STAT2_HUMAN
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 03-AUG-2022, entry version 211.
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 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 [37]
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 -!- 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 ---------------------------------------------------------------------------
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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 SMR; P52630; -.
DR BioGRID; 112650; 66.
DR ComplexPortal; CPX-6016; ISGF3 complex.
DR ComplexPortal; CPX-6047; STAT2/STAT6 complex.
DR CORUM; P52630; -.
DR DIP; DIP-38511N; -.
DR IntAct; P52630; 84.
DR MINT; P52630; -.
DR STRING; 9606.ENSP00000315768; -.
DR BindingDB; P52630; -.
DR ChEMBL; CHEMBL4523239; -.
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; P52630; -.
DR PeptideAtlas; P52630; -.
DR PRIDE; P52630; -.
DR ProteomicsDB; 32682; -.
DR ProteomicsDB; 56498; -. [P52630-3]
DR ABCD; P52630; 1 sequenced antibody.
DR Antibodypedia; 3552; 1067 antibodies from 47 providers.
DR DNASU; 6773; -.
DR Ensembl; ENST00000314128.9; ENSP00000315768.4; ENSG00000170581.14. [P52630-3]
DR Ensembl; ENST00000557235.5; ENSP00000450751.1; ENSG00000170581.14. [P52630-4]
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 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; NTMDEAY; -.
DR OrthoDB; 327469at2759; -.
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 1104 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 182 other tissues.
DR ExpressionAtlas; P52630; baseline and differential.
DR Genevisible; P52630; HS.
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:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
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:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central.
DR GO; GO:0060337; P:type I interferon signaling pathway; IMP:UniProtKB.
DR CDD; cd10373; SH2_STAT2; 1.
DR DisProt; DP00961; -.
DR Gene3D; 1.10.532.10; -; 1.
DR Gene3D; 2.60.40.630; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID00053; -.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
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; 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; PTHR11801; 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 SMART; SM00252; SH2; 1.
DR SMART; SM00964; STAT_int; 1.
DR SUPFAM; SSF47655; SSF47655; 1.
DR SUPFAM; SSF48092; SSF48092; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
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 I IFNs; fails to appropriately traffic USP18
FT thereby 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 I IFNs; 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
