ID HSF1_HUMAN Reviewed; 529 AA. AC Q00613; A8K4L0; A8MW26; Q53XT4; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 27-MAR-2024, entry version 217. DE RecName: Full=Heat shock factor protein 1 {ECO:0000305}; DE Short=HSF 1; DE AltName: Full=Heat shock transcription factor 1 {ECO:0000312|HGNC:HGNC:5224}; DE Short=HSTF 1; GN Name=HSF1 {ECO:0000312|HGNC:HGNC:5224}; Synonyms=HSTF1; 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], FUNCTION, AND DNA-BINDING. RX PubMed=1871105; DOI=10.1073/pnas.88.16.6906; RA Rabindran S.K., Giorgi G., Clos J., Wu C.; RT "Molecular cloning and expression of a human heat shock factor, HSF1."; RL Proc. Natl. Acad. Sci. U.S.A. 88:6906-6910(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Muscle; 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 [6] RP PROTEIN SEQUENCE OF 73-79; 81-93; 97-106; 163-170 AND 337-352. RX PubMed=1871106; DOI=10.1073/pnas.88.16.6911; RA Schuetz T.J., Gallo G.J., Sheldon L., Tempst P., Kingston R.E.; RT "Isolation of a cDNA for HSF2: evidence for two heat shock factor genes in RT humans."; RL Proc. Natl. Acad. Sci. U.S.A. 88:6911-6915(1991). RN [7] RP PROTEIN SEQUENCE OF 228-241 AND 297-310, PHOSPHORYLATION AT SER-230 BY RP CAMK2, PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, SUBCELLULAR RP LOCATION, MUTAGENESIS OF SER-230, DOMAIN, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=11447121; DOI=10.1093/emboj/20.14.3800; RA Holmberg C.I., Hietakangas V., Mikhailov A., Rantanen J.O., Kallio M., RA Meinander A., Hellman J., Morrice N., MacKintosh C., Morimoto R.I., RA Eriksson J.E., Sistonen L.; RT "Phosphorylation of serine 230 promotes inducible transcriptional activity RT of heat shock factor 1."; RL EMBO J. 20:3800-3810(2001). RN [8] RP FUNCTION, AND DNA-BINDING. RX PubMed=1986252; DOI=10.1128/mcb.11.1.586-592.1991; RA Abravaya K., Phillips B., Morimoto R.I.; RT "Heat shock-induced interactions of heat shock transcription factor and the RT human hsp70 promoter examined by in vivo footprinting."; RL Mol. Cell. Biol. 11:586-592(1991). RN [9] RP FUNCTION, DNA-BINDING, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=8455624; DOI=10.1128/mcb.13.4.2486-2496.1993; RA Baler R., Dahl G., Voellmy R.; RT "Activation of human heat shock genes is accompanied by oligomerization, RT modification, and rapid translocation of heat shock transcription factor RT HSF1."; RL Mol. Cell. Biol. 13:2486-2496(1993). RN [10] RP SUBUNIT, AND INTERACTION WITH HSPA1A. RX PubMed=7935376; DOI=10.1128/mcb.14.10.6552-6560.1994; RA Rabindran S.K., Wisniewski J., Li L., Li G.C., Wu C.; RT "Interaction between heat shock factor and hsp70 is insufficient to RT suppress induction of DNA-binding activity in vivo."; RL Mol. Cell. Biol. 14:6552-6560(1994). RN [11] RP FUNCTION, DNA-BINDING, SUBUNIT, DOMAIN, AND MUTAGENESIS OF LEU-140; RP MET-147; LEU-189; LEU-193; MET-391 AND LEU-395. RX PubMed=7935471; DOI=10.1128/mcb.14.11.7557-7568.1994; RA Zuo J., Baler R., Dahl G., Voellmy R.; RT "Activation of the DNA-binding ability of human heat shock transcription RT factor 1 may involve the transition from an intramolecular to an RT intermolecular triple-stranded coiled-coil structure."; RL Mol. Cell. Biol. 14:7557-7568(1994). RN [12] RP FUNCTION, AND DOMAIN. RX PubMed=7760831; DOI=10.1128/mcb.15.6.3354; RA Green M., Schuetz T.J., Sullivan E.K., Kingston R.E.; RT "A heat shock-responsive domain of human HSF1 that regulates transcription RT activation domain function."; RL Mol. Cell. Biol. 15:3354-3362(1995). RN [13] RP FUNCTION, SUBUNIT, DNA-BINDING, SUBCELLULAR LOCATION, DOMAIN, AND RP MUTAGENESIS OF LEU-140; MET-147; LEU-189 AND MET-391. RX PubMed=7623826; DOI=10.1128/mcb.15.8.4319; RA Zuo J., Rungger D., Voellmy R.; RT "Multiple layers of regulation of human heat shock transcription factor RT 1."; RL Mol. Cell. Biol. 15:4319-4330(1995). RN [14] RP SUBUNIT, AND INTERACTION WITH HSPA1A. RX PubMed=9222587; DOI=10.1379/1466-1268(1996)001<0033:efaroh>2.3.co;2; RA Baler R., Zou J., Voellmy R.; RT "Evidence for a role of Hsp70 in the regulation of the heat shock response RT in mammalian cells."; RL Cell Stress Chaperones 1:33-39(1996). RN [15] RP PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, DOMAIN, MUTAGENESIS OF RP ARG-296; VAL-297; LYS-298; GLU-299; GLU-300; SER-303; SER-307; ARG-309 AND RP GLU-311, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=8946918; DOI=10.1101/gad.10.21.2782; RA Knauf U., Newton E.M., Kyriakis J., Kingston R.E.; RT "Repression of human heat shock factor 1 activity at control temperature by RT phosphorylation."; RL Genes Dev. 10:2782-2793(1996). RN [16] RP PHOSPHORYLATION AT SER-275; SER-303 BY GSK3B AND SER-307 BY MAPK3, RP FUNCTION, DNA-BINDING, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS RP OF SER-275; SER-303 AND SER-307. RX PubMed=8940068; DOI=10.1074/jbc.271.48.30847; RA Chu B., Soncin F., Price B.D., Stevenson M.A., Calderwood S.K.; RT "Sequential phosphorylation by mitogen-activated protein kinase and RT glycogen synthase kinase 3 represses transcriptional activation by heat RT shock factor-1."; RL J. Biol. Chem. 271:30847-30857(1996). RN [17] RP FUNCTION, AND MUTAGENESIS OF LEU-22. RX PubMed=9341107; DOI=10.1074/jbc.272.43.26803; RA Chen C., Xie Y., Stevenson M.A., Auron P.E., Calderwood S.K.; RT "Heat shock factor 1 represses Ras-induced transcriptional activation of RT the c-fos gene."; RL J. Biol. Chem. 272:26803-26806(1997). RN [18] RP PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, DOMAIN, MUTAGENESIS OF RP SER-303 AND SER-307, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=9121459; DOI=10.1128/mcb.17.4.2107; RA Kline M.P., Morimoto R.I.; RT "Repression of the heat shock factor 1 transcriptional activation domain is RT modulated by constitutive phosphorylation."; RL Mol. Cell. Biol. 17:2107-2115(1997). RN [19] RP FUNCTION, SUBUNIT, AND INTERACTION WITH HSP90 PROTEINS. RX PubMed=9727490; DOI=10.1016/s0092-8674(00)81588-3; RA Zou J., Guo Y., Guettouche T., Smith D.F., Voellmy R.; RT "Repression of heat shock transcription factor HSF1 activation by HSP90 RT (HSP90 complex) that forms a stress-sensitive complex with HSF1."; RL Cell 94:471-480(1998). RN [20] RP INTERACTION WITH DNAJB1; HSPA1A AND HSPA8, FUNCTION, DNA-BINDING, AND RP PHOSPHORYLATION. RX PubMed=9499401; DOI=10.1101/gad.12.5.654; RA Shi Y., Mosser D.D., Morimoto R.I.; RT "Molecular chaperones as HSF1-specific transcriptional repressors."; RL Genes Dev. 12:654-666(1998). RN [21] RP PHOSPHORYLATION AT SER-307, FUNCTION, MUTAGENESIS OF SER-275; SER-303 AND RP SER-307, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=9535852; DOI=10.1074/jbc.273.15.8749; RA Xia W., Guo Y., Vilaboa N., Zuo J., Voellmy R.; RT "Transcriptional activation of heat shock factor HSF1 probed by RT phosphopeptide analysis of factor 32P-labeled in vivo."; RL J. Biol. Chem. 273:8749-8755(1998). RN [22] RP SUBCELLULAR LOCATION. RX PubMed=10413683; DOI=10.1242/jcs.112.16.2765; RA Mercier P.A., Winegarden N.A., Westwood J.T.; RT "Human heat shock factor 1 is predominantly a nuclear protein before and RT after heat stress."; RL J. Cell Sci. 112:2765-2774(1999). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND DNA-BINDING. RX PubMed=10359787; DOI=10.1073/pnas.96.12.6769; RA Jolly C., Usson Y., Morimoto R.I.; RT "Rapid and reversible relocalization of heat shock factor 1 within seconds RT to nuclear stress granules."; RL Proc. Natl. Acad. Sci. U.S.A. 96:6769-6774(1999). RN [24] RP INTERACTION WITH GTF2A2; GTF2B AND TBP. RX PubMed=11005381; DOI=10.1379/1466-1268(2000)005<0229:ptfhwt>2.0.co;2; RA Yuan C.X., Gurley W.B.; RT "Potential targets for HSF1 within the preinitiation complex."; RL Cell Stress Chaperones 5:229-242(2000). RN [25] RP INTERACTION WITH MAPK3 AND MAPK8, PHOSPHORYLATION AT SER-363 BY MAPK8, RP SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF SER-363, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=10747973; DOI=10.1074/jbc.m000958200; RA Dai R., Frejtag W., He B., Zhang Y., Mivechi N.F.; RT "c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock RT factor-1 suppress its transcriptional activity."; RL J. Biol. Chem. 275:18210-18218(2000). RN [26] RP SUMOYLATION AT LYS-298, MUTAGENESIS OF LYS-298, AND SUBCELLULAR LOCATION. RX PubMed=11514557; DOI=10.1074/jbc.m104714200; RA Hong Y., Rogers R., Matunis M.J., Mayhew C.N., Goodson M.L., RA Park-Sarge O.K., Sarge K.D.; RT "Regulation of heat shock transcription factor 1 by stress-induced SUMO-1 RT modification."; RL J. Biol. Chem. 276:40263-40267(2001). RN [27] RP COMPONENT OF A CHAPERONE COMPLEX, INTERACTION WITH FKBP4 AND HSP90 RP PROTEINS, SUBUNIT, PHOSPHORYLATION, FUNCTION, AND DNA-BINDING. RX PubMed=11583998; DOI=10.1074/jbc.m105931200; RA Guo Y., Guettouche T., Fenna M., Boellmann F., Pratt W.B., Toft D.O., RA Smith D.F., Voellmy R.; RT "Evidence for a mechanism of repression of heat shock factor 1 RT transcriptional activity by a multichaperone complex."; RL J. Biol. Chem. 276:45791-45799(2001). RN [28] RP PHOSPHORYLATION AT SER-307, SUMOYLATION, AND MUTAGENESIS OF LYS-298; RP SER-303 AND SER-307. RX PubMed=12646186; DOI=10.1016/s0006-291x(03)00312-7; RA Hilgarth R.S., Hong Y., Park-Sarge O.K., Sarge K.D.; RT "Insights into the regulation of heat shock transcription factor 1 SUMO-1 RT modification."; RL Biochem. Biophys. Res. Commun. 303:196-200(2003). RN [29] RP PHOSPHORYLATION AT THR-142 BY CK2, FUNCTION, MUTAGENESIS OF THR-142, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12659875; DOI=10.1016/s0006-291x(03)00398-x; RA Soncin F., Zhang X., Chu B., Wang X., Asea A., Ann Stevenson M., RA Sacks D.B., Calderwood S.K.; RT "Transcriptional activity and DNA binding of heat shock factor-1 involve RT phosphorylation on threonine 142 by CK2."; RL Biochem. Biophys. Res. Commun. 303:700-706(2003). RN [30] RP SUMOYLATION AT LYS-298, PHOSPHORYLATION AT SER-303, SUBCELLULAR LOCATION, RP MUTAGENESIS OF LYS-91; LYS-126; LYS-150; LYS-162; SER-230; LYS-298; RP SER-303; SER-307; SER-363 AND LYS-381, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=12665592; DOI=10.1128/mcb.23.8.2953-2968.2003; RA Hietakangas V., Ahlskog J.K., Jakobsson A.M., Hellesuo M., Sahlberg N.M., RA Holmberg C.I., Mikhailov A., Palvimo J.J., Pirkkala L., Sistonen L.; RT "Phosphorylation of serine 303 is a prerequisite for the stress-inducible RT SUMO modification of heat shock factor 1."; RL Mol. Cell. Biol. 23:2953-2968(2003). RN [31] RP FUNCTION, DNA-BINDING, INTERACTION WITH YWHAE, PHOSPHORYLATION, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF SER-303 AND SER-307. RX PubMed=12917326; DOI=10.1128/mcb.23.17.6013-6026.2003; RA Wang X., Grammatikakis N., Siganou A., Calderwood S.K.; RT "Regulation of molecular chaperone gene transcription involves the serine RT phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of RT heat shock factor 1."; RL Mol. Cell. Biol. 23:6013-6026(2003). RN [32] RP FUNCTION, INTERACTION WITH SYMPK AND CSTF2, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LEU-22. RX PubMed=14707147; DOI=10.1074/jbc.m311719200; RA Xing H., Mayhew C.N., Cullen K.E., Park-Sarge O.-K., Sarge K.D.; RT "HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with RT symplekin."; RL J. Biol. Chem. 279:10551-10555(2004). RN [33] RP FUNCTION, INTERACTION WITH DAXX, IDENTIFICATION IN A RIBONUCLEOPROTEIN RP COMPLEX, AND MUTAGENESIS OF LYS-298 AND SER-326. RX PubMed=15016915; DOI=10.1073/pnas.0304768101; RA Boellmann F., Guettouche T., Guo Y., Fenna M., Mnayer L., Voellmy R.; RT "DAXX interacts with heat shock factor 1 during stress activation and RT enhances its transcriptional activity."; RL Proc. Natl. Acad. Sci. U.S.A. 101:4100-4105(2004). RN [34] RP PHOSPHORYLATION AT SER-121; SER-230; SER-292; SER-303; SER-307; SER-314; RP SER-319; SER-326; SER-344; SER-363; SER-419 AND SER-444, MUTAGENESIS OF RP SER-326, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15760475; DOI=10.1186/1471-2091-6-4; RA Guettouche T., Boellmann F., Lane W.S., Voellmy R.; RT "Analysis of phosphorylation of human heat shock factor 1 in cells RT experiencing a stress."; RL BMC Biochem. 6:4-4(2005). RN [35] RP INTERACTION WITH PLK1 AND HSP90 PROTEINS, PHOSPHORYLATION AT SER-419 BY RP PLK1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-292; SER-314; SER-319; RP SER-326 AND SER-419. RX PubMed=15661742; DOI=10.1074/jbc.m411908200; RA Kim S.A., Yoon J.H., Lee S.H., Ahn S.G.; RT "Polo-like kinase 1 phosphorylates heat shock transcription factor 1 and RT mediates its nuclear translocation during heat stress."; RL J. Biol. Chem. 280:12653-12657(2005). RN [36] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-323, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [37] RP PHOSPHORYLATION AT SER-121 BY MAPKAPK2, FUNCTION, INTERACTION WITH HSP90 RP PROTEINS AND MAPKAPK2, MUTAGENESIS OF THR-120; SER-121; SER-123; THR-124; RP THR-527 AND SER-529, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16278218; DOI=10.1074/jbc.m505822200; RA Wang X., Khaleque M.A., Zhao M.J., Zhong R., Gaestel M., Calderwood S.K.; RT "Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, RT inhibits transcriptional activity and promotes HSP90 binding."; RL J. Biol. Chem. 281:782-791(2006). RN [38] RP SUMOYLATION AT LYS-298, AND PHOSPHORYLATION AT SER-303. RX PubMed=16371476; DOI=10.1073/pnas.0503698102; RA Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J., RA Nakai A., Sistonen L.; RT "PDSM, a motif for phosphorylation-dependent SUMO modification."; RL Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006). RN [39] RP INTERACTION WITH EEF1A PROTEINS, AND IDENTIFICATION IN A RIBONUCLEOPROTEIN RP COMPLEX. RX PubMed=16554823; DOI=10.1038/nature04518; RA Shamovsky I., Ivannikov M., Kandel E.S., Gershon D., Nudler E.; RT "RNA-mediated response to heat shock in mammalian cells."; RL Nature 440:556-560(2006). RN [40] RP DOMAIN. RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003; RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.; RT "Nine-amino-acid transactivation domain: establishment and prediction RT utilities."; RL Genomics 89:756-768(2007). RN [41] RP FUNCTION IN STRESS-INDUCED NUCLEAR MRNA EXPORT, AND INTERACTION WITH TPR. RX PubMed=17897941; DOI=10.1074/jbc.m704054200; RA Skaggs H.S., Xing H., Wilkerson D.C., Murphy L.A., Hong Y., Mayhew C.N., RA Sarge K.D.; RT "HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA."; RL J. Biol. Chem. 282:33902-33907(2007). RN [42] RP FUNCTION IN MITOTIC PROGRESSION REGULATION, INTERACTION WITH BTRC; CDC20; RP MAD2L1 AND PLK1, PHOSPHORYLATION AT SER-216 BY PLK1, SUBCELLULAR LOCATION, RP UBIQUITINATION, PROTEASOMAL DEGRADATION, AND MUTAGENESIS OF SER-216; RP SER-230; SER-303; SER-307 AND SER-419. RX PubMed=18794143; DOI=10.1158/0008-5472.can-08-0129; RA Lee Y.J., Kim E.H., Lee J.S., Jeoung D., Bae S., Kwon S.H., Lee Y.S.; RT "HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential RT for mitotic progression."; RL Cancer Res. 68:7550-7560(2008). RN [43] RP FUNCTION, AND INTERACTION WITH TTC5 AND EP300. RX PubMed=18451878; DOI=10.1038/embor.2008.70; RA Xu D., Zalmas L.P., La Thangue N.B.; RT "A transcription cofactor required for the heat-shock response."; RL EMBO Rep. 9:662-669(2008). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [45] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, 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 [46] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; THR-323 AND SER-326, AND RP IDENTIFICATION BY 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 [48] RP DEACETYLATION AT LYS-80 BY SIRT1, ACETYLATION AT LYS-80, SUBCELLULAR RP LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-80. RX PubMed=19229036; DOI=10.1126/science.1165946; RA Westerheide S.D., Anckar J., Stevens S.M. Jr., Sistonen L., Morimoto R.I.; RT "Stress-inducible regulation of heat shock factor 1 by the deacetylase RT SIRT1."; RL Science 323:1063-1066(2009). RN [49] RP INTERACTION WITH PRKACA, PHOSPHORYLATION AT SER-320 BY PRKACA, SUBCELLULAR RP LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-320. RX PubMed=21085490; DOI=10.1371/journal.pone.0013830; RA Murshid A., Chou S.D., Prince T., Zhang Y., Bharti A., Calderwood S.K.; RT "Protein kinase A binds and activates heat shock factor 1."; RL PLoS ONE 5:E13830-E13830(2010). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND SER-326, AND RP IDENTIFICATION BY 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 [51] RP INTERACTION WITH EEF1D. RX PubMed=21597468; DOI=10.1038/embor.2011.82; RA Kaitsuka T., Tomizawa K., Matsushita M.; RT "Transformation of eEF1Bdelta into heat-shock response transcription factor RT by alternative splicing."; RL EMBO Rep. 12:673-681(2011). RN [52] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [53] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-307 AND SER-363, AND RP IDENTIFICATION BY 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 [54] RP ACETYLATION AT LYS-80; LYS-91; LYS-118; LYS-150; LYS-188; LYS-208; LYS-298 RP AND LYS-524, PHOSPHORYLATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, RP SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-80; LYS-118; LYS-208 AND LYS-298, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=24581496; DOI=10.1016/j.cell.2014.01.055; RA Raychaudhuri S., Loew C., Koerner R., Pinkert S., Theis M., Hayer-Hartl M., RA Buchholz F., Hartl F.U.; RT "Interplay of acetyltransferase EP300 and the proteasome system in RT regulating heat shock transcription factor 1."; RL Cell 156:975-985(2014). RN [55] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND SER-363, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [56] RP INTERACTION WITH BAG3, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND RP NUCLEOCYTOPLASMIC SHUTTLING. RX PubMed=26159920; DOI=10.1016/j.bbrc.2015.07.006; RA Jin Y.H., Ahn S.G., Kim S.A.; RT "BAG3 affects the nucleocytoplasmic shuttling of HSF1 upon heat stress."; RL Biochem. Biophys. Res. Commun. 464:561-567(2015). RN [57] RP INTERACTION WITH IER5. RX PubMed=25816751; DOI=10.1016/j.febslet.2015.03.019; RA Ishikawa Y., Kawabata S., Sakurai H.; RT "HSF1 transcriptional activity is modulated by IER5 and PP2A/B55."; RL FEBS Lett. 589:1150-1155(2015). RN [58] RP INTERACTION WITH IER5. RX PubMed=26496226; DOI=10.1016/j.febslet.2015.10.013; RA Kawabata S., Ishita Y., Ishikawa Y., Sakurai H.; RT "Immediate-early response 5 (IER5) interacts with protein phosphatase 2A RT and regulates the phosphorylation of ribosomal protein S6 kinase and heat RT shock factor 1."; RL FEBS Lett. 589:3679-3685(2015). RN [59] RP FUNCTION, DNA-BINDING, CHROMATIN BINDING, SUBCELLULAR LOCATION, AND RP PHOSPHORYLATIONS. RX PubMed=25963659; DOI=10.1128/mcb.00816-14; RA Budzynski M.A., Puustinen M.C., Joutsen J., Sistonen L.; RT "Uncoupling stress-inducible phosphorylation of heat shock factor 1 from RT its activation."; RL Mol. Cell. Biol. 35:2530-2540(2015). RN [60] RP FUNCTION IN DNA REPAIR, INTERACTION WITH XRCC5 AND XRCC6, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF LYS-80; SER-216; LYS-298; SER-326 AND SER-419. RX PubMed=26359349; DOI=10.18632/oncotarget.5073; RA Kang G.Y., Kim E.H., Lee H.J., Gil N.Y., Cha H.J., Lee Y.S.; RT "Heat shock factor 1, an inhibitor of non-homologous end joining repair."; RL Oncotarget 6:29712-29724(2015). RN [61] RP INTERACTION WITH HSP90AA1 AND HSP90AB1. RX PubMed=26517842; DOI=10.1371/journal.pone.0141786; RA Prince T.L., Kijima T., Tatokoro M., Lee S., Tsutsumi S., Yim K., Rivas C., RA Alarcon S., Schwartz H., Khamit-Kush K., Scroggins B.T., Beebe K., RA Trepel J.B., Neckers L.; RT "Client proteins and small molecule inhibitors display distinct binding RT preferences for constitutive and stress-induced HSP90 isoforms and their RT conformationally restricted mutants."; RL PLoS ONE 10:E0141786-E0141786(2015). RN [62] RP PHOSPHORYLATION AT SER-326 BY MAPK12, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF SER-326. RX PubMed=27354066; DOI=10.1128/mcb.00292-16; RA Dayalan Naidu S., Sutherland C., Zhang Y., Risco A., de la Vega L., RA Caunt C.J., Hastie C.J., Lamont D.J., Torrente L., Chowdhry S., RA Benjamin I.J., Keyse S.M., Cuenda A., Dinkova-Kostova A.T.; RT "Heat shock factor 1 is a substrate for p38 mitogen-activated protein RT kinases."; RL Mol. Cell. Biol. 36:2403-2417(2016). RN [63] RP DEPHOSPHORYLATION AT SER-121; SER-307; SER-314; THR-323 AND THR-367 BY RP PPP2CA, ACETYLATION AT LYS-118, IDENTIFICATION IN COMPLEX WITH IER5 AND RP PPP2CA, INTERACTION WITH HSP90AA1 AND IER5, FUNCTION, SUBUNIT, DNA-BINDING, RP AND MUTAGENESIS OF SER-121; SER-307; SER-314; THR-323 AND THR-367. RX PubMed=26754925; DOI=10.1038/srep19174; RA Asano Y., Kawase T., Okabe A., Tsutsumi S., Ichikawa H., Tatebe S., RA Kitabayashi I., Tashiro F., Namiki H., Kondo T., Semba K., Aburatani H., RA Taya Y., Nakagama H., Ohki R.; RT "IER5 generates a novel hypo-phosphorylated active form of HSF1 and RT contributes to tumorigenesis."; RL Sci. Rep. 6:19174-19174(2016). RN [64] RP FUNCTION IN LATENT HIV-1 TRANSCRIPTIONAL REACTIVATION (MICROBIAL RP INFECTION), INTERACTION WITH CDK9; CCNT1 AND EP300, PHOSPHORYLATION AT RP SER-320, ACETYLATION, AND SUBCELLULAR LOCATION. RX PubMed=27189267; DOI=10.1038/srep26294; RA Pan X.Y., Zhao W., Zeng X.Y., Lin J., Li M.M., Shen X.T., Liu S.W.; RT "Heat shock factor 1 mediates latent HIV reactivation."; RL Sci. Rep. 6:26294-26294(2016). RN [65] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-91; LYS-126; LYS-131; LYS-208; RP LYS-224 AND LYS-298, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [66] RP FUNCTION. RX PubMed=34723967; DOI=10.1371/journal.pgen.1009854; RA Mota A., Waxman H.K., Hong R., Lagani G.D., Niu S.Y., Bertherat F.L., RA Wolfe L., Malicdan C.M., Markello T.C., Adams D.R., Gahl W.A., Cheng C.S., RA Beffert U., Ho A.; RT "FOXR1 regulates stress response pathways and is necessary for proper brain RT development."; RL PLoS Genet. 17:e1009854-e1009854(2021). RN [67] RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 1-120 IN COMPLEX WITH DNA, RP DNA-BINDING, SUBUNIT, AND FUNCTION. RX PubMed=26727489; DOI=10.1038/nsmb.3149; RA Neudegger T., Verghese J., Hayer-Hartl M., Hartl F.U., Bracher A.; RT "Structure of human heat-shock transcription factor 1 in complex with RT DNA."; RL Nat. Struct. Mol. Biol. 23:140-146(2016). CC -!- FUNCTION: Functions as a stress-inducible and DNA-binding transcription CC factor that plays a central role in the transcriptional activation of CC the heat shock response (HSR), leading to the expression of a large CC class of molecular chaperones, heat shock proteins (HSPs), that protect CC cells from cellular insult damage (PubMed:1871105, PubMed:11447121, CC PubMed:1986252, PubMed:7760831, PubMed:7623826, PubMed:8946918, CC PubMed:8940068, PubMed:9341107, PubMed:9121459, PubMed:9727490, CC PubMed:9499401, PubMed:9535852, PubMed:12659875, PubMed:12917326, CC PubMed:15016915, PubMed:25963659, PubMed:26754925, PubMed:18451878). In CC unstressed cells, is present in a HSP90-containing multichaperone CC complex that maintains it in a non-DNA-binding inactivated monomeric CC form (PubMed:9727490, PubMed:11583998, PubMed:16278218). Upon exposure CC to heat and other stress stimuli, undergoes homotrimerization and CC activates HSP gene transcription through binding to site-specific heat CC shock elements (HSEs) present in the promoter regions of HSP genes CC (PubMed:1871105, PubMed:1986252, PubMed:8455624, PubMed:7935471, CC PubMed:7623826, PubMed:8940068, PubMed:9727490, PubMed:9499401, CC PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, CC PubMed:25963659, PubMed:26754925). Upon heat shock stress, forms a CC chromatin-associated complex with TTC5/STRAP and p300/EP300 to CC stimulate HSR transcription, therefore increasing cell survival CC (PubMed:18451878). Activation is reversible, and during the attenuation CC and recovery phase period of the HSR, returns to its unactivated form CC (PubMed:11583998, PubMed:16278218). Binds to inverted 5'-NGAAN-3' CC pentamer DNA sequences (PubMed:1986252, PubMed:26727489). Binds to CC chromatin at heat shock gene promoters (PubMed:25963659). Activates CC transcription of transcription factor FOXR1 which in turn activates CC transcription of the heat shock chaperones HSPA1A and HSPA6 and the CC antioxidant NADPH-dependent reductase DHRS2 (PubMed:34723967). Also CC serves several other functions independently of its transcriptional CC activity. Involved in the repression of Ras-induced transcriptional CC activation of the c-fos gene in heat-stressed cells (PubMed:9341107). CC Positively regulates pre-mRNA 3'-end processing and polyadenylation of CC HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent CC manner (PubMed:14707147). Plays a role in nuclear export of stress- CC induced HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of CC mitotic progression (PubMed:18794143). Also plays a role as a negative CC regulator of non-homologous end joining (NHEJ) repair activity in a DNA CC damage-dependent manner (PubMed:26359349). Involved in stress-induced CC cancer cell proliferation in a IER5-dependent manner (PubMed:26754925). CC {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:11447121, CC ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12659875, CC ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, CC ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:16278218, CC ECO:0000269|PubMed:17897941, ECO:0000269|PubMed:18451878, CC ECO:0000269|PubMed:1871105, ECO:0000269|PubMed:18794143, CC ECO:0000269|PubMed:1986252, ECO:0000269|PubMed:25963659, CC ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26727489, CC ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:34723967, CC ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, CC ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, CC ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, CC ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9341107, CC ECO:0000269|PubMed:9499401, ECO:0000269|PubMed:9535852, CC ECO:0000269|PubMed:9727490}. CC -!- FUNCTION: (Microbial infection) Plays a role in latent human CC immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to CC the HIV-1 long terminal repeat promoter (LTR) to reactivate viral CC transcription by recruiting cellular transcriptional elongation CC factors, such as CDK9, CCNT1 and EP300. {ECO:0000269|PubMed:27189267}. CC -!- SUBUNIT: Monomer; cytoplasmic latent and transcriptionally inactive CC monomeric form in unstressed cells (PubMed:8455624, PubMed:7935376, CC PubMed:7935471, PubMed:7623826, PubMed:9222587, PubMed:9727490, CC PubMed:11583998). Homotrimer; in response to stress, such as heat CC shock, homotrimerizes and translocates into the nucleus, binds to heat CC shock element (HSE) sequences in promoter of heat shock protein (HSP) CC genes and acquires transcriptional ability (PubMed:8455624, CC PubMed:7935471, PubMed:7623826, PubMed:9222587, PubMed:9727490, CC PubMed:11583998, PubMed:26754925, PubMed:26727489). Interacts (via CC monomeric form) with FKBP4; this interaction occurs in unstressed cells CC (PubMed:11583998). Associates (via monomeric form) with HSP90 proteins CC in a multichaperone complex in unnstressed cell; this association CC maintains HSF1 in a non-DNA-binding and transcriptional inactive form CC by preventing HSF1 homotrimerization (PubMed:9727490, PubMed:11583998, CC PubMed:15661742, PubMed:16278218). Homotrimeric transactivation CC activity is modulated by protein-protein interactions and post- CC translational modifications (PubMed:11583998, PubMed:15016915, CC PubMed:16554823, PubMed:26754925). Interacts with HSP90AA1; this CC interaction is decreased in a IER5-dependent manner, promoting HSF1 CC accumulation in the nucleus, homotrimerization and DNA-binding CC activities (PubMed:26754925). Part (via regulatory domain in the CC homotrimeric form) of a large heat shock-induced HSP90-dependent CC multichaperone complex at least composed of FKBP4, FKBP5, HSP90 CC proteins, PPID, PPP5C and PTGES3; this association maintains the HSF1 CC homotrimeric DNA-bound form in a transcriptionally inactive form CC (PubMed:9727490, PubMed:11583998, PubMed:16278218). Interacts with BAG3 CC (via BAG domain); this interaction occurs in normal and heat-shocked CC cells promoting nuclear shuttling of HSF1 in a BAG3-dependent manner CC (PubMed:26159920). Interacts (via homotrimeric and hyperphosphorylated CC form) with FKBP4; this interaction occurs upon heat shock in a HSP90- CC dependent multichaperone complex (PubMed:11583998). Interacts (via CC homotrimeric form preferentially) with EEF1A proteins CC (PubMed:15016915). In heat shocked cells, stress-denatured proteins CC compete with HSF1 homotrimeric DNA-bound form for association of the CC HSP90-dependent multichaperone complex, and hence alleviating CC repression of HSF1-mediated transcriptional activity (PubMed:11583998). CC Interacts (via homotrimeric form preferentially) with DAXX; this CC interaction relieves homotrimeric HSF1 from repression of its CC transcriptional activity by HSP90-dependent multichaperone complex upon CC heat shock (PubMed:15016915). Interacts (via D domain and CC preferentially with hyperphosphorylated form) with JNK1; this CC interaction occurs under both normal growth conditions and immediately CC upon heat shock (PubMed:10747973). Interacts (via D domain and CC preferentially with hyperphosphorylated form) with MAPK3; this CC interaction occurs upon heat shock (PubMed:10747973). Interacts with CC IER5 (via central region); this interaction promotes PPP2CA-induced CC dephosphorylation on Ser-121, Ser-307, Ser-314, Thr-323 and Thr-367 and CC HSF1 transactivation activity (PubMed:25816751, PubMed:26496226, CC PubMed:26754925). Found in a ribonucleoprotein complex composed of the CC HSF1 homotrimeric form, translation elongation factor eEF1A proteins CC and non-coding RNA heat shock RNA-1 (HSR1); this complex occurs upon CC heat shock and stimulates HSF1 DNA-binding activity (PubMed:16554823). CC Interacts (via transactivation domain) with HSPA1A/HSP70 and DNAJB1; CC these interactions result in the inhibition of heat shock- and HSF1- CC induced transcriptional activity during the attenuation and recovery CC phase from heat shock (PubMed:7935376, PubMed:9222587, PubMed:9499401). CC Interacts (via Ser-303 and Ser-307 phosphorylated form) with YWHAE; CC this interaction promotes HSF1 sequestration in the cytoplasm in an CC ERK-dependent manner (PubMed:12917326). Found in a complex with IER5 CC and PPP2CA (PubMed:26754925). Interacts with TPR; this interaction CC increases upon heat shock and stimulates export of HSP70 mRNA CC (PubMed:17897941). Interacts with SYMPK (via N-terminus) and CSTF2; CC these interactions occur upon heat shock (PubMed:14707147). Interacts CC (via transactivation domain) with HSPA8 (PubMed:9499401). Interacts CC with EEF1D; this interaction occurs at heat shock promoter element CC (HSE) sequences (PubMed:21597468). Interacts with MAPKAPK2 CC (PubMed:16278218). Interacts with PRKACA/PKA (PubMed:21085490). CC Interacts (via transactivation domain) with GTF2A2 (PubMed:11005381). CC Interacts (via transactivation domain) with GTF2B (PubMed:11005381). CC Interacts (via transactivation domain) with TBP (PubMed:11005381). CC Interacts with CDK9, CCNT1 and EP300 (PubMed:27189267). Interacts (via CC N-terminus) with XRCC5 (via N-terminus) and XRCC6 (via N-terminus); CC these interactions are direct and prevent XRCC5/XRCC6 heterodimeric CC binding and non-homologous end joining (NHEJ) repair activities induced CC by ionizing radiation (IR) (PubMed:26359349). Interacts with PLK1; this CC interaction occurs during the early mitotic period, increases upon heat CC shock but does not modulate neither HSF1 homotrimerization and DNA- CC binding activities (PubMed:15661742, PubMed:18794143). Interacts (via CC Ser-216 phosphorylated form) with CDC20; this interaction occurs in CC mitosis in a MAD2L1-dependent manner and prevents PLK1-stimulated CC degradation of HSF1 by blocking the recruitment of the SCF(BTRC) CC ubiquitin ligase complex (PubMed:18794143). Interacts with MAD2L1; this CC interaction occurs in mitosis (PubMed:18794143). Interacts with BTRC; CC this interaction occurs during mitosis, induces its ubiquitin-dependent CC degradation following stimulus-dependent phosphorylation at Ser-216, a CC process inhibited by CDC20 (PubMed:18794143). Interacts with HSP90AA1 CC and HSP90AB1 (PubMed:26517842). Forms a complex with TTC5/STRAP and CC p300/EP300; these interactions augment chromatin-bound HSF1 and CC p300/EP300 histone acetyltransferase activity (PubMed:18451878). CC {ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11005381, CC ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12917326, CC ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915, CC ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16278218, CC ECO:0000269|PubMed:16554823, ECO:0000269|PubMed:17897941, CC ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:18794143, CC ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21597468, CC ECO:0000269|PubMed:25816751, ECO:0000269|PubMed:26159920, CC ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26496226, CC ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:26727489, CC ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27189267, CC ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935376, CC ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624, CC ECO:0000269|PubMed:9222587, ECO:0000269|PubMed:9499401, CC ECO:0000269|PubMed:9727490, ECO:0000305|PubMed:15016915}. CC -!- INTERACTION: CC Q00613; Q00613: HSF1; NbExp=2; IntAct=EBI-719620, EBI-719620; CC Q00613; Q03933: HSF2; NbExp=8; IntAct=EBI-719620, EBI-2556750; CC Q00613; Q5VY09: IER5; NbExp=3; IntAct=EBI-719620, EBI-1774000; CC Q00613; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-719620, EBI-712105; CC Q00613; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-719620, EBI-2796400; CC Q00613; Q14693: LPIN1; NbExp=3; IntAct=EBI-719620, EBI-5278370; CC Q00613; P49137: MAPKAPK2; NbExp=5; IntAct=EBI-719620, EBI-993299; CC Q00613; Q8N4C8: MINK1; NbExp=2; IntAct=EBI-719620, EBI-2133481; CC Q00613; Q04759: PRKCQ; NbExp=2; IntAct=EBI-719620, EBI-374762; CC Q00613; O14744: PRMT5; NbExp=3; IntAct=EBI-719620, EBI-351098; CC Q00613; Q96CM3: RPUSD4; NbExp=3; IntAct=EBI-719620, EBI-7825200; CC Q00613; P11684: SCGB1A1; NbExp=3; IntAct=EBI-719620, EBI-7797649; CC Q00613; P63165: SUMO1; NbExp=2; IntAct=EBI-719620, EBI-80140; CC Q00613; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-719620, EBI-21757569; CC Q00613; Q6ZMY6-2: WDR88; NbExp=3; IntAct=EBI-719620, EBI-25857007; CC Q00613; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-719620, EBI-749023; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10413683, CC ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121, CC ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12665592, CC ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147, CC ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:19229036, CC ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:25963659, CC ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27189267, CC ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:7623826, CC ECO:0000269|PubMed:8455624}. Cytoplasm {ECO:0000269|PubMed:10413683, CC ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:12917326, CC ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:21085490, CC ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:26359349, CC ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:7623826, CC ECO:0000269|PubMed:8455624}. Nucleus, nucleoplasm CC {ECO:0000269|PubMed:10359787}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:21085490}. Cytoplasm, cytoskeleton, spindle pole CC {ECO:0000269|PubMed:18794143}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:18794143}. CC Chromosome, centromere, kinetochore {ECO:0000269|PubMed:18794143}. CC Note=The monomeric form is cytoplasmic in unstressed cells CC (PubMed:8455624, PubMed:26159920). Predominantly nuclear protein in CC both unstressed and heat shocked cells (PubMed:10413683, CC PubMed:10359787). Translocates in the nucleus upon heat shock CC (PubMed:8455624). Nucleocytoplasmic shuttling protein CC (PubMed:26159920). Colocalizes with IER5 in the nucleus CC (PubMed:27354066). Colocalizes with BAG3 to the nucleus upon heat CC stress (PubMed:8455624, PubMed:26159920). Localizes in subnuclear CC granules called nuclear stress bodies (nSBs) upon heat shock CC (PubMed:11447121, PubMed:11514557, PubMed:10359787, PubMed:25963659, CC PubMed:10747973, PubMed:24581496, PubMed:19229036). Colocalizes with CC SYMPK and SUMO1 in nSBs upon heat shock (PubMed:11447121, CC PubMed:12665592, PubMed:11514557, PubMed:14707147, PubMed:10359787). CC Colocalizes with PRKACA/PKA in the nucleus and nSBs upon heat shock CC (PubMed:21085490). Relocalizes from the nucleus to the cytoplasm during CC the attenuation and recovery phase period of the heat shock response CC (PubMed:26159920). Translocates in the cytoplasm in a YWHAE- and CC XPO1/CRM1-dependent manner (PubMed:12917326). Together with histone CC H2AX, redistributed in discrete nuclear DNA damage-induced foci after CC ionizing radiation (IR) (PubMed:26359349). Colocalizes with calcium- CC responsive transactivator SS18L1 at kinetochore region on the mitotic CC chromosomes (PubMed:18794143). Colocalizes with gamma tubulin at CC centrosome (PubMed:18794143). Localizes at spindle pole in metaphase CC (PubMed:18794143). Colocalizes with PLK1 at spindle poles during CC prometaphase (PubMed:18794143). {ECO:0000269|PubMed:10359787, CC ECO:0000269|PubMed:10413683, ECO:0000269|PubMed:10747973, CC ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11514557, CC ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:12917326, CC ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:18794143, CC ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:24581496, CC ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26159920, CC ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066, CC ECO:0000269|PubMed:8455624}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q00613-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q00613-2; Sequence=VSP_002414, VSP_002415; CC -!- DOMAIN: In unstressed cells, spontaneous homotrimerization is inhibited CC (PubMed:7935471, PubMed:7760831). Intramolecular interactions between CC the hydrophobic repeat HR-A/B and HR-C regions are necessary to CC maintain HSF1 in the inactive, monomeric conformation (PubMed:7935471, CC PubMed:7623826). Furthermore, intramolecular interactions between the CC regulatory domain and the nonadjacent transactivation domain prevents CC transcriptional activation, a process that is relieved upon heat shock CC (PubMed:7760831). The regulatory domain is necessary for full CC repression of the transcriptional activation domain in unstressed cells CC through its phosphorylation on Ser-303 and Ser-307 (PubMed:8946918, CC PubMed:9121459). In heat stressed cells, HSF1 homotrimerization occurs CC through formation of a three-stranded coiled-coil structure generated CC by intermolecular interactions between HR-A/B regions allowing DNA- CC binding activity (PubMed:7935471). The D domain is necessary for CC translocation to the nucleus, interaction with JNK1 and MAPK3 and CC efficient JNK1- and MAPK3-dependent phosphorylation (PubMed:10747973). CC The regulatory domain confers heat shock inducibility on the CC transcriptional transactivation domain (PubMed:7760831). The regulatory CC domain is necessary for transcriptional activation through its CC phosphorylation on Ser-230 upon heat shock (PubMed:11447121). 9aaTAD is CC a transactivation motif present in a large number of yeast and animal CC transcription factors (PubMed:17467953). {ECO:0000269|PubMed:10747973, CC ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:17467953, CC ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831, CC ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8946918, CC ECO:0000269|PubMed:9121459}. CC -!- PTM: Phosphorylated (PubMed:9499401, PubMed:10359787, PubMed:11583998, CC PubMed:26159920). Phosphorylated in unstressed cells; this CC phosphorylation is constitutive and implicated in the repression of CC HSF1 transcriptional activity (PubMed:8946918, PubMed:8940068, CC PubMed:9121459, PubMed:16278218). Phosphorylated on Ser-121 by CC MAPKAPK2; this phosphorylation promotes interaction with HSP90 proteins CC and inhibits HSF1 homotrimerization, DNA-binding and transactivation CC activities (PubMed:16278218). Phosphorylation on Ser-303 by GSK3B/GSK3- CC beta and on Ser-307 by MAPK3 within the regulatory domain is involved CC in the repression of HSF1 transcriptional activity and occurs in a CC RAF1-dependent manner (PubMed:8946918, PubMed:8940068, PubMed:9121459, CC PubMed:9535852, PubMed:10747973, PubMed:12646186). Phosphorylation on CC Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and CC XPO1/CRM1-dependent manner (PubMed:12917326). Phosphorylation on Ser- CC 307 is a prerequisite for phosphorylation on Ser-303 (PubMed:8940068). CC According to PubMed:9535852, Ser-303 is not phosphorylated in CC unstressed cells. Phosphorylated on Ser-419 by PLK1; phosphorylation CC promotes nuclear translocation upon heat shock (PubMed:15661742). CC Hyperphosphorylated upon heat shock and during the attenuation and CC recovery phase period of the heat shock response (PubMed:11447121, CC PubMed:12659875, PubMed:24581496). Phosphorylated on Thr-142; this CC phosphorylation increases HSF1 transactivation activity upon heat shock CC (PubMed:12659875). Phosphorylation on Ser-230 by CAMK2A; this CC phosphorylation enhances HSF1 transactivation activity upon heat shock CC (PubMed:11447121). Phosphorylation on Ser-326 by MAPK12; this CC phosphorylation enhances HSF1 nuclear translocation, homotrimerization CC and transactivation activities upon heat shock (PubMed:15760475, CC PubMed:27354066). Phosphorylated on Ser-320 by PRKACA/PKA; this CC phosphorylation promotes nuclear localization and transcriptional CC activity upon heat shock (PubMed:21085490). Phosphorylated on Ser-363 CC by MAPK8; this phosphorylation occurs upon heat shock, induces HSF1 CC translocation into nuclear stress bodies and negatively regulates CC transactivation activity (PubMed:10747973). Neither basal nor stress- CC inducible phosphorylation on Ser-230, Ser-292, Ser-303, Ser-307, Ser- CC 314, Ser-319, Ser-320, Thr-323, Ser-326, Ser-338, Ser-344, Ser-363, CC Thr-367, Ser-368 and Thr-369 within the regulatory domain is involved CC in the regulation of HSF1 subcellular localization or DNA-binding CC activity; however, it negatively regulates HSF1 transactivation CC activity (PubMed:25963659). Phosphorylated on Ser-216 by PLK1 in the CC early mitotic period; this phosphorylation regulates HSF1 localization CC to the spindle pole, the recruitment of the SCF(BTRC) ubiquitin ligase CC complex inducing HSF1 degradation, and hence mitotic progression CC (PubMed:18794143). Dephosphorylated on Ser-121, Ser-307, Ser-314, Thr- CC 323 and Thr-367 by phosphatase PPP2CA in an IER5-dependent manner, CC leading to HSF1-mediated transactivation activity (PubMed:26754925). CC {ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:10747973, CC ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998, CC ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12659875, CC ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:15760475, CC ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:18794143, CC ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:24581496, CC ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26159920, CC ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27354066, CC ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918, CC ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9499401, CC ECO:0000269|PubMed:9535852}. CC -!- PTM: Sumoylated with SUMO1 and SUMO2 upon heat shock in a ERK2- CC dependent manner (PubMed:12646186, PubMed:12665592). Sumoylated by CC SUMO1 on Lys-298; sumoylation occurs upon heat shock and promotes its CC localization to nuclear stress bodies and DNA-binding activity CC (PubMed:11514557). Phosphorylation on Ser-303 and Ser-307 is probably a CC prerequisite for sumoylation (PubMed:12646186, PubMed:12665592). CC {ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12646186, CC ECO:0000269|PubMed:12665592}. CC -!- PTM: Acetylated on Lys-118; this acetylation is decreased in a IER5- CC dependent manner (PubMed:26754925). Acetylated on Lys-118, Lys-208 and CC Lys-298; these acetylations occur in a EP300-dependent manner CC (PubMed:24581496, PubMed:27189267). Acetylated on Lys-80; this CC acetylation inhibits DNA-binding activity upon heat shock CC (PubMed:19229036). Deacetylated on Lys-80 by SIRT1; this deacetylation CC increases DNA-binding activity (PubMed:19229036). CC {ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:24581496, CC ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27189267}. CC -!- PTM: Ubiquitinated by SCF(BTRC) and degraded following stimulus- CC dependent phosphorylation at Ser-216 by PLK1 in mitosis CC (PubMed:18794143). Polyubiquitinated (PubMed:24581496). Undergoes CC proteasomal degradation upon heat shock and during the attenuation and CC recovery phase period of the heat shock response (PubMed:24581496). CC {ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:24581496}. CC -!- SIMILARITY: Belongs to the HSF family. {ECO:0000305}. 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; M64673; AAA52695.1; -; mRNA. DR EMBL; AK290975; BAF83664.1; -; mRNA. DR EMBL; BT007351; AAP36015.1; -; mRNA. DR EMBL; AC110280; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF205589; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014638; AAH14638.1; -; mRNA. DR CCDS; CCDS6419.1; -. [Q00613-1] DR PIR; A41137; A41137. DR RefSeq; NP_005517.1; NM_005526.3. [Q00613-1] DR RefSeq; XP_016868866.1; XM_017013377.1. [Q00613-2] DR PDB; 2LDU; NMR; -; A=10-123. DR PDB; 5D5U; X-ray; 2.91 A; B=1-120. DR PDB; 5D5V; X-ray; 2.55 A; B/D=1-120. DR PDB; 5HDG; X-ray; 1.70 A; A=15-120. DR PDB; 5HDN; X-ray; 1.68 A; A/B/C/D=15-120. DR PDB; 7DCJ; X-ray; 2.00 A; A/B=15-120. DR PDB; 7DCS; X-ray; 2.40 A; A/B/C/D/E/F=15-120. DR PDB; 7DCT; X-ray; 2.36 A; A/B/C/D/E/F=15-120. DR PDBsum; 2LDU; -. DR PDBsum; 5D5U; -. DR PDBsum; 5D5V; -. DR PDBsum; 5HDG; -. DR PDBsum; 5HDN; -. DR PDBsum; 7DCJ; -. DR PDBsum; 7DCS; -. DR PDBsum; 7DCT; -. DR AlphaFoldDB; Q00613; -. DR BMRB; Q00613; -. DR SMR; Q00613; -. DR BioGRID; 109530; 406. DR CORUM; Q00613; -. DR DIP; DIP-35670N; -. DR IntAct; Q00613; 51. DR MINT; Q00613; -. DR STRING; 9606.ENSP00000431512; -. DR BindingDB; Q00613; -. DR ChEMBL; CHEMBL5869; -. DR DrugBank; DB06258; Bimoclomol. DR MoonDB; Q00613; Predicted. DR GlyGen; Q00613; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q00613; -. DR MetOSite; Q00613; -. DR PhosphoSitePlus; Q00613; -. DR BioMuta; HSF1; -. DR DMDM; 462333; -. DR EPD; Q00613; -. DR jPOST; Q00613; -. DR MassIVE; Q00613; -. DR MaxQB; Q00613; -. DR PaxDb; 9606-ENSP00000431512; -. DR PeptideAtlas; Q00613; -. DR ProteomicsDB; 57864; -. [Q00613-1] DR ProteomicsDB; 57865; -. [Q00613-2] DR Pumba; Q00613; -. DR Antibodypedia; 1848; 2014 antibodies from 50 providers. DR DNASU; 3297; -. DR Ensembl; ENST00000528838.6; ENSP00000431512.1; ENSG00000185122.11. [Q00613-1] DR Ensembl; ENST00000646252.2; ENSP00000493830.1; ENSG00000284774.2. [Q00613-1] DR GeneID; 3297; -. DR KEGG; hsa:3297; -. DR MANE-Select; ENST00000528838.6; ENSP00000431512.1; NM_005526.4; NP_005517.1. DR UCSC; uc003zbt.5; human. [Q00613-1] DR AGR; HGNC:5224; -. DR CTD; 3297; -. DR DisGeNET; 3297; -. DR GeneCards; HSF1; -. DR HGNC; HGNC:5224; HSF1. DR HPA; ENSG00000185122; Low tissue specificity. DR MIM; 140580; gene. DR neXtProt; NX_Q00613; -. DR OpenTargets; ENSG00000185122; -. DR PharmGKB; PA29493; -. DR VEuPathDB; HostDB:ENSG00000185122; -. DR eggNOG; KOG0627; Eukaryota. DR GeneTree; ENSGT00940000158421; -. DR HOGENOM; CLU_038829_2_0_1; -. DR InParanoid; Q00613; -. DR OMA; MPIFFEL; -. DR OrthoDB; 1117127at2759; -. DR PhylomeDB; Q00613; -. DR TreeFam; TF330401; -. DR PathwayCommons; Q00613; -. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-HSA-3371511; HSF1 activation. DR Reactome; R-HSA-3371568; Attenuation phase. DR Reactome; R-HSA-3371571; HSF1-dependent transactivation. DR Reactome; R-HSA-9646399; Aggrephagy. DR SignaLink; Q00613; -. DR SIGNOR; Q00613; -. DR BioGRID-ORCS; 3297; 263 hits in 1179 CRISPR screens. DR ChiTaRS; HSF1; human. DR GeneWiki; HSF1; -. DR GenomeRNAi; 3297; -. DR Pharos; Q00613; Tchem. DR PRO; PR:Q00613; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q00613; Protein. DR Bgee; ENSG00000185122; Expressed in apex of heart and 99 other cell types or tissues. DR ExpressionAtlas; Q00613; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0000792; C:heterochromatin; IEA:Ensembl. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB. DR GO; GO:0097165; C:nuclear stress granule; IDA:UniProtKB. 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:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0101031; C:protein folding chaperone complex; IDA:GO_Central. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:ARUK-UCL. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0140296; F:general transcription initiation factor binding; IPI:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; IDA:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0001162; F:RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0098847; F:sequence-specific single stranded DNA binding; IEA:Ensembl. DR GO; GO:0097677; F:STAT family protein binding; IEA:Ensembl. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:ARUK-UCL. DR GO; GO:0061770; F:translation elongation factor binding; IDA:UniProtKB. DR GO; GO:1904385; P:cellular response to angiotensin; IEA:Ensembl. DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:UniProtKB. DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB. DR GO; GO:0072738; P:cellular response to diamide; IDA:UniProtKB. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:UniProtKB. DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:1904845; P:cellular response to L-glutamine; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:1904843; P:cellular response to nitroglycerin; IEA:Ensembl. DR GO; GO:0035865; P:cellular response to potassium ion; IEA:Ensembl. DR GO; GO:1903936; P:cellular response to sodium arsenite; IDA:UniProtKB. DR GO; GO:0034620; P:cellular response to unfolded protein; IDA:UniProtKB. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0006952; P:defense response; IEA:Ensembl. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0000165; P:MAPK cascade; IDA:UniProtKB. DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW. DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:2001033; P:negative regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0090084; P:negative regulation of inclusion body assembly; IEA:Ensembl. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:GO_Central. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:1902512; P:positive regulation of apoptotic DNA fragmentation; IEA:Ensembl. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:ARUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. DR GO; GO:0090261; P:positive regulation of inclusion body assembly; IEA:Ensembl. DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IMP:ARUK-UCL. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:1900034; P:regulation of cellular response to heat; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:1990910; P:response to hypobaric hypoxia; IEA:Ensembl. DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl. DR GO; GO:1990911; P:response to psychosocial stress; IEA:Ensembl. DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1. DR IDEAL; IID00461; -. DR InterPro; IPR000232; HSF_DNA-bd. DR InterPro; IPR027725; HSF_fam. DR InterPro; IPR010542; Vert_HSTF_C. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. DR PANTHER; PTHR10015:SF274; HEAT SHOCK FACTOR PROTEIN 1; 1. DR PANTHER; PTHR10015; HEAT SHOCK TRANSCRIPTION FACTOR; 1. DR Pfam; PF00447; HSF_DNA-bind; 1. DR Pfam; PF06546; Vert_HS_TF; 1. DR PRINTS; PR00056; HSFDOMAIN. DR SMART; SM00415; HSF; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS00434; HSF_DOMAIN; 1. DR Genevisible; Q00613; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; Centromere; KW Chromosome; Cytoplasm; Cytoskeleton; Direct protein sequencing; DNA damage; KW DNA repair; DNA-binding; Host-virus interaction; Isopeptide bond; KW Kinetochore; mRNA processing; mRNA transport; Nucleus; Phosphoprotein; KW Reference proteome; Stress response; Transcription; KW Transcription regulation; Transport; Ubl conjugation. FT CHAIN 1..529 FT /note="Heat shock factor protein 1" FT /id="PRO_0000124567" FT REGION 15..120 FT /note="DNA-binding domain" FT /evidence="ECO:0000269|PubMed:26727489, FT ECO:0000269|PubMed:7935471" FT REGION 130..203 FT /note="Hydrophobic repeat HR-A/B" FT /evidence="ECO:0000269|PubMed:7935471" FT REGION 203..224 FT /note="D domain" FT /evidence="ECO:0000269|PubMed:10747973" FT REGION 221..310 FT /note="Regulatory domain" FT /evidence="ECO:0000269|PubMed:7760831" FT REGION 295..324 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 336..372 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 371..529 FT /note="Transactivation domain" FT /evidence="ECO:0000269|PubMed:7623826, FT ECO:0000269|PubMed:7760831" FT REGION 384..409 FT /note="Hydrophobic repeat HR-C" FT /evidence="ECO:0000269|PubMed:7935471" FT REGION 444..463 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 502..529 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 412..420 FT /note="9aaTAD" FT /evidence="ECO:0000303|PubMed:17467953" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 80 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19229036, FT ECO:0000269|PubMed:24581496" FT MOD_RES 91 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:24581496" FT MOD_RES 118 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24581496, FT ECO:0000269|PubMed:26754925" FT MOD_RES 121 FT /note="Phosphoserine; by MAPKAPK2" FT /evidence="ECO:0000269|PubMed:15760475, FT ECO:0000269|PubMed:16278218" FT MOD_RES 142 FT /note="Phosphothreonine; by CK2" FT /evidence="ECO:0000269|PubMed:12659875" FT MOD_RES 150 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24581496" FT MOD_RES 188 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24581496" FT MOD_RES 208 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:24581496" FT MOD_RES 216 FT /note="Phosphoserine; by PLK1" FT /evidence="ECO:0000269|PubMed:18794143" FT MOD_RES 230 FT /note="Phosphoserine; by CAMK2A" FT /evidence="ECO:0000269|PubMed:11447121, FT ECO:0000269|PubMed:15760475" FT MOD_RES 275 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:8940068" FT MOD_RES 292 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15760475" FT MOD_RES 298 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:24581496" FT MOD_RES 303 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:11447121, FT ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:15760475, FT ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:8940068, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 307 FT /note="Phosphoserine; by MAPK3" FT /evidence="ECO:0000269|PubMed:11447121, FT ECO:0000269|PubMed:15760475, ECO:0000269|PubMed:8940068, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, FT ECO:0000269|PubMed:9535852, ECO:0007744|PubMed:23186163" FT MOD_RES 314 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15760475, FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 319 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15760475" FT MOD_RES 320 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:21085490, FT ECO:0000269|PubMed:27189267" FT MOD_RES 323 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:19690332" FT MOD_RES 326 FT /note="Phosphoserine; by MAPK12" FT /evidence="ECO:0000269|PubMed:15760475, FT ECO:0000269|PubMed:27354066, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15760475" FT MOD_RES 363 FT /note="Phosphoserine; by MAPK8" FT /evidence="ECO:0000269|PubMed:10747973, FT ECO:0000269|PubMed:15760475, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 419 FT /note="Phosphoserine; by PLK1" FT /evidence="ECO:0000269|PubMed:15661742" FT MOD_RES 444 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:15760475" FT MOD_RES 524 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24581496" FT CROSSLNK 91 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 126 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 131 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 208 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 224 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 298 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:11514557, FT ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:16371476" FT CROSSLNK 298 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 462..489 FT /note="GKQLVHYTAQPLFLLDPGSVDTGSNDLP -> AGALHSAAAVPAGPRLRGHR FT EQRPAGAV (in isoform Short)" FT /evidence="ECO:0000305" FT /id="VSP_002414" FT VAR_SEQ 490..529 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000305" FT /id="VSP_002415" FT MUTAGEN 22 FT /note="L->A: Inhibits HSEDNA-binding activity and FT transcriptional activation." FT /evidence="ECO:0000269|PubMed:9341107" FT MUTAGEN 80 FT /note="K->Q: Loss of nuclear stress bodies localization. FT Loss of DNA-binding and transcriptional activities upon FT heat shock. No change in homotrimerization upon heat FT shock." FT /evidence="ECO:0000269|PubMed:19229036, FT ECO:0000269|PubMed:24581496" FT MUTAGEN 80 FT /note="K->R: Does not change interaction with XRCC5 and FT XRCC6. Loss of nuclear stress bodies localization. FT Decreased nuclear stress bodies localization. Loss of FT DNA-binding and transcriptional activities upon heat FT shock." FT /evidence="ECO:0000269|PubMed:19229036, FT ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:26359349" FT MUTAGEN 91 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:12665592" FT MUTAGEN 118 FT /note="K->Q: Loss of nuclear stress bodies localization. No FT change in protein abundance." FT /evidence="ECO:0000269|PubMed:24581496" FT MUTAGEN 118 FT /note="K->R: No change in nuclear stress bodies FT localization." FT /evidence="ECO:0000269|PubMed:24581496" FT MUTAGEN 120 FT /note="T->A: No effect on binding HSE nor on FT transcriptional activity." FT /evidence="ECO:0000269|PubMed:16278218" FT MUTAGEN 121 FT /note="S->A: Increased binding HSE and transcriptional FT activity. Greatly reduced binding to HSP90AA1. No effect on FT MAPKAPK2 binding." FT /evidence="ECO:0000269|PubMed:16278218" FT MUTAGEN 121 FT /note="S->D: Some inhibition of binding HSE and FT transcriptional activity. No change in binding HSP90AA1. FT Inhibits MAPKAPK2 binding. Decreased HSF1-induced FT expression of HSPA1A mRNA in a IER5-dependent manner; when FT associated with D-307; D-314; D-323 and D-367." FT /evidence="ECO:0000269|PubMed:16278218, FT ECO:0000269|PubMed:26754925" FT MUTAGEN 123 FT /note="S->A: No effect on binding HSE nor on FT transcriptional activity." FT /evidence="ECO:0000269|PubMed:16278218" FT MUTAGEN 124 FT /note="T->A: No effect on binding HSE nor on FT transcriptional activity." FT /evidence="ECO:0000269|PubMed:16278218" FT MUTAGEN 126 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:12665592" FT MUTAGEN 140 FT /note="L->K: Leads to constitutive homotrimerization and FT DNA-binding activities at 20 degrees Celsius. Does not lead FT to constitutive transactivation activity at 20 degrees FT Celsius. Decreased DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7623826, FT ECO:0000269|PubMed:7935471" FT MUTAGEN 142 FT /note="T->A: Reduced promoter activity by about 90%. Almost FT no transcriptional activity when coexpressed with CK2." FT /evidence="ECO:0000269|PubMed:12659875" FT MUTAGEN 147 FT /note="M->A: Leads to constitutive homotrimerization and FT DNA-binding activities at 20 degrees Celsius. Does not lead FT to constitutive transactivation activity at 20 degrees FT Celsius. No effect on DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7623826, FT ECO:0000269|PubMed:7935471" FT MUTAGEN 147 FT /note="M->E: Does not lead to constitutive FT homotrimerization and DNA-binding activities at 20 degrees FT Celsius. Loss of DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 147 FT /note="M->K: Does not lead to constitutive FT homotrimerization and DNA-binding activities at 20 degrees FT Celsius. Loss of DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 150 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:12665592" FT MUTAGEN 162 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:12665592" FT MUTAGEN 189 FT /note="L->A: Does not lead to constitutive FT homotrimerization and DNA-binding activities at 20 degrees FT Celsius. Leads to constitutive homotrimerization and FT DNA-binding activities at 30 degrees Celsius. No effect on FT DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 189 FT /note="L->E: Leads to constitutive homotrimerization, FT DNA-binding and transactivation activities at 20 degrees FT Celsius. Decreased DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7623826, FT ECO:0000269|PubMed:7935471" FT MUTAGEN 189 FT /note="L->K: Leads to constitutive homotrimerization and FT DNA-binding activities at 20 degrees Celsius. No effect on FT DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 193 FT /note="L->A: Does not lead to constitutive FT homotrimerization and DNA-binding activities at 20 degrees FT Celsius. Leads to constitutive homotrimerization and FT DNA-binding activities at 30 degrees Celsius. No effect on FT DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 193 FT /note="L->E: Leads to constitutive homotrimerization and FT DNA-binding activities at 20 degrees Celsius. Decreased FT DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 193 FT /note="L->K: Leads to constitutive homotrimerization and FT DNA-binding activities at 20 degrees Celsius. Loss of FT DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 208 FT /note="K->Q: No change in nuclear stress bodies FT localization. Increased protein abundance." FT /evidence="ECO:0000269|PubMed:24581496" FT MUTAGEN 208 FT /note="K->R: No change in nuclear stress bodies FT localization. No change in protein abundance." FT /evidence="ECO:0000269|PubMed:24581496" FT MUTAGEN 216 FT /note="S->A: Does not change interaction with XRCC5 and FT XRCC6. No PLK1-induced phosphorylation in mitosis. Inhibits FT PLK1-stimulated ubiquitinylation. Increased protein FT stability." FT /evidence="ECO:0000269|PubMed:18794143, FT ECO:0000269|PubMed:26359349" FT MUTAGEN 216 FT /note="S->E: Does not change interaction with XRCC5 and FT XRCC6. No change in spindle pole localization. Increases FT weakly PLK1-stimulated ubiquitinylation. No change in FT protein stability. Increased interaction with BTRC." FT /evidence="ECO:0000269|PubMed:18794143, FT ECO:0000269|PubMed:26359349" FT MUTAGEN 216 FT /note="S->N: Decreased spindle pole localization. Decreased FT interaction with BTRC. Increased protein stability." FT /evidence="ECO:0000269|PubMed:18794143" FT MUTAGEN 230 FT /note="S->A: No phosphorylation. No change in PLK1-induced FT phosphorylation in mitosis. No change in DNA-binding FT activity upon heat shock. Decreased transcriptional FT activity upon heat shock." FT /evidence="ECO:0000269|PubMed:11447121, FT ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143" FT MUTAGEN 230 FT /note="S->D: Mimics phosphorylation. No effect on FT transcriptional activity upon heat shock." FT /evidence="ECO:0000269|PubMed:11447121, FT ECO:0000269|PubMed:12665592" FT MUTAGEN 275 FT /note="S->A: Reduced increase in heat-induced FT transcriptional activity." FT /evidence="ECO:0000269|PubMed:9535852" FT MUTAGEN 275 FT /note="S->G: Leads to weak constitutive transactivation FT activity at room temperature." FT /evidence="ECO:0000269|PubMed:8940068" FT MUTAGEN 292 FT /note="S->A: Weak decreased PLK1-induced phosphorylation. FT Increased nuclear localization upon heat shock." FT /evidence="ECO:0000269|PubMed:15661742" FT MUTAGEN 296 FT /note="R->A: No effect neither on repression of FT transcriptional activity at control temperature nor on FT transcriptional activation upon heat shock." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 297 FT /note="V->A: Slight effect on derepression of FT transcriptional activity at control temperature and on FT transcriptional activation upon heat shock." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 298 FT /note="K->A: Induces derepression of transcriptional FT activity at control temperature." FT /evidence="ECO:0000269|PubMed:12665592, FT ECO:0000269|PubMed:8946918" FT MUTAGEN 298 FT /note="K->Q: No change in nuclear stress bodies FT localization. Increased protein abundance." FT /evidence="ECO:0000269|PubMed:24581496" FT MUTAGEN 298 FT /note="K->R: Abolishes sumoylation. No effect on FT phosphorylation of S-303 nor of S-307. No change in FT subcellular location to nuclear stress granules upon heat FT shock. Loss of colocalization with SUMO1 to nuclear stress FT granules upon heat shock. Does not change interaction with FT XRCC5 and XRCC6. No effect on binding to HSE nor on FT transactivation of HSP70. Increases transcriptional FT activity in a DAXX-dependent manner. No change in protein FT abundance." FT /evidence="ECO:0000269|PubMed:11514557, FT ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592, FT ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:24581496, FT ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:8946918" FT MUTAGEN 299 FT /note="E->A: No effect on repression of transcriptional FT activity at control temperature." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 300 FT /note="E->A: Induces derepression of transcriptional FT activity at control temperature." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 303 FT /note="S->A: No phosphorylation nor sumoylation. No change FT in nuclear stress granules subcellular location upon heat FT shock. Loss of colocalization with SUMO1 to nuclear stress FT granules upon heat shock. Slight decrease in FT transcriptional activity on heat treatment. No change in FT PLK1-induced phosphorylation in mitosis, induces FT derepression of transcription activation at control FT temperature, abolishes sumoylation and induces 2.5-fold FT increase in transcriptional activity on heat treatment; FT when associated with A-307." FT /evidence="ECO:0000269|PubMed:12646186, FT ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, FT ECO:0000269|PubMed:9535852" FT MUTAGEN 303 FT /note="S->D: Mimics phosphorylation. No effect on in vitro FT sumoylation. Greatly increased transcriptional activity on FT heat induction. 5-fold derepression of transcriptional FT activity at control temperature; when associated with FT D-307." FT /evidence="ECO:0000269|PubMed:12665592, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, FT ECO:0000269|PubMed:9535852" FT MUTAGEN 303 FT /note="S->G: Leads to constitutive transactivation activity FT at room temperature. Inhibits interaction with YWHAE and FT increases cytoplasmic localization; when associated with FT G-307." FT /evidence="ECO:0000269|PubMed:12917326, FT ECO:0000269|PubMed:8940068" FT MUTAGEN 307 FT /note="S->A: No phosphorylation. Does not reduce Ser-303 FT phosphorylation. 1.5% increase in transcriptional activity FT on heat-treatment. No change in PLK1-induced FT phosphorylation in mitosis, induces derepression of FT transcription activation at control temperature, abolishes FT sumoylation and induces 2.5-fold increase in FT transcriptional activity on heat treatment; when associated FT with A-303." FT /evidence="ECO:0000269|PubMed:12646186, FT ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459, FT ECO:0000269|PubMed:9535852" FT MUTAGEN 307 FT /note="S->D: 5-fold derepression of transcriptional FT activity at control temperature; when associated with FT D-303. Decreased HSF1-induced expression of HSPA1A mRNA in FT a IER5-dependent manner; when associated with D-121; D-314; FT D-323 and D-367." FT /evidence="ECO:0000269|PubMed:26754925, FT ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459" FT MUTAGEN 307 FT /note="S->G: Leads to constitutive transactivation activity FT at room temperature. Inhibits interaction with YWHAE and FT increases cytoplasmic localization; when associated with FT G-303." FT /evidence="ECO:0000269|PubMed:12917326, FT ECO:0000269|PubMed:8940068" FT MUTAGEN 309 FT /note="R->A: No effect on repression of transcriptional FT activity at control temperature." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 311 FT /note="E->A: No effect neither on repression of FT transcriptional activity at control temperature nor on FT transcriptional activation upon heat shock." FT /evidence="ECO:0000269|PubMed:8946918" FT MUTAGEN 314 FT /note="S->A: Weak decreased PLK1-induced phosphorylation." FT /evidence="ECO:0000269|PubMed:15661742" FT MUTAGEN 314 FT /note="S->D: Decreased HSF1-induced expression of HSPA1A FT mRNA in a IER5-dependent manner; when associated with FT D-121; D-307; D-323 and D-367." FT /evidence="ECO:0000269|PubMed:26754925" FT MUTAGEN 319 FT /note="S->A: Weak decreased PLK1-induced phosphorylation." FT /evidence="ECO:0000269|PubMed:15661742" FT MUTAGEN 320 FT /note="S->A: Decreased nuclear localization and FT transcriptional activity upon heat shock." FT /evidence="ECO:0000269|PubMed:21085490" FT MUTAGEN 320 FT /note="S->D: Increased nuclear localization and FT transcriptional activity upon heat shock." FT /evidence="ECO:0000269|PubMed:21085490" FT MUTAGEN 323 FT /note="T->D: Decreased HSF1-induced expression of HSPA1A FT mRNA in a IER5-dependent manner; when associated with FT D-121; D-307; D-314 and D-367." FT /evidence="ECO:0000269|PubMed:26754925" FT MUTAGEN 326 FT /note="S->A: No phosphorylation. Increased nuclear FT localization upon heat shock. No effect on oligomerization, FT DNA-binding activities and nuclear localization. FT Significant decrease in transcriptional activity by heat FT shock. Decreases transcriptional activity in a FT DAXX-dependent manner. Does not change interaction with FT XRCC5 and XRCC6. Weak decreased PLK1-induced FT phosphorylation." FT /evidence="ECO:0000269|PubMed:15016915, FT ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:15760475, FT ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066" FT MUTAGEN 326 FT /note="S->E: Does not change interaction with XRCC5 and FT XRCC6." FT /evidence="ECO:0000269|PubMed:26359349" FT MUTAGEN 363 FT /note="S->A: Decreases MAPK8-induced phosphorylation and FT does not negatively regulates transactivating activity upon FT heat shock. No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:10747973, FT ECO:0000269|PubMed:12665592" FT MUTAGEN 367 FT /note="T->D: Decreased HSF1-induced expression of HSPA1A FT mRNA in a IER5-dependent manner; when associated with FT D-121; D-307; D-314 and D-323." FT /evidence="ECO:0000269|PubMed:26754925" FT MUTAGEN 381 FT /note="K->R: No effect on sumoylation." FT /evidence="ECO:0000269|PubMed:12665592" FT MUTAGEN 391 FT /note="M->A: Does not lead to constitutive DNA-binding FT activity at 20 degrees Celsius. Leads to weak constitutive FT DNA-binding and homotrimerization activities at 30 degrees FT Celsius. Decreased DNA-binding activity at 37 degrees FT Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 391 FT /note="M->E: Leads to constitutive DNA-binding and FT homotrimerization activities at 20 degrees Celsius. Does FT not lead to constitutive transactivation activity at 20 FT degrees Celsius. No effect on DNA-binding activity at 37 FT degrees Celsius." FT /evidence="ECO:0000269|PubMed:7623826, FT ECO:0000269|PubMed:7935471" FT MUTAGEN 391 FT /note="M->K: Leads to constitutive DNA-binding and FT homotrimerization activities at 20 degrees Celsius. No FT effect on DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 395 FT /note="L->E: Leads to constitutive DNA-binding and FT homotrimerization activities at 20 degrees Celsius. No FT effect on DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 395 FT /note="L->K: Leads to constitutive DNA-binding and FT homotrimerization activities at 20 degrees Celsius. No FT effect on DNA-binding activity at 37 degrees Celsius." FT /evidence="ECO:0000269|PubMed:7935471" FT MUTAGEN 419 FT /note="S->A: Does not change interaction with XRCC5 and FT XRCC6. Decreased nuclear localization upon heat shock. FT Strongly decreases PLK1-induced phosphorylation. No change FT in PLK1-induced phosphorylation in mitosis." FT /evidence="ECO:0000269|PubMed:15661742, FT ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:26359349" FT MUTAGEN 419 FT /note="S->E: Does not change interaction with XRCC5 and FT XRCC6." FT /evidence="ECO:0000269|PubMed:26359349" FT MUTAGEN 527 FT /note="T->A: No change in binding HSE nor on FT transcriptional activity. Decreased binding HSE; when FT associated with A-529." FT /evidence="ECO:0000269|PubMed:16278218" FT MUTAGEN 529 FT /note="S->A: No change in binding HSE nor on FT transcriptional activity. Decreased binding HSE; when FT associated with A-527." FT /evidence="ECO:0000269|PubMed:16278218" FT HELIX 17..27 FT /evidence="ECO:0007829|PDB:5HDN" FT HELIX 29..31 FT /evidence="ECO:0007829|PDB:5HDN" FT TURN 32..34 FT /evidence="ECO:0007829|PDB:5HDN" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:5HDN" FT STRAND 39..42 FT /evidence="ECO:0007829|PDB:5D5U" FT STRAND 44..47 FT /evidence="ECO:0007829|PDB:5HDN" FT HELIX 49..55 FT /evidence="ECO:0007829|PDB:5HDN" FT HELIX 57..60 FT /evidence="ECO:0007829|PDB:5HDN" FT HELIX 66..75 FT /evidence="ECO:0007829|PDB:5HDN" FT STRAND 79..83 FT /evidence="ECO:0007829|PDB:5HDN" FT STRAND 87..89 FT /evidence="ECO:0007829|PDB:7DCJ" FT STRAND 96..100 FT /evidence="ECO:0007829|PDB:5HDN" FT HELIX 109..114 FT /evidence="ECO:0007829|PDB:5HDN" SQ SEQUENCE 529 AA; 57260 MW; 735074507C954365 CRC64; MDLPVGPGAA GPSNVPAFLT KLWTLVSDPD TDALICWSPS GNSFHVFDQG QFAKEVLPKY FKHNNMASFV RQLNMYGFRK VVHIEQGGLV KPERDDTEFQ HPCFLRGQEQ LLENIKRKVT SVSTLKSEDI KIRQDSVTKL LTDVQLMKGK QECMDSKLLA MKHENEALWR EVASLRQKHA QQQKVVNKLI QFLISLVQSN RILGVKRKIP LMLNDSGSAH SMPKYSRQFS LEHVHGSGPY SAPSPAYSSS SLYAPDAVAS SGPIISDITE LAPASPMASP GGSIDERPLS SSPLVRVKEE PPSPPQSPRV EEASPGRPSS VDTLLSPTAL IDSILRESEP APASVTALTD ARGHTDTEGR PPSPPPTSTP EKCLSVACLD KNELSDHLDA MDSNLDNLQT MLSSHGFSVD TSALLDLFSP SVTVPDMSLP DLDSSLASIQ ELLSPQEPPR PPEAENSSPD SGKQLVHYTA QPLFLLDPGS VDTGSNDLPV LFELGEGSYF SEGDGFAEDP TISLLTGSEP PKAKDPTVS //