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 27-MAR-2024, entry version 258.
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.
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.
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.
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 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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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:9724754, PubMed:12855578,
CC PubMed:12764129, PubMed:15322115, PubMed:34508746, PubMed:35568036,
CC PubMed:23940278). 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). Involved in
CC food tolerance in small intestine: associates with the Gasdermin-D, p13
CC cleavage product (13 kDa GSDMD) and promotes transcription of CIITA,
CC inducing type 1 regulatory T (Tr1) cells in upper small intestine (By
CC 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:34508746,
CC ECO:0000269|PubMed:35568036, ECO:0000269|PubMed:8156998,
CC ECO:0000269|PubMed:9724754, ECO:0000303|PubMed:15526160}.
CC -!- SUBUNIT: Isoform alpha homodimerizes upon IFN-gamma induced
CC phosphorylation (PubMed:8605877, PubMed:28753426). 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:9724754, PubMed:17897103). 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). Interacts with OTOP1 (By similarity). Interacts with
CC IFNGR1 (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 -!- 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=16; IntAct=EBI-1057697, EBI-1546963;
CC P42224; P40763: STAT3; NbExp=8; 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}. Nucleus {ECO:0000269|PubMed:15322115,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426}.
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:28753426, PubMed:26479788). 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:7657660, PubMed:28753426). 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:7543024, PubMed:15322115,
CC PubMed:16799645, PubMed:17897103). 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). {ECO:0000269|PubMed:11278462,
CC ECO:0000269|PubMed:11972023, ECO:0000269|PubMed:12138178,
CC ECO:0000269|PubMed:15322115, ECO:0000269|PubMed:16257975,
CC ECO:0000269|PubMed:16799645, ECO:0000269|PubMed:17561467,
CC ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:19088846,
CC ECO:0000269|PubMed:21135090, ECO:0000269|PubMed:22065572,
CC ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28753426,
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=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/stat1/";
CC -!- WEB RESOURCE: Name=STAT1base; Note=STAT1 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/STAT1base/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=STAT1 entry;
CC URL="https://en.wikipedia.org/wiki/STAT1";
CC ---------------------------------------------------------------------------
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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_007315.3. [P42224-1]
DR RefSeq; NP_644671.1; NM_139266.2. [P42224-2]
DR RefSeq; XP_006712781.1; XM_006712718.1. [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; 324.
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 IntAct; P42224; 193.
DR MINT; P42224; -.
DR STRING; 9606.ENSP00000354394; -.
DR BindingDB; P42224; -.
DR ChEMBL; CHEMBL6101; -.
DR CarbonylDB; P42224; -.
DR GlyCosmos; P42224; 2 sites, 1 glycan.
DR GlyGen; P42224; 2 sites, 1 O-linked glycan (2 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 EPD; P42224; -.
DR jPOST; P42224; -.
DR MassIVE; P42224; -.
DR MaxQB; P42224; -.
DR PaxDb; 9606-ENSP00000354394; -.
DR PeptideAtlas; P42224; -.
DR ProteomicsDB; 55491; -. [P42224-1]
DR ProteomicsDB; 55492; -. [P42224-2]
DR Pumba; P42224; -.
DR Antibodypedia; 688; 2673 antibodies from 55 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; 391487; Autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome.
DR Orphanet; 319595; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.
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; SNEMEVG; -.
DR OrthoDB; 7823at2759; -.
DR PhylomeDB; P42224; -.
DR TreeFam; TF318648; -.
DR PathwayCommons; P42224; -.
DR Reactome; R-HSA-1059683; Interleukin-6 signaling. [P42224-1]
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT. [P42224-1]
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. [P42224-1]
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-982772; Growth hormone receptor signaling.
DR Reactome; R-HSA-9833482; PKR-mediated signaling.
DR SignaLink; P42224; -.
DR SIGNOR; P42224; -.
DR BioGRID-ORCS; 6772; 34 hits in 1188 CRISPR screens.
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 Genevisible; P42224; HS.
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:0016922; F:nuclear receptor binding; IPI:UniProtKB.
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:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:UniProt.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
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:0038113; P:interleukin-9-mediated signaling pathway; IDA:UniProt.
DR GO; GO:0010742; P:macrophage derived foam cell differentiation; IDA:UniProtKB.
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:0051770; P:positive regulation of nitric-oxide synthase 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:0007259; P:receptor signaling pathway via JAK-STAT; 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 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 PANTHER; PTHR11801:SF18; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 1-ALPHA_BETA; 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; Reference proteome; SH2 domain; Transcription;
KW 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: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:7543024, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 745
FT /note="Phosphoserine; by IKKE"
FT /evidence="ECO:0000250|UniProtKB:P42225"
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->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 IFN-
FT gamma-mediated transactivation."
FT /evidence="ECO:0000269|PubMed:12764129,
FT ECO:0000269|PubMed:12855578"
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 /evidence="ECO:0000269|PubMed:22065572"
FT MUTAGEN 708
FT /note="S->D: Not phosphorylated at Y-701 upon IFNB
FT induction."
FT /evidence="ECO:0000269|PubMed:22065572"
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."
FT /evidence="ECO:0000269|PubMed:15322115,
FT ECO:0000269|PubMed:17897103, ECO:0000269|PubMed:22065572"
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 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
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