HSF1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HSF1_HUMAN
• UniProt AC: Q00613
• Protein Name: Heat shock factor protein 1 {ECO:0000305}
• Gene Name: HSF1 {ECO:0000312|HGNC:HGNC:5224}
• Organism: Homo sapiens (Human).
• Sequence Length: 529
• Subcellular Localization: Nucleus . Cytoplasm . Nucleus, nucleoplasm . Cytoplasm, perinuclear region . Cytoplasm, cytoskeleton, spindle pole . Cytoplasm, cytoskeleton, microtubule organizing center, centrosome . Chromosome, centromere, kinetochore . The monomeric form is cyto
• Protein Description: Function 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 insults' damage. [PubMed: 1871105]
• Protein Sequence: MDLPVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKYFKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVTSVSTLKSEDIKIRQDSVTKLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHAQQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLNDSGSAHSMPKYSRQFSLEHVHGSGPYSAPSPAYSSSSLYAPDAVASSGPIISDITELAPASPMASPGGSIDERPLSSSPLVRVKEEPPSPPQSPRVEEASPGRPSSVDTLLSPTALIDSILRESEPAPASVTALTDARGHTDTEGRPPSPPPTSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLSSHGFSVDTSALLDLFSPSVTVPDMSLPDLDSSLASIQELLSPQEPPRPPEAENSSPDSGKQLVHYTAQPLFLLDPGSVDTGSNDLPVLFELGEGSYFSEGDGFAEDPTISLLTGSEPPKAKDPTVS

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDLPVGPG -------CCCCCCCC	12.31	19413330
13	Phosphorylation	GPGAAGPSNVPAFLT CCCCCCCCCHHHHHH	49.93	-
54	Ubiquitination	FDQGQFAKEVLPKYF EECCHHHHHHHHHHH	50.04	-
59	Ubiquitination	FAKEVLPKYFKHNNM HHHHHHHHHHCCCCH	60.19	23000965
62	Malonylation	EVLPKYFKHNNMASF HHHHHHHCCCCHHHH	42.19	26320211
62	Ubiquitination	EVLPKYFKHNNMASF HHHHHHHCCCCHHHH	42.19	21890473
80	Acetylation	LNMYGFRKVVHIEQG HHHHCCEEEEEEEEC	46.47	19229036
91	Acetylation	IEQGGLVKPERDDTE EEECCCCCCCCCCCC	46.32	24581496
91	Sumoylation	IEQGGLVKPERDDTE EEECCCCCCCCCCCC	46.32	28112733
91	Ubiquitination	IEQGGLVKPERDDTE EEECCCCCCCCCCCC	46.32	29967540
116	Acetylation	EQLLENIKRKVTSVS HHHHHHHHHHCCCHH	58.72	19229036
116	Ubiquitination	EQLLENIKRKVTSVS HHHHHHHHHHCCCHH	58.72	24816145
118	Acetylation	LLENIKRKVTSVSTL HHHHHHHHCCCHHHH	44.88	26754925
118	Ubiquitination	LLENIKRKVTSVSTL HHHHHHHHCCCHHHH	44.88	26754925
120	Phosphorylation	ENIKRKVTSVSTLKS HHHHHHCCCHHHHCH	26.84	28450419
121	Phosphorylation	NIKRKVTSVSTLKSE HHHHHCCCHHHHCHH	19.63	25159151
123	Phosphorylation	KRKVTSVSTLKSEDI HHHCCCHHHHCHHCC	27.99	28450419
124	Phosphorylation	RKVTSVSTLKSEDIK HHCCCHHHHCHHCCC	35.73	28450419
126	Sumoylation	VTSVSTLKSEDIKIR CCCHHHHCHHCCCCC	52.46	-
126	Acetylation	VTSVSTLKSEDIKIR CCCHHHHCHHCCCCC	52.46	19229036
126	Sumoylation	VTSVSTLKSEDIKIR CCCHHHHCHHCCCCC	52.46	28112733
126	Ubiquitination	VTSVSTLKSEDIKIR CCCHHHHCHHCCCCC	52.46	32015554
127	Phosphorylation	TSVSTLKSEDIKIRQ CCHHHHCHHCCCCCH	43.55	20068231
131	Sumoylation	TLKSEDIKIRQDSVT HHCHHCCCCCHHHHH	44.13	28112733
131	Ubiquitination	TLKSEDIKIRQDSVT HHCHHCCCCCHHHHH	44.13	32015554
136	Phosphorylation	DIKIRQDSVTKLLTD CCCCCHHHHHHHHHH	24.29	28348404
138	Phosphorylation	KIRQDSVTKLLTDVQ CCCHHHHHHHHHHHH	21.67	29083192
142	Phosphorylation	DSVTKLLTDVQLMKG HHHHHHHHHHHHHCC	44.56	12659875
147	Sulfoxidation	LLTDVQLMKGKQECM HHHHHHHHCCCHHHH	2.76	21406390
148	Acetylation	LTDVQLMKGKQECMD HHHHHHHCCCHHHHH	72.11	19229036
148	Ubiquitination	LTDVQLMKGKQECMD HHHHHHHCCCHHHHH	72.11	-
150	Acetylation	DVQLMKGKQECMDSK HHHHHCCCHHHHHHH	37.09	24581496
157	Sumoylation	KQECMDSKLLAMKHE CHHHHHHHHHHHHHH	43.16	-
157	Acetylation	KQECMDSKLLAMKHE CHHHHHHHHHHHHHH	43.16	25953088
157	Sumoylation	KQECMDSKLLAMKHE CHHHHHHHHHHHHHH	43.16	-
157	Ubiquitination	KQECMDSKLLAMKHE CHHHHHHHHHHHHHH	43.16	29967540
162	Ubiquitination	DSKLLAMKHENEALW HHHHHHHHHHHHHHH	42.00	29967540
184	Ubiquitination	QKHAQQQKVVNKLIQ HHHHHHHHHHHHHHH	43.76	29967540
188	Acetylation	QQQKVVNKLIQFLIS HHHHHHHHHHHHHHH	35.04	24581496
208	Sumoylation	RILGVKRKIPLMLND CCCCCCCCCCEEECC	42.85	-
208	Acetylation	RILGVKRKIPLMLND CCCCCCCCCCEEECC	42.85	24581496
208	Sumoylation	RILGVKRKIPLMLND CCCCCCCCCCEEECC	42.85	28112733
208	Ubiquitination	RILGVKRKIPLMLND CCCCCCCCCCEEECC	42.85	29967540
216	Phosphorylation	IPLMLNDSGSAHSMP CCEEECCCCCCCCCC	33.31	25159151
218	Phosphorylation	LMLNDSGSAHSMPKY EEECCCCCCCCCCCH	27.10	25159151
221	Phosphorylation	NDSGSAHSMPKYSRQ CCCCCCCCCCCHHCC	36.17	25159151
224	Sumoylation	GSAHSMPKYSRQFSL CCCCCCCCHHCCEEC	47.41	-
224	Acetylation	GSAHSMPKYSRQFSL CCCCCCCCHHCCEEC	47.41	19229036
224	Sumoylation	GSAHSMPKYSRQFSL CCCCCCCCHHCCEEC	47.41	28112733
224	Ubiquitination	GSAHSMPKYSRQFSL CCCCCCCCHHCCEEC	47.41	29967540
230	Phosphorylation	PKYSRQFSLEHVHGS CCHHCCEECCCCCCC	25.22	26074081
237	Phosphorylation	SLEHVHGSGPYSAPS ECCCCCCCCCCCCCC	23.01	26074081
240	Phosphorylation	HVHGSGPYSAPSPAY CCCCCCCCCCCCCCC	22.46	26074081
241	Phosphorylation	VHGSGPYSAPSPAYS CCCCCCCCCCCCCCC	36.52	26074081
244	Phosphorylation	SGPYSAPSPAYSSSS CCCCCCCCCCCCCCC	23.14	26074081
247	Phosphorylation	YSAPSPAYSSSSLYA CCCCCCCCCCCCCCC	16.69	26074081
248	Phosphorylation	SAPSPAYSSSSLYAP CCCCCCCCCCCCCCC	26.33	26074081
249	Phosphorylation	APSPAYSSSSLYAPD CCCCCCCCCCCCCCH	15.98	26074081
250	Phosphorylation	PSPAYSSSSLYAPDA CCCCCCCCCCCCCHH	20.58	26074081
251	Phosphorylation	SPAYSSSSLYAPDAV CCCCCCCCCCCCHHH	27.61	26074081
253	Phosphorylation	AYSSSSLYAPDAVAS CCCCCCCCCCHHHHC	20.31	26074081
269	Phosphorylation	GPIISDITELAPASP CCEECCHHHHCCCCC	29.91	26074081
275	Phosphorylation	ITELAPASPMASPGG HHHHCCCCCCCCCCC	17.72	26074081
279	Phosphorylation	APASPMASPGGSIDE CCCCCCCCCCCCCCC	20.16	26074081
283	Phosphorylation	PMASPGGSIDERPLS CCCCCCCCCCCCCCC	32.55	26074081
290	Phosphorylation	SIDERPLSSSPLVRV CCCCCCCCCCCCEEE	31.30	20873877
291	Phosphorylation	IDERPLSSSPLVRVK CCCCCCCCCCCEEEC	43.59	29255136
292	Phosphorylation	DERPLSSSPLVRVKE CCCCCCCCCCEEECC	20.91	19664994
298	Sumoylation	SSPLVRVKEEPPSPP CCCCEEECCCCCCCC	45.88	-
298	Acetylation	SSPLVRVKEEPPSPP CCCCEEECCCCCCCC	45.88	24581496
298	Sumoylation	SSPLVRVKEEPPSPP CCCCEEECCCCCCCC	45.88	15016915
303	Phosphorylation	RVKEEPPSPPQSPRV EECCCCCCCCCCCCC	60.99	19664994
307	Phosphorylation	EPPSPPQSPRVEEAS CCCCCCCCCCCCCCC	22.05	19664994
314	Phosphorylation	SPRVEEASPGRPSSV CCCCCCCCCCCCCCH	31.03	29255136
319	Phosphorylation	EASPGRPSSVDTLLS CCCCCCCCCHHHHCC	41.45	22167270
320	Phosphorylation	ASPGRPSSVDTLLSP CCCCCCCCHHHHCCH	27.05	22167270
323	Phosphorylation	GRPSSVDTLLSPTAL CCCCCHHHHCCHHHH	27.69	19664994
326	Phosphorylation	SSVDTLLSPTALIDS CCHHHHCCHHHHHHH	24.26	30278072
328	Phosphorylation	VDTLLSPTALIDSIL HHHHCCHHHHHHHHH	30.62	22115753
333	Phosphorylation	SPTALIDSILRESEP CHHHHHHHHHHCCCC	19.27	22115753
338	Phosphorylation	IDSILRESEPAPASV HHHHHHCCCCCCCEE	42.31	26074081
344	Phosphorylation	ESEPAPASVTALTDA CCCCCCCEEEEEECC	20.95	21082442
346	Phosphorylation	EPAPASVTALTDARG CCCCCEEEEEECCCC	17.29	26074081
349	Phosphorylation	PASVTALTDARGHTD CCEEEEEECCCCCCC	25.75	26074081
355	Phosphorylation	LTDARGHTDTEGRPP EECCCCCCCCCCCCC	47.65	29255136
357	Phosphorylation	DARGHTDTEGRPPSP CCCCCCCCCCCCCCC	41.30	29255136
363	Phosphorylation	DTEGRPPSPPPTSTP CCCCCCCCCCCCCCH	53.36	29255136
367	Phosphorylation	RPPSPPPTSTPEKCL CCCCCCCCCCHHHEE	51.51	29255136
368	Phosphorylation	PPSPPPTSTPEKCLS CCCCCCCCCHHHEEE	47.97	29255136
369	Phosphorylation	PSPPPTSTPEKCLSV CCCCCCCCHHHEEEE	37.63	29255136
375	Phosphorylation	STPEKCLSVACLDKN CCHHHEEEEEECCHH	19.69	26074081
419	Phosphorylation	SALLDLFSPSVTVPD HHHHHHHCCCCCCCC	24.46	15661742
438	Phosphorylation	DLDSSLASIQELLSP CHHHHHHHHHHHHCC	30.05	26074081
444	Phosphorylation	ASIQELLSPQEPPRP HHHHHHHCCCCCCCC	36.84	26074081
457	Phosphorylation	RPPEAENSSPDSGKQ CCCCCCCCCCCCCCC	34.45	26074081
458	Phosphorylation	PPEAENSSPDSGKQL CCCCCCCCCCCCCCC	44.29	26074081
461	Phosphorylation	AENSSPDSGKQLVHY CCCCCCCCCCCCEEE	51.80	26074081
468	Phosphorylation	SGKQLVHYTAQPLFL CCCCCEEEEECCEEE	9.04	26074081
498	Phosphorylation	LFELGEGSYFSEGDG EEEECCCCCCCCCCC	20.78	26074081
499	Phosphorylation	FELGEGSYFSEGDGF EEECCCCCCCCCCCC	23.21	26074081
501	Phosphorylation	LGEGSYFSEGDGFAE ECCCCCCCCCCCCCC	32.22	26074081
511	Phosphorylation	DGFAEDPTISLLTGS CCCCCCCCEEEECCC	35.20	26074081
513	Phosphorylation	FAEDPTISLLTGSEP CCCCCCEEEECCCCC	21.58	26074081
516	Phosphorylation	DPTISLLTGSEPPKA CCCEEEECCCCCCCC	43.91	26074081
518	Phosphorylation	TISLLTGSEPPKAKD CEEEECCCCCCCCCC	41.51	26074081
524	Acetylation	GSEPPKAKDPTVS-- CCCCCCCCCCCCC--	71.07	24581496
527	Phosphorylation	PPKAKDPTVS----- CCCCCCCCCC-----	43.44	26074081
529	Phosphorylation	KAKDPTVS------- CCCCCCCC-------	36.66	26074081

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
120	T	Phosphorylation	Kinase	PIM2	Q9P1W9	PSP
121	S	Phosphorylation	Kinase	AMPKA1	Q13131	PSP
121	S	Phosphorylation	Kinase	MAPK2	P49137	PhosphoELM
142	T	Phosphorylation	Kinase	CK2	-	Uniprot
142	T	Phosphorylation	Kinase	CK2-FAMILY	-	GPS
142	T	Phosphorylation	Kinase	CK2_GROUP	-	PhosphoELM
142	T	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
142	T	Phosphorylation	Kinase	CSNK2A2	P19784	GPS
216	S	Phosphorylation	Kinase	PLK1	P53350	Uniprot
230	S	Phosphorylation	Kinase	KCC2A	Q9UQM7	PhosphoELM
230	S	Phosphorylation	Kinase	DAPK1	P53355	PSP
230	S	Phosphorylation	Kinase	CAM-KII_GROUP	-	PhosphoELM
230	S	Phosphorylation	Kinase	CAMK2-FAMILY	-	GPS
303	S	Phosphorylation	Kinase	MAPK3	P27361	GPS
303	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
303	S	Phosphorylation	Kinase	MAPK13	O15264	GPS
303	S	Phosphorylation	Kinase	MTOR	P42345	PSP
303	S	Phosphorylation	Kinase	MAPK12	P53778	GPS
303	S	Phosphorylation	Kinase	MAPK11	Q15759	GPS
303	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
303	S	Phosphorylation	Kinase	GSK-FAMILY	-	GPS
303	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
303	S	Phosphorylation	Kinase	GSK3A	P49840	GPS
303	S	Phosphorylation	Kinase	GSK-3_GROUP	-	PhosphoELM
307	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
307	S	Phosphorylation	Kinase	MAPK_GROUP	-	PhosphoELM
307	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
307	S	Phosphorylation	Kinase	MAPK13	O15264	GPS
307	S	Phosphorylation	Kinase	MAPK12	P53778	GPS
307	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
307	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
307	S	Phosphorylation	Kinase	MAPK11	Q15759	GPS
307	S	Phosphorylation	Kinase	ERK1	P27361	PSP
320	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
320	S	Phosphorylation	Kinase	PKA	-	Uniprot
326	S	Phosphorylation	Kinase	AKT1	P31749	PSP
326	S	Phosphorylation	Kinase	MAPK13	O15264	GPS
326	S	Phosphorylation	Kinase	ERK2	P28482	PSP
326	S	Phosphorylation	Kinase	ERK1	P27361	PSP
326	S	Phosphorylation	Kinase	MAPK11	Q15759	GPS
326	S	Phosphorylation	Kinase	P38G	P53778	PSP
326	S	Phosphorylation	Kinase	MTOR	P42345	PSP
326	S	Phosphorylation	Kinase	MAP2K1	Q02750	GPS
326	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
363	S	Phosphorylation	Kinase	JNK-SUBFAMILY	-	GPS
363	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
363	S	Phosphorylation	Kinase	MAPK8	P45983	Uniprot
363	S	Phosphorylation	Kinase	JNK_GROUP	-	PhosphoELM
419	S	Phosphorylation	Kinase	PLK1	P53350	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:23344957
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:24658274

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
80	K	Acetylation	Acetylated on Lys-80; this acetylation inhibits DNA-binding activity upon heat shock.	19229036
80	K	Acetylation	Deacetylated on Lys-80 by SIRT1; this deacetylation increases DNA-binding activity.	19229036
118	K	Acetylation	Acetylated on Lys-118; this acetylation is decreased in a IER5-dependent manner.	24581496
118	K	Acetylation	Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.	24581496
121	S	Phosphorylation	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.	15760475
121	S	Phosphorylation	Phosphorylated on Ser-121 by MAPKAPK2; this phosphorylation promotes interaction with HSP90 proteins and inhibits HSF1 homotrimerization, DNA-binding and transactivation activities.	15760475
142	T	Phosphorylation	Phosphorylated on Thr-142; this phosphorylation increases HSF1 transactivation activity upon heat shock.	12659875
208	K	Acetylation	Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.	24581496
216	S	Phosphorylation	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.	18794143
216	S	Phosphorylation	Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis.	18794143
216	S	ubiquitylation	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.	18794143
216	S	ubiquitylation	Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis.	18794143
230	S	Phosphorylation	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.	11447121
230	S	Phosphorylation	Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances HSF1 transactivation activity upon heat shock.	11447121
292	S	Phosphorylation	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.	15760475
298	K	Sumoylation	Sumoylated by SUMO1 on Lys-298; sumoylation occurs upon heat shock and promotes its localization to nuclear stress bodies and DNA-binding activity.	8946918
298	K	Acetylation	Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.	8946918
303	S	Phosphorylation	According to PubMed:9535852, Ser-303 is not phosphorylated in unstressed cells.	11447121
303	S	Phosphorylation	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.	11447121
303	S	Phosphorylation	Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner.	11447121
303	S	Phosphorylation	Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.	11447121
303	S	Phosphorylation	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.	11447121
303	S	Phosphorylation	Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303.	11447121
303	S	Sumoylation	Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.	11447121
307	S	Phosphorylation	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.	11447121
307	S	Sumoylation	Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.	11447121
307	S	Phosphorylation	Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303.	11447121
307	S	Phosphorylation	Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.	11447121
307	S	Phosphorylation	Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner.	11447121
307	S	Phosphorylation	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.	11447121
307	S	Phosphorylation	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.	11447121
314	S	Phosphorylation	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.	15760475
314	S	Phosphorylation	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.	15760475
319	S	Phosphorylation	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.	15760475
320	S	Phosphorylation	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.	21085490
320	S	Phosphorylation	Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation promotes nuclear localization and transcriptional activity upon heat shock.	21085490
323	T	Phosphorylation	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.	17081983
323	T	Phosphorylation	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.	17081983
326	S	Phosphorylation	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.	15016915
326	S	Phosphorylation	Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances HSF1 nuclear translocation, homotrimerization and transactivation activities upon heat shock.	15016915
338	S	Phosphorylation	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.	25963659
344	S	Phosphorylation	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.	15760475
363	S	Phosphorylation	Phosphorylated on Ser-363 by MAPK8; this phosphorylation occurs upon heat shock, induces HSF1 translocation into nuclear stress bodies and negatively regulates transactivation activity.	10747973
363	S	Phosphorylation	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.	10747973
367	T	Phosphorylation	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.	26754925
367	T	Phosphorylation	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.	26754925
368	S	Phosphorylation	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.	25963659
369	T	Phosphorylation	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.	25963659
419	S	Phosphorylation	Phosphorylated on Ser-419 by PLK1; phosphorylation promotes nuclear translocation upon heat shock.	15760475

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of HSF1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
SYMPK_HUMAN	SYMPK	physical	14707147
HSF2_HUMAN	HSF2	physical	12813038
RBP1_HUMAN	RALBP1	physical	12621024
SMCA4_HUMAN	SMARCA4	physical	11486022
HS90A_HUMAN	HSP90AA1	physical	9222609
HSP74_HUMAN	HSPA4	physical	9222609
FKBP5_HUMAN	FKBP5	physical	9222609
FKBP4_HUMAN	FKBP4	physical	9222609
PPID_HUMAN	PPID	physical	9222609
TEBP_HUMAN	PTGES3	physical	9222609
DNJB1_HUMAN	DNAJB1	physical	9499401
TBP_HUMAN	TBP	physical	11005381
TF2B_HUMAN	GTF2B	physical	11005381
HSP74_HUMAN	HSPA4	physical	1628823
CEBPB_HUMAN	CEBPB	physical	11801594
XRCC5_HUMAN	XRCC5	physical	9325337
PRKDC_HUMAN	PRKDC	physical	9325337
HSP7C_HUMAN	HSPA8	physical	7639722
XRCC6_HUMAN	XRCC6	physical	11162511
HSBP1_HUMAN	HSBP1	physical	9649501
SIR1_HUMAN	SIRT1	physical	19229036
MTA1_HUMAN	MTA1	physical	17922035
HDAC1_HUMAN	HDAC1	physical	17922035
HDAC2_HUMAN	HDAC2	physical	17922035
CHD3_HUMAN	CHD3	physical	17922035
SMCA4_HUMAN	SMARCA4	physical	20353823
FLIP1_HUMAN	FILIP1	physical	21784850
HSPB1_HUMAN	HSPB1	physical	19597476
HSPB2_HUMAN	HSPB2	physical	19597476
TAF9_HUMAN	TAF9	physical	10821850
HSP74_HUMAN	HSPA4	physical	14532117
CHIP_HUMAN	STUB1	physical	14532117
PCGF2_HUMAN	PCGF2	physical	18211895
HS90A_HUMAN	HSP90AA1	physical	20885985
FBW1A_HUMAN	BTRC	physical	18794143
MD2L1_HUMAN	MAD2L1	physical	18794143
DAXX_HUMAN	DAXX	physical	15016915
STRAP_HUMAN	STRAP	physical	18451878
MAPK2_HUMAN	MAPKAPK2	physical	16278218
HS90A_HUMAN	HSP90AA1	physical	16278218
TEBP_HUMAN	PTGES3	physical	23022381
BAG3_HUMAN	BAG3	physical	23824909
CHIP_HUMAN	STUB1	physical	16293251
HSP7C_HUMAN	HSPA8	physical	16293251
SYAC_HUMAN	AARS	physical	22863883
NC2B_HUMAN	DR1	physical	22863883
IPO11_HUMAN	IPO11	physical	22863883
PAF15_HUMAN	KIAA0101	physical	22863883
PLIN3_HUMAN	PLIN3	physical	22863883
SRP09_HUMAN	SRP9	physical	22863883
BAG3_HUMAN	BAG3	physical	25036637
HSF2_HUMAN	HSF2	physical	25036637
IMA4_HUMAN	KPNA3	physical	25036637
HS74L_HUMAN	HSPA4L	physical	25036637
NDKB_HUMAN	NME2	physical	25036637
IMA3_HUMAN	KPNA4	physical	25036637
HSPB1_HUMAN	HSPB1	physical	25036637
HPBP1_HUMAN	HSPBP1	physical	25036637
NCOA6_HUMAN	NCOA6	physical	14960326
CBP_HUMAN	CREBBP	physical	14960326
HSF1_HUMAN	HSF1	physical	20098725
HSF1_HUMAN	HSF1	physical	19758120
NEDD4_HUMAN	NEDD4	physical	26503960
IMA4_HUMAN	KPNA3	physical	27173435
IMA3_HUMAN	KPNA4	physical	27173435

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Acetylation

"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGESCALE ANALYSIS] AT SER-303 AND SER-307, AND MASS SPECTROMETRY.
PubMed: 19413330

Phosphorylation

"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; THR-323 ANDSER-326, AND MASS SPECTROMETRY.
PubMed: 19690332

"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGESCALE ANALYSIS] AT SER-303 AND SER-307, AND MASS SPECTROMETRY.
PubMed: 19413330

"A quantitative atlas of mitotic phosphorylation.";
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-307; SER-363AND THR-369, AND MASS SPECTROMETRY.
PubMed: 18669648

"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis.";
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III;
J. Proteome Res. 7:1346-1351(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-314; THR-323 ANDSER-326, AND MASS SPECTROMETRY.
PubMed: 18220336

"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
Anal. Sci. 24:161-166(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303, AND MASSSPECTROMETRY.
PubMed: 18187866

"PDSM, a motif for phosphorylation-dependent SUMO modification.";
Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J.,Nakai A., Sistonen L.;
Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006).
Cited for: SUMOYLATION AT LYS-298, AND PHOSPHORYLATION AT SER-303.
PubMed: 16371476

"Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine121, inhibits transcriptional activity and promotes HSP90 binding.";
Wang X., Khaleque M.A., Zhao M.J., Zhong R., Gaestel M.,Calderwood S.K.;
J. Biol. Chem. 281:782-791(2006).
Cited for: PHOSPHORYLATION AT SER-121, FUNCTION, INTERACTION WITH HSP90AA1 ANDMAPKAPK2, MUTAGENESIS OF THR-120; SER-121; SER-123; THR-124; THR-527AND SER-529, AND MASS SPECTROMETRY.
PubMed: 16278218

"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks.";
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.;
Cell 127:635-648(2006).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303; SER-307; THR-323AND SER-363, AND MASS SPECTROMETRY.
PubMed: 17081983

"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND SER-307, ANDMASS SPECTROMETRY.
PubMed: 15302935

"Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1.";
Hietakangas V., Ahlskog J.K., Jakobsson A.M., Hellesuo M.,Sahlberg N.M., Holmberg C.I., Mikhailov A., Palvimo J.J., Pirkkala L.,Sistonen L.;
Mol. Cell. Biol. 23:2953-2968(2003).
Cited for: SUMOYLATION AT LYS-298, PHOSPHORYLATION AT SER-303, FUNCTION,SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-91; LYS-126; LYS-150;LYS-162; SER-230; LYS-298; SER-303; SER-307; SER-363 AND LYS-381.
PubMed: 12665592

"Transcriptional activation of heat shock factor HSF1 probed byphosphopeptide analysis of factor 32P-labeled in vivo.";
Xia W., Guo Y., Vilaboa N., Zuo J., Voellmy R.;
J. Biol. Chem. 273:8749-8755(1998).
Cited for: PHOSPHORYLATION AT SER-307, FUNCTION, AND MUTAGENESIS OF SER-275;SER-303 AND SER-307.
PubMed: 9535852

"Repression of the heat shock factor 1 transcriptional activationdomain is modulated by constitutive phosphorylation.";
Kline M.P., Morimoto R.I.;
Mol. Cell. Biol. 17:2107-2115(1997).
Cited for: PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, AND MUTAGENESIS OFSER-303 AND SER-307.
PubMed: 9121459

"Repression of human heat shock factor 1 activity at controltemperature by phosphorylation.";
Knauf U., Newton E.M., Kyriakis J., Kingston R.E.;
Genes Dev. 10:2782-2793(1996).
Cited for: PHOSPHORYLATION AT SER-303 AND SER-307, FUNCTION, AND MUTAGENESIS OFARG-296; VAL-297; LYS-298; GLU-299; GLU-300; SER-303; SER-307; ARG-309AND GLU-311.
PubMed: 8946918

"Phosphorylation of serine 230 promotes inducible transcriptionalactivity of heat shock factor 1.";
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., Sistonen L.;
EMBO J. 20:3800-3810(2001).
Cited for: PROTEIN SEQUENCE OF 228-241 AND 297-310, PHOSPHORYLATION AT SER-230;SER-303 AND SER-307, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESISOF SER-230.
PubMed: 11447121

"Transcriptional activity and DNA binding of heat shock factor-1involve phosphorylation on threonine 142 by CK2.";
Soncin F., Zhang X., Chu B., Wang X., Asea A., Ann Stevenson M.,Sacks D.B., Calderwood S.K.;
Biochem. Biophys. Res. Commun. 303:700-706(2003).
Cited for: PHOSPHORYLATION AT THR-142, FUNCTION, AND MUTAGENESIS OF THR-142.
PubMed: 12659875

Sumoylation

"PDSM, a motif for phosphorylation-dependent SUMO modification.";
Hietakangas V., Anckar J., Blomster H.A., Fujimoto M., Palvimo J.J.,Nakai A., Sistonen L.;
Proc. Natl. Acad. Sci. U.S.A. 103:45-50(2006).
Cited for: SUMOYLATION AT LYS-298, AND PHOSPHORYLATION AT SER-303.
PubMed: 16371476

"Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1.";
Hietakangas V., Ahlskog J.K., Jakobsson A.M., Hellesuo M.,Sahlberg N.M., Holmberg C.I., Mikhailov A., Palvimo J.J., Pirkkala L.,Sistonen L.;
Mol. Cell. Biol. 23:2953-2968(2003).
Cited for: SUMOYLATION AT LYS-298, PHOSPHORYLATION AT SER-303, FUNCTION,SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-91; LYS-126; LYS-150;LYS-162; SER-230; LYS-298; SER-303; SER-307; SER-363 AND LYS-381.
PubMed: 12665592

"Regulation of heat shock transcription factor 1 by stress-inducedSUMO-1 modification.";
Hong Y., Rogers R., Matunis M.J., Mayhew C.N., Goodson M.L.,Park-Sarge O.K., Sarge K.D.;
J. Biol. Chem. 276:40263-40267(2001).
Cited for: SUMOYLATION AT LYS-298, AND MUTAGENESIS OF LYS-298.
PubMed: 11514557