HSF1_HUMAN
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 03-AUG-2022, entry version 208.
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 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 insults' 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). Also serves
CC several other functions independently of its transcriptional activity.
CC Involved in the repression of Ras-induced transcriptional activation of
CC the c-fos gene in heat-stressed cells (PubMed:9341107). Positively
CC regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA
CC upon heat-stressed cells in a symplekin (SYMPK)-dependent manner
CC (PubMed:14707147). Plays a role in nuclear export of stress-induced
CC HSP70 mRNA (PubMed:17897941). Plays a role in the regulation of mitotic
CC 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:7623826,
CC ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471,
CC ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068,
CC ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
CC ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401,
CC ECO:0000269|PubMed:9535852, 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}.
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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; 158.
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; 1 site, 1 O-linked glycan (1 site).
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; Q00613; -.
DR PeptideAtlas; Q00613; -.
DR PRIDE; Q00613; -.
DR ProteomicsDB; 57864; -. [Q00613-1]
DR ProteomicsDB; 57865; -. [Q00613-2]
DR Antibodypedia; 1848; 1788 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 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; LICWSPQ; -.
DR OrthoDB; 1154048at2759; -.
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; 239 hits in 1102 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 97 other tissues.
DR ExpressionAtlas; Q00613; baseline and differential.
DR Genevisible; Q00613; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0101031; C:chaperone complex; IDA:GO_Central.
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:UniProtKB.
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: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: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; IDA:UniProtKB.
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:0009299; P:mRNA transcription; IDA:UniProtKB.
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:1901215; P:negative regulation of neuron death; 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:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
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:1904528; P:positive regulation of microtubule binding; IEA:Ensembl.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:1900365; P:positive regulation of mRNA polyadenylation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0061408; P:positive regulation of transcription from RNA polymerase II promoter in response to heat stress; 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; IBA:GO_Central.
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; -; 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; PTHR10015; 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; SSF46785; 1.
DR PROSITE; PS00434; HSF_DOMAIN; 1.
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 HSE DNA-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 DNA-
FT binding and transcriptional activities upon heat 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 DNA-
FT binding activities at 30 degrees Celsius. No effect on DNA-
FT binding activity at 37 degrees Celsius."
FT /evidence="ECO:0000269|PubMed:7935471"
FT MUTAGEN 189
FT /note="L->E: Leads to constitutive homotrimerization, DNA-
FT 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 DNA-
FT binding activities at 30 degrees Celsius. No effect on DNA-
FT 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 DNA-
FT 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 D-
FT 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 G-
FT 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 D-
FT 303. Decreased HSF1-induced expression of HSPA1A mRNA in a
FT 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 G-
FT 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 D-
FT 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 D-
FT 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 DAXX-
FT dependent manner. Does not change interaction with XRCC5
FT and XRCC6. Weak decreased PLK1-induced 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 D-
FT 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
