LOCUS HSF1_HUMAN 529 aa linear PRI 27-NOV-2024
DEFINITION RecName: Full=Heat shock factor protein 1; Short=HSF 1; AltName:
Full=Heat shock transcription factor 1; Short=HSTF 1.
ACCESSION Q00613
VERSION Q00613.1
DBSOURCE UniProtKB: locus HSF1_HUMAN, accession Q00613;
class: standard.
extra accessions:A8K4L0,A8MW26,Q53XT4
created: Feb 1, 1994.
sequence updated: Feb 1, 1994.
annotation updated: Nov 27, 2024.
xrefs: M64673.1, AAA52695.1, AK290975.1, BAF83664.1, BT007351.1,
AAP36015.1, AC110280.8, AF205589.5, BC014638.1, AAH14638.1, A41137,
NP_005517.1, XP_016868866.1, 2LDU_A, 5D5U_B, 5D5V_B, 5D5V_D,
5HDG_A, 5HDN_A, 5HDN_B, 5HDN_C, 5HDN_D, 7DCJ_A, 7DCJ_B, 7DCS_A,
7DCS_B, 7DCS_C, 7DCS_D, 7DCS_E, 7DCS_F, 7DCT_A, 7DCT_B, 7DCT_C,
7DCT_D, 7DCT_E, 7DCT_F
xrefs (non-sequence databases): CCDS:CCDS6419.1, PDBsum:2LDU,
PDBsum:5D5U, PDBsum:5D5V, PDBsum:5HDG, PDBsum:5HDN, PDBsum:7DCJ,
PDBsum:7DCS, PDBsum:7DCT, AlphaFoldDB:Q00613, BMRB:Q00613,
SMR:Q00613, BioGRID:109530, CORUM:Q00613, DIP:DIP-35670N,
IntAct:Q00613, MINT:Q00613, STRING:9606.ENSP00000431512,
BindingDB:Q00613, ChEMBL:CHEMBL5869, DrugBank:DB06258,
MoonDB:Q00613, GlyGen:Q00613, iPTMnet:Q00613, MetOSite:Q00613,
PhosphoSitePlus:Q00613, BioMuta:HSF1, DMDM:462333, jPOST:Q00613,
MassIVE:Q00613, PaxDb:9606-ENSP00000431512, PeptideAtlas:Q00613,
ProteomicsDB:57864, ProteomicsDB:57865, Pumba:Q00613,
Antibodypedia:1848, DNASU:3297, Ensembl:ENST00000528838.6,
Ensembl:ENSP00000431512.1, Ensembl:ENSG00000185122.11,
Ensembl:ENST00000646252.2, Ensembl:ENSP00000493830.1,
Ensembl:ENSG00000284774.2, GeneID:3297, KEGG:hsa:3297,
MANE-Select:ENST00000528838.6, UCSC:uc003zbt.5, AGR:HGNC:5224,
CTD:3297, DisGeNET:3297, GeneCards:HSF1, HGNC:5224,
HPA:ENSG00000185122, MIM 140580, neXtProt:NX_Q00613,
OpenTargets:ENSG00000185122, PharmGKB:PA29493,
VEuPathDB:HostDB:ENSG00000185122, eggNOG:KOG0627,
GeneTree:ENSGT00940000158421, HOGENOM:CLU_038829_2_0_1,
InParanoid:Q00613, OMA:MPIFFEL, OrthoDB:1117127at2759,
PhylomeDB:Q00613, TreeFam:TF330401, PathwayCommons:Q00613,
Reactome:R-HSA-3371453, Reactome:R-HSA-3371511,
Reactome:R-HSA-3371568, Reactome:R-HSA-3371571,
Reactome:R-HSA-9646399, SignaLink:Q00613, SIGNOR:Q00613,
BioGRID-ORCS:3297, ChiTaRS:HSF1, EvolutionaryTrace:Q00613,
GeneWiki:HSF1, GenomeRNAi:3297, Pharos:Q00613, PRO:PR:Q00613,
Proteomes:UP000005640, RNAct:Q00613, Bgee:ENSG00000185122,
ExpressionAtlas:Q00613, GO:0005813, GO:0000785, GO:0005737,
GO:0005829, GO:0000791, GO:0000792, GO:0000776, GO:0097431,
GO:0097165, GO:0005654, GO:0005634, GO:0048471, GO:0016605,
GO:0101031, GO:1990904, GO:0031490, GO:0003677, GO:0001228,
GO:0003700, GO:0000981, GO:0001227, GO:0140296, GO:0031072,
GO:0051879, GO:0042802, GO:1990841, GO:0046982, GO:0019901,
GO:0000978, GO:0001162, GO:0043565, GO:1990837, GO:0098847,
GO:0097677, GO:0000976, GO:0061770, GO:1904385, GO:0071276,
GO:0071280, GO:0072738, GO:0071392, GO:0071480, GO:0034605,
GO:0070301, GO:1904845, GO:0071222, GO:1904843, GO:0035865,
GO:1903936, GO:0034620, GO:0071466, GO:0006952, GO:0006281,
GO:0000165, GO:0006397, GO:0051028, GO:0010667, GO:2001033,
GO:0010629, GO:0090084, GO:0031333, GO:0000122, GO:1902512,
GO:0120162, GO:0051091, GO:0010628, GO:0090261, GO:0045651,
GO:0045931, GO:0062029, GO:0045944, GO:0065003, GO:1900034,
GO:0006357, GO:0014823, GO:1990910, GO:0007584, GO:1901652,
GO:1990911, GO:0033574, FunFam:1.10.10.10:FF:000027,
Gene3D:1.10.10.10, IDEAL:IID00461, InterPro:IPR000232,
InterPro:IPR027725, InterPro:IPR010542, InterPro:IPR036388,
InterPro:IPR036390, PANTHER:PTHR10015:SF274, PANTHER:PTHR10015,
Pfam:PF00447, Pfam:PF06546, PRINTS:PR00056, SMART:SM00415,
SUPFAM:SSF46785, PROSITE:PS00434
KEYWORDS 3D-structure; Acetylation; Activator; Alternative splicing;
Centromere; Chromosome; Cytoplasm; Cytoskeleton; Direct protein
sequencing; DNA damage; DNA repair; DNA-binding; Host-virus
interaction; Isopeptide bond; Kinetochore; mRNA processing; mRNA
transport; Nucleus; Phosphoprotein; Proteomics identification;
Reference proteome; Stress response; Transcription; Transcription
regulation; Transport; Ubl conjugation.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 529)
AUTHORS Rabindran,S.K., Giorgi,G., Clos,J. and Wu,C.
TITLE Molecular cloning and expression of a human heat shock factor, HSF1
JOURNAL Proc Natl Acad Sci U S A 88 (16), 6906-6910 (1991)
PUBMED 1871105
REMARK NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DNA-BINDING.
REFERENCE 2 (residues 1 to 529)
AUTHORS Ota,T., Suzuki,Y., Nishikawa,T., Otsuki,T., Sugiyama,T., Irie,R.,
Wakamatsu,A., Hayashi,K., Sato,H., Nagai,K., Kimura,K., Makita,H.,
Sekine,M., Obayashi,M., Nishi,T., Shibahara,T., Tanaka,T.,
Ishii,S., Yamamoto,J., Saito,K., Kawai,Y., Isono,Y., Nakamura,Y.,
Nagahari,K., Murakami,K., Yasuda,T., Iwayanagi,T., Wagatsuma,M.,
Shiratori,A., Sudo,H., Hosoiri,T., Kaku,Y., Kodaira,H., Kondo,H.,
Sugawara,M., Takahashi,M., Kanda,K., Yokoi,T., Furuya,T.,
Kikkawa,E., Omura,Y., Abe,K., Kamihara,K., Katsuta,N., Sato,K.,
Tanikawa,M., Yamazaki,M., Ninomiya,K., Ishibashi,T., Yamashita,H.,
Murakawa,K., Fujimori,K., Tanai,H., Kimata,M., Watanabe,M.,
Hiraoka,S., Chiba,Y., Ishida,S., Ono,Y., Takiguchi,S., Watanabe,S.,
Yosida,M., Hotuta,T., Kusano,J., Kanehori,K., Takahashi-Fujii,A.,
Hara,H., Tanase,T.O., Nomura,Y., Togiya,S., Komai,F., Hara,R.,
Takeuchi,K., Arita,M., Imose,N., Musashino,K., Yuuki,H., Oshima,A.,
Sasaki,N., Aotsuka,S., Yoshikawa,Y., Matsunawa,H., Ichihara,T.,
Shiohata,N., Sano,S., Moriya,S., Momiyama,H., Satoh,N., Takami,S.,
Terashima,Y., Suzuki,O., Nakagawa,S., Senoh,A., Mizoguchi,H.,
Goto,Y., Shimizu,F., Wakebe,H., Hishigaki,H., Watanabe,T.,
Sugiyama,A., Takemoto,M., Kawakami,B., Yamazaki,M., Watanabe,K.,
Kumagai,A., Itakura,S., Fukuzumi,Y., Fujimori,Y., Komiyama,M.,
Tashiro,H., Tanigami,A., Fujiwara,T., Ono,T., Yamada,K., Fujii,Y.,
Ozaki,K., Hirao,M., Ohmori,Y., Kawabata,A., Hikiji,T., Kobatake,N.,
Inagaki,H., Ikema,Y., Okamoto,S., Okitani,R., Kawakami,T.,
Noguchi,S., Itoh,T., Shigeta,K., Senba,T., Matsumura,K.,
Nakajima,Y., Mizuno,T., Morinaga,M., Sasaki,M., Togashi,T.,
Oyama,M., Hata,H., Watanabe,M., Komatsu,T., Mizushima-Sugano,J.,
Satoh,T., Shirai,Y., Takahashi,Y., Nakagawa,K., Okumura,K.,
Nagase,T., Nomura,N., Kikuchi,H., Masuho,Y., Yamashita,R.,
Nakai,K., Yada,T., Nakamura,Y., Ohara,O., Isogai,T. and Sugano,S.
TITLE Complete sequencing and characterization of 21,243 full-length
human cDNAs
JOURNAL Nat Genet 36 (1), 40-45 (2004)
PUBMED 14702039
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
REFERENCE 3 (residues 1 to 529)
AUTHORS Kalnine,N., Chen,X., Rolfs,A., Halleck,A., Hines,L., Eisenstein,S.,
Koundinya,M., Raphael,J., Moreira,D., Kelley,T., LaBaer,J., Lin,Y.,
Phelan,M. and Farmer,A.
TITLE Direct Submission
JOURNAL Submitted (??-MAY-2003) to the EMBL/GenBank/DDBJ databases
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
REFERENCE 4 (residues 1 to 529)
AUTHORS Nusbaum,C., Mikkelsen,T.S., Zody,M.C., Asakawa,S., Taudien,S.,
Garber,M., Kodira,C.D., Schueler,M.G., Shimizu,A., Whittaker,C.A.,
Chang,J.L., Cuomo,C.A., Dewar,K., FitzGerald,M.G., Yang,X.,
Allen,N.R., Anderson,S., Asakawa,T., Blechschmidt,K., Bloom,T.,
Borowsky,M.L., Butler,J., Cook,A., Corum,B., DeArellano,K.,
DeCaprio,D., Dooley,K.T., Dorris,L. III, Engels,R., Glockner,G.,
Hafez,N., Hagopian,D.S., Hall,J.L., Ishikawa,S.K., Jaffe,D.B.,
Kamat,A., Kudoh,J., Lehmann,R., Lokitsang,T., Macdonald,P.,
Major,J.E., Matthews,C.D., Mauceli,E., Menzel,U., Mihalev,A.H.,
Minoshima,S., Murayama,Y., Naylor,J.W., Nicol,R., Nguyen,C.,
O'Leary,S.B., O'Neill,K., Parker,S.C., Polley,A., Raymond,C.K.,
Reichwald,K., Rodriguez,J., Sasaki,T., Schilhabel,M., Siddiqui,R.,
Smith,C.L., Sneddon,T.P., Talamas,J.A., Tenzin,P., Topham,K.,
Venkataraman,V., Wen,G., Yamazaki,S., Young,S.K., Zeng,Q.,
Zimmer,A.R., Rosenthal,A., Birren,B.W., Platzer,M., Shimizu,N. and
Lander,E.S.
TITLE DNA sequence and analysis of human chromosome 8
JOURNAL Nature 439 (7074), 331-335 (2006)
PUBMED 16421571
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
REFERENCE 5 (residues 1 to 529)
AUTHORS Gerhard,D.S., Wagner,L., Feingold,E.A., Shenmen,C.M., Grouse,L.H.,
Schuler,G., Klein,S.L., Old,S., Rasooly,R., Good,P., Guyer,M.,
Peck,A.M., Derge,J.G., Lipman,D., Collins,F.S., Jang,W., Sherry,S.,
Feolo,M., Misquitta,L., Lee,E., Rotmistrovsky,K., Greenhut,S.F.,
Schaefer,C.F., Buetow,K., Bonner,T.I., Haussler,D., Kent,J.,
Kiekhaus,M., Furey,T., Brent,M., Prange,C., Schreiber,K.,
Shapiro,N., Bhat,N.K., Hopkins,R.F., Hsie,F., Driscoll,T.,
Soares,M.B., Casavant,T.L., Scheetz,T.E., Brown-stein,M.J.,
Usdin,T.B., Toshiyuki,S., Carninci,P., Piao,Y., Dudekula,D.B.,
Ko,M.S., Kawakami,K., Suzuki,Y., Sugano,S., Gruber,C.E.,
Smith,M.R., Simmons,B., Moore,T., Waterman,R., Johnson,S.L.,
Ruan,Y., Wei,C.L., Mathavan,S., Gunaratne,P.H., Wu,J., Garcia,A.M.,
Hulyk,S.W., Fuh,E., Yuan,Y., Sneed,A., Kowis,C., Hodgson,A.,
Muzny,D.M., McPherson,J., Gibbs,R.A., Fahey,J., Helton,E.,
Ketteman,M., Madan,A., Rodrigues,S., Sanchez,A., Whiting,M.,
Madari,A., Young,A.C., Wetherby,K.D., Granite,S.J., Kwong,P.N.,
Brinkley,C.P., Pearson,R.L., Bouffard,G.G., Blakesly,R.W.,
Green,E.D., Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J.,
Myers,R.M., Butterfield,Y.S., Griffith,M., Griffith,O.L.,
Krzywinski,M.I., Liao,N., Morin,R., Palmquist,D., Petrescu,A.S.,
Skalska,U., Smailus,D.E., Stott,J.M., Schnerch,A., Schein,J.E.,
Jones,S.J., Holt,R.A., Baross,A., Marra,M.A., Clifton,S.,
Makowski,K.A., Bosak,S. and Malek,J.
CONSRTM MGC Project Team
TITLE The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC)
JOURNAL Genome Res 14 (10B), 2121-2127 (2004)
PUBMED 15489334
REMARK NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).;
TISSUE=Muscle
Erratum:[Genome Res. 2006 Jun;16(6):804. Morrin, Ryan [corrected to
Morin, Ryan]]
REFERENCE 6 (residues 1 to 529)
AUTHORS Schuetz,T.J., Gallo,G.J., Sheldon,L., Tempst,P. and Kingston,R.E.
TITLE Isolation of a cDNA for HSF2: evidence for two heat shock factor
genes in humans
JOURNAL Proc Natl Acad Sci U S A 88 (16), 6911-6915 (1991)
PUBMED 1871106
REMARK PROTEIN SEQUENCE OF 73-79; 81-93; 97-106; 163-170 AND 337-352.
REFERENCE 7 (residues 1 to 529)
AUTHORS Holmberg,C.I., Hietakangas,V., Mikhailov,A., Rantanen,J.O.,
Kallio,M., Meinander,A., Hellman,J., Morrice,N., MacKintosh,C.,
Morimoto,R.I., Eriksson,J.E. and Sistonen,L.
TITLE Phosphorylation of serine 230 promotes inducible transcriptional
activity of heat shock factor 1
JOURNAL EMBO J 20 (14), 3800-3810 (2001)
PUBMED 11447121
REMARK PROTEIN SEQUENCE OF 228-241 AND 297-310, PHOSPHORYLATION AT SER-230
BY CAMK2, PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION,
SUBCELLULAR LOCATION, MUTAGENESIS OF SER-230, DOMAIN, AND
IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 8 (residues 1 to 529)
AUTHORS Abravaya,K., Phillips,B. and Morimoto,R.I.
TITLE Heat shock-induced interactions of heat shock transcription factor
and the human hsp70 promoter examined by in vivo footprinting
JOURNAL Mol Cell Biol 11 (1), 586-592 (1991)
PUBMED 1986252
REMARK FUNCTION, AND DNA-BINDING.
REFERENCE 9 (residues 1 to 529)
AUTHORS Baler,R., Dahl,G. and Voellmy,R.
TITLE Activation of human heat shock genes is accompanied by
oligomerization, modification, and rapid translocation of heat
shock transcription factor HSF1
JOURNAL Mol Cell Biol 13 (4), 2486-2496 (1993)
PUBMED 8455624
REMARK FUNCTION, DNA-BINDING, SUBUNIT, AND SUBCELLULAR LOCATION.
REFERENCE 10 (residues 1 to 529)
AUTHORS Rabindran,S.K., Wisniewski,J., Li,L., Li,G.C. and Wu,C.
TITLE Interaction between heat shock factor and hsp70 is insufficient to
suppress induction of DNA-binding activity in vivo
JOURNAL Mol Cell Biol 14 (10), 6552-6560 (1994)
PUBMED 7935376
REMARK SUBUNIT, AND INTERACTION WITH HSPA1A.
REFERENCE 11 (residues 1 to 529)
AUTHORS Zuo,J., Baler,R., Dahl,G. and Voellmy,R.
TITLE Activation of the DNA-binding ability of human heat shock
transcription factor 1 may involve the transition from an
intramolecular to an intermolecular triple-stranded coiled-coil
structure
JOURNAL Mol Cell Biol 14 (11), 7557-7568 (1994)
PUBMED 7935471
REMARK FUNCTION, DNA-BINDING, SUBUNIT, DOMAIN, AND MUTAGENESIS OF LEU-140;
MET-147; LEU-189; LEU-193; MET-391 AND LEU-395.
REFERENCE 12 (residues 1 to 529)
AUTHORS Green,M., Schuetz,T.J., Sullivan,E.K. and Kingston,R.E.
TITLE A heat shock-responsive domain of human HSF1 that regulates
transcription activation domain function
JOURNAL Mol Cell Biol 15 (6), 3354-3362 (1995)
PUBMED 7760831
REMARK FUNCTION, AND DOMAIN.
REFERENCE 13 (residues 1 to 529)
AUTHORS Zuo,J., Rungger,D. and Voellmy,R.
TITLE Multiple layers of regulation of human heat shock transcription
factor 1
JOURNAL Mol Cell Biol 15 (8), 4319-4330 (1995)
PUBMED 7623826
REMARK FUNCTION, SUBUNIT, DNA-BINDING, SUBCELLULAR LOCATION, DOMAIN, AND
MUTAGENESIS OF LEU-140; MET-147; LEU-189 AND MET-391.
REFERENCE 14 (residues 1 to 529)
AUTHORS Baler,R., Zou,J. and Voellmy,R.
TITLE Evidence for a role of Hsp70 in the regulation of the heat shock
response in mammalian cells
JOURNAL Cell Stress Chaperones 1 (1), 33-39 (1996)
PUBMED 9222587
REMARK SUBUNIT, AND INTERACTION WITH HSPA1A.
REFERENCE 15 (residues 1 to 529)
AUTHORS Knauf,U., Newton,E.M., Kyriakis,J. and Kingston,R.E.
TITLE Repression of human heat shock factor 1 activity at control
temperature by phosphorylation
JOURNAL Genes Dev 10 (21), 2782-2793 (1996)
PUBMED 8946918
REMARK PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, DOMAIN,
MUTAGENESIS OF ARG-296; VAL-297; LYS-298; GLU-299; GLU-300;
SER-303; SER-307; ARG-309 AND GLU-311, AND IDENTIFICATION BY MASS
SPECTROMETRY.
REFERENCE 16 (residues 1 to 529)
AUTHORS Chu,B., Soncin,F., Price,B.D., Stevenson,M.A. and Calderwood,S.K.
TITLE Sequential phosphorylation by mitogen-activated protein kinase and
glycogen synthase kinase 3 represses transcriptional activation by
heat shock factor-1
JOURNAL J Biol Chem 271 (48), 30847-30857 (1996)
PUBMED 8940068
REMARK PHOSPHORYLATION AT SER-275; SER-303 BY GSK3B AND SER-307 BY MAPK3,
FUNCTION, DNA-BINDING, IDENTIFICATION BY MASS SPECTROMETRY, AND
MUTAGENESIS OF SER-275; SER-303 AND SER-307.
REFERENCE 17 (residues 1 to 529)
AUTHORS Chen,C., Xie,Y., Stevenson,M.A., Auron,P.E. and Calderwood,S.K.
TITLE Heat shock factor 1 represses Ras-induced transcriptional
activation of the c-fos gene
JOURNAL J Biol Chem 272 (43), 26803-26806 (1997)
PUBMED 9341107
REMARK FUNCTION, AND MUTAGENESIS OF LEU-22.
REFERENCE 18 (residues 1 to 529)
AUTHORS Kline,M.P. and Morimoto,R.I.
TITLE Repression of the heat shock factor 1 transcriptional activation
domain is modulated by constitutive phosphorylation
JOURNAL Mol Cell Biol 17 (4), 2107-2115 (1997)
PUBMED 9121459
REMARK PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, DOMAIN,
MUTAGENESIS OF SER-303 AND SER-307, AND IDENTIFICATION BY MASS
SPECTROMETRY.
REFERENCE 19 (residues 1 to 529)
AUTHORS Zou,J., Guo,Y., Guettouche,T., Smith,D.F. and Voellmy,R.
TITLE Repression of heat shock transcription factor HSF1 activation by
HSP90 (HSP90 complex) that forms a stress-sensitive complex with
HSF1
JOURNAL Cell 94 (4), 471-480 (1998)
PUBMED 9727490
REMARK FUNCTION, SUBUNIT, AND INTERACTION WITH HSP90 PROTEINS.
REFERENCE 20 (residues 1 to 529)
AUTHORS Shi,Y., Mosser,D.D. and Morimoto,R.I.
TITLE Molecular chaperones as HSF1-specific transcriptional repressors
JOURNAL Genes Dev 12 (5), 654-666 (1998)
PUBMED 9499401
REMARK INTERACTION WITH DNAJB1; HSPA1A AND HSPA8, FUNCTION, DNA-BINDING,
AND PHOSPHORYLATION.
REFERENCE 21 (residues 1 to 529)
AUTHORS Xia,W., Guo,Y., Vilaboa,N., Zuo,J. and Voellmy,R.
TITLE Transcriptional activation of heat shock factor HSF1 probed by
phosphopeptide analysis of factor 32P-labeled in vivo
JOURNAL J Biol Chem 273 (15), 8749-8755 (1998)
PUBMED 9535852
REMARK PHOSPHORYLATION AT SER-307, FUNCTION, MUTAGENESIS OF SER-275;
SER-303 AND SER-307, AND IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 22 (residues 1 to 529)
AUTHORS Mercier,P.A., Winegarden,N.A. and Westwood,J.T.
TITLE Human heat shock factor 1 is predominantly a nuclear protein before
and after heat stress
JOURNAL J Cell Sci 112 (Pt 16), 2765-2774 (1999)
PUBMED 10413683
REMARK SUBCELLULAR LOCATION.
REFERENCE 23 (residues 1 to 529)
AUTHORS Jolly,C., Usson,Y. and Morimoto,R.I.
TITLE Rapid and reversible relocalization of heat shock factor 1 within
seconds to nuclear stress granules
JOURNAL Proc Natl Acad Sci U S A 96 (12), 6769-6774 (1999)
PUBMED 10359787
REMARK FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND DNA-BINDING.
REFERENCE 24 (residues 1 to 529)
AUTHORS Yuan,C.X. and Gurley,W.B.
TITLE Potential targets for HSF1 within the preinitiation complex
JOURNAL Cell Stress Chaperones 5 (3), 229-242 (2000)
PUBMED 11005381
REMARK INTERACTION WITH GTF2A2; GTF2B AND TBP.
REFERENCE 25 (residues 1 to 529)
AUTHORS Dai,R., Frejtag,W., He,B., Zhang,Y. and Mivechi,N.F.
TITLE c-Jun NH2-terminal kinase targeting and phosphorylation of heat
shock factor-1 suppress its transcriptional activity
JOURNAL J Biol Chem 275 (24), 18210-18218 (2000)
PUBMED 10747973
REMARK INTERACTION WITH MAPK3 AND MAPK8, PHOSPHORYLATION AT SER-363 BY
MAPK8, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF SER-363, AND
IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 26 (residues 1 to 529)
AUTHORS Hong,Y., Rogers,R., Matunis,M.J., Mayhew,C.N., Goodson,M.L.,
Park-Sarge,O.K. and Sarge,K.D.
TITLE Regulation of heat shock transcription factor 1 by stress-induced
SUMO-1 modification
JOURNAL J Biol Chem 276 (43), 40263-40267 (2001)
PUBMED 11514557
REMARK SUMOYLATION AT LYS-298, MUTAGENESIS OF LYS-298, AND SUBCELLULAR
LOCATION.
Erratum:[J Biol Chem 2002 Jul 19;277(29):26708. Goodson M
[corrected to Goodson ML]]
REFERENCE 27 (residues 1 to 529)
AUTHORS Guo,Y., Guettouche,T., Fenna,M., Boellmann,F., Pratt,W.B.,
Toft,D.O., Smith,D.F. and Voellmy,R.
TITLE Evidence for a mechanism of repression of heat shock factor 1
transcriptional activity by a multichaperone complex
JOURNAL J Biol Chem 276 (49), 45791-45799 (2001)
PUBMED 11583998
REMARK COMPONENT OF A CHAPERONE COMPLEX, INTERACTION WITH FKBP4 AND HSP90
PROTEINS, SUBUNIT, PHOSPHORYLATION, FUNCTION, AND DNA-BINDING.
REFERENCE 28 (residues 1 to 529)
AUTHORS Hilgarth,R.S., Hong,Y., Park-Sarge,O.K. and Sarge,K.D.
TITLE Insights into the regulation of heat shock transcription factor 1
SUMO-1 modification
JOURNAL Biochem Biophys Res Commun 303 (1), 196-200 (2003)
PUBMED 12646186
REMARK PHOSPHORYLATION AT SER-307, SUMOYLATION, AND MUTAGENESIS OF
LYS-298; SER-303 AND SER-307.
REFERENCE 29 (residues 1 to 529)
AUTHORS Soncin,F., Zhang,X., Chu,B., Wang,X., Asea,A., Ann Stevenson,M.,
Sacks,D.B. and Calderwood,S.K.
TITLE Transcriptional activity and DNA binding of heat shock factor-1
involve phosphorylation on threonine 142 by CK2
JOURNAL Biochem Biophys Res Commun 303 (2), 700-706 (2003)
PUBMED 12659875
REMARK PHOSPHORYLATION AT THR-142 BY CK2, FUNCTION, MUTAGENESIS OF
THR-142, AND IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 30 (residues 1 to 529)
AUTHORS Hietakangas,V., Ahlskog,J.K., Jakobsson,A.M., Hellesuo,M.,
Sahlberg,N.M., Holmberg,C.I., Mikhailov,A., Palvimo,J.J.,
Pirkkala,L. and Sistonen,L.
TITLE Phosphorylation of serine 303 is a prerequisite for the
stress-inducible SUMO modification of heat shock factor 1
JOURNAL Mol Cell Biol 23 (8), 2953-2968 (2003)
PUBMED 12665592
REMARK SUMOYLATION AT LYS-298, PHOSPHORYLATION AT SER-303, SUBCELLULAR
LOCATION, MUTAGENESIS OF LYS-91; LYS-126; LYS-150; LYS-162;
SER-230; LYS-298; SER-303; SER-307; SER-363 AND LYS-381, AND
IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 31 (residues 1 to 529)
AUTHORS Wang,X., Grammatikakis,N., Siganou,A. and Calderwood,S.K.
TITLE Regulation of molecular chaperone gene transcription involves the
serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic
sequestration of heat shock factor 1
JOURNAL Mol Cell Biol 23 (17), 6013-6026 (2003)
PUBMED 12917326
REMARK FUNCTION, DNA-BINDING, INTERACTION WITH YWHAE, PHOSPHORYLATION,
SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-303 AND SER-307.
REFERENCE 32 (residues 1 to 529)
AUTHORS Xing,H., Mayhew,C.N., Cullen,K.E., Park-Sarge,O.K. and Sarge,K.D.
TITLE HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with
symplekin
JOURNAL J Biol Chem 279 (11), 10551-10555 (2004)
PUBMED 14707147
REMARK FUNCTION, INTERACTION WITH SYMPK AND CSTF2, SUBCELLULAR LOCATION,
AND MUTAGENESIS OF LEU-22.
REFERENCE 33 (residues 1 to 529)
AUTHORS Boellmann,F., Guettouche,T., Guo,Y., Fenna,M., Mnayer,L. and
Voellmy,R.
TITLE DAXX interacts with heat shock factor 1 during stress activation
and enhances its transcriptional activity
JOURNAL Proc Natl Acad Sci U S A 101 (12), 4100-4105 (2004)
PUBMED 15016915
REMARK FUNCTION, INTERACTION WITH DAXX, IDENTIFICATION IN A
RIBONUCLEOPROTEIN COMPLEX, AND MUTAGENESIS OF LYS-298 AND SER-326.
REFERENCE 34 (residues 1 to 529)
AUTHORS Guettouche,T., Boellmann,F., Lane,W.S. and Voellmy,R.
TITLE Analysis of phosphorylation of human heat shock factor 1 in cells
experiencing a stress
JOURNAL BMC Biochem 6, 4 (2005)
PUBMED 15760475
REMARK PHOSPHORYLATION AT SER-121; SER-230; SER-292; SER-303; SER-307;
SER-314; SER-319; SER-326; SER-344; SER-363; SER-419 AND SER-444,
MUTAGENESIS OF SER-326, AND IDENTIFICATION BY MASS SPECTROMETRY.
Publication Status: Online-Only
REFERENCE 35 (residues 1 to 529)
AUTHORS Kim,S.A., Yoon,J.H., Lee,S.H. and Ahn,S.G.
TITLE Polo-like kinase 1 phosphorylates heat shock transcription factor 1
and mediates its nuclear translocation during heat stress
JOURNAL J Biol Chem 280 (13), 12653-12657 (2005)
PUBMED 15661742
REMARK INTERACTION WITH PLK1 AND HSP90 PROTEINS, PHOSPHORYLATION AT
SER-419 BY PLK1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-292;
SER-314; SER-319; SER-326 AND SER-419.
REFERENCE 36 (residues 1 to 529)
AUTHORS Olsen,J.V., Blagoev,B., Gnad,F., Macek,B., Kumar,C., Mortensen,P.
and Mann,M.
TITLE Global, in vivo, and site-specific phosphorylation dynamics in
signaling networks
JOURNAL Cell 127 (3), 635-648 (2006)
PUBMED 17081983
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-323, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].;
TISSUE=Cervix carcinoma
REFERENCE 37 (residues 1 to 529)
AUTHORS Wang,X., Khaleque,M.A., Zhao,M.J., Zhong,R., Gaestel,M. and
Calderwood,S.K.
TITLE Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on
serine 121, inhibits transcriptional activity and promotes HSP90
binding
JOURNAL J Biol Chem 281 (2), 782-791 (2006)
PUBMED 16278218
REMARK PHOSPHORYLATION AT SER-121 BY MAPKAPK2, FUNCTION, INTERACTION WITH
HSP90 PROTEINS AND MAPKAPK2, MUTAGENESIS OF THR-120; SER-121;
SER-123; THR-124; THR-527 AND SER-529, AND IDENTIFICATION BY MASS
SPECTROMETRY.
REFERENCE 38 (residues 1 to 529)
AUTHORS Hietakangas,V., Anckar,J., Blomster,H.A., Fujimoto,M.,
Palvimo,J.J., Nakai,A. and Sistonen,L.
TITLE PDSM, a motif for phosphorylation-dependent SUMO modification
JOURNAL Proc Natl Acad Sci U S A 103 (1), 45-50 (2006)
PUBMED 16371476
REMARK SUMOYLATION AT LYS-298, AND PHOSPHORYLATION AT SER-303.
REFERENCE 39 (residues 1 to 529)
AUTHORS Shamovsky,I., Ivannikov,M., Kandel,E.S., Gershon,D. and Nudler,E.
TITLE RNA-mediated response to heat shock in mammalian cells
JOURNAL Nature 440 (7083), 556-560 (2006)
PUBMED 16554823
REMARK INTERACTION WITH EEF1A PROTEINS, AND IDENTIFICATION IN A
RIBONUCLEOPROTEIN COMPLEX.
REFERENCE 40 (residues 1 to 529)
AUTHORS Piskacek,S., Gregor,M., Nemethova,M., Grabner,M., Kovarik,P. and
Piskacek,M.
TITLE Nine-amino-acid transactivation domain: establishment and
prediction utilities
JOURNAL Genomics 89 (6), 756-768 (2007)
PUBMED 17467953
REMARK DOMAIN.
REFERENCE 41 (residues 1 to 529)
AUTHORS Skaggs,H.S., Xing,H., Wilkerson,D.C., Murphy,L.A., Hong,Y.,
Mayhew,C.N. and Sarge,K.D.
TITLE HSF1-TPR interaction facilitates export of stress-induced HSP70
mRNA
JOURNAL J Biol Chem 282 (47), 33902-33907 (2007)
PUBMED 17897941
REMARK FUNCTION IN STRESS-INDUCED NUCLEAR MRNA EXPORT, AND INTERACTION
WITH TPR.
REFERENCE 42 (residues 1 to 529)
AUTHORS Lee,Y.J., Kim,E.H., Lee,J.S., Jeoung,D., Bae,S., Kwon,S.H. and
Lee,Y.S.
TITLE HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is
essential for mitotic progression
JOURNAL Cancer Res 68 (18), 7550-7560 (2008)
PUBMED 18794143
REMARK FUNCTION IN MITOTIC PROGRESSION REGULATION, INTERACTION WITH BTRC;
CDC20; MAD2L1 AND PLK1, PHOSPHORYLATION AT SER-216 BY PLK1,
SUBCELLULAR LOCATION, UBIQUITINATION, PROTEASOMAL DEGRADATION, AND
MUTAGENESIS OF SER-216; SER-230; SER-303; SER-307 AND SER-419.
REFERENCE 43 (residues 1 to 529)
AUTHORS Xu,D., Zalmas,L.P. and La Thangue,N.B.
TITLE A transcription cofactor required for the heat-shock response
JOURNAL EMBO Rep 9 (7), 662-669 (2008)
PUBMED 18451878
REMARK FUNCTION, AND INTERACTION WITH TTC5 AND EP300.
REFERENCE 44 (residues 1 to 529)
AUTHORS Cantin,G.T., Yi,W., Lu,B., Park,S.K., Xu,T., Lee,J.D. and
Yates,J.R. III.
TITLE Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
efficient phosphoproteomic analysis
JOURNAL J Proteome Res 7 (3), 1346-1351 (2008)
PUBMED 18220336
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].;
TISSUE=Cervix carcinoma
REFERENCE 45 (residues 1 to 529)
AUTHORS Dephoure,N., Zhou,C., Villen,J., Beausoleil,S.A., Bakalarski,C.E.,
Elledge,S.J. and Gygi,S.P.
TITLE A quantitative atlas of mitotic phosphorylation
JOURNAL Proc Natl Acad Sci U S A 105 (31), 10762-10767 (2008)
PUBMED 18669648
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].;
TISSUE=Cervix carcinoma
REFERENCE 46 (residues 1 to 529)
AUTHORS Gauci,S., Helbig,A.O., Slijper,M., Krijgsveld,J., Heck,A.J. and
Mohammed,S.
TITLE Lys-N and trypsin cover complementary parts of the phosphoproteome
in a refined SCX-based approach
JOURNAL Anal Chem 81 (11), 4493-4501 (2009)
PUBMED 19413330
REMARK ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
REFERENCE 47 (residues 1 to 529)
AUTHORS Mayya,V., Lundgren,D.H., Hwang,S.I., Rezaul,K., Wu,L., Eng,J.K.,
Rodionov,V. and Han,D.K.
TITLE Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions
JOURNAL Sci Signal 2 (84), ra46 (2009)
PUBMED 19690332
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; THR-323 AND
SER-326, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].;
TISSUE=Leukemic T-cell
Publication Status: Online-Only
REFERENCE 48 (residues 1 to 529)
AUTHORS Westerheide,S.D., Anckar,J., Stevens,S.M. Jr., Sistonen,L. and
Morimoto,R.I.
TITLE Stress-inducible regulation of heat shock factor 1 by the
deacetylase SIRT1
JOURNAL Science 323 (5917), 1063-1066 (2009)
PUBMED 19229036
REMARK DEACETYLATION AT LYS-80 BY SIRT1, ACETYLATION AT LYS-80,
SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
MUTAGENESIS OF LYS-80.
Erratum:[Science. 2013 Nov 22;342(6161):931]
REFERENCE 49 (residues 1 to 529)
AUTHORS Murshid,A., Chou,S.D., Prince,T., Zhang,Y., Bharti,A. and
Calderwood,S.K.
TITLE Protein kinase A binds and activates heat shock factor 1
JOURNAL PLoS One 5 (11), e13830 (2010)
PUBMED 21085490
REMARK INTERACTION WITH PRKACA, PHOSPHORYLATION AT SER-320 BY PRKACA,
SUBCELLULAR LOCATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
MUTAGENESIS OF SER-320.
Publication Status: Online-Only
REFERENCE 50 (residues 1 to 529)
AUTHORS Olsen,J.V., Vermeulen,M., Santamaria,A., Kumar,C., Miller,M.L.,
Jensen,L.J., Gnad,F., Cox,J., Jensen,T.S., Nigg,E.A., Brunak,S. and
Mann,M.
TITLE Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis
JOURNAL Sci Signal 3 (104), ra3 (2010)
PUBMED 20068231
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314 AND SER-326, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].;
TISSUE=Cervix carcinoma
Publication Status: Online-Only
REFERENCE 51 (residues 1 to 529)
AUTHORS Kaitsuka,T., Tomizawa,K. and Matsushita,M.
TITLE Transformation of eEF1Bdelta into heat-shock response transcription
factor by alternative splicing
JOURNAL EMBO Rep 12 (7), 673-681 (2011)
PUBMED 21597468
REMARK INTERACTION WITH EEF1D.
Publication Status: Online-Only
REFERENCE 52 (residues 1 to 529)
AUTHORS Rigbolt,K.T., Prokhorova,T.A., Akimov,V., Henningsen,J.,
Johansen,P.T., Kratchmarova,I., Kassem,M., Mann,M., Olsen,J.V. and
Blagoev,B.
TITLE System-wide temporal characterization of the proteome and
phosphoproteome of human embryonic stem cell differentiation
JOURNAL Sci Signal 4 (164), rs3 (2011)
PUBMED 21406692
REMARK IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Publication Status: Online-Only
REFERENCE 53 (residues 1 to 529)
AUTHORS Zhou,H., Di Palma,S., Preisinger,C., Peng,M., Polat,A.N., Heck,A.J.
and Mohammed,S.
TITLE Toward a comprehensive characterization of a human cancer cell
phosphoproteome
JOURNAL J Proteome Res 12 (1), 260-271 (2013)
PUBMED 23186163
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-307 AND
SER-363, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].;
TISSUE=Cervix carcinoma, and Erythroleukemia
REFERENCE 54 (residues 1 to 529)
AUTHORS Raychaudhuri,S., Loew,C., Korner,R., Pinkert,S., Theis,M.,
Hayer-Hartl,M., Buchholz,F. and Hartl,F.U.
TITLE Interplay of acetyltransferase EP300 and the proteasome system in
regulating heat shock transcription factor 1
JOURNAL Cell 156 (5), 975-985 (2014)
PUBMED 24581496
REMARK ACETYLATION AT LYS-80; LYS-91; LYS-118; LYS-150; LYS-188; LYS-208;
LYS-298 AND LYS-524, PHOSPHORYLATION, UBIQUITINATION, PROTEASOMAL
DEGRADATION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-80; LYS-118;
LYS-208 AND LYS-298, AND IDENTIFICATION BY MASS SPECTROMETRY.
REFERENCE 55 (residues 1 to 529)
AUTHORS Bian,Y., Song,C., Cheng,K., Dong,M., Wang,F., Huang,J., Sun,D.,
Wang,L., Ye,M. and Zou,H.
TITLE An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome
JOURNAL J Proteomics 96, 253-262 (2014)
PUBMED 24275569
REMARK PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND SER-363, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].;
TISSUE=Liver
REFERENCE 56 (residues 1 to 529)
AUTHORS Jin,Y.H., Ahn,S.G. and Kim,S.A.
TITLE BAG3 affects the nucleocytoplasmic shuttling of HSF1 upon heat
stress
JOURNAL Biochem Biophys Res Commun 464 (2), 561-567 (2015)
PUBMED 26159920
REMARK INTERACTION WITH BAG3, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND
NUCLEOCYTOPLASMIC SHUTTLING.
REFERENCE 57 (residues 1 to 529)
AUTHORS Ishikawa,Y., Kawabata,S. and Sakurai,H.
TITLE HSF1 transcriptional activity is modulated by IER5 and PP2A/B55
JOURNAL FEBS Lett 589 (10), 1150-1155 (2015)
PUBMED 25816751
REMARK INTERACTION WITH IER5.
REFERENCE 58 (residues 1 to 529)
AUTHORS Kawabata,S., Ishita,Y., Ishikawa,Y. and Sakurai,H.
TITLE Immediate-early response 5 (IER5) interacts with protein
phosphatase 2A and regulates the phosphorylation of ribosomal
protein S6 kinase and heat shock factor 1
JOURNAL FEBS Lett 589 (23), 3679-3685 (2015)
PUBMED 26496226
REMARK INTERACTION WITH IER5.
REFERENCE 59 (residues 1 to 529)
AUTHORS Budzynski,M.A., Puustinen,M.C., Joutsen,J. and Sistonen,L.
TITLE Uncoupling Stress-Inducible Phosphorylation of Heat Shock Factor 1
from Its Activation
JOURNAL Mol Cell Biol 35 (14), 2530-2540 (2015)
PUBMED 25963659
REMARK FUNCTION, DNA-BINDING, CHROMATIN BINDING, SUBCELLULAR LOCATION, AND
PHOSPHORYLATIONS.
REFERENCE 60 (residues 1 to 529)
AUTHORS Kang,G.Y., Kim,E.H., Lee,H.J., Gil,N.Y., Cha,H.J. and Lee,Y.S.
TITLE Heat shock factor 1, an inhibitor of non-homologous end joining
repair
JOURNAL Oncotarget 6 (30), 29712-29724 (2015)
PUBMED 26359349
REMARK FUNCTION IN DNA REPAIR, INTERACTION WITH XRCC5 AND XRCC6,
SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-80; SER-216; LYS-298;
SER-326 AND SER-419.
REFERENCE 61 (residues 1 to 529)
AUTHORS Prince,T.L., Kijima,T., Tatokoro,M., Lee,S., Tsutsumi,S., Yim,K.,
Rivas,C., Alarcon,S., Schwartz,H., Khamit-Kush,K., Scroggins,B.T.,
Beebe,K., Trepel,J.B. and Neckers,L.
TITLE Client Proteins and Small Molecule Inhibitors Display Distinct
Binding Preferences for Constitutive and Stress-Induced HSP90
Isoforms and Their Conformationally Restricted Mutants
JOURNAL PLoS One 10 (10), e0141786 (2015)
PUBMED 26517842
REMARK INTERACTION WITH HSP90AA1 AND HSP90AB1.
Publication Status: Online-Only
REFERENCE 62 (residues 1 to 529)
AUTHORS Dayalan Naidu,S., Sutherland,C., Zhang,Y., Risco,A., de la Vega,L.,
Caunt,C.J., Hastie,C.J., Lamont,D.J., Torrente,L., Chowdhry,S.,
Benjamin,I.J., Keyse,S.M., Cuenda,A. and Dinkova-Kostova,A.T.
TITLE Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated
Protein Kinases
JOURNAL Mol Cell Biol 36 (18), 2403-2417 (2016)
PUBMED 27354066
REMARK PHOSPHORYLATION AT SER-326 BY MAPK12, SUBCELLULAR LOCATION, AND
MUTAGENESIS OF SER-326.
Publication Status: Online-Only
REFERENCE 63 (residues 1 to 529)
AUTHORS Asano,Y., Kawase,T., Okabe,A., Tsutsumi,S., Ichikawa,H., Tatebe,S.,
Kitabayashi,I., Tashiro,F., Namiki,H., Kondo,T., Semba,K.,
Aburatani,H., Taya,Y., Nakagama,H. and Ohki,R.
TITLE IER5 generates a novel hypo-phosphorylated active form of HSF1 and
contributes to tumorigenesis
JOURNAL Sci Rep 6, 19174 (2016)
PUBMED 26754925
REMARK DEPHOSPHORYLATION AT SER-121; SER-307; SER-314; THR-323 AND THR-367
BY PPP2CA, ACETYLATION AT LYS-118, IDENTIFICATION IN COMPLEX WITH
IER5 AND PPP2CA, INTERACTION WITH HSP90AA1 AND IER5, FUNCTION,
SUBUNIT, DNA-BINDING, AND MUTAGENESIS OF SER-121; SER-307; SER-314;
THR-323 AND THR-367.
Publication Status: Online-Only
REFERENCE 64 (residues 1 to 529)
AUTHORS Pan,X.Y., Zhao,W., Zeng,X.Y., Lin,J., Li,M.M., Shen,X.T. and
Liu,S.W.
TITLE Heat Shock Factor 1 Mediates Latent HIV Reactivation
JOURNAL Sci Rep 6, 26294 (2016)
PUBMED 27189267
REMARK FUNCTION IN LATENT HIV-1 TRANSCRIPTIONAL REACTIVATION (MICROBIAL
INFECTION), INTERACTION WITH CDK9; CCNT1 AND EP300, PHOSPHORYLATION
AT SER-320, ACETYLATION, AND SUBCELLULAR LOCATION.
Publication Status: Online-Only
REFERENCE 65 (residues 1 to 529)
AUTHORS Hendriks,I.A., Lyon,D., Young,C., Jensen,L.J., Vertegaal,A.C. and
Nielsen,M.L.
TITLE Site-specific mapping of the human SUMO proteome reveals
co-modification with phosphorylation
JOURNAL Nat Struct Mol Biol 24 (3), 325-336 (2017)
PUBMED 28112733
REMARK SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-91; LYS-126; LYS-131;
LYS-208; LYS-224 AND LYS-298, AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
REFERENCE 66 (residues 1 to 529)
AUTHORS Mota,A., Waxman,H.K., Hong,R., Lagani,G.D., Niu,S.Y.,
Bertherat,F.L., Wolfe,L., Malicdan,C.M., Markello,T.C., Adams,D.R.,
Gahl,W.A., Cheng,C.S., Beffert,U. and Ho,A.
TITLE FOXR1 regulates stress response pathways and is necessary for
proper brain development
JOURNAL PLoS Genet 17 (11), e1009854 (2021)
PUBMED 34723967
REMARK FUNCTION.
Publication Status: Online-Only
REFERENCE 67 (residues 1 to 529)
AUTHORS Neudegger,T., Verghese,J., Hayer-Hartl,M., Hartl,F.U. and
Bracher,A.
TITLE Structure of human heat-shock transcription factor 1 in complex
with DNA
JOURNAL Nat Struct Mol Biol 23 (2), 140-146 (2016)
PUBMED 26727489
REMARK X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 1-120 IN COMPLEX WITH
DNA, DNA-BINDING, SUBUNIT, AND FUNCTION.
COMMENT On or before Dec 1, 2006 this sequence version replaced
gi:74740826, gi:87630.
[FUNCTION] Functions as a stress-inducible and DNA-binding
transcription factor that plays a central role in the
transcriptional activation of the heat shock response (HSR),
leading to the expression of a large class of molecular chaperones,
heat shock proteins (HSPs), that protect cells from cellular insult
damage (PubMed:11447121, PubMed:12659875, PubMed:12917326,
PubMed:15016915, PubMed:18451878, PubMed:1871105, PubMed:1986252,
PubMed:25963659, PubMed:26754925, PubMed:7623826, PubMed:7760831,
PubMed:8940068, PubMed:8946918, PubMed:9121459, PubMed:9341107,
PubMed:9499401, PubMed:9535852, PubMed:9727490). In unstressed
cells, is present in a HSP90-containing multichaperone complex that
maintains it in a non-DNA-binding inactivated monomeric form
(PubMed:11583998, PubMed:16278218, PubMed:9727490). Upon exposure
to heat and other stress stimuli, undergoes homotrimerization and
activates HSP gene transcription through binding to site-specific
heat shock elements (HSEs) present in the promoter regions of HSP
genes (PubMed:10359787, PubMed:11583998, PubMed:12659875,
PubMed:16278218, PubMed:1871105, PubMed:1986252, PubMed:25963659,
PubMed:26754925, PubMed:7623826, PubMed:7935471, PubMed:8455624,
PubMed:8940068, PubMed:9499401, PubMed:9727490). Upon heat shock
stress, forms a chromatin-associated complex with TTC5/STRAP and
p300/EP300 to stimulate HSR transcription, therefore increasing
cell survival (PubMed:18451878). Activation is reversible, and
during the attenuation and recovery phase period of the HSR,
returns to its unactivated form (PubMed:11583998, PubMed:16278218).
Binds to inverted 5'-NGAAN-3' pentamer DNA sequences
(PubMed:1986252, PubMed:26727489). Binds to chromatin at heat shock
gene promoters (PubMed:25963659). Activates transcription of
transcription factor FOXR1 which in turn activates transcription of
the heat shock chaperones HSPA1A and HSPA6 and the antioxidant
NADPH-dependent reductase DHRS2 (PubMed:34723967). Also serves
several other functions independently of its transcriptional
activity. Involved in the repression of Ras-induced transcriptional
activation of the c-fos gene in heat-stressed cells
(PubMed:9341107). Positively regulates pre-mRNA 3'-end processing
and polyadenylation of HSP70 mRNA upon heat-stressed cells in a
symplekin (SYMPK)-dependent manner (PubMed:14707147). Plays a role
in nuclear export of stress-induced HSP70 mRNA (PubMed:17897941).
Plays a role in the regulation of mitotic progression
(PubMed:18794143). Also plays a role as a negative regulator of
non-homologous end joining (NHEJ) repair activity in a DNA
damage-dependent manner (PubMed:26359349). Involved in
stress-induced cancer cell proliferation in a IER5-dependent manner
(PubMed:26754925). {ECO:0000269|PubMed:10359787,
ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998,
ECO:0000269|PubMed:12659875, ECO:0000269|PubMed:12917326,
ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915,
ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:17897941,
ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:1871105,
ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:1986252,
ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26359349,
ECO:0000269|PubMed:26727489, ECO:0000269|PubMed:26754925,
ECO:0000269|PubMed:34723967, ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7760831, ECO:0000269|PubMed:7935471,
ECO:0000269|PubMed:8455624, ECO:0000269|PubMed:8940068,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0000269|PubMed:9341107, ECO:0000269|PubMed:9499401,
ECO:0000269|PubMed:9535852, ECO:0000269|PubMed:9727490}.
[FUNCTION] (Microbial infection) Plays a role in latent human
immunodeficiency virus (HIV-1) transcriptional reactivation. Binds
to the HIV-1 long terminal repeat promoter (LTR) to reactivate
viral transcription by recruiting cellular transcriptional
elongation factors, such as CDK9, CCNT1 and EP300.
{ECO:0000269|PubMed:27189267}.
[SUBUNIT] Monomer; cytoplasmic latent and transcriptionally
inactive monomeric form in unstressed cells (PubMed:11583998,
PubMed:7623826, PubMed:7935376, PubMed:7935471, PubMed:8455624,
PubMed:9222587, PubMed:9727490). Homotrimer; in response to stress,
such as heat shock, homotrimerizes and translocates into the
nucleus, binds to heat shock element (HSE) sequences in promoter of
heat shock protein (HSP) genes and acquires transcriptional ability
(PubMed:11583998, PubMed:26727489, PubMed:26754925, PubMed:7623826,
PubMed:7935471, PubMed:8455624, PubMed:9222587, PubMed:9727490).
Interacts (via monomeric form) with FKBP4; this interaction occurs
in unstressed cells (PubMed:11583998). Associates (via monomeric
form) with HSP90 proteins in a multichaperone complex in
unnstressed cell; this association maintains HSF1 in a
non-DNA-binding and transcriptional inactive form by preventing
HSF1 homotrimerization (PubMed:11583998, PubMed:15661742,
PubMed:16278218, PubMed:9727490). Homotrimeric transactivation
activity is modulated by protein-protein interactions and
post-translational modifications (PubMed:11583998, PubMed:15016915,
PubMed:16554823, PubMed:26754925). Interacts with HSP90AA1; this
interaction is decreased in a IER5-dependent manner, promoting HSF1
accumulation in the nucleus, homotrimerization and DNA-binding
activities (PubMed:26754925). Part (via regulatory domain in the
homotrimeric form) of a large heat shock-induced HSP90-dependent
multichaperone complex at least composed of FKBP4, FKBP5, HSP90
proteins, PPID, PPP5C and PTGES3; this association maintains the
HSF1 homotrimeric DNA-bound form in a transcriptionally inactive
form (PubMed:11583998, PubMed:16278218, PubMed:9727490). Interacts
with BAG3 (via BAG domain); this interaction occurs in normal and
heat-shocked cells promoting nuclear shuttling of HSF1 in a
BAG3-dependent manner (PubMed:26159920). Interacts (via
homotrimeric and hyperphosphorylated form) with FKBP4; this
interaction occurs upon heat shock in a HSP90-dependent
multichaperone complex (PubMed:11583998). Interacts (via
homotrimeric form preferentially) with EEF1A proteins
(PubMed:15016915). In heat shocked cells, stress-denatured proteins
compete with HSF1 homotrimeric DNA-bound form for association of
the HSP90-dependent multichaperone complex, and hence alleviating
repression of HSF1-mediated transcriptional activity
(PubMed:11583998). Interacts (via homotrimeric form preferentially)
with DAXX; this interaction relieves homotrimeric HSF1 from
repression of its transcriptional activity by HSP90-dependent
multichaperone complex upon heat shock (PubMed:15016915). Interacts
(via D domain and preferentially with hyperphosphorylated form)
with JNK1; this interaction occurs under both normal growth
conditions and immediately upon heat shock (PubMed:10747973).
Interacts (via D domain and preferentially with hyperphosphorylated
form) with MAPK3; this interaction occurs upon heat shock
(PubMed:10747973). Interacts with IER5 (via central region); this
interaction promotes PPP2CA-induced dephosphorylation on Ser-121,
Ser-307, Ser-314, Thr-323 and Thr-367 and HSF1 transactivation
activity (PubMed:25816751, PubMed:26496226, PubMed:26754925). Found
in a ribonucleoprotein complex composed of the HSF1 homotrimeric
form, translation elongation factor eEF1A proteins and non-coding
RNA heat shock RNA-1 (HSR1); this complex occurs upon heat shock
and stimulates HSF1 DNA-binding activity (PubMed:16554823).
Interacts (via transactivation domain) with HSPA1A/HSP70 and
DNAJB1; these interactions result in the inhibition of heat shock-
and HSF1-induced transcriptional activity during the attenuation
and recovery phase from heat shock (PubMed:7935376, PubMed:9222587,
PubMed:9499401). Interacts (via Ser-303 and Ser-307 phosphorylated
form) with YWHAE; this interaction promotes HSF1 sequestration in
the cytoplasm in an ERK-dependent manner (PubMed:12917326). Found
in a complex with IER5 and PPP2CA (PubMed:26754925). Interacts with
TPR; this interaction increases upon heat shock and stimulates
export of HSP70 mRNA (PubMed:17897941). Interacts with SYMPK (via
N-terminus) and CSTF2; these interactions occur upon heat shock
(PubMed:14707147). Interacts (via transactivation domain) with
HSPA8 (PubMed:9499401). Interacts with EEF1D; this interaction
occurs at heat shock promoter element (HSE) sequences
(PubMed:21597468). Interacts with MAPKAPK2 (PubMed:16278218).
Interacts with PRKACA/PKA (PubMed:21085490). Interacts (via
transactivation domain) with GTF2A2 (PubMed:11005381). Interacts
(via transactivation domain) with GTF2B (PubMed:11005381).
Interacts (via transactivation domain) with TBP (PubMed:11005381).
Interacts with CDK9, CCNT1 and EP300 (PubMed:27189267). Interacts
(via N-terminus) with XRCC5 (via N-terminus) and XRCC6 (via
N-terminus); these interactions are direct and prevent XRCC5/XRCC6
heterodimeric binding and non-homologous end joining (NHEJ) repair
activities induced by ionizing radiation (IR) (PubMed:26359349).
Interacts with PLK1; this interaction occurs during the early
mitotic period, increases upon heat shock but does not modulate
neither HSF1 homotrimerization and DNA-binding activities
(PubMed:15661742, PubMed:18794143). Interacts (via Ser-216
phosphorylated form) with CDC20; this interaction occurs in mitosis
in a MAD2L1-dependent manner and prevents PLK1-stimulated
degradation of HSF1 by blocking the recruitment of the SCF(BTRC)
ubiquitin ligase complex (PubMed:18794143). Interacts with MAD2L1;
this interaction occurs in mitosis (PubMed:18794143). Interacts
with BTRC; this interaction occurs during mitosis, induces its
ubiquitin-dependent degradation following stimulus-dependent
phosphorylation at Ser-216, a process inhibited by CDC20
(PubMed:18794143). Interacts with HSP90AA1 and HSP90AB1
(PubMed:26517842). Forms a complex with TTC5/STRAP and p300/EP300;
these interactions augment chromatin-bound HSF1 and p300/EP300
histone acetyltransferase activity (PubMed:18451878).
{ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11005381,
ECO:0000269|PubMed:11583998, ECO:0000269|PubMed:12917326,
ECO:0000269|PubMed:14707147, ECO:0000269|PubMed:15016915,
ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:16278218,
ECO:0000269|PubMed:16554823, ECO:0000269|PubMed:17897941,
ECO:0000269|PubMed:18451878, ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:21597468,
ECO:0000269|PubMed:25816751, ECO:0000269|PubMed:26159920,
ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:26496226,
ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:26727489,
ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27189267,
ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7935376,
ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8455624,
ECO:0000269|PubMed:9222587, ECO:0000269|PubMed:9499401,
ECO:0000269|PubMed:9727490, ECO:0000305|PubMed:15016915}.
[INTERACTION] Q00613; Q00613: HSF1; NbExp=2; IntAct=EBI-719620,
EBI-719620; Q00613; Q03933: HSF2; NbExp=11; IntAct=EBI-719620,
EBI-2556750; Q00613; Q5VY09: IER5; NbExp=3; IntAct=EBI-719620,
EBI-1774000; Q00613; Q13352: ITGB3BP; NbExp=3; IntAct=EBI-719620,
EBI-712105; Q00613; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-719620,
EBI-2796400; Q00613; Q14693: LPIN1; NbExp=3; IntAct=EBI-719620,
EBI-5278370; Q00613; P49137: MAPKAPK2; NbExp=5; IntAct=EBI-719620,
EBI-993299; Q00613; Q8N4C8: MINK1; NbExp=2; IntAct=EBI-719620,
EBI-2133481; Q00613; Q04759: PRKCQ; NbExp=2; IntAct=EBI-719620,
EBI-374762; Q00613; O14744: PRMT5; NbExp=3; IntAct=EBI-719620,
EBI-351098; Q00613; Q96CM3: RPUSD4; NbExp=3; IntAct=EBI-719620,
EBI-7825200; Q00613; P11684: SCGB1A1; NbExp=3; IntAct=EBI-719620,
EBI-7797649; Q00613; P63165: SUMO1; NbExp=2; IntAct=EBI-719620,
EBI-80140; Q00613; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-719620,
EBI-21757569; Q00613; Q6ZMY6-2: WDR88; NbExp=3; IntAct=EBI-719620,
EBI-25857007; Q00613; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-719620,
EBI-749023.
[SUBCELLULAR LOCATION] Nucleus {ECO:0000269|PubMed:10413683,
ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12665592,
ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147,
ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:19229036,
ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:25963659,
ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27189267,
ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:8455624}. Cytoplasm
{ECO:0000269|PubMed:10413683, ECO:0000269|PubMed:10747973,
ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:15661742,
ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:26159920,
ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066,
ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:8455624}. Nucleus,
nucleoplasm {ECO:0000269|PubMed:10359787}. Cytoplasm, perinuclear
region {ECO:0000269|PubMed:21085490}. Cytoplasm, cytoskeleton,
spindle pole {ECO:0000269|PubMed:18794143}. Cytoplasm,
cytoskeleton, microtubule organizing center, centrosome
{ECO:0000269|PubMed:18794143}. Chromosome, centromere, kinetochore
{ECO:0000269|PubMed:18794143}. Note=The monomeric form is
cytoplasmic in unstressed cells (PubMed:26159920, PubMed:8455624).
Predominantly nuclear protein in both unstressed and heat shocked
cells (PubMed:10359787, PubMed:10413683). Translocates in the
nucleus upon heat shock (PubMed:8455624). Nucleocytoplasmic
shuttling protein (PubMed:26159920). Colocalizes with IER5 in the
nucleus (PubMed:27354066). Colocalizes with BAG3 to the nucleus
upon heat stress (PubMed:26159920, PubMed:8455624). Localizes in
subnuclear granules called nuclear stress bodies (nSBs) upon heat
shock (PubMed:10359787, PubMed:10747973, PubMed:11447121,
PubMed:11514557, PubMed:19229036, PubMed:24581496,
PubMed:25963659). Colocalizes with SYMPK and SUMO1 in nSBs upon
heat shock (PubMed:10359787, PubMed:11447121, PubMed:11514557,
PubMed:12665592, PubMed:14707147). Colocalizes with PRKACA/PKA in
the nucleus and nSBs upon heat shock (PubMed:21085490). Relocalizes
from the nucleus to the cytoplasm during the attenuation and
recovery phase period of the heat shock response (PubMed:26159920).
Translocates in the cytoplasm in a YWHAE- and XPO1/CRM1-dependent
manner (PubMed:12917326). Together with histone H2AX, redistributed
in discrete nuclear DNA damage-induced foci after ionizing
radiation (IR) (PubMed:26359349). Colocalizes with
calcium-responsive transactivator SS18L1 at kinetochore region on
the mitotic chromosomes (PubMed:18794143). Colocalizes with gamma
tubulin at centrosome (PubMed:18794143). Localizes at spindle pole
in metaphase (PubMed:18794143). Colocalizes with PLK1 at spindle
poles during prometaphase (PubMed:18794143).
{ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:10413683,
ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:11514557, ECO:0000269|PubMed:12665592,
ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:14707147,
ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:21085490,
ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:25963659,
ECO:0000269|PubMed:26159920, ECO:0000269|PubMed:26359349,
ECO:0000269|PubMed:27354066, ECO:0000269|PubMed:8455624}.
[ALTERNATIVE PRODUCTS] Event=Alternative splicing; Named
isoforms=2; Name=Long; IsoId=Q00613-1; Sequence=Displayed;
Name=Short; IsoId=Q00613-2; Sequence=VSP_002414, VSP_002415.
[DOMAIN] In unstressed cells, spontaneous homotrimerization is
inhibited (PubMed:7760831, PubMed:7935471). Intramolecular
interactions between the hydrophobic repeat HR-A/B and HR-C regions
are necessary to maintain HSF1 in the inactive, monomeric
conformation (PubMed:7623826, PubMed:7935471). Furthermore,
intramolecular interactions between the regulatory domain and the
nonadjacent transactivation domain prevents transcriptional
activation, a process that is relieved upon heat shock
(PubMed:7760831). The regulatory domain is necessary for full
repression of the transcriptional activation domain in unstressed
cells through its phosphorylation on Ser-303 and Ser-307
(PubMed:8946918, PubMed:9121459). In heat stressed cells, HSF1
homotrimerization occurs through formation of a three-stranded
coiled-coil structure generated by intermolecular interactions
between HR-A/B regions allowing DNA-binding activity
(PubMed:7935471). The D domain is necessary for translocation to
the nucleus, interaction with JNK1 and MAPK3 and efficient JNK1-
and MAPK3-dependent phosphorylation (PubMed:10747973). The
regulatory domain confers heat shock inducibility on the
transcriptional transactivation domain (PubMed:7760831). The
regulatory domain is necessary for transcriptional activation
through its phosphorylation on Ser-230 upon heat shock
(PubMed:11447121). 9aaTAD is a transactivation motif present in a
large number of yeast and animal transcription factors
(PubMed:17467953). {ECO:0000269|PubMed:10747973,
ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:17467953,
ECO:0000269|PubMed:7623826, ECO:0000269|PubMed:7760831,
ECO:0000269|PubMed:7935471, ECO:0000269|PubMed:8946918,
ECO:0000269|PubMed:9121459}.
[PTM] Phosphorylated (PubMed:10359787, PubMed:11583998,
PubMed:26159920, PubMed:9499401). Phosphorylated in unstressed
cells; this phosphorylation is constitutive and implicated in the
repression of HSF1 transcriptional activity (PubMed:16278218,
PubMed:8940068, PubMed:8946918, PubMed:9121459). Phosphorylated on
Ser-121 by MAPKAPK2; this phosphorylation promotes interaction with
HSP90 proteins and inhibits HSF1 homotrimerization, DNA-binding and
transactivation activities (PubMed:16278218). Phosphorylation on
Ser-303 by GSK3B/GSK3-beta and on Ser-307 by MAPK3 within the
regulatory domain is involved in the repression of HSF1
transcriptional activity and occurs in a RAF1-dependent manner
(PubMed:10747973, PubMed:12646186, PubMed:8940068, PubMed:8946918,
PubMed:9121459, PubMed:9535852). Phosphorylation on Ser-303 and
Ser-307 increases HSF1 nuclear export in a YWHAE- and
XPO1/CRM1-dependent manner (PubMed:12917326). Phosphorylation on
Ser-307 is a prerequisite for phosphorylation on Ser-303
(PubMed:8940068). According to PubMed:9535852, Ser-303 is not
phosphorylated in unstressed cells. Phosphorylated on Ser-419 by
PLK1; phosphorylation promotes nuclear translocation upon heat
shock (PubMed:15661742). Hyperphosphorylated upon heat shock and
during the attenuation and recovery phase period of the heat shock
response (PubMed:11447121, PubMed:12659875, PubMed:24581496).
Phosphorylated on Thr-142; this phosphorylation increases HSF1
transactivation activity upon heat shock (PubMed:12659875).
Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances
HSF1 transactivation activity upon heat shock (PubMed:11447121).
Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances
HSF1 nuclear translocation, homotrimerization and transactivation
activities upon heat shock (PubMed:15760475, PubMed:27354066).
Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation
promotes nuclear localization and transcriptional activity upon
heat shock (PubMed:21085490). Phosphorylated on Ser-363 by MAPK8;
this phosphorylation occurs upon heat shock, induces HSF1
translocation into nuclear stress bodies and negatively regulates
transactivation activity (PubMed:10747973). Neither basal nor
stress-inducible phosphorylation on Ser-230, Ser-292, Ser-303,
Ser-307, Ser-314, Ser-319, Ser-320, Thr-323, Ser-326, Ser-338,
Ser-344, Ser-363, Thr-367, Ser-368 and Thr-369 within the
regulatory domain is involved in the regulation of HSF1 subcellular
localization or DNA-binding activity; however, it negatively
regulates HSF1 transactivation activity (PubMed:25963659).
Phosphorylated on Ser-216 by PLK1 in the early mitotic period; this
phosphorylation regulates HSF1 localization to the spindle pole,
the recruitment of the SCF(BTRC) ubiquitin ligase complex inducing
HSF1 degradation, and hence mitotic progression (PubMed:18794143).
Dephosphorylated on Ser-121, Ser-307, Ser-314, Thr-323 and Thr-367
by phosphatase PPP2CA in an IER5-dependent manner, leading to
HSF1-mediated transactivation activity (PubMed:26754925).
{ECO:0000269|PubMed:10359787, ECO:0000269|PubMed:10747973,
ECO:0000269|PubMed:11447121, ECO:0000269|PubMed:11583998,
ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12659875,
ECO:0000269|PubMed:12917326, ECO:0000269|PubMed:15760475,
ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:21085490, ECO:0000269|PubMed:24581496,
ECO:0000269|PubMed:25963659, ECO:0000269|PubMed:26159920,
ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27354066,
ECO:0000269|PubMed:8940068, ECO:0000269|PubMed:8946918,
ECO:0000269|PubMed:9121459, ECO:0000269|PubMed:9499401,
ECO:0000269|PubMed:9535852}.
[PTM] Sumoylated with SUMO1 and SUMO2 upon heat shock in a
ERK2-dependent manner (PubMed:12646186, PubMed:12665592).
Sumoylated by SUMO1 on Lys-298; sumoylation occurs upon heat shock
and promotes its localization to nuclear stress bodies and
DNA-binding activity (PubMed:11514557). Phosphorylation on Ser-303
and Ser-307 is probably a prerequisite for sumoylation
(PubMed:12646186, PubMed:12665592). {ECO:0000269|PubMed:11514557,
ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592}.
[PTM] Acetylated on Lys-118; this acetylation is decreased in a
IER5-dependent manner (PubMed:26754925). Acetylated on Lys-118,
Lys-208 and Lys-298; these acetylations occur in a EP300-dependent
manner (PubMed:24581496, PubMed:27189267). Acetylated on Lys-80;
this acetylation inhibits DNA-binding activity upon heat shock
(PubMed:19229036). Deacetylated on Lys-80 by SIRT1; this
deacetylation increases DNA-binding activity (PubMed:19229036).
{ECO:0000269|PubMed:19229036, ECO:0000269|PubMed:24581496,
ECO:0000269|PubMed:26754925, ECO:0000269|PubMed:27189267}.
[PTM] Ubiquitinated by SCF(BTRC) and degraded following
stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis
(PubMed:18794143). Polyubiquitinated (PubMed:24581496). Undergoes
proteasomal degradation upon heat shock and during the attenuation
and recovery phase period of the heat shock response
(PubMed:24581496). {ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:24581496}.
[SIMILARITY] Belongs to the HSF family. {ECO:0000305}.
FEATURES Location/Qualifiers
source 1..529
/organism="Homo sapiens"
/db_xref="taxon:9606"
gene 1..529
/gene="HSF1"
/gene_synonym="HSTF1"
Protein 1..529
/product="Heat shock factor protein 1"
/note="HSF 1; Heat shock transcription factor 1; HSTF 1"
/UniProtKB_evidence="Evidence at protein level"
Region 1..529
/region_name="Mature chain"
/note="Heat shock factor protein 1. /id=PRO_0000124567."
Site 1
/site_type="acetylation"
/note="N-acetylmethionine.
/evidence=ECO:0007744|PubMed:19413330."
Region 14..118
/region_name="HSF"
/note="heat shock factor; smart00415"
/db_xref="CDD:214654"
Region 15..120
/region_name="Region of interest in the sequence"
/note="DNA-binding domain.
/evidence=ECO:0000269|PubMed:26727489,
ECO:0000269|PubMed:7935471."
Region 17..27
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Site 22
/site_type="mutagenized"
/note="L->A: Inhibits HSE DNA-binding activity and
transcriptional activation.
/evidence=ECO:0000269|PubMed:9341107."
Region 29..31
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 32..34
/region_name="Hydrogen bonded turn"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 35..37
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 39..42
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:5D5U."
Region 44..47
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 49..55
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 57..60
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 66..75
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 79..83
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Site 80
/site_type="mutagenized"
/note="K->Q: Loss of nuclear stress bodies localization.
Loss of DNA-binding and transcriptional activities upon
heat shock. No change in homotrimerization upon heat
shock. /evidence=ECO:0000269|PubMed:19229036,
ECO:0000269|PubMed:24581496."
Site 80
/site_type="mutagenized"
/note="K->R: Does not change interaction with XRCC5 and
XRCC6. Loss of nuclear stress bodies localization.
Decreased nuclear stress bodies localization. Loss of
DNA-binding and transcriptional activities upon heat
shock. /evidence=ECO:0000269|PubMed:19229036,
ECO:0000269|PubMed:24581496, ECO:0000269|PubMed:26359349."
Site 80
/site_type="acetylation"
/note="N6-acetyllysine.
/evidence=ECO:0000269|PubMed:19229036,
ECO:0000269|PubMed:24581496."
Region 87..89
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:7DCJ."
Bond bond(91)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2); alternate.
/evidence=ECO:0007744|PubMed:28112733."
Site 91
/site_type="mutagenized"
/note="K->R: No effect on sumoylation.
/evidence=ECO:0000269|PubMed:12665592."
Site 91
/site_type="acetylation"
/note="N6-acetyllysine; alternate.
/evidence=ECO:0000269|PubMed:24581496."
Region 96..100
/region_name="Beta-strand region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Region 109..114
/region_name="Helical region"
/note="/evidence=ECO:0007829|PDB:5HDN."
Site 118
/site_type="mutagenized"
/note="K->Q: Loss of nuclear stress bodies localization.
No change in protein abundance.
/evidence=ECO:0000269|PubMed:24581496."
Site 118
/site_type="mutagenized"
/note="K->R: No change in nuclear stress bodies
localization. /evidence=ECO:0000269|PubMed:24581496."
Site 118
/site_type="acetylation"
/note="N6-acetyllysine.
/evidence=ECO:0000269|PubMed:24581496,
ECO:0000269|PubMed:26754925."
Site 120
/site_type="mutagenized"
/note="T->A: No effect on binding HSE nor on
transcriptional activity.
/evidence=ECO:0000269|PubMed:16278218."
Site 121
/site_type="phosphorylation"
/note="Phosphoserine; by MAPKAPK2.
/evidence=ECO:0000269|PubMed:15760475,
ECO:0000269|PubMed:16278218."
Site 121
/site_type="mutagenized"
/note="S->A: Increased binding HSE and transcriptional
activity. Greatly reduced binding to HSP90AA1. No effect
on MAPKAPK2 binding.
/evidence=ECO:0000269|PubMed:16278218."
Site 121
/site_type="mutagenized"
/note="S->D: Some inhibition of binding HSE and
transcriptional activity. No change in binding HSP90AA1.
Inhibits MAPKAPK2 binding. Decreased HSF1-induced
expression of HSPA1A mRNA in a IER5-dependent manner; when
associated with D-307; D-314; D-323 and D-367.
/evidence=ECO:0000269|PubMed:16278218,
ECO:0000269|PubMed:26754925."
Site 123
/site_type="mutagenized"
/note="S->A: No effect on binding HSE nor on
transcriptional activity.
/evidence=ECO:0000269|PubMed:16278218."
Site 124
/site_type="mutagenized"
/note="T->A: No effect on binding HSE nor on
transcriptional activity.
/evidence=ECO:0000269|PubMed:16278218."
Bond bond(126)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2). /evidence=ECO:0007744|PubMed:28112733."
Site 126
/site_type="mutagenized"
/note="K->R: No effect on sumoylation.
/evidence=ECO:0000269|PubMed:12665592."
Region 130..203
/region_name="Region of interest in the sequence"
/note="Hydrophobic repeat HR-A/B.
/evidence=ECO:0000269|PubMed:7935471."
Bond bond(131)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2). /evidence=ECO:0007744|PubMed:28112733."
Site 140
/site_type="mutagenized"
/note="L->K: Leads to constitutive homotrimerization and
DNA-binding activities at 20 degrees Celsius. Does not
lead to constitutive transactivation activity at 20
degrees Celsius. Decreased DNA-binding activity at 37
degrees Celsius. /evidence=ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7935471."
Site 142
/site_type="phosphorylation"
/note="Phosphothreonine; by CK2.
/evidence=ECO:0000269|PubMed:12659875."
Site 142
/site_type="mutagenized"
/note="T->A: Reduced promoter activity by about 90%.
Almost no transcriptional activity when coexpressed with
CK2. /evidence=ECO:0000269|PubMed:12659875."
Site 147
/site_type="mutagenized"
/note="M->A: Leads to constitutive homotrimerization and
DNA-binding activities at 20 degrees Celsius. Does not
lead to constitutive transactivation activity at 20
degrees Celsius. No effect on DNA-binding activity at 37
degrees Celsius. /evidence=ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7935471."
Site 147
/site_type="mutagenized"
/note="M->E: Does not lead to constitutive
homotrimerization and DNA-binding activities at 20 degrees
Celsius. Loss of DNA-binding activity at 37 degrees
Celsius. /evidence=ECO:0000269|PubMed:7935471."
Site 147
/site_type="mutagenized"
/note="M->K: Does not lead to constitutive
homotrimerization and DNA-binding activities at 20 degrees
Celsius. Loss of DNA-binding activity at 37 degrees
Celsius. /evidence=ECO:0000269|PubMed:7935471."
Site 150
/site_type="mutagenized"
/note="K->R: No effect on sumoylation.
/evidence=ECO:0000269|PubMed:12665592."
Site 150
/site_type="acetylation"
/note="N6-acetyllysine.
/evidence=ECO:0000269|PubMed:24581496."
Site 162
/site_type="mutagenized"
/note="K->R: No effect on sumoylation.
/evidence=ECO:0000269|PubMed:12665592."
Site 188
/site_type="acetylation"
/note="N6-acetyllysine.
/evidence=ECO:0000269|PubMed:24581496."
Site 189
/site_type="mutagenized"
/note="L->A: Does not lead to constitutive
homotrimerization and DNA-binding activities at 20 degrees
Celsius. Leads to constitutive homotrimerization and
DNA-binding activities at 30 degrees Celsius. No effect on
DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 189
/site_type="mutagenized"
/note="L->E: Leads to constitutive homotrimerization,
DNA-binding and transactivation activities at 20 degrees
Celsius. Decreased DNA-binding activity at 37 degrees
Celsius. /evidence=ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7935471."
Site 189
/site_type="mutagenized"
/note="L->K: Leads to constitutive homotrimerization and
DNA-binding activities at 20 degrees Celsius. No effect on
DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 193
/site_type="mutagenized"
/note="L->A: Does not lead to constitutive
homotrimerization and DNA-binding activities at 20 degrees
Celsius. Leads to constitutive homotrimerization and
DNA-binding activities at 30 degrees Celsius. No effect on
DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 193
/site_type="mutagenized"
/note="L->E: Leads to constitutive homotrimerization and
DNA-binding activities at 20 degrees Celsius. Decreased
DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 193
/site_type="mutagenized"
/note="L->K: Leads to constitutive homotrimerization and
DNA-binding activities at 20 degrees Celsius. Loss of
DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Region 203..224
/region_name="Region of interest in the sequence"
/note="D domain. /evidence=ECO:0000269|PubMed:10747973."
Bond bond(208)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2); alternate.
/evidence=ECO:0007744|PubMed:28112733."
Site 208
/site_type="mutagenized"
/note="K->Q: No change in nuclear stress bodies
localization. Increased protein abundance.
/evidence=ECO:0000269|PubMed:24581496."
Site 208
/site_type="mutagenized"
/note="K->R: No change in nuclear stress bodies
localization. No change in protein abundance.
/evidence=ECO:0000269|PubMed:24581496."
Site 208
/site_type="acetylation"
/note="N6-acetyllysine; alternate.
/evidence=ECO:0000269|PubMed:24581496."
Site 216
/site_type="phosphorylation"
/note="Phosphoserine; by PLK1.
/evidence=ECO:0000269|PubMed:18794143."
Site 216
/site_type="mutagenized"
/note="S->A: Does not change interaction with XRCC5 and
XRCC6. No PLK1-induced phosphorylation in mitosis.
Inhibits PLK1-stimulated ubiquitinylation. Increased
protein stability. /evidence=ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:26359349."
Site 216
/site_type="mutagenized"
/note="S->E: Does not change interaction with XRCC5 and
XRCC6. No change in spindle pole localization. Increases
weakly PLK1-stimulated ubiquitinylation. No change in
protein stability. Increased interaction with BTRC.
/evidence=ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:26359349."
Site 216
/site_type="mutagenized"
/note="S->N: Decreased spindle pole localization.
Decreased interaction with BTRC. Increased protein
stability. /evidence=ECO:0000269|PubMed:18794143."
Region 221..310
/region_name="Region of interest in the sequence"
/note="Regulatory domain.
/evidence=ECO:0000269|PubMed:7760831."
Bond bond(224)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2). /evidence=ECO:0007744|PubMed:28112733."
Site 230
/site_type="phosphorylation"
/note="Phosphoserine; by CAMK2A.
/evidence=ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:15760475."
Site 230
/site_type="mutagenized"
/note="S->A: No phosphorylation. No change in PLK1-induced
phosphorylation in mitosis. No change in DNA-binding
activity upon heat shock. Decreased transcriptional
activity upon heat shock.
/evidence=ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143."
Site 230
/site_type="mutagenized"
/note="S->D: Mimics phosphorylation. No effect on
transcriptional activity upon heat shock.
/evidence=ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:12665592."
Region 252..529
/region_name="Vert_HS_TF"
/note="Vertebrate heat shock transcription factor;
pfam06546"
/db_xref="CDD:461944"
Site 275
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:8940068."
Site 275
/site_type="mutagenized"
/note="S->A: Reduced increase in heat-induced
transcriptional activity.
/evidence=ECO:0000269|PubMed:9535852."
Site 275
/site_type="mutagenized"
/note="S->G: Leads to weak constitutive transactivation
activity at room temperature.
/evidence=ECO:0000269|PubMed:8940068."
Site 292
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:15760475."
Site 292
/site_type="mutagenized"
/note="S->A: Weak decreased PLK1-induced phosphorylation.
Increased nuclear localization upon heat shock.
/evidence=ECO:0000269|PubMed:15661742."
Region 295..324
/region_name="Region of interest in the sequence"
/note="Disordered. /evidence=ECO:0000256|SAM:MobiDB-lite."
Site 296
/site_type="mutagenized"
/note="R->A: No effect neither on repression of
transcriptional activity at control temperature nor on
transcriptional activation upon heat shock.
/evidence=ECO:0000269|PubMed:8946918."
Site 297
/site_type="mutagenized"
/note="V->A: Slight effect on derepression of
transcriptional activity at control temperature and on
transcriptional activation upon heat shock.
/evidence=ECO:0000269|PubMed:8946918."
Bond bond(298)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO); alternate.
/evidence=ECO:0000269|PubMed:11514557,
ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:16371476."
Bond bond(298)
/bond_type="xlink"
/note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
G-Cter in SUMO2); alternate.
/evidence=ECO:0007744|PubMed:28112733."
Site 298
/site_type="mutagenized"
/note="K->A: Induces derepression of transcriptional
activity at control temperature.
/evidence=ECO:0000269|PubMed:12665592,
ECO:0000269|PubMed:8946918."
Site 298
/site_type="mutagenized"
/note="K->Q: No change in nuclear stress bodies
localization. Increased protein abundance.
/evidence=ECO:0000269|PubMed:24581496."
Site 298
/site_type="mutagenized"
/note="K->R: Abolishes sumoylation. No effect on
phosphorylation of S-303 nor of S-307. No change in
subcellular location to nuclear stress granules upon heat
shock. Loss of colocalization with SUMO1 to nuclear stress
granules upon heat shock. Does not change interaction with
XRCC5 and XRCC6. No effect on binding to HSE nor on
transactivation of HSP70. Increases transcriptional
activity in a DAXX-dependent manner. No change in protein
abundance. /evidence=ECO:0000269|PubMed:11514557,
ECO:0000269|PubMed:12646186, ECO:0000269|PubMed:12665592,
ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:24581496,
ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:8946918."
Site 298
/site_type="acetylation"
/note="N6-acetyllysine; alternate.
/evidence=ECO:0000269|PubMed:24581496."
Site 299
/site_type="mutagenized"
/note="E->A: No effect on repression of transcriptional
activity at control temperature.
/evidence=ECO:0000269|PubMed:8946918."
Site 300
/site_type="mutagenized"
/note="E->A: Induces derepression of transcriptional
activity at control temperature.
/evidence=ECO:0000269|PubMed:8946918."
Site 303
/site_type="phosphorylation"
/note="Phosphoserine; by GSK3-beta.
/evidence=ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:15760475,
ECO:0000269|PubMed:16371476, ECO:0000269|PubMed:8940068,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569."
Site 303
/site_type="mutagenized"
/note="S->A: No phosphorylation nor sumoylation. No change
in nuclear stress granules subcellular location upon heat
shock. Loss of colocalization with SUMO1 to nuclear stress
granules upon heat shock. Slight decrease in
transcriptional activity on heat treatment. No change in
PLK1-induced phosphorylation in mitosis, induces
derepression of transcription activation at control
temperature, abolishes sumoylation and induces 2.5-fold
increase in transcriptional activity on heat treatment;
when associated with A-307.
/evidence=ECO:0000269|PubMed:12646186,
ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0000269|PubMed:9535852."
Site 303
/site_type="mutagenized"
/note="S->D: Mimics phosphorylation. No effect on in vitro
sumoylation. Greatly increased transcriptional activity on
heat induction. 5-fold derepression of transcriptional
activity at control temperature; when associated with
D-307. /evidence=ECO:0000269|PubMed:12665592,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0000269|PubMed:9535852."
Site 303
/site_type="mutagenized"
/note="S->G: Leads to constitutive transactivation
activity at room temperature. Inhibits interaction with
YWHAE and increases cytoplasmic localization; when
associated with G-307.
/evidence=ECO:0000269|PubMed:12917326,
ECO:0000269|PubMed:8940068."
Site 307
/site_type="phosphorylation"
/note="Phosphoserine; by MAPK3.
/evidence=ECO:0000269|PubMed:11447121,
ECO:0000269|PubMed:15760475, ECO:0000269|PubMed:8940068,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0000269|PubMed:9535852, ECO:0007744|PubMed:23186163."
Site 307
/site_type="mutagenized"
/note="S->A: No phosphorylation. Does not reduce Ser-303
phosphorylation. 1.5% increase in transcriptional activity
on heat-treatment. No change in PLK1-induced
phosphorylation in mitosis, induces derepression of
transcription activation at control temperature, abolishes
sumoylation and induces 2.5-fold increase in
transcriptional activity on heat treatment; when
associated with A-303.
/evidence=ECO:0000269|PubMed:12646186,
ECO:0000269|PubMed:12665592, ECO:0000269|PubMed:18794143,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459,
ECO:0000269|PubMed:9535852."
Site 307
/site_type="mutagenized"
/note="S->D: 5-fold derepression of transcriptional
activity at control temperature; when associated with
D-303. Decreased HSF1-induced expression of HSPA1A mRNA in
a IER5-dependent manner; when associated with D-121;
D-314; D-323 and D-367.
/evidence=ECO:0000269|PubMed:26754925,
ECO:0000269|PubMed:8946918, ECO:0000269|PubMed:9121459."
Site 307
/site_type="mutagenized"
/note="S->G: Leads to constitutive transactivation
activity at room temperature. Inhibits interaction with
YWHAE and increases cytoplasmic localization; when
associated with G-303.
/evidence=ECO:0000269|PubMed:12917326,
ECO:0000269|PubMed:8940068."
Site 309
/site_type="mutagenized"
/note="R->A: No effect on repression of transcriptional
activity at control temperature.
/evidence=ECO:0000269|PubMed:8946918."
Site 311
/site_type="mutagenized"
/note="E->A: No effect neither on repression of
transcriptional activity at control temperature nor on
transcriptional activation upon heat shock.
/evidence=ECO:0000269|PubMed:8946918."
Site 314
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:15760475,
ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:19690332,
ECO:0007744|PubMed:20068231."
Site 314
/site_type="mutagenized"
/note="S->A: Weak decreased PLK1-induced phosphorylation.
/evidence=ECO:0000269|PubMed:15661742."
Site 314
/site_type="mutagenized"
/note="S->D: Decreased HSF1-induced expression of HSPA1A
mRNA in a IER5-dependent manner; when associated with
D-121; D-307; D-323 and D-367.
/evidence=ECO:0000269|PubMed:26754925."
Site 319
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:15760475."
Site 319
/site_type="mutagenized"
/note="S->A: Weak decreased PLK1-induced phosphorylation.
/evidence=ECO:0000269|PubMed:15661742."
Site 320
/site_type="phosphorylation"
/note="Phosphoserine; by PKA.
/evidence=ECO:0000269|PubMed:21085490,
ECO:0000269|PubMed:27189267."
Site 320
/site_type="mutagenized"
/note="S->A: Decreased nuclear localization and
transcriptional activity upon heat shock.
/evidence=ECO:0000269|PubMed:21085490."
Site 320
/site_type="mutagenized"
/note="S->D: Increased nuclear localization and
transcriptional activity upon heat shock.
/evidence=ECO:0000269|PubMed:21085490."
Site 323
/site_type="phosphorylation"
/note="Phosphothreonine.
/evidence=ECO:0007744|PubMed:17081983,
ECO:0007744|PubMed:19690332."
Site 323
/site_type="mutagenized"
/note="T->D: Decreased HSF1-induced expression of HSPA1A
mRNA in a IER5-dependent manner; when associated with
D-121; D-307; D-314 and D-367.
/evidence=ECO:0000269|PubMed:26754925."
Site 326
/site_type="phosphorylation"
/note="Phosphoserine; by MAPK12.
/evidence=ECO:0000269|PubMed:15760475,
ECO:0000269|PubMed:27354066, ECO:0007744|PubMed:19690332,
ECO:0007744|PubMed:20068231."
Site 326
/site_type="mutagenized"
/note="S->A: No phosphorylation. Increased nuclear
localization upon heat shock. No effect on
oligomerization, DNA-binding activities and nuclear
localization. Significant decrease in transcriptional
activity by heat shock. Decreases transcriptional activity
in a DAXX-dependent manner. Does not change interaction
with XRCC5 and XRCC6. Weak decreased PLK1-induced
phosphorylation. /evidence=ECO:0000269|PubMed:15016915,
ECO:0000269|PubMed:15661742, ECO:0000269|PubMed:15760475,
ECO:0000269|PubMed:26359349, ECO:0000269|PubMed:27354066."
Site 326
/site_type="mutagenized"
/note="S->E: Does not change interaction with XRCC5 and
XRCC6. /evidence=ECO:0000269|PubMed:26359349."
Region 336..372
/region_name="Region of interest in the sequence"
/note="Disordered. /evidence=ECO:0000256|SAM:MobiDB-lite."
Site 344
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:15760475."
Site 363
/site_type="phosphorylation"
/note="Phosphoserine; by MAPK8.
/evidence=ECO:0000269|PubMed:10747973,
ECO:0000269|PubMed:15760475, ECO:0007744|PubMed:18669648,
ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569."
Site 363
/site_type="mutagenized"
/note="S->A: Decreases MAPK8-induced phosphorylation and
does not negatively regulates transactivating activity
upon heat shock. No effect on sumoylation.
/evidence=ECO:0000269|PubMed:10747973,
ECO:0000269|PubMed:12665592."
Site 367
/site_type="mutagenized"
/note="T->D: Decreased HSF1-induced expression of HSPA1A
mRNA in a IER5-dependent manner; when associated with
D-121; D-307; D-314 and D-323.
/evidence=ECO:0000269|PubMed:26754925."
Region 371..529
/region_name="Region of interest in the sequence"
/note="Transactivation domain.
/evidence=ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7760831."
Site 381
/site_type="mutagenized"
/note="K->R: No effect on sumoylation.
/evidence=ECO:0000269|PubMed:12665592."
Region 384..409
/region_name="Region of interest in the sequence"
/note="Hydrophobic repeat HR-C.
/evidence=ECO:0000269|PubMed:7935471."
Site 391
/site_type="mutagenized"
/note="M->A: Does not lead to constitutive DNA-binding
activity at 20 degrees Celsius. Leads to weak constitutive
DNA-binding and homotrimerization activities at 30 degrees
Celsius. Decreased DNA-binding activity at 37 degrees
Celsius. /evidence=ECO:0000269|PubMed:7935471."
Site 391
/site_type="mutagenized"
/note="M->E: Leads to constitutive DNA-binding and
homotrimerization activities at 20 degrees Celsius. Does
not lead to constitutive transactivation activity at 20
degrees Celsius. No effect on DNA-binding activity at 37
degrees Celsius. /evidence=ECO:0000269|PubMed:7623826,
ECO:0000269|PubMed:7935471."
Site 391
/site_type="mutagenized"
/note="M->K: Leads to constitutive DNA-binding and
homotrimerization activities at 20 degrees Celsius. No
effect on DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 395
/site_type="mutagenized"
/note="L->E: Leads to constitutive DNA-binding and
homotrimerization activities at 20 degrees Celsius. No
effect on DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Site 395
/site_type="mutagenized"
/note="L->K: Leads to constitutive DNA-binding and
homotrimerization activities at 20 degrees Celsius. No
effect on DNA-binding activity at 37 degrees Celsius.
/evidence=ECO:0000269|PubMed:7935471."
Region 412..420
/region_name="Short sequence motif of biological interest"
/note="9aaTAD. /evidence=ECO:0000303|PubMed:17467953."
Site 419
/site_type="phosphorylation"
/note="Phosphoserine; by PLK1.
/evidence=ECO:0000269|PubMed:15661742."
Site 419
/site_type="mutagenized"
/note="S->A: Does not change interaction with XRCC5 and
XRCC6. Decreased nuclear localization upon heat shock.
Strongly decreases PLK1-induced phosphorylation. No change
in PLK1-induced phosphorylation in mitosis.
/evidence=ECO:0000269|PubMed:15661742,
ECO:0000269|PubMed:18794143, ECO:0000269|PubMed:26359349."
Site 419
/site_type="mutagenized"
/note="S->E: Does not change interaction with XRCC5 and
XRCC6. /evidence=ECO:0000269|PubMed:26359349."
Region 444..463
/region_name="Region of interest in the sequence"
/note="Disordered. /evidence=ECO:0000256|SAM:MobiDB-lite."
Site 444
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0000269|PubMed:15760475."
Region 462..489
/region_name="Splicing variant"
/note="GKQLVHYTAQPLFLLDPGSVDTGSNDLP ->
AGALHSAAAVPAGPRLRGHREQRPAGAV (in isoform Short).
/evidence=ECO:0000305. /id=VSP_002414."
Region 490..529
/region_name="Splicing variant"
/note="Missing (in isoform Short). /evidence=ECO:0000305.
/id=VSP_002415."
Region 502..529
/region_name="Region of interest in the sequence"
/note="Disordered. /evidence=ECO:0000256|SAM:MobiDB-lite."
Site 524
/site_type="acetylation"
/note="N6-acetyllysine.
/evidence=ECO:0000269|PubMed:24581496."
Site 527
/site_type="mutagenized"
/note="T->A: No change in binding HSE nor on
transcriptional activity. Decreased binding HSE; when
associated with A-529.
/evidence=ECO:0000269|PubMed:16278218."
Site 529
/site_type="mutagenized"
/note="S->A: No change in binding HSE nor on
transcriptional activity. Decreased binding HSE; when
associated with A-527.
/evidence=ECO:0000269|PubMed:16278218."
ORIGIN
1 mdlpvgpgaa gpsnvpaflt klwtlvsdpd tdalicwsps gnsfhvfdqg qfakevlpky
61 fkhnnmasfv rqlnmygfrk vvhieqgglv kperddtefq hpcflrgqeq llenikrkvt
121 svstlksedi kirqdsvtkl ltdvqlmkgk qecmdsklla mkhenealwr evaslrqkha
181 qqqkvvnkli qflislvqsn rilgvkrkip lmlndsgsah smpkysrqfs lehvhgsgpy
241 sapspaysss slyapdavas sgpiisdite lapaspmasp ggsiderpls ssplvrvkee
301 ppsppqsprv eeaspgrpss vdtllsptal idsilresep apasvtaltd arghtdtegr
361 ppsppptstp ekclsvacld knelsdhlda mdsnldnlqt mlsshgfsvd tsalldlfsp
421 svtvpdmslp dldsslasiq ellspqeppr ppeaensspd sgkqlvhyta qplflldpgs
481 vdtgsndlpv lfelgegsyf segdgfaedp tislltgsep pkakdptvs
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