EBI-958408; CC P52630; Q00978: IRF9; NbExp=7; IntAct=EBI-1546963, EBI-626526; CC P52630; P42224: STAT1; NbExp=16; IntAct=EBI-1546963, EBI-1057697; CC P52630; P52630: STAT2; NbExp=3; IntAct=EBI-1546963, EBI-1546963; CC P52630; P29597: TYK2; NbExp=4; IntAct=EBI-1546963, EBI-1383454; CC P52630; P0DTC9: N; Xeno; NbExp=7; IntAct=EBI-1546963, EBI-25475856; CC P52630; P0C774: P/V; Xeno; NbExp=4; IntAct=EBI-1546963, EBI-3650423; CC P52630; P11207: P/V; Xeno; NbExp=2; IntAct=EBI-1546963, EBI-6148694; CC P52630; Q77PU6: U90; Xeno; NbExp=2; IntAct=EBI-1546963, EBI-15849356; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11150296, CC ECO:0000269|PubMed:23139419, ECO:0000269|PubMed:27782195}. Nucleus CC {ECO:0000269|PubMed:11150296, ECO:0000269|PubMed:23139419}. CC Note=Translocated into the nucleus upon activation by IFN-alpha/beta. CC {ECO:0000269|PubMed:11150296, ECO:0000269|PubMed:23139419}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P52630-3; Sequence=Displayed; CC Name=2; CC IsoId=P52630-4; Sequence=VSP_046705; CC -!- PTM: Tyrosine phosphorylated in response to IFN-alpha. Phosphorylation CC at Ser-287 negatively regulates the transcriptional response. CC {ECO:0000269|PubMed:1638633, ECO:0000269|PubMed:23139419, CC ECO:0000269|PubMed:7532278, ECO:0000269|PubMed:9121453}. CC -!- PTM: 'Lys-48'-linked ubiquitination by DCST1 leads to STAT2 proteasomal CC degradation. {ECO:0000269|PubMed:27782195}. CC -!- PTM: (Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 CC ubiquitin ligase ICP22. {ECO:0000269|PubMed:32699158}. CC -!- DISEASE: Immunodeficiency 44 (IMD44) [MIM:616636]: An autosomal CC recessive disorder characterized by increased susceptibility to viral CC infection, resulting in some patients in encephalopathy and infection- CC associated neurologic decompensation. {ECO:0000269|PubMed:23391734, CC ECO:0000269|PubMed:26122121}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Pseudo-TORCH syndrome 3 (PTORCH3) [MIM:618886]: An autosomal CC recessive disorder characterized by developmental delay with acute CC episodes of fever and multisystemic organ involvement, including CC coagulopathy, elevated liver enzymes, and proteinuria, often associated CC with thrombotic microangiopathy. Brain imaging shows progressive CC intracranial calcifications, white matter abnormalities, and sometimes CC cerebral or cerebellar atrophy. Disease onset is in the neonatal CC period, and death in early childhood is common. CC {ECO:0000269|PubMed:31836668, ECO:0000269|PubMed:32092142}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to competing acceptor splice CC site. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB36226.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=AAB36227.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/stat2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M97934; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; U18671; AAA98760.1; -; Genomic_DNA. DR EMBL; S81491; AAB36226.1; ALT_SEQ; Genomic_DNA. DR EMBL; S81491; AAB36227.1; ALT_SEQ; Genomic_DNA. DR EMBL; AY525126; AAS00091.1; -; Genomic_DNA. DR EMBL; AK296939; BAG59489.1; -; mRNA. DR EMBL; AC025574; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC051284; AAH51284.1; -; mRNA. DR CCDS; CCDS55836.1; -. [P52630-4] DR CCDS; CCDS8917.1; -. [P52630-3] DR PIR; A46160; A46160. DR RefSeq; NP_005410.1; NM_005419.3. [P52630-3] DR RefSeq; NP_938146.1; NM_198332.1. [P52630-4] DR PDB; 2KA4; NMR; -; B=786-838. DR PDB; 6UX2; X-ray; 3.01 A; A=1-713. DR PDB; 6WCZ; EM; 4.00 A; A=1-851. DR PDBsum; 2KA4; -. DR PDBsum; 6UX2; -. DR PDBsum; 6WCZ; -. DR AlphaFoldDB; P52630; -. DR EMDB; EMD-21618; -. DR SMR; P52630; -. DR BioGRID; 112650; 79. DR ComplexPortal; CPX-6016; ISGF3 complex. DR ComplexPortal; CPX-6047; STAT2/STAT6 complex. DR CORUM; P52630; -. DR DIP; DIP-38511N; -. DR IntAct; P52630; 86. DR MINT; P52630; -. DR STRING; 9606.ENSP00000315768; -. DR BindingDB; P52630; -. DR ChEMBL; CHEMBL4523239; -. DR GlyCosmos; P52630; 2 sites, 1 glycan. DR GlyGen; P52630; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P52630; -. DR MetOSite; P52630; -. DR PhosphoSitePlus; P52630; -. DR BioMuta; STAT2; -. DR DMDM; 1711552; -. DR CPTAC; CPTAC-1273; -. DR CPTAC; CPTAC-1274; -. DR EPD; P52630; -. DR jPOST; P52630; -. DR MassIVE; P52630; -. DR MaxQB; P52630; -. DR PaxDb; 9606-ENSP00000315768; -. DR PeptideAtlas; P52630; -. DR ProteomicsDB; 32682; -. DR ProteomicsDB; 56498; -. [P52630-3] DR Pumba; P52630; -. DR ABCD; P52630; 1 sequenced antibody. DR Antibodypedia; 3552; 1163 antibodies from 47 providers. DR DNASU; 6773; -. DR Ensembl; ENST00000314128.9; ENSP00000315768.4; ENSG00000170581.15. [P52630-3] DR Ensembl; ENST00000557235.5; ENSP00000450751.1; ENSG00000170581.15. [P52630-4] DR Ensembl; ENST00000698192.1; ENSP00000513599.1; ENSG00000170581.15. [P52630-3] DR GeneID; 6773; -. DR KEGG; hsa:6773; -. DR MANE-Select; ENST00000314128.9; ENSP00000315768.4; NM_005419.4; NP_005410.1. DR UCSC; uc001sld.4; human. [P52630-3] DR AGR; HGNC:11363; -. DR CTD; 6773; -. DR DisGeNET; 6773; -. DR GeneCards; STAT2; -. DR HGNC; HGNC:11363; STAT2. DR HPA; ENSG00000170581; Low tissue specificity. DR MalaCards; STAT2; -. DR MIM; 600556; gene. DR MIM; 616636; phenotype. DR MIM; 618886; phenotype. DR neXtProt; NX_P52630; -. DR OpenTargets; ENSG00000170581; -. DR Orphanet; 431166; Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection. DR PharmGKB; PA36184; -. DR VEuPathDB; HostDB:ENSG00000170581; -. DR eggNOG; KOG3667; Eukaryota. DR GeneTree; ENSGT01050000244905; -. DR HOGENOM; CLU_014189_0_0_1; -. DR InParanoid; P52630; -. DR OMA; MDEAYIF; -. DR OrthoDB; 7823at2759; -. DR PhylomeDB; P52630; -. DR TreeFam; TF318648; -. DR PathwayCommons; P52630; -. DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. 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; P52630; -. DR SIGNOR; P52630; -. DR BioGRID-ORCS; 6773; 18 hits in 1182 CRISPR screens. DR ChiTaRS; STAT2; human. DR EvolutionaryTrace; P52630; -. DR GeneWiki; STAT2; -. DR GenomeRNAi; 6773; -. DR Pharos; P52630; Tbio. DR PRO; PR:P52630; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P52630; Protein. DR Bgee; ENSG00000170581; Expressed in granulocyte and 184 other cell types or tissues. DR ExpressionAtlas; P52630; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070721; C:ISGF3 complex; IPI:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProt. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; NAS:ComplexPortal. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProt. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProt. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB. DR GO; GO:0006952; P:defense response; IBA:GO_Central. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ComplexPortal. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:UniProt. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0090140; P:regulation of mitochondrial fission; IMP:UniProtKB. DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProt. DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IMP:UniProtKB. DR CDD; cd10373; SH2_STAT2; 1. DR CDD; cd16852; STAT2_CCD; 1. DR DisProt; DP00961; -. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 1.20.1050.20; STAT transcription factor, all-alpha domain; 1. DR Gene3D; 2.60.40.630; STAT transcription factor, DNA-binding domain; 1. DR Gene3D; 1.10.532.10; STAT transcription factor, N-terminal domain; 1. DR IDEAL; IID00053; -. DR InterPro; IPR008967; p53-like_TF_DNA-bd_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR001217; STAT. DR InterPro; IPR022756; STAT2_C. DR InterPro; IPR035854; STAT2_SH2. DR InterPro; IPR048988; STAT_linker. DR InterPro; IPR036535; STAT_N_sf. DR InterPro; IPR013800; STAT_TF_alpha. DR InterPro; IPR015988; STAT_TF_coiled-coil. DR InterPro; IPR013801; STAT_TF_DNA-bd. DR InterPro; IPR012345; STAT_TF_DNA-bd_N. DR InterPro; IPR013799; STAT_TF_prot_interaction. DR PANTHER; PTHR11801; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; 1. DR PANTHER; PTHR11801:SF41; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 2; 1. DR Pfam; PF00017; SH2; 1. DR Pfam; PF12188; STAT2_C; 1. DR Pfam; PF01017; STAT_alpha; 1. DR Pfam; PF02864; STAT_bind; 1. DR Pfam; PF02865; STAT_int; 1. DR Pfam; PF21354; STAT_linker; 1. DR SMART; SM00252; SH2; 1. DR SMART; SM00964; STAT_int; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF47655; STAT; 1. DR SUPFAM; SSF48092; Transcription factor STAT-4 N-domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; P52630; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Antiviral defense; KW Cytoplasm; Direct protein sequencing; Disease variant; DNA-binding; KW Host-virus interaction; Nucleus; Phosphoprotein; Reference proteome; KW SH2 domain; Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1..851 FT /note="Signal transducer and activator of transcription 2" FT /id="PRO_0000182413" FT DOMAIN 572..667 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT REGION 138..572 FT /note="Mediates interaction with USP18" FT /evidence="ECO:0000269|PubMed:28165510" FT REGION 316..575 FT /note="Interaction with heartland virus NSs" FT /evidence="ECO:0000269|PubMed:31040183" FT REGION 316..486 FT /note="Interaction with SFTSV virus NSs" FT /evidence="ECO:0000269|PubMed:25631085" FT MOD_RES 283 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23139419" FT MOD_RES 287 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:23139419" FT MOD_RES 294 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:23139419" FT MOD_RES 690 FT /note="Phosphotyrosine; by JAK" FT /evidence="ECO:0000269|PubMed:7532278, FT ECO:0000269|PubMed:9121453" FT MOD_RES 753 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 800 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT VAR_SEQ 96..99 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046705" FT VARIANT 66 FT /note="Q -> H (in dbSNP:rs2066816)" FT /id="VAR_014896" FT VARIANT 148 FT /note="R -> Q (in PTORCH3; increased cellular sensitivity FT to type IIFNs; fails to appropriately traffic USP18 thereby FT preventing USP18 to inhibit responses to IFN-I)" FT /evidence="ECO:0000269|PubMed:32092142" FT /id="VAR_084450" FT VARIANT 148 FT /note="R -> W (in PTORCH3; increased cellular sensitivity FT to type IIFNs; loss of interaction with USP18 thereby FT preventing USP18 to inhibit responses to IFN-I; FT dbSNP:rs1458224681)" FT /evidence="ECO:0000269|PubMed:31836668" FT /id="VAR_084451" FT VARIANT 220 FT /note="L -> P (in dbSNP:rs2066817)" FT /id="VAR_014897" FT VARIANT 246 FT /note="C -> S (in dbSNP:rs2228259)" FT /id="VAR_052072" FT VARIANT 448 FT /note="T -> M (in dbSNP:rs2066815)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_014898" FT VARIANT 464 FT /note="I -> V (in dbSNP:rs2066811)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_014899" FT VARIANT 501 FT /note="S -> I (in dbSNP:rs2066809)" FT /id="VAR_014900" FT VARIANT 594 FT /note="M -> I (in dbSNP:rs2066807)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_014901" FT VARIANT 826 FT /note="Q -> H (in dbSNP:rs2229363)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_019213" FT MUTAGEN 374 FT /note="R->A: Prevents the nuclear import; when associated FT with A-375." FT /evidence="ECO:0000269|PubMed:11150296" FT MUTAGEN 375 FT /note="K->A: Prevents the nuclear import; when associated FT with A-374." FT /evidence="ECO:0000269|PubMed:11150296" FT MUTAGEN 409 FT /note="R->A: Prevents the nuclear import; when associated FT with A-415." FT /evidence="ECO:0000269|PubMed:11150296" FT MUTAGEN 415 FT /note="K->A: Prevents the nuclear import; when associated FT with A-409." FT /evidence="ECO:0000269|PubMed:11150296" FT MUTAGEN 690 FT /note="Y->F: Reduces phosphorylation of STAT1 in response FT to IFN-ALPHA." FT /evidence="ECO:0000269|PubMed:7532278" FT CONFLICT 240 FT /note="A -> T (in Ref. 4; BAG59489)" FT /evidence="ECO:0000305" FT TURN 32..35 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 36..41 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 54..67 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 83..93 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 101..110 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 141..182 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 194..246 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 256..284 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 293..315 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 316..323 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 332..335 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 340..348 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 357..363 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 376..380 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 388..394 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 396..407 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 424..426 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 431..439 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 442..449 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 453..458 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 459..461 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 462..475 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 493..507 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 514..525 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 531..533 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 538..542 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 544..546 FT /evidence="ECO:0007829|PDB:6UX2" FT TURN 547..550 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 553..567 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 569..573 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 583..591 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 597..602 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 604..606 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 610..616 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 619..628 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 633..636 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 641..646 FT /evidence="ECO:0007829|PDB:6UX2" FT TURN 665..667 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 670..673 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 675..677 FT /evidence="ECO:0007829|PDB:6UX2" FT STRAND 693..699 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 700..704 FT /evidence="ECO:0007829|PDB:6UX2" FT HELIX 793..796 FT /evidence="ECO:0007829|PDB:2KA4" FT HELIX 802..806 FT /evidence="ECO:0007829|PDB:2KA4" FT TURN 812..814 FT /evidence="ECO:0007829|PDB:2KA4" FT HELIX 824..827 FT /evidence="ECO:0007829|PDB:2KA4" FT HELIX 831..834 FT /evidence="ECO:0007829|PDB:2KA4" SQ SEQUENCE 851 AA; 97916 MW; E4C74674CB7A3215 CRC64; MAQWEMLQNL DSPFQDQLHQ LYSHSLLPVD IRQYLAVWIE DQNWQEAALG SDDSKATMLF FHFLDQLNYE CGRCSQDPES LLLQHNLRKF CRDIQPFSQD PTQLAEMIFN LLLEEKRILI QAQRAQLEQG EPVLETPVES QQHEIESRIL DLRAMMEKLV KSISQLKDQQ DVFCFRYKIQ AKGKTPSLDP HQTKEQKILQ ETLNELDKRR KEVLDASKAL LGRLTTLIEL LLPKLEEWKA QQQKACIRAP IDHGLEQLET WFTAGAKLLF HLRQLLKELK GLSCLVSYQD DPLTKGVDLR NAQVTELLQR LLHRAFVVET QPCMPQTPHR PLILKTGSKF TVRTRLLVRL QEGNESLTVE VSIDRNPPQL QGFRKFNILT SNQKTLTPEK GQSQGLIWDF GYLTLVEQRS GGSGKGSNKG PLGVTEELHI ISFTVKYTYQ GLKQELKTDT LPVVIISNMN QLSIAWASVL WFNLLSPNLQ NQQFFSNPPK APWSLLGPAL SWQFSSYVGR GLNSDQLSML RNKLFGQNCR TEDPLLSWAD FTKRESPPGK LPFWTWLDKI LELVHDHLKD LWNDGRIMGF VSRSQERRLL KKTMSGTFLL RFSESSEGGI TCSWVEHQDD DKVLIYSVQP YTKEVLQSLP LTEIIRHYQL LTEENIPENP LRFLYPRIPR DEAFGCYYQE KVNLQERRKY LKHRLIVVSN RQVDELQQPL ELKPEPELES LELELGLVPE PELSLDLEPL LKAGLDLGPE LESVLESTLE PVIEPTLCMV SQTVPEPDQG PVSQPVPEPD LPCDLRHLNT EPMEIFRNCV KIEEIMPNGD PLLAGQNTVD EVYVSRPSHF YTDGPLMPSD F //