ID STAT1_HUMAN Reviewed; 750 AA. AC P42224; A8K989; B2RCA0; D2KFR8; D3DPI7; Q53S88; Q53XW4; Q68D00; Q9UDL5; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 18-JUN-2025, entry version 265. DE RecName: Full=Signal transducer and activator of transcription 1-alpha/beta; DE AltName: Full=Transcription factor ISGF-3 components p91/p84; GN Name=STAT1; 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 ALPHA), AND PROTEIN SEQUENCE OF RP 514-524; 654-660 AND 667-672. RX PubMed=1502203; DOI=10.1073/pnas.89.16.7836; RA Schindler C., Fu X.-Y., Improta T., Aebersold R., Darnell J.E. Jr.; RT "Proteins of transcription factor ISGF-3: one gene encodes the 91- and 84- RT kDa ISGF-3 proteins that are activated by interferon alpha."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7836-7839(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA). RA Kristensen I., Veirum J.E., Moeller B.K., Christiansen M.; RT "Novel STAT1 alleles in a patient with impaired resistance to RT mycobacteria."; RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Placenta, and Testis; 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 MRNA] (ISOFORM ALPHA). RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA). RC TISSUE=Brain; 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 [10] RP PARTIAL 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 [11] 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 [12] RP FUNCTION, AND INTERACTION WITH IFNGR1. RX PubMed=8156998; DOI=10.1002/j.1460-2075.1994.tb06422.x; RA Greenlund A.C., Farrar M.A., Viviano B.L., Schreiber R.D.; RT "Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the RT receptor to its signal transduction system (p91)."; RL EMBO J. 13:1591-1600(1994). RN [13] RP PHOSPHORYLATION AT SER-727. RX PubMed=7543024; DOI=10.1016/0092-8674(95)90311-9; RA Wen Z., Zhong Z., Darnell J.E. Jr.; RT "Maximal activation of transcription by Stat1 and Stat3 requires both RT tyrosine and serine phosphorylation."; RL Cell 82:241-250(1995). RN [14] RP PHOSPHORYLATION AT TYR-701. RX PubMed=7657660; DOI=10.1074/jbc.270.35.20775; RA Quelle F.W., Thierfelder W., Witthuhn B.A., Tang B., Cohen S., Ihle J.N.; RT "Phosphorylation and activation of the DNA binding activity of purified RT Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor RT receptor."; RL J. Biol. Chem. 270:20775-20780(1995). RN [15] RP TYROSINE PHOSPHORYLATION, HETERODIMERIZATION, AND DNA-BINDING. RX PubMed=8605877; DOI=10.1002/j.1460-2075.1996.tb00445.x; RA Gupta S., Yan H., Wong L.H., Ralph S., Krolewski J., Schindler C.; RT "The SH2 domains of Stat1 and Stat2 mediate multiple interactions in the RT transduction of IFN-alpha signals."; RL EMBO J. 15:1075-1084(1996). RN [16] RP INTERACTION WITH IFNAR1 AND IFNAR2, AND PHOSPHORYLATION. 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 [17] RP INTERACTION WITH PIAS1, AND FUNCTION. RC TISSUE=B-cell; RX PubMed=9724754; DOI=10.1073/pnas.95.18.10626; RA Liu B., Liao J., Rao X., Kushner S.A., Chung C.D., Chang D.D., Shuai K.; RT "Inhibition of Stat1-mediated gene activation by PIAS1."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10626-10631(1998). RN [18] RP INTERACTION WITH NMI, AND IDENTIFICATION IN A COMPLEX WITH NMI AND CREBBP. RX PubMed=9989503; DOI=10.1016/s0092-8674(00)80965-4; RA Zhu M.-H., John S., Berg M., Leonard W.J.; RT "Functional association of Nmi with Stat5 and Stat1 in IL-2- and IFNgamma- RT mediated signaling."; RL Cell 96:121-130(1999). RN [19] 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 [20] RP INTERACTION WITH SENDAI VIRUS C PROTEIN (MICROBIAL INFECTION). RX PubMed=11442634; DOI=10.1046/j.1365-2443.2001.00442.x; RA Takeuchi K., Komatsu T., Yokoo J., Kato A., Shioda T., Nagai Y., Gotoh B.; RT "Sendai virus C protein physically associates with Stat1."; RL Genes Cells 6:545-557(2001). RN [21] RP INTERACTION WITH PTK2/FAK1, AND PHOSPHORYLATION. RX PubMed=11278462; DOI=10.1074/jbc.m009063200; RA Xie B., Zhao J., Kitagawa M., Durbin J., Madri J.A., Guan J.L., Fu X.Y.; RT "Focal adhesion kinase activates Stat1 in integrin-mediated cell migration RT and adhesion."; RL J. Biol. Chem. 276:19512-19523(2001). RN [22] RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPN2. RX PubMed=12138178; DOI=10.1128/mcb.22.16.5662-5668.2002; RA ten Hoeve J., de Jesus Ibarra-Sanchez M., Fu Y., Zhu W., Tremblay M., RA David M., Shuai K.; RT "Identification of a nuclear Stat1 protein tyrosine phosphatase."; RL Mol. Cell. Biol. 22:5662-5668(2002). RN [23] RP PHOSPHORYLATION AT SER-727. RX PubMed=11972023; DOI=10.1073/pnas.052159099; RA Nair J.S., DaFonseca C.J., Tjernberg A., Sun W., Darnell J.E. Jr., RA Chait B.T., Zhang J.J.; RT "Requirement of Ca2+ and CaMKII for Stat1 Ser-727 phosphorylation in RT response to IFN-gamma."; RL Proc. Natl. Acad. Sci. U.S.A. 99:5971-5976(2002). RN [24] RP SUMOYLATION AT LYS-703, FUNCTION, AND MUTAGENESIS OF LYS-703. RX PubMed=12855578; DOI=10.1182/blood-2002-12-3816; RA Ungureanu D., Vanhatupa S., Kotaja N., Yang J., Aittomaeki S., Jaenne O.A., RA Palvimo J.J., Silvennoinen O.; RT "PIAS proteins promote SUMO-1 conjugation to STAT1."; RL Blood 102:3311-3313(2003). RN [25] RP SUMOYLATION AT LYS-703, FUNCTION, AND MUTAGENESIS OF LYS-110 AND LYS-703. RX PubMed=12764129; DOI=10.1074/jbc.m301344200; RA Rogers R.S., Horvath C.M., Matunis M.J.; RT "SUMO modification of STAT1 and its role in PIAS-mediated inhibition of RT gene activation."; RL J. Biol. Chem. 278:30091-30097(2003). RN [26] RP REVIEW ON ROLE IN KIT SIGNALING. RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6; RA Ronnstrand L.; RT "Signal transduction via the stem cell factor receptor/c-Kit."; RL Cell. Mol. Life Sci. 61:2535-2548(2004). RN [27] RP PHOSPHORYLATION AT SER-727, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF SER-727. RX PubMed=15322115; DOI=10.1074/jbc.m407448200; RA DeVries T.A., Kalkofen R.L., Matassa A.A., Reyland M.E.; RT "Protein kinase Cdelta regulates apoptosis via activation of STAT1."; RL J. Biol. Chem. 279:45603-45612(2004). RN [28] RP INTERACTION WITH NIPAH V AND W PROTEINS (MICROBIAL INFECTION). RX PubMed=15140960; DOI=10.1128/jvi.78.11.5633-5641.2004; RA Shaw M.L., Garcia-Sastre A., Palese P., Basler C.F.; RT "Nipah virus V and W proteins have a common STAT1-binding domain yet RT inhibit STAT1 activation from the cytoplasmic and nuclear compartments, RT respectively."; RL J. Virol. 78:5633-5641(2004). RN [29] RP ISGYLATION. RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132; RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.; RT "Proteomic identification of proteins conjugated to ISG15 in mouse and RT human cells."; RL Biochem. Biophys. Res. Commun. 336:496-506(2005). RN [30] RP INTERACTION WITH HEPATITIS C VIRUS CORE PROTEIN (MICROBIAL INFECTION). RX PubMed=15825084; DOI=10.1053/j.gastro.2005.02.006; RA Lin W., Choe W.H., Hiasa Y., Kamegaya Y., Blackard J.T., Schmidt E.V., RA Chung R.T.; RT "Hepatitis C virus expression suppresses interferon signaling by degrading RT STAT1."; RL Gastroenterology 128:1034-1041(2005). RN [31] RP FUNCTION, INTERACTION WITH EP300, PHOSPHORYLATION AT SER-727, AND RP MUTAGENESIS OF LEU-724. RX PubMed=16257975; DOI=10.1074/jbc.m505797200; RA Sun W., Xu W., Snyder M., He W., Ho H., Ivashkiv L.B., Zhang J.J.; RT "The conserved Leu-724 residue is required for both serine phosphorylation RT and co-activator recruitment for Stat1-mediated transcription activation in RT response to interferon-gamma."; RL J. Biol. Chem. 280:41844-41851(2005). RN [32] RP PHOSPHORYLATION AT SER-727. RX PubMed=16799645; DOI=10.1038/sj.onc.1209742; RA Timofeeva O.A., Plisov S., Evseev A.A., Peng S., Jose-Kampfner M., RA Lovvorn H.N., Dome J.S., Perantoni A.O.; RT "Serine-phosphorylated STAT1 is a prosurvival factor in Wilms' tumor RT pathogenesis."; RL Oncogene 25:7555-7564(2006). RN [33] RP PHOSPHORYLATION IN RESPONSE TO ACTIVATED FGFR3, AND PHOSPHORYLATION AT RP TYR-701. RX PubMed=17561467; DOI=10.1016/j.bone.2006.11.030; RA Harada D., Yamanaka Y., Ueda K., Nishimura R., Morishima T., Seino Y., RA Tanaka H.; RT "Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic RT dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via RT PLCgamma-activated STAT1."; RL Bone 41:273-281(2007). RN [34] RP PHOSPHORYLATION IN RESPONSE TO ACTIVATED FGFR1; FGFR2; FGFR3 AND FGFR4. RX PubMed=17311277; DOI=10.1002/jcp.21014; RA Citores L., Bai L., Sorensen V., Olsnes S.; RT "Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the RT Golgi apparatus without translocation to the nucleus."; RL J. Cell. Physiol. 212:148-156(2007). RN [35] RP PHOSPHORYLATION AT SER-727, INTERACTION WITH PIAS1, SUMOYLATION, AND RP MUTAGENESIS OF TYR-701 AND SER-727. RX PubMed=17897103; DOI=10.1042/bj20070620; RA Vanhatupa S., Ungureanu D., Paakkunainen M., Silvennoinen O.; RT "MAPK-induced Ser727 phosphorylation promotes SUMOylation of STAT1."; RL Biochem. J. 409:179-185(2008). RN [36] RP INTERACTION WITH ERBB4. RX PubMed=18721752; DOI=10.1016/j.chembiol.2008.07.006; RA Kaushansky A., Gordus A., Budnik B.A., Lane W.S., Rush J., MacBeath G.; RT "System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation RT that are unusually selective in their recruitment properties."; RL Chem. Biol. 15:808-817(2008). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [38] RP FUNCTION, AND PHOSPHORYLATION AT TYR-701 IN RESPONSE TO CONSTITUTIVELY RP ACTIVATED FGFR3. RX PubMed=19088846; DOI=10.1371/journal.pone.0003961; RA Krejci P., Salazar L., Kashiwada T.A., Chlebova K., Salasova A., RA Thompson L.M., Bryja V., Kozubik A., Wilcox W.R.; RT "Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal RT dysplasia undermines dominant role of STAT1 in FGFR3 signaling in RT cartilage."; RL PLoS ONE 3:E3961-E3961(2008). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [40] RP RETRACTED PAPER. RX PubMed=19136629; DOI=10.1101/gad.489409; RA Weber S., Maass F., Schuemann M., Krause E., Suske G., Bauer U.M.; RT "PRMT1-mediated arginine methylation of PIAS1 regulates STAT1 signaling."; RL Genes Dev. 23:118-132(2009). RN [41] RP RETRACTION NOTICE OF PUBMED:19136629. RX PubMed=21724836; RA Weber S., Maass F., Schuemann M., Krause E., Suske G., Bauer U.M.; RT "Retraction. PRMT1-mediated arginine methylation of PIAS1 regulates STAT1 RT signaling."; RL Genes Dev. 25:1451-1451(2011). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, 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 [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [44] 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 [45] RP PHOSPHORYLATION AT TYR-701 IN RESPONSE TO KIT SIGNALING, AND RP PHOSPHORYLATION AT SER-727. RX PubMed=21135090; DOI=10.1074/jbc.m110.182642; RA Chaix A., Lopez S., Voisset E., Gros L., Dubreuil P., De Sepulveda P.; RT "Mechanisms of STAT protein activation by oncogenic KIT mutants in RT neoplastic mast cells."; RL J. Biol. Chem. 286:5956-5966(2011). RN [46] RP PHOSPHORYLATION AT TYR-701; SER-708 AND SER-727, AND MUTAGENESIS OF RP TYR-701; SER-708 AND SER-727. RX PubMed=22065572; DOI=10.1074/jbc.m111.285205; RA Perwitasari O., Cho H., Diamond M.S., Gale M. Jr.; RT "Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 RT proteins define novel innate immune effector pathway against West Nile RT virus infection."; RL J. Biol. Chem. 286:44412-44423(2011). RN [47] RP INTERACTION WITH EBOLAVIRUS PROTEIN VP24 (MICROBIAL INFECTION). RX PubMed=22383882; DOI=10.1371/journal.ppat.1002550; RA Zhang A.P., Bornholdt Z.A., Liu T., Abelson D.M., Lee D.E., Li S., RA Woods V.L. Jr., Saphire E.O.; RT "The ebola virus interferon antagonist VP24 directly binds STAT1 and has a RT novel, pyramidal fold."; RL PLoS Pathog. 8:E1002550-E1002550(2012). RN [48] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [49] RP FUNCTION, AND DEUBIQUITINATION BY USP13. RX PubMed=23940278; DOI=10.4049/jimmunol.1300225; RA Yeh H.M., Yu C.Y., Yang H.C., Ko S.H., Liao C.L., Lin Y.L.; RT "Ubiquitin-specific protease 13 regulates IFN signaling by stabilizing RT STAT1."; RL J. Immunol. 191:3328-3336(2013). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-727, 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 [51] 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 [52] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-703, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [53] RP FUNCTION, INTERACTION WITH PARP9; DTX3L AND EP300, IDENTIFICATION IN A RP COMPLEX WITH PARP9 AND DTX3L, SUBCELLULAR LOCATION, PHOSPHORYLATION AT RP TYR-701 AND SER-727, AND MUTAGENESIS OF 656-ALA--ASN-658 AND TYR-701. RX PubMed=26479788; DOI=10.1038/ni.3279; RA Zhang Y., Mao D., Roswit W.T., Jin X., Patel A.C., Patel D.A., Agapov E., RA Wang Z., Tidwell R.M., Atkinson J.J., Huang G., McCarthy R., Yu J., RA Yun N.E., Paessler S., Lawson T.G., Omattage N.S., Brett T.J., RA Holtzman M.J.; RT "PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C RT protease to enhance interferon signaling and control viral infection."; RL Nat. Immunol. 16:1215-1227(2015). RN [54] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-701, ADP-RIBOSYLATION AT RP GLU-657 AND GLU-705, AND MUTAGENESIS OF GLU-657 AND GLU-705. RX PubMed=27796300; DOI=10.1038/ncomms12849; RA Iwata H., Goettsch C., Sharma A., Ricchiuto P., Goh W.W., Halu A., RA Yamada I., Yoshida H., Hara T., Wei M., Inoue N., Fukuda D., Mojcher A., RA Mattson P.C., Barabasi A.L., Boothby M., Aikawa E., Singh S.A., Aikawa M.; RT "PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP- RT ribosylation."; RL Nat. Commun. 7:12849-12849(2016). RN [55] RP METHYLATION AT LYS-114; LYS-175; LYS-296; LYS-366; LYS-525; LYS-637 AND RP LYS-665, PHOSPHORYLATION AT TYR-701, FUNCTION, SUBCELLULAR LOCATION, RP SUBUNIT, AND MUTAGENESIS OF LYS-114; LYS-175; LYS-296; LYS-366; LYS-525; RP 636-LYS-LYS-637 AND LYS-665. RX PubMed=28753426; DOI=10.1016/j.cell.2017.06.042; RA Chen K., Liu J., Liu S., Xia M., Zhang X., Han D., Jiang Y., Wang C., RA Cao X.; RT "Methyltransferase SETD2-mediated methylation of STAT1 is critical for RT interferon antiviral activity."; RL Cell 170:492-506(2017). RN [56] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-703, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [57] RP COMMENT ON ADP-RIBOSYLATION. RX PubMed=29858569; DOI=10.1038/s41467-018-04522-z; RA Begitt A., Cavey J., Droescher M., Vinkemeier U.; RT "On the role of STAT1 and STAT6 ADP-ribosylation in the regulation of RT macrophage activation."; RL Nat. Commun. 9:2144-2144(2018). RN [58] 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 [59] RP INTERACTION WITH MEASLES VIRUS V PROTEIN (MICROBIAL INFECTION). RX PubMed=32581091; DOI=10.1128/jvi.01169-20; RA Nagano Y., Sugiyama A., Kimoto M., Wakahara T., Noguchi Y., Jiang X., RA Saijo S., Shimizu N., Yabuno N., Yao M., Gooley P.R., Moseley G.W., RA Tadokoro T., Maenaka K., Ose T.; RT "The Measles Virus V Protein Binding Site to STAT2 Overlaps That of IRF9."; RL J. Virol. 94:0-0(2020). RN [60] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-749, AND MUTAGENESIS RP OF TYR-701; THR-704; SER-708; SER-710; SER-715; THR-719; THR-720; SER-727; RP SER-735; SER-740; SER-745 AND THR-749. RX PubMed=32209697; DOI=10.1126/scisignal.aay0574; RA Metwally H., Tanaka T., Li S., Parajuli G., Kang S., Hanieh H., RA Hashimoto S., Chalise J.P., Gemechu Y., Standley D.M., Kishimoto T.; RT "Noncanonical STAT1 phosphorylation expands its transcriptional activity RT into promoting LPS-induced IL-6 and IL-12p40 production."; RL Sci. Signal. 13:0-0(2020). RN [61] RP FUNCTION, AND INTERACTION WITH STAT4. RX PubMed=34508746; DOI=10.1016/j.yexcr.2021.112784; RA Li M., Liu Y., Fu Y., Gong R., Xia H., Huang X., Wu Y.; RT "Interleukin-35 inhibits lipopolysaccharide-induced endothelial cell RT activation by downregulating inflammation and apoptosis."; RL Exp. Cell Res. 407:112784-112784(2021). RN [62] 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 [63] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=35568036; DOI=10.1016/j.cell.2022.04.028; RA Alphonse N., Wanford J.J., Voak A.A., Gay J., Venkhaya S., Burroughs O., RA Mathew S., Lee T., Evans S.L., Zhao W., Frowde K., Alrehaili A., RA Dickenson R.E., Munk M., Panina S., Mahmood I.F., Llorian M., RA Stanifer M.L., Boulant S., Berchtold M.W., Bergeron J.R.C., Wack A., RA Lesser C.F., Odendall C.; RT "A family of conserved bacterial virulence factors dampens interferon RT responses by blocking calcium signaling."; RL Cell 185:2354-2369(2022). RN [64] RP PHOSPHORYLATION AT TYR-701; SER-727 AND THR-749, AND MUTAGENESIS OF RP THR-749. RX PubMed=38621137; DOI=10.1073/pnas.2402226121; RA Metwally H., Elbrashy M.M., Ozawa T., Okuyama K., White J.T., Tulyeu J., RA Soendergaard J.N., Wing J.B., Muratsu A., Matsumoto H., Ikawa M., Kishi H., RA Taniuchi I., Kishimoto T.; RT "Threonine phosphorylation of STAT1 restricts interferon signaling and RT promotes innate inflammatory responses."; RL Proc. Natl. Acad. Sci. U.S.A. 121:e2402226121-e2402226121(2024). RN [65] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 136-710, AND COILED-COIL. RX PubMed=9630226; DOI=10.1016/s0092-8674(00)81443-9; RA Chen X., Vinkemeier U., Zhao Y., Jeruzalmi D., Darnell J.E. Jr., RA Kuriyan J.; RT "Crystal structure of a tyrosine phosphorylated STAT-1 dimer bound to RT DNA."; RL Cell 93:827-839(1998). RN [66] RP VARIANT IMD31A SER-706. RX PubMed=11452125; DOI=10.1126/science.1061154; RA Dupuis S., Dargemont C., Fieschi C., Thomassin N., Rosenzweig S., RA Harris J., Holland S.M., Schreiber R.D., Casanova J.-L.; RT "Impairment of mycobacterial but not viral immunity by a germline human RT STAT1 mutation."; RL Science 293:300-303(2001). RN [67] RP VARIANT IMD31B PRO-600. RX PubMed=12590259; DOI=10.1038/ng1097; RA Dupuis S., Jouanguy E., Al-Hajjar S., Fieschi C., Al-Mohsen I.Z., RA Al-Jumaah S., Yang K., Chapgier A., Eidenschenk C., Eid P., Al-Ghonaium A., RA Tufenkeji H., Frayha H., Al-Gazlan S., Al-Rayes H., Schreiber R.D., RA Gresser I., Casanova J.L.; RT "Impaired response to interferon-alpha/beta and lethal viral disease in RT human STAT1 deficiency."; RL Nat. Genet. 33:388-391(2003). RN [68] RP VARIANTS IMD31A GLN-320 AND HIS-463, AND CHARACTERIZATION OF VARIANTS RP GLN-320; HIS-463 AND SER-706. RX PubMed=16934001; DOI=10.1371/journal.pgen.0020131; RA Chapgier A., Boisson-Dupuis S., Jouanguy E., Vogt G., Feinberg J., RA Prochnicka-Chalufour A., Casrouge A., Yang K., Soudais C., Fieschi C., RA Santos O.F., Bustamante J., Picard C., de Beaucoudrey L., Emile J.F., RA Arkwright P.D., Schreiber R.D., Rolinck-Werninghaus C., Rosen-Wolff A., RA Magdorf K., Roesler J., Casanova J.L.; RT "Novel STAT1 alleles in otherwise healthy patients with mycobacterial RT disease."; RL PLoS Genet. 2:E131-E131(2006). RN [69] RP VARIANT [LARGE SCALE ANALYSIS] ALA-491. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [70] RP INTERACTION WITH HOST STAT1 (MICROBIAL INFECTION). RX PubMed=17686504; DOI=10.1016/j.virol.2007.06.037; RG Infectious Mapping Project I-MAP; RA Caignard G., Guerbois M., Labernardiere J.L., Jacob Y., Jones L.M., RA Wild F., Tangy F., Vidalain P.O.; RT "Measles virus V protein blocks Jak1-mediated phosphorylation of STAT1 to RT escape IFN-alpha/beta signaling."; RL Virology 368:351-362(2007). RN [71] RP VARIANT IMD31B ASN-201, AND CHARACTERIZATION OF VARIANT IMD31B ASN-201. RX PubMed=20841510; DOI=10.1182/blood-2010-04-280586; RA Kong X.F., Ciancanelli M., Al-Hajjar S., Alsina L., Zumwalt T., RA Bustamante J., Feinberg J., Audry M., Prando C., Bryant V., Kreins A., RA Bogunovic D., Halwani R., Zhang X.X., Abel L., Chaussabel D., Al-Muhsen S., RA Casanova J.L., Boisson-Dupuis S.; RT "A novel form of human STAT1 deficiency impairing early but not late RT responses to interferons."; RL Blood 116:5895-5906(2010). RN [72] RP VARIANTS IMD31C GLY-165; HIS-165; ASN-170; ARG-174; ILE-202; VAL-202; RP VAL-267; PRO-271; GLN-274; TRP-274; ILE-286 AND ALA-288, AND RP CHARACTERIZATION OF VARIANTS IMD31C GLY-165 AND GLN-274. RX PubMed=21727188; DOI=10.1084/jem.20110958; RA Liu L., Okada S., Kong X.F., Kreins A.Y., Cypowyj S., Abhyankar A., RA Toubiana J., Itan Y., Audry M., Nitschke P., Masson C., Toth B., Flatot J., RA Migaud M., Chrabieh M., Kochetkov T., Bolze A., Borghesi A., Toulon A., RA Hiller J., Eyerich S., Eyerich K., Gulacsy V., Chernyshova L., RA Chernyshov V., Bondarenko A., Maria Cortes Grimaldo R., Blancas-Galicia L., RA Madrigal Beas I.M., Roesler J., Magdorf K., Engelhard D., Thumerelle C., RA Burgel P.R., Hoernes M., Drexel B., Seger R., Kusuma T., Jansson A.F., RA Sawalle-Belohradsky J., Belohradsky B., Jouanguy E., Bustamante J., Bue M., RA Karin N., Wildbaum G., Bodemer C., Lortholary O., Fischer A., Blanche S., RA Al-Muhsen S., Reichenbach J., Kobayashi M., Rosales F.E., Lozano C.T., RA Kilic S.S., Oleastro M., Etzioni A., Traidl-Hoffmann C., Renner E.D., RA Abel L., Picard C., Marodi L., Boisson-Dupuis S., Puel A., Casanova J.L.; RT "Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie RT chronic mucocutaneous candidiasis."; RL J. Exp. Med. 208:1635-1648(2011). RN [73] RP VARIANTS IMD31C VAL-267 AND TRP-274. RX PubMed=21714643; DOI=10.1056/nejmoa1100102; RA van de Veerdonk F.L., Plantinga T.S., Hoischen A., Smeekens S.P., RA Joosten L.A., Gilissen C., Arts P., Rosentul D.C., Carmichael A.J., RA Smits-van der Graaf C.A., Kullberg B.J., van der Meer J.W., Lilic D., RA Veltman J.A., Netea M.G.; RT "STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis."; RL N. Engl. J. Med. 365:54-61(2011). RN [74] RP VARIANTS IMD31A GLU-637 AND ARG-673, AND CHARACTERIZATION OF VARIANTS RP IMD31A GLU-637 AND ARG-673. RX PubMed=22573496; DOI=10.1002/humu.22113; RA Tsumura M., Okada S., Sakai H., Yasunaga S., Ohtsubo M., Murata T., RA Obata H., Yasumi T., Kong X.F., Abhyankar A., Heike T., Nakahata T., RA Nishikomori R., Al-Muhsen S., Boisson-Dupuis S., Casanova J.L., RA Alzahrani M., Shehri M.A., Elghazali G., Takihara Y., Kobayashi M.; RT "Dominant-negative STAT1 SH2 domain mutations in unrelated patients with RT Mendelian susceptibility to mycobacterial disease."; RL Hum. Mutat. 33:1377-1387(2012). RN [75] RP VARIANTS IMD31C GLY-165; LYS-179; GLN-274; TRP-274; ARG-285 AND MET-385, RP CHARACTERIZATION OF VARIANTS IMD31C LYS-179; GLN-274; TRP-274; ARG-285 AND RP MET-385, AND CHARACTERIZATION OF VARIANT IMD31B CYS-701. RX PubMed=23709754; DOI=10.1136/jmedgenet-2013-101570; RA Soltesz B., Toth B., Shabashova N., Bondarenko A., Okada S., Cypowyj S., RA Abhyankar A., Csorba G., Tasko S., Sarkadi A.K., Mehes L., Rozsival P., RA Neumann D., Chernyshova L., Tulassay Z., Puel A., Casanova J.L., Sediva A., RA Litzman J., Marodi L.; RT "New and recurrent gain-of-function STAT1 mutations in patients with RT chronic mucocutaneous candidiasis from Eastern and Central Europe."; RL J. Med. Genet. 50:567-578(2013). RN [76] RP VARIANTS IMD31C GLU-278 AND ASP-384, AND CHARACTERIZATION OF VARIANTS RP IMD31C GLU-278; ASP-384 AND MET-385. RX PubMed=25288569; DOI=10.4049/jimmunol.1401467; RA Yamazaki Y., Yamada M., Kawai T., Morio T., Onodera M., Ueki M., RA Watanabe N., Takada H., Takezaki S., Chida N., Kobayashi I., Ariga T.; RT "Two novel gain-of-function mutations of STAT1 responsible for chronic RT mucocutaneous candidiasis disease: impaired production of IL-17A and IL-22, RT and the presence of anti-IL-17F autoantibody."; RL J. Immunol. 193:4880-4887(2014). RN [77] RP VARIANT IMD31C ASN-298, AND CHARACTERIZATION OF VARIANT IMD31C ASN-298. RX PubMed=26514428; DOI=10.1016/j.molimm.2015.09.014; RA Martinez-Martinez L., Martinez-Saavedra M.T., Fuentes-Prior P., RA Barnadas M., Rubiales M.V., Noda J., Badell I., Rodriguez-Gallego C., RA Calle-Martin O.L.; RT "A novel gain-of-function STAT1 mutation resulting in basal phosphorylation RT of STAT1 and increased distal IFN-gamma-mediated responses in chronic RT mucocutaneous candidiasis."; RL Mol. Immunol. 68:597-605(2015). CC -!- FUNCTION: Signal transducer and transcription activator that mediates CC cellular responses to interferons (IFNs), cytokine KITLG/SCF and other CC cytokines and other growth factors (PubMed:12764129, PubMed:12855578, CC PubMed:15322115, PubMed:23940278, PubMed:34508746, PubMed:35568036, CC PubMed:9724754). Following type I IFN (IFN-alpha and IFN-beta) binding CC to cell surface receptors, signaling via protein kinases leads to CC activation of Jak kinases (TYK2 and JAK1) and to tyrosine CC phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize CC and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 CC transcription factor, that enters the nucleus (PubMed:28753426, CC PubMed:35568036). ISGF3 binds to the IFN stimulated response element CC (ISRE) to activate the transcription of IFN-stimulated genes (ISG), CC which drive the cell in an antiviral state (PubMed:28753426, CC PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is CC tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a CC homodimer termed IFN-gamma-activated factor (GAF), migrates into the CC nucleus and binds to the IFN gamma activated sequence (GAS) to drive CC the expression of the target genes, inducing a cellular antiviral state CC (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT CC signaling (PubMed:15526160). May mediate cellular responses to CC activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Following CC bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, CC phosphorylated at Thr-749 by IKBKB which promotes binding of STAT1 to CC the 5'-TTTGAGGC-3' sequence in the ARID5A promoter, resulting in CC transcriptional activation of ARID5A and subsequent ARID5A-mediated CC stabilization of IL6 (PubMed:32209697). Phosphorylation at Thr-749 also CC promotes binding of STAT1 to the 5'-TTTGAGTC-3' sequence in the IL12B CC promoter and activation of IL12B transcription (PubMed:32209697). CC Involved in food tolerance in small intestine: associates with the CC Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes CC transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in CC upper small intestine (By similarity). {ECO:0000250|UniProtKB:P42225, CC ECO:0000269|PubMed:12764129, ECO:0000269|PubMed:12855578, CC ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:19088846, CC ECO:0000269|PubMed:23940278, ECO:0000269|PubMed:26479788, CC ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, CC ECO:0000269|PubMed:34508746, ECO:0000269|PubMed:35568036, CC ECO:0000269|PubMed:8156998, ECO:0000269|PubMed:9724754, CC ECO:0000303|PubMed:15526160}. CC -!- SUBUNIT: Isoform alpha homodimerizes upon IFN-gamma induced CC phosphorylation (PubMed:28753426, PubMed:8605877). Heterodimer with CC STAT2 upon IFN-alpha/beta induced phosphorylation (PubMed:8605877). The CC heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 CC complex (ISGF3) with IRF9 (By similarity). Interacts (phosphorylated at CC Ser-727) with PIAS1; the interaction results in release of STAT1 from CC its target gene (PubMed:17897103, PubMed:9724754). Interacts with CC IFNAR1; the interaction requires the phosphorylation of IFNAR1 at 'Tyr- CC 466' (PubMed:9121453). Interacts with IFNAR2 (PubMed:9121453). Found in CC a complex with NMI and CREBBP/CBP (PubMed:9989503). Interacts with NMI CC which is required for CREBBP/CBP recruitment to the complex CC (PubMed:9989503). Interacts with PTK2/FAK1 (PubMed:11278462). Interacts CC with SRC (By similarity). Interacts with ERBB4 (phosphorylated) CC (PubMed:18721752). Interacts with PARP9 and DTX3L independently of IFN- CC beta or IFN-gamma-mediated STAT1 'Tyr-701' phosphorylation CC (PubMed:26479788). Interacts with histone acetyltransferase EP300/p300 CC in response to INF-gamma stimulation (PubMed:16257975, CC PubMed:26479788). Independently of its phosphorylation status, CC interacts with OTOP1 (By similarity). Interacts with IFNGR1 CC (PubMed:8156998). Interacts with STAT4 (PubMed:34508746). CC {ECO:0000250|UniProtKB:P42225, ECO:0000269|PubMed:11278462, CC ECO:0000269|PubMed:16257975, ECO:0000269|PubMed:17897103, CC ECO:0000269|PubMed:18721752, ECO:0000269|PubMed:26479788, CC ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:34508746, CC ECO:0000269|PubMed:8156998, ECO:0000269|PubMed:8605877, CC ECO:0000269|PubMed:9121453, ECO:0000269|PubMed:9724754, CC ECO:0000269|PubMed:9989503}. CC -!- SUBUNIT: (Microbial infection) Interacts with Sendai virus C', C, Y1 CC and Y2 proteins, preventing activation of ISRE and GAS promoter. CC {ECO:0000269|PubMed:11442634}. CC -!- SUBUNIT: (Microbial infection) Interacts with Nipah virus P, V and W CC proteins preventing activation of ISRE and GAS promoter. CC {ECO:0000269|PubMed:15140960}. CC -!- SUBUNIT: (Microbial infection) Interacts with Rabies virus CC phosphoprotein preventing activation of ISRE and GAS promoter. CC {ECO:0000269|PubMed:11442634, ECO:0000269|PubMed:15140960}. CC -!- SUBUNIT: (Microbial infection) Interacts with HCV core protein; the CC interaction results in STAT1 degradation. CC {ECO:0000269|PubMed:15825084}. CC -!- SUBUNIT: (Microbial infection) Interacts with ebolavirus protein VP24. CC {ECO:0000269|PubMed:22383882}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus (EBV) CC tegument protein BGLF2; this interaction leads to STAT1 CC dephosphorylation and inhibition. {ECO:0000269|PubMed:34319780}. CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with measles CC V protein; this interaction inhibits STAT1 phosphorylation by Jak1 and CC thereby the type I interferon signaling pathway. CC {ECO:0000269|PubMed:17686504, ECO:0000269|PubMed:32581091}. CC -!- INTERACTION: CC P42224; Q16531: DDB1; NbExp=2; IntAct=EBI-1057697, EBI-350322; CC P42224; Q01094: E2F1; NbExp=2; IntAct=EBI-1057697, EBI-448924; CC P42224; P00533: EGFR; NbExp=7; IntAct=EBI-1057697, EBI-297353; CC P42224; Q8N9N8: EIF1AD; NbExp=4; IntAct=EBI-1057697, EBI-750700; CC P42224; P04626: ERBB2; NbExp=3; IntAct=EBI-1057697, EBI-641062; CC P42224; P01100: FOS; NbExp=6; IntAct=EBI-1057697, EBI-852851; CC P42224; P17181: IFNAR1; NbExp=2; IntAct=EBI-1057697, EBI-1547250; CC P42224; P48551: IFNAR2; NbExp=2; IntAct=EBI-1057697, EBI-958408; CC P42224; P15260: IFNGR1; NbExp=4; IntAct=EBI-1057697, EBI-1030755; CC P42224; P23458: JAK1; NbExp=6; IntAct=EBI-1057697, EBI-1383438; CC P42224; P52294: KPNA1; NbExp=4; IntAct=EBI-1057697, EBI-358383; CC P42224; Q7Z434: MAVS; NbExp=3; IntAct=EBI-1057697, EBI-995373; CC P42224; Q01804: OTUD4; NbExp=3; IntAct=EBI-1057697, EBI-1054396; CC P42224; Q05397: PTK2; NbExp=3; IntAct=EBI-1057697, EBI-702142; CC P42224; O95786: RIGI; NbExp=4; IntAct=EBI-1057697, EBI-995350; CC P42224; P19793: RXRA; NbExp=2; IntAct=EBI-1057697, EBI-78598; CC P42224; P42224: STAT1; NbExp=4; IntAct=EBI-1057697, EBI-1057697; CC P42224; P52630: STAT2; NbExp=19; IntAct=EBI-1057697, EBI-1546963; CC P42224; P40763: STAT3; NbExp=10; IntAct=EBI-1057697, EBI-518675; CC P42224; P0DTC9: N; Xeno; NbExp=6; IntAct=EBI-1057697, EBI-25475856; CC P42224; P07239: OPG106; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-7789600; CC P42224; P0DTC2: S; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-25474821; CC P42224; Q4VW77: UL47; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-11499224; CC P42224; P03255-1; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-6692439; CC P42224; P03255-2; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-6859460; CC P42224; P26664; Xeno; NbExp=5; IntAct=EBI-1057697, EBI-6941357; CC P42224; PRO_0000037566 [P27958]; Xeno; NbExp=2; IntAct=EBI-1057697, EBI-6377335; CC P42224; PRO_0000037576 [P27958]; Xeno; NbExp=4; IntAct=EBI-1057697, EBI-8753518; CC P42224-1; Q9Y4C1: KDM3A; NbExp=8; IntAct=EBI-15711971, EBI-2515339; CC P42224-1; P42224-1: STAT1; NbExp=3; IntAct=EBI-15711971, EBI-15711971; CC P42224-1; P06498; Xeno; NbExp=2; IntAct=EBI-15711971, EBI-16085959; CC P42224-2; P42224-2: STAT1; NbExp=4; IntAct=EBI-15712015, EBI-15712015; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15322115, CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:27796300, CC ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697}. Nucleus CC {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:26479788, CC ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697}. CC Note=Translocated into the nucleus upon tyrosine phosphorylation and CC dimerization, in response to IFN-gamma and signaling by activated CC FGFR1, FGFR2, FGFR3 or FGFR4 (PubMed:15322115). Monomethylation at Lys- CC 525 is required for phosphorylation at Tyr-701 and translocation into CC the nucleus (PubMed:28753426). Translocates into the nucleus in CC response to interferon-beta stimulation (PubMed:26479788). CC {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:26479788, CC ECO:0000269|PubMed:28753426}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Alpha; Synonyms=p91; CC IsoId=P42224-1; Sequence=Displayed; CC Name=Beta; Synonyms=p84; CC IsoId=P42224-2; Sequence=VSP_006282; CC -!- PTM: Deubiquitinated by USP13; leading to STAT1 stabilization and CC positive regulation of type I and type II IFN signalings. CC {ECO:0000269|PubMed:23940278}. CC -!- PTM: Phosphorylated on tyrosine and serine residues in response to a CC variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, CC PDGF and EGF (PubMed:26479788, PubMed:28753426). Activated KIT promotes CC phosphorylation on tyrosine residues and subsequent translocation to CC the nucleus (PubMed:21135090). Upon EGF stimulation, phosphorylation on CC Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes CC dimerization and subsequent translocation to the nucleus CC (PubMed:28753426, PubMed:7657660). Growth hormone (GH) activates STAT1 CC signaling only via JAK2 (PubMed:7657660). Tyrosine phosphorylated in CC response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 CC (PubMed:17561467, PubMed:19088846). Phosphorylation on Ser-727 by CC several kinases including MAPK14, ERK1/2, CAMK2/CAMKII and CK2 in CC response to IFN-gamma stimulation, is required for maximal CC transcriptional activity (PubMed:15322115, PubMed:16799645, CC PubMed:17897103, PubMed:7543024). Phosphorylated on Ser-727 by CC CAMK2/CAMKII in response to IFN-gamma stimulation and calcium CC mobilization, promoting activity (PubMed:11972023, PubMed:16257975). CC Phosphorylated by CAMK2/CAMKII in response to IFN-beta stimulation and CC calcium mobilization in epithelial cells, promoting activity CC (PubMed:35568036). Phosphorylation on Ser-727 promotes sumoylation CC though increasing interaction with PIAS (PubMed:17897103). CC Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to CC DNA-damaging agents (PubMed:15322115). Phosphorylated on tyrosine CC residues when PTK2/FAK1 is activated; most likely this is catalyzed by CC a SRC family kinase (PubMed:11278462). Dephosphorylation on tyrosine CC residues by PTPN2 negatively regulates interferon-mediated signaling CC (PubMed:12138178). Upon viral infection or IFN induction, CC phosphorylation on Ser-708 occurs much later than phosphorylation on CC Tyr-701 and is required for the binding of ISGF3 on the ISREs of a CC subset of IFN-stimulated genes IKBKE-dependent (PubMed:22065572). CC Phosphorylation at Tyr-701 and Ser-708 are mutually exclusive, CC phosphorylation at Ser-708 requires previous dephosphorylation of Tyr- CC 701 (PubMed:22065572). Phosphorylation at Thr-749 by IKBKB/IKKB CC promotes transcriptional activation of ARID5A and IL12B by STAT1 CC (PubMed:32209697). Phosphorylation at Thr-749 restricts interferon CC signaling and anti-inflammatory responses and promotes innate CC inflammatory responses (By similarity). {ECO:0000250|UniProtKB:P42225, CC ECO:0000269|PubMed:11278462, ECO:0000269|PubMed:11972023, CC ECO:0000269|PubMed:12138178, ECO:0000269|PubMed:15322115, CC ECO:0000269|PubMed:16257975, ECO:0000269|PubMed:16799645, CC ECO:0000269|PubMed:17561467, ECO:0000269|PubMed:17897103, CC ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:21135090, CC ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:26479788, CC ECO:0000269|PubMed:28753426, ECO:0000269|PubMed:32209697, CC ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:7543024, CC ECO:0000269|PubMed:7657660}. CC -!- PTM: Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by CC IFN-gamma-induced phosphorylation on Ser-727, and by interaction with CC PIAS proteins. Enhances the transactivation activity. CC {ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:17897103, CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:22065572, CC ECO:0000269|PubMed:7543024}. CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}. CC -!- PTM: Mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14; ADP- CC ribosylation prevents phosphorylation at Tyr-701 (PubMed:27796300). CC However, the role of ADP-ribosylation in the prevention of CC phosphorylation has been called into question and the lack of CC phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569). CC {ECO:0000269|PubMed:27796300, ECO:0000305|PubMed:29858569}. CC -!- PTM: Monomethylated at Lys-525 by SETD2; monomethylation is necessary CC for phosphorylation at Tyr-701, translocation into the nucleus and CC activation of the antiviral defense. {ECO:0000269|PubMed:28753426}. CC -!- PTM: (Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 CC ubiquitin ligase ICP22. {ECO:0000269|PubMed:32699158}. CC -!- DISEASE: Immunodeficiency 31B (IMD31B) [MIM:613796]: A disorder CC characterized by susceptibility to severe mycobacterial and viral CC infections. Affected individuals can develop disseminated infections CC and die of viral illness. {ECO:0000269|PubMed:12590259, CC ECO:0000269|PubMed:20841510, ECO:0000269|PubMed:23709754}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Immunodeficiency 31A (IMD31A) [MIM:614892]: A form of CC Mendelian susceptibility to mycobacterial disease, a rare condition CC caused by impairment of interferon-gamma mediated immunity. It is CC characterized by predisposition to illness caused by moderately CC virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) CC vaccine, environmental non-tuberculous mycobacteria, and by the more CC virulent Mycobacterium tuberculosis. Other microorganisms rarely cause CC severe clinical disease in individuals with susceptibility to CC mycobacterial infections, with the exception of Salmonella which CC infects less than 50% of these individuals. Clinical outcome severity CC depends on the degree of impairment of interferon-gamma mediated CC immunity. Some patients die of overwhelming mycobacterial disease with CC lepromatous-like lesions in early childhood, whereas others develop, CC later in life, disseminated but curable infections with tuberculoid CC granulomas. IMD31A has low penetrance, and affected individuals have CC relatively mild disease and good prognosis. IMD31A confers a CC predisposition to mycobacterial infections only, with no increased CC susceptibility to viral infections. {ECO:0000269|PubMed:11452125, CC ECO:0000269|PubMed:16934001, ECO:0000269|PubMed:22573496}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Immunodeficiency 31C (IMD31C) [MIM:614162]: A primary CC immunodeficiency disorder with altered immune responses and impaired CC clearance of fungal infections, selective against Candida. It is CC characterized by persistent and/or recurrent infections of the skin, CC nails and mucous membranes caused by organisms of the genus Candida, CC mainly Candida albicans. {ECO:0000269|PubMed:21714643, CC ECO:0000269|PubMed:21727188, ECO:0000269|PubMed:23709754, CC ECO:0000269|PubMed:25288569, ECO:0000269|PubMed:26514428}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. STAT1 mutations in patients with autosomal dominant candidiasis CC lead to defective responses of type 1 and type 17 helper T-cells, CC characterized by reduced production of interferon-alpha, interleukin- CC 17, and interleukin-22. These cytokines are crucial for the antifungal CC defense of skin and mucosa (PubMed:21714643). CC {ECO:0000269|PubMed:21714643}. CC -!- SIMILARITY: Belongs to the transcription factor STAT family. CC {ECO:0000305}. CC -!- CAUTION: Has been shown to be mono-ADP-ribosylated at Glu-657 and Glu- CC 705 by PARP14 which prevents phosphorylation at Tyr-701 CC (PubMed:27796300). However, the role of ADP-ribosylation in the CC prevention of phosphorylation has been called into question CC (PubMed:29858569). It has been suggested that the lack of CC phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569). CC {ECO:0000269|PubMed:27796300, ECO:0000305|PubMed:29858569}. CC -!- WEB RESOURCE: Name=STAT1base; Note=STAT1 mutation db; CC URL="https://databases.lovd.nl/shared/genes/STAT1"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT1 entry; CC URL="https://en.wikipedia.org/wiki/STAT1"; 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; M97935; AAB64012.1; -; mRNA. DR EMBL; M97936; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; GU211347; ADA59516.1; -; mRNA. DR EMBL; AY865620; AAW56072.1; -; Genomic_DNA. DR EMBL; AK292604; BAF85293.1; -; mRNA. DR EMBL; AK315002; BAG37497.1; -; mRNA. DR EMBL; CR749636; CAH18430.1; -; mRNA. DR EMBL; BT007241; AAP35905.1; -; mRNA. DR EMBL; AC067945; AAY24183.1; -; Genomic_DNA. DR EMBL; CH471058; EAX10850.1; -; Genomic_DNA. DR EMBL; CH471058; EAX10851.1; -; Genomic_DNA. DR EMBL; CH471058; EAX10852.1; -; Genomic_DNA. DR EMBL; CH471058; EAX10855.1; -; Genomic_DNA. DR EMBL; BC002704; AAH02704.1; -; mRNA. DR EMBL; U18662; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18663; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18664; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18665; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18666; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18667; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18668; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18669; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U18670; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS2309.1; -. [P42224-1] DR CCDS; CCDS42793.1; -. [P42224-2] DR PIR; A46159; A46159. DR RefSeq; NP_009330.1; NM_007315.4. [P42224-1] DR RefSeq; NP_644671.1; NM_139266.3. [P42224-2] DR RefSeq; XP_006712781.1; XM_006712718.2. [P42224-1] DR RefSeq; XP_054199535.1; XM_054343560.1. [P42224-1] DR PDB; 1BF5; X-ray; 2.90 A; A=136-710. DR PDB; 1YVL; X-ray; 3.00 A; A/B=1-683. DR PDB; 2KA6; NMR; -; B=710-750. DR PDB; 3WWT; X-ray; 2.00 A; A=1-126. DR PDB; 7NUF; X-ray; 2.00 A; A=132-684. DR PDB; 8D3F; X-ray; 2.97 A; A=132-713. DR PDBsum; 1BF5; -. DR PDBsum; 1YVL; -. DR PDBsum; 2KA6; -. DR PDBsum; 3WWT; -. DR PDBsum; 7NUF; -. DR PDBsum; 8D3F; -. DR AlphaFoldDB; P42224; -. DR SMR; P42224; -. DR BioGRID; 112649; 340. DR ComplexPortal; CPX-6016; ISGF3 complex. DR ComplexPortal; CPX-6041; STAT1/STAT3 complex. DR ComplexPortal; CPX-6042; STAT1/STAT4 complex. DR ComplexPortal; CPX-6048; STAT1 homodimer. DR CORUM; P42224; -. DR DIP; DIP-46140N; -. DR FunCoup; P42224; 1896. DR IntAct; P42224; 225. DR MINT; P42224; -. DR STRING; 9606.ENSP00000354394; -. DR BindingDB; P42224; -. DR ChEMBL; CHEMBL6101; -. DR DrugCentral; P42224; -. DR CarbonylDB; P42224; -. DR GlyCosmos; P42224; 2 sites, 1 glycan. DR GlyGen; P42224; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; P42224; -. DR MetOSite; P42224; -. DR PhosphoSitePlus; P42224; -. DR SwissPalm; P42224; -. DR BioMuta; STAT1; -. DR DMDM; 2507413; -. DR CPTAC; CPTAC-1272; -. DR CPTAC; CPTAC-1746; -. DR CPTAC; CPTAC-5964; -. DR jPOST; P42224; -. DR MassIVE; P42224; -. DR PaxDb; 9606-ENSP00000354394; -. DR PeptideAtlas; P42224; -. DR ProteomicsDB; 55491; -. [P42224-1] DR ProteomicsDB; 55492; -. [P42224-2] DR Pumba; P42224; -. DR ABCD; P42224; 2 sequenced antibodies. DR Antibodypedia; 688; 2426 antibodies from 54 providers. DR CPTC; P42224; 3 antibodies. DR DNASU; 6772; -. DR Ensembl; ENST00000361099.8; ENSP00000354394.4; ENSG00000115415.21. [P42224-1] DR Ensembl; ENST00000392322.7; ENSP00000376136.3; ENSG00000115415.21. [P42224-2] DR Ensembl; ENST00000392323.6; ENSP00000376137.3; ENSG00000115415.21. [P42224-2] DR Ensembl; ENST00000409465.5; ENSP00000386244.1; ENSG00000115415.21. [P42224-1] DR Ensembl; ENST00000415035.2; ENSP00000388240.2; ENSG00000115415.21. [P42224-1] DR Ensembl; ENST00000540176.6; ENSP00000438703.2; ENSG00000115415.21. [P42224-1] DR Ensembl; ENST00000673841.1; ENSP00000501225.1; ENSG00000115415.21. [P42224-2] DR Ensembl; ENST00000674080.1; ENSP00000501164.1; ENSG00000115415.21. [P42224-2] DR Ensembl; ENST00000698141.1; ENSP00000513582.1; ENSG00000115415.21. [P42224-1] DR GeneID; 6772; -. DR KEGG; hsa:6772; -. DR MANE-Select; ENST00000361099.8; ENSP00000354394.4; NM_007315.4; NP_009330.1. DR UCSC; uc002usj.3; human. [P42224-1] DR AGR; HGNC:11362; -. DR CTD; 6772; -. DR DisGeNET; 6772; -. DR GeneCards; STAT1; -. DR HGNC; HGNC:11362; STAT1. DR HPA; ENSG00000115415; Low tissue specificity. DR MalaCards; STAT1; -. DR MIM; 600555; gene. DR MIM; 613796; phenotype. DR MIM; 614162; phenotype. DR MIM; 614892; phenotype. DR neXtProt; NX_P42224; -. DR OpenTargets; ENSG00000115415; -. DR Orphanet; 319595; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency. DR Orphanet; 391487; STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome. DR Orphanet; 391311; Susceptibility to viral and mycobacterial infections due to STAT1 deficiency. DR PharmGKB; PA36183; -. DR VEuPathDB; HostDB:ENSG00000115415; -. DR eggNOG; KOG3667; Eukaryota. DR GeneTree; ENSGT01050000244905; -. DR HOGENOM; CLU_014189_3_0_1; -. DR InParanoid; P42224; -. DR OMA; FDTMMNA; -. DR OrthoDB; 19300at2759; -. DR PAN-GO; P42224; 7 GO annotations based on evolutionary models. DR PhylomeDB; P42224; -. DR TreeFam; TF318648; -. DR PathwayCommons; P42224; -. DR Reactome; R-HSA-1059683; Interleukin-6 signaling. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. DR Reactome; R-HSA-1839117; Signaling by cytosolic FGFR1 fusion mutants. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. [P42224-1] DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-877300; Interferon gamma signaling. [P42224-1] DR Reactome; R-HSA-877312; Regulation of IFNG signaling. [P42224-1] DR Reactome; R-HSA-8854691; Interleukin-20 family signaling. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-8984722; Interleukin-35 Signalling. DR Reactome; R-HSA-8985947; Interleukin-9 signaling. DR Reactome; R-HSA-9013508; NOTCH3 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-9020956; Interleukin-27 signaling. DR Reactome; R-HSA-9020958; Interleukin-21 signaling. DR Reactome; R-HSA-909733; Interferon alpha/beta signaling. DR Reactome; R-HSA-912694; Regulation of IFNA/IFNB signaling. DR Reactome; R-HSA-9670439; Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants. DR Reactome; R-HSA-9673767; Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants. DR Reactome; R-HSA-9673770; Signaling by PDGFRA extracellular domain mutants. DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR Reactome; R-HSA-9860927; Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells. DR SignaLink; P42224; -. DR SIGNOR; P42224; -. DR BioGRID-ORCS; 6772; 34 hits in 1188 CRISPR screens. DR CD-CODE; DEE660B4; Stress granule. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; STAT1; human. DR EvolutionaryTrace; P42224; -. DR GeneWiki; STAT1; -. DR GenomeRNAi; 6772; -. DR Pharos; P42224; Tchem. DR PRO; PR:P42224; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P42224; protein. DR Bgee; ENSG00000115415; Expressed in epithelium of nasopharynx and 208 other cell types or tissues. DR ExpressionAtlas; P42224; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0070721; C:ISGF3 complex; IPI:ComplexPortal. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:AgBase. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:ComplexPortal. DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL. DR GO; GO:0031730; F:CCR5 chemokine receptor binding; IEA:Ensembl. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB. DR GO; GO:0042393; F:histone binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB. DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:UniProtKB. DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB. DR GO; GO:0008015; P:blood circulation; ISS:UniProtKB. DR GO; GO:0007259; P:cell surface receptor signaling pathway via JAK-STAT; IDA:UniProtKB. DR GO; GO:0097696; P:cell surface receptor signaling pathway via STAT; IDA:BHF-UCL. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProt. DR GO; GO:0071346; P:cellular response to type II interferon; IDA:UniProtKB. DR GO; GO:0006952; P:defense response; IBA:GO_Central. DR GO; GO:0051607; P:defense response to virus; IDA:UniProtKB. DR GO; GO:0070106; P:interleukin-27-mediated signaling pathway; IDA:ARUK-UCL. DR GO; GO:0038111; P:interleukin-7-mediated signaling pathway; IDA:UniProt. DR GO; GO:0038113; P:interleukin-9-mediated signaling pathway; IDA:UniProt. DR GO; GO:0072162; P:metanephric mesenchymal cell differentiation; ISS:UniProtKB. DR GO; GO:0072136; P:metanephric mesenchymal cell proliferation involved in metanephros development; ISS:UniProtKB. DR GO; GO:0046725; P:negative regulation by virus of viral protein levels in host cell; IMP:AgBase. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB. DR GO; GO:0003340; P:negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; ISS:UniProtKB. DR GO; GO:0072308; P:negative regulation of metanephric nephron tubule epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProt. DR GO; GO:0061326; P:renal tubule development; IMP:UniProtKB. DR GO; GO:0051591; P:response to cAMP; ISS:UniProtKB. DR GO; GO:0034097; P:response to cytokine; ISS:UniProtKB. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0035456; P:response to interferon-beta; IMP:UniProtKB. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:0043434; P:response to peptide hormone; ISS:UniProtKB. DR GO; GO:0034341; P:response to type II interferon; IDA:UniProtKB. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0060333; P:type II interferon-mediated signaling pathway; IDA:BHF-UCL. DR CDD; cd10372; SH2_STAT1; 1. DR CDD; cd16851; STAT1_CCD; 1. DR CDD; cd16845; STAT1_DBD; 1. DR DisProt; DP00962; -. DR FunFam; 1.10.238.10:FF:000012; Signal transducer and activator of transcription; 1. DR FunFam; 1.10.532.10:FF:000001; Signal transducer and activator of transcription; 1. DR FunFam; 1.20.1050.20:FF:000001; Signal transducer and activator of transcription; 1. DR FunFam; 2.60.40.630:FF:000001; Signal transducer and activator of transcription; 1. DR FunFam; 3.30.505.10:FF:000003; Signal transducer and activator of transcription; 1. DR FunFam; 6.10.250.3310:FF:000001; Signal transducer and activator of transcription; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 6.10.250.3310; signal transducer and activator of transcription 1; 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; IID00046; -. 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; IPR038295; STAT1_C_sf. DR InterPro; IPR035859; STAT1_SH2. DR InterPro; IPR022752; STAT1_TAZ2-bd_C. 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 Pfam; PF00017; SH2; 1. DR Pfam; PF12162; STAT1_TAZ2bind; 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; 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. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; ADP-ribosylation; KW Alternative splicing; Antiviral defense; Coiled coil; Cytoplasm; KW Direct protein sequencing; Disease variant; DNA-binding; KW Host-virus interaction; Isopeptide bond; Methylation; Nucleus; KW Phosphoprotein; Proteomics identification; Reference proteome; SH2 domain; KW Transcription; Transcription regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..750 FT /note="Signal transducer and activator of transcription 1- FT alpha/beta" FT /id="PRO_0000182410" FT DOMAIN 573..670 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT COILED 136..317 FT /evidence="ECO:0000269|PubMed:9630226" FT SITE 724 FT /note="Required for recruitment of EP300/p300" FT /evidence="ECO:0000269|PubMed:16257975" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 114 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 175 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 296 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 366 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 525 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 637 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 657 FT /note="ADP-ribosyl glutamic acid; by PARP14" FT /evidence="ECO:0000269|PubMed:27796300" FT MOD_RES 665 FT /note="N6-methyllysine" FT /evidence="ECO:0000269|PubMed:28753426" FT MOD_RES 701 FT /note="Phosphotyrosine; by JAK1, JAK2 or TYK2" FT /evidence="ECO:0000269|PubMed:17561467, FT ECO:0000269|PubMed:19088846, ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:26479788, FT ECO:0000269|PubMed:27796300, ECO:0000269|PubMed:28753426, FT ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:7657660" FT MOD_RES 705 FT /note="ADP-ribosyl glutamic acid; by PARP14" FT /evidence="ECO:0000269|PubMed:27796300" FT MOD_RES 708 FT /note="Phosphoserine; by IKKE" FT /evidence="ECO:0000269|PubMed:22065572" FT MOD_RES 727 FT /note="Phosphoserine; by CAMK2 and MAPK14" FT /evidence="ECO:0000269|PubMed:11972023, FT ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:16257975, FT ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:21135090, FT ECO:0000269|PubMed:22065572, ECO:0000269|PubMed:26479788, FT ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:7543024, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 745 FT /note="Phosphoserine; by IKKE" FT /evidence="ECO:0000250|UniProtKB:P42225" FT MOD_RES 749 FT /note="Phosphothreonine; by IKKB" FT /evidence="ECO:0000269|PubMed:32209697, FT ECO:0000269|PubMed:38621137" FT CROSSLNK 703 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 703 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 713..750 FT /note="Missing (in isoform Beta)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_006282" FT VARIANT 30 FT /note="I -> T (in dbSNP:rs34255470)" FT /id="VAR_034521" FT VARIANT 165 FT /note="D -> G (in IMD31C; gain of function mutation FT associated with increased STAT1 phosphorylation due to FT impaired nuclear dephosphorylation; dbSNP:rs387906764)" FT /evidence="ECO:0000269|PubMed:21727188, FT ECO:0000269|PubMed:23709754" FT /id="VAR_065934" FT VARIANT 165 FT /note="D -> H (in IMD31C; dbSNP:rs387906767)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065935" FT VARIANT 170 FT /note="Y -> N (in IMD31C; dbSNP:rs387906766)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065936" FT VARIANT 174 FT /note="C -> R (in IMD31C; dbSNP:rs387906763)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065937" FT VARIANT 179 FT /note="N -> K (in IMD31C; gain of function; increases FT transactivation activity in response to IFNG; FT dbSNP:rs587777628)" FT /evidence="ECO:0000269|PubMed:23709754" FT /id="VAR_075494" FT VARIANT 201 FT /note="K -> N (in IMD31B; not deleterious in terms of most FT STAT1 functions; causes abnormal splicing out of exon 8 FT from most mRNAs thereby decreasing protein levels by FT approximately 70%; dbSNP:rs587776870)" FT /evidence="ECO:0000269|PubMed:20841510" FT /id="VAR_065815" FT VARIANT 202 FT /note="M -> I (in IMD31C)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065938" FT VARIANT 202 FT /note="M -> V (in IMD31C; dbSNP:rs387906762)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065939" FT VARIANT 267 FT /note="A -> V (in IMD31C; dbSNP:rs387906759)" FT /evidence="ECO:0000269|PubMed:21714643, FT ECO:0000269|PubMed:21727188" FT /id="VAR_065940" FT VARIANT 271 FT /note="Q -> P (in IMD31C; dbSNP:rs387906768)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065941" FT VARIANT 274 FT /note="R -> Q (in IMD31C; gain of function; increases STAT1 FT phosphorylation due to impaired nuclear dephosphorylation; FT increases transactivation activity in response to IFNG; FT dbSNP:rs387906760)" FT /evidence="ECO:0000269|PubMed:21727188, FT ECO:0000269|PubMed:23709754" FT /id="VAR_065942" FT VARIANT 274 FT /note="R -> W (in IMD31C; gain of function; increases FT phosphorylation in response to IFNG, IFNA and IL27 due to a FT loss of dephosphorylation; dbSNP:rs387906758)" FT /evidence="ECO:0000269|PubMed:21714643, FT ECO:0000269|PubMed:21727188, ECO:0000269|PubMed:23709754" FT /id="VAR_065943" FT VARIANT 278 FT /note="K -> E (in IMD31C; gain of function; increases FT phosphorylation in response to IFNG and IFNA due to a loss FT of dephosphorylation; dbSNP:rs863223398)" FT /evidence="ECO:0000269|PubMed:25288569" FT /id="VAR_075495" FT VARIANT 285 FT /note="Q -> R (in IMD31C; gain of function; increases FT transactivation activity in response to IFNG; FT dbSNP:rs587777629)" FT /evidence="ECO:0000269|PubMed:23709754" FT /id="VAR_075496" FT VARIANT 286 FT /note="K -> I (in IMD31C; dbSNP:rs387906761)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065944" FT VARIANT 288 FT /note="T -> A (in IMD31C; dbSNP:rs387906765)" FT /evidence="ECO:0000269|PubMed:21727188" FT /id="VAR_065945" FT VARIANT 298 FT /note="K -> N (in IMD31C; gain of function; increases basal FT STAT1 phosphorylation levels which are 10-20 fold higher FT than controls after IFNG stimulation)" FT /evidence="ECO:0000269|PubMed:26514428" FT /id="VAR_075497" FT VARIANT 320 FT /note="E -> Q (in IMD31A; affects the DNA-binding activity FT of the protein; dbSNP:rs137852680)" FT /evidence="ECO:0000269|PubMed:16934001" FT /id="VAR_065816" FT VARIANT 384 FT /note="G -> D (in IMD31C; gain of function; increases FT phosphorylation in response to IFNG and IFNA due to a loss FT of dephosphorylation; dbSNP:rs796065052)" FT /evidence="ECO:0000269|PubMed:25288569" FT /id="VAR_075498" FT VARIANT 385 FT /note="T -> M (in IMD31C; gain of function; increases FT phosphorylation in response to IFNG, IFNA and IL27 due to a FT loss of dephosphorylation; dbSNP:rs587777630)" FT /evidence="ECO:0000269|PubMed:23709754, FT ECO:0000269|PubMed:25288569" FT /id="VAR_075499" FT VARIANT 463 FT /note="Q -> H (in IMD31A; affects the DNA-binding activity FT of the protein; dbSNP:rs137852679)" FT /evidence="ECO:0000269|PubMed:16934001" FT /id="VAR_065817" FT VARIANT 491 FT /note="P -> A (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036001" FT VARIANT 600 FT /note="L -> P (in IMD31B; found in an infant who died of a FT viral-like illness associated with complete STAT1 FT deficiency; dbSNP:rs137852678)" FT /evidence="ECO:0000269|PubMed:12590259" FT /id="VAR_018265" FT VARIANT 637 FT /note="K -> E (in IMD31A; affects both phosphorylation and FT DNA-binding activity; results in impaired STAT1-mediated FT cellular response to IFN-gamma and interleukin-27; FT dbSNP:rs587777705)" FT /evidence="ECO:0000269|PubMed:22573496" FT /id="VAR_068713" FT VARIANT 673 FT /note="K -> R (in IMD31A; impairs tyrosine phosphorylation; FT results in impaired STAT1-mediated cellular response to FT IFN-gamma and interleukin-27; dbSNP:rs587777704)" FT /evidence="ECO:0000269|PubMed:22573496" FT /id="VAR_068714" FT VARIANT 701 FT /note="Y -> C (in IMD31B; disrupts transactivation activity FT in response to IFNG)" FT /evidence="ECO:0000269|PubMed:23709754" FT /id="VAR_075500" FT VARIANT 706 FT /note="L -> S (in IMD31A; loss of GAF and ISGF3 activation; FT impairs the nuclear accumulation of GAF but not of ISGF3 in FT heterozygous cells stimulated by IFNs; affects FT phosphorylation of the protein; dbSNP:rs137852677)" FT /evidence="ECO:0000269|PubMed:11452125, FT ECO:0000269|PubMed:16934001" FT /id="VAR_018266" FT MUTAGEN 110 FT /note="K->R: Sumoylated." FT /evidence="ECO:0000269|PubMed:12764129" FT MUTAGEN 114 FT /note="K->A: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 175 FT /note="K->A: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 296 FT /note="K->A: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 366 FT /note="K->A: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 525 FT /note="K->A: Strongly reduced IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation. Does not affect FT ability to homodimerize." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 636..637 FT /note="KK->AA: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 656..658 FT /note="AEN->CEC: Enhances STAT1 nuclear translocation and FT interferon (IFN)-stimulated gene (ISG) expression in FT response to IFN-beta stimulation. Reduces viral load in FT infected cultured cells." FT /evidence="ECO:0000269|PubMed:26479788" FT MUTAGEN 657 FT /note="E->Q: Loss of ADP-ribosylation and increased Tyr-701 FT phosphorylation; when associated with Q-705." FT /evidence="ECO:0000269|PubMed:27796300" FT MUTAGEN 665 FT /note="K->A: No effect on IFN-alpha-induced STAT1 FT phosphorylation and nuclear translocation." FT /evidence="ECO:0000269|PubMed:28753426" FT MUTAGEN 701 FT /note="Y->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 701 FT /note="Y->E: Not phosphorylated at S-708 upon IFNB FT induction." FT /evidence="ECO:0000269|PubMed:17897103, FT ECO:0000269|PubMed:22065572" FT MUTAGEN 701 FT /note="Y->F: No effect on basal sumoylation. Enhances FT sumoylation in the presence of MAPK stimulation. FT Phosphorylated at S-708 upon IFNB induction." FT /evidence="ECO:0000269|PubMed:17897103, FT ECO:0000269|PubMed:22065572" FT MUTAGEN 703 FT /note="K->R: Abolishes sumoylation by SUMO1. Increased FT IFN-gamma-mediated transactivation." FT /evidence="ECO:0000269|PubMed:12764129, FT ECO:0000269|PubMed:12855578" FT MUTAGEN 704 FT /note="T->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 705 FT /note="E->Q: Loss of ADP-ribosylation and increased Tyr-701 FT phosphorylation; when associated with Q-657." FT /evidence="ECO:0000269|PubMed:27796300" FT MUTAGEN 708 FT /note="S->A: Phosphorylated at Y-701 upon IFNB induction. FT No effect on transcriptional activation of ARID5A." FT /evidence="ECO:0000269|PubMed:22065572, FT ECO:0000269|PubMed:32209697" FT MUTAGEN 708 FT /note="S->D: Not phosphorylated at Y-701 upon IFNB FT induction." FT /evidence="ECO:0000269|PubMed:22065572" FT MUTAGEN 710 FT /note="S->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 715 FT /note="S->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 719 FT /note="T->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 720 FT /note="T->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 724 FT /note="L->A: Impaired phosphorylation at S-727." FT /evidence="ECO:0000269|PubMed:16257975" FT MUTAGEN 727 FT /note="S->A: Decreased transcriptional activation. No FT effect on basal sumoylation. No enhancement of sumoylation FT on MAPK stimulation. No PRKCD-induced apoptosis. Upon IFNB FT induction, phosphorylated at Y-701 but not at S-708. No FT effect on transcriptional activation of ARID5A." FT /evidence="ECO:0000269|PubMed:15322115, FT ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572, FT ECO:0000269|PubMed:32209697" FT MUTAGEN 727 FT /note="S->D: No change in enhancement of MAPK-induced FT sumoylation. Basal interaction with PIAS1. Interaction with FT PIAS1 increased on MAPK stimulation." FT /evidence="ECO:0000269|PubMed:15322115, FT ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572" FT MUTAGEN 727 FT /note="S->E: No change in enhancement of MAPK-induced FT sumoylation." FT /evidence="ECO:0000269|PubMed:15322115, FT ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572" FT MUTAGEN 735 FT /note="S->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 740 FT /note="S->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 745 FT /note="S->A: No effect on transcriptional activation of FT ARID5A." FT /evidence="ECO:0000269|PubMed:32209697" FT MUTAGEN 749 FT /note="T->A: Reduced transcriptional activation of ARID5A FT and IL12B. No effect on nuclear translocation. Abolishes FT IKKB-mediated phosphorylation at this position." FT /evidence="ECO:0000269|PubMed:32209697, FT ECO:0000269|PubMed:38621137" FT MUTAGEN 749 FT /note="T->E: Phosphomimetic mutant; no effect on FT transcriptional activation of ARID5A or IL12B. No effect on FT nuclear translocation." FT /evidence="ECO:0000269|PubMed:32209697" FT CONFLICT 46 FT /note="A -> T (in Ref. 2; ADA59516)" FT /evidence="ECO:0000305" FT CONFLICT 307 FT /note="S -> G (in Ref. 4; BAF85293)" FT /evidence="ECO:0000305" FT CONFLICT 718 FT /note="Q -> R (in Ref. 5; CAH18430)" FT /evidence="ECO:0000305" FT HELIX 3..8 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 12..21 FT /evidence="ECO:0007829|PDB:3WWT" FT STRAND 23..26 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 28..33 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 35..40 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 43..46 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 50..73 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 77..94 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 99..122 FT /evidence="ECO:0007829|PDB:3WWT" FT HELIX 134..175 FT /evidence="ECO:0007829|PDB:7NUF" FT TURN 176..179 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 192..233 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 235..247 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 257..286 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 293..315 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 317..324 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 334..336 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 341..349 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 352..354 FT /evidence="ECO:0007829|PDB:7NUF" FT TURN 355..357 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 359..365 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 370..373 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 374..376 FT /evidence="ECO:0007829|PDB:1BF5" FT STRAND 380..384 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 387..389 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 391..395 FT /evidence="ECO:0007829|PDB:1BF5" FT TURN 396..398 FT /evidence="ECO:0007829|PDB:1BF5" FT STRAND 401..411 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 421..425 FT /evidence="ECO:0007829|PDB:1BF5" FT HELIX 426..428 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 433..441 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 444..451 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 455..460 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 461..463 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 464..477 FT /evidence="ECO:0007829|PDB:7NUF" FT TURN 484..488 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 495..509 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 516..527 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 539..542 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:1BF5" FT HELIX 554..568 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 570..574 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 584..591 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 592..594 FT /evidence="ECO:0007829|PDB:1YVL" FT STRAND 598..603 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 612..618 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 621..624 FT /evidence="ECO:0007829|PDB:1BF5" FT STRAND 627..631 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 636..641 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 644..650 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 652..654 FT /evidence="ECO:0007829|PDB:8D3F" FT STRAND 657..659 FT /evidence="ECO:0007829|PDB:1BF5" FT TURN 668..670 FT /evidence="ECO:0007829|PDB:7NUF" FT HELIX 673..677 FT /evidence="ECO:0007829|PDB:7NUF" FT TURN 678..680 FT /evidence="ECO:0007829|PDB:7NUF" FT STRAND 709..711 FT /evidence="ECO:0007829|PDB:8D3F" FT HELIX 728..738 FT /evidence="ECO:0007829|PDB:2KA6" FT TURN 739..742 FT /evidence="ECO:0007829|PDB:2KA6" FT HELIX 743..745 FT /evidence="ECO:0007829|PDB:2KA6" FT TURN 746..748 FT /evidence="ECO:0007829|PDB:2KA6" SQ SEQUENCE 750 AA; 87335 MW; 054A813522364BA6 CRC64; MSQWYELQQL DSKFLEQVHQ LYDDSFPMEI RQYLAQWLEK QDWEHAANDV SFATIRFHDL LSQLDDQYSR FSLENNFLLQ HNIRKSKRNL QDNFQEDPIQ MSMIIYSCLK EERKILENAQ RFNQAQSGNI QSTVMLDKQK ELDSKVRNVK DKVMCIEHEI KSLEDLQDEY DFKCKTLQNR EHETNGVAKS DQKQEQLLLK KMYLMLDNKR KEVVHKIIEL LNVTELTQNA LINDELVEWK RRQQSACIGG PPNACLDQLQ NWFTIVAESL QQVRQQLKKL EELEQKYTYE HDPITKNKQV LWDRTFSLFQ QLIQSSFVVE RQPCMPTHPQ RPLVLKTGVQ FTVKLRLLVK LQELNYNLKV KVLFDKDVNE RNTVKGFRKF NILGTHTKVM NMEESTNGSL AAEFRHLQLK EQKNAGTRTN EGPLIVTEEL HSLSFETQLC QPGLVIDLET TSLPVVVISN VSQLPSGWAS ILWYNMLVAE PRNLSFFLTP PCARWAQLSE VLSWQFSSVT KRGLNVDQLN MLGEKLLGPN ASPDGLIPWT RFCKENINDK NFPFWLWIES ILELIKKHLL PLWNDGCIMG FISKERERAL LKDQQPGTFL LRFSESSREG AITFTWVERS QNGGEPDFHA VEPYTKKELS AVTFPDIIRN YKVMAAENIP ENPLKYLYPN IDKDHAFGKY YSRPKEAPEP MELDGPKGTG YIKTELISVS EVHPSRLQTT DNLLPMSPEE FDEVSRIVGS VEFDSMMNTV //