dbPTM

HSF1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HSF1_MOUSE
UniProt AC	P38532
Protein Name	Heat shock factor protein 1 {ECO:0000250\|UniProtKB:Q00613}
Gene Name	Hsf1 {ECO:0000312\|MGI:MGI:96238}
Organism	Mus musculus (Mouse).
Sequence Length	525
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. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. 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. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Plays also 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. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Plays also a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner..
Protein Sequence	MDLAVGPGAAGPSNVPAFLTKLWTLVSDPDTDALICWSPSGNSFHVFDQGQFAKEVLPKYFKHNNMASFVRQLNMYGFRKVVHIEQGGLVKPERDDTEFQHPCFLRGQEQLLENIKRKVTSVSTLKSEDIKIRQDSVTRLLTDVQLMKGKQECMDSKLLAMKHENEALWREVASLRQKHAQQQKVVNKLIQFLISLVQSNRILGVKRKIPLMLSDSNSAHSVPKYGRQYSLEHVHGPGPYSAPSPAYSSSSLYSSDAVTSSGPIISDITELAPTSPLASPGRSIDERPLSSSTLVRVKQEPPSPPHSPRVLEASPGRPSSMDTPLSPTAFIDSILRESEPTPAASNTAPMDTTGAQAPALPTPSTPEKCLSVACLDKNELSDHLDAMDSNLDNLQTMLTSHGFSVDTSALLDLFSPSVTMPDMSLPDLDSSLASIQELLSPQEPPRPIEAENSNPDSGKQLVHYTAQPLFLLDPDAVDTGSSELPVLFELGESSYFSEGDDYTDDPTISLLTGTEPHKAKDPTVS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
1	Acetylation	-------MDLAVGPG -------CCCCCCCC	9.57	-
80	Acetylation	LNMYGFRKVVHIEQG HHHHCCEEEEEEEEC	46.47	-
91	Acetylation	IEQGGLVKPERDDTE EEECCCCCCCCCCCC	46.32	-
118	Acetylation	LLENIKRKVTSVSTL HHHHHHHHCCCCCCC	44.88	-
120	Phosphorylation	ENIKRKVTSVSTLKS HHHHHHCCCCCCCCH	26.84	29472430
121	Phosphorylation	NIKRKVTSVSTLKSE HHHHHCCCCCCCCHH	19.63	21454597
123	Phosphorylation	KRKVTSVSTLKSEDI HHHCCCCCCCCHHCC	27.99	21454597
124	Phosphorylation	RKVTSVSTLKSEDIK HHCCCCCCCCHHCCC	35.73	21454597
142	Phosphorylation	DSVTRLLTDVQLMKG HHHHHHHHHHHHHCC	38.42	-
150	Acetylation	DVQLMKGKQECMDSK HHHHHCCCHHHHHHH	37.09	-
188	Acetylation	QQQKVVNKLIQFLIS HHHHHHHHHHHHHHH	35.04	-
208	Acetylation	RILGVKRKIPLMLSD CCCCCCCCCCEEECC	42.85	-
216	Phosphorylation	IPLMLSDSNSAHSVP CCEEECCCCCCCCCC	29.34	-
230	Phosphorylation	PKYGRQYSLEHVHGP CCCCCEEECCCCCCC	20.95	-
275	Phosphorylation	ITELAPTSPLASPGR HHHHCCCCCCCCCCC	19.50	29514104
279	Phosphorylation	APTSPLASPGRSIDE CCCCCCCCCCCCCCC	35.25	29514104
283	Phosphorylation	PLASPGRSIDERPLS CCCCCCCCCCCCCCC	40.06	28833060
290	Phosphorylation	SIDERPLSSSTLVRV CCCCCCCCCCCEEEE	25.56	28833060
291	Phosphorylation	IDERPLSSSTLVRVK CCCCCCCCCCEEEEE	34.72	28833060
292	Phosphorylation	DERPLSSSTLVRVKQ CCCCCCCCCEEEEEC	23.53	28833060
293	Phosphorylation	ERPLSSSTLVRVKQE CCCCCCCCEEEEECC	31.08	28833060
298	Acetylation	SSTLVRVKQEPPSPP CCCEEEEECCCCCCC	38.08	-
303 (in isoform 2)	Phosphorylation	-	62.87	24719451
303	Phosphorylation	RVKQEPPSPPHSPRV EEECCCCCCCCCCCE	62.87	27087446
307 (in isoform 2)	Phosphorylation	-	21.85	24719451
307	Phosphorylation	EPPSPPHSPRVLEAS CCCCCCCCCCEEECC	21.85	27087446
314	Phosphorylation	SPRVLEASPGRPSSM CCCEEECCCCCCCCC	20.64	26824392
314 (in isoform 2)	Phosphorylation	-	20.64	24719451
319	Phosphorylation	EASPGRPSSMDTPLS ECCCCCCCCCCCCCC	36.61	26239621
320	Phosphorylation	ASPGRPSSMDTPLSP CCCCCCCCCCCCCCH	24.30	26239621
323	Phosphorylation	GRPSSMDTPLSPTAF CCCCCCCCCCCHHHH	19.93	23649490
326	Phosphorylation	SSMDTPLSPTAFIDS CCCCCCCCHHHHHHH	22.77	26824392
328	Phosphorylation	MDTPLSPTAFIDSIL CCCCCCHHHHHHHHH	30.72	26160508
333	Phosphorylation	SPTAFIDSILRESEP CHHHHHHHHHHHCCC	20.78	24224561
345	Phosphorylation	SEPTPAASNTAPMDT CCCCCCCCCCCCCCC	36.50	26239621
353	Phosphorylation	NTAPMDTTGAQAPAL CCCCCCCCCCCCCCC	26.67	26239621
362	Phosphorylation	AQAPALPTPSTPEKC CCCCCCCCCCCHHHE	30.62	26239621
364	Phosphorylation	APALPTPSTPEKCLS CCCCCCCCCHHHEEE	60.10	26239621
365	Phosphorylation	PALPTPSTPEKCLSV CCCCCCCCHHHEEEE	36.35	22942356
399 (in isoform 2)	Phosphorylation	-	14.09	-
399	Phosphorylation	DNLQTMLTSHGFSVD HHHHHHHHHCCCCCC	14.09	-
400	Phosphorylation	NLQTMLTSHGFSVDT HHHHHHHHCCCCCCH	20.04	-
400 (in isoform 2)	Phosphorylation	-	20.04	-
415	Phosphorylation	SALLDLFSPSVTMPD HHHHHHHCCCCCCCC	24.46	15661742
440	Phosphorylation	ASIQELLSPQEPPRP HHHHHHHCCCCCCCC	36.84	-
520	Acetylation	GTEPHKAKDPTVS-- CCCCCCCCCCCCC--	69.88	-

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
121	S	Phosphorylation	Kinase	AMPKA1	Q13131	PSP
121	S	Phosphorylation	Kinase	MAPKAPK2	P49138	Uniprot
142	T	Phosphorylation	Kinase	CSNK2A1	Q60737	GPS
142	T	Phosphorylation	Kinase	CK2	-	Uniprot
216	S	Phosphorylation	Kinase	PLK1	Q07832	Uniprot
230	S	Phosphorylation	Kinase	CAMK2A	P11798	Uniprot
320	S	Phosphorylation	Kinase	PKA	-	Uniprot
326	S	Phosphorylation	Kinase	MAPK12	O08911	Uniprot
415	S	Phosphorylation	Kinase	PLK1	Q07832	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
80	K	Acetylation	-
Acetylated on Lys-80; this acetylation inhibits DNA-binding activity upon heat shock.
80	K	Acetylation	-
Deacetylated on Lys-80 by SIRT1; this deacetylation increases DNA-binding activity.
118	K	Acetylation	-
Acetylated on Lys-118; this acetylation is decreased in a IER5-dependent manner.
118	K	Acetylation	-
Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.
121	S	Phosphorylation	-
Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.
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.
142	T	Phosphorylation	-
Phosphorylated on Thr-142; this phosphorylation increases HSF1 transactivation activity upon heat shock.
208	K	Acetylation	-
Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.
216	S	Phosphorylation	-
Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis.
216	S	ubiquitylation	-
Ubiquitinated by SCF(BTRC) and degraded following stimulus-dependent phosphorylation at Ser-216 by PLK1 in mitosis.
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.
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.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
230	S	Phosphorylation	-
Phosphorylation on Ser-230 by CAMK2A; this phosphorylation enhances HSF1 transactivation activity upon heat shock.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
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.
298	K	Acetylation	-
Acetylated on Lys-118, Lys-208 and Lys-298; these acetylations occur in a EP300-dependent manner.
303	S	Sumoylation	19131326
Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.
303	S	Phosphorylation	19131326
Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303.
303	S	Phosphorylation	19131326
Phosphorylation on Ser-303 by GSK3B/GSK3-beat 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.
303	S	Phosphorylation	19131326
Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner.
303	S	Phosphorylation	19131326
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
303	S	Phosphorylation	19131326
Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.
303	S	Phosphorylation	19131326
According to, Ser-303 is not phosphorylated in unstressed cells.
307	S	Phosphorylation	19131326
Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.
307	S	Phosphorylation	19131326
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
307	S	Phosphorylation	19131326
Phosphorylation on Ser-303 and Ser-307 increases HSF1 nuclear export in a YWHAE- and XPO1/CRM1-dependent manner.
307	S	Phosphorylation	19131326
Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.
307	S	Phosphorylation	19131326
Phosphorylation on Ser-303 by GSK3B/GSK3-beat 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.
307	S	Phosphorylation	19131326
Phosphorylation on Ser-307 is a prerequisite for phosphorylation on Ser-303.
307	S	Sumoylation	19131326
Phosphorylation on Ser-303 and Ser-307 is probably a prerequisite for sumoylation.
314	S	Phosphorylation	-
Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
320	S	Phosphorylation	-
Phosphorylated on Ser-320 by PRKACA/PKA; this phosphorylation promotes nuclear localization and transcriptional activity upon heat shock.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
323	T	Phosphorylation	-
Dephosphorylated on Ser-121, Ser-307, Ser-314 and Thr-323 by phosphatase PPP2CA in an IER5-dependent manner, leading to HSF1-mediated transactivation activity.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
326	S	Phosphorylation	-
Phosphorylation on Ser-326 by MAPK12; this phosphorylation enhances HSF1 nuclear translocation, homotrimerization and transactivation activities upon heat shock.
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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
345	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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
364	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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
365	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-345, Ser-364 and Thr-365 within the regulatory domain is involved in the regulation of HSF1 subcellular localization or DNA-binding activity; however, it negatively regulates HSF1 transactivation activity.
415	S	Phosphorylation	-
Phosphorylated on Ser-415 by PLK1; phosphorylation promotes nuclear translocation upon heat shock.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of HSF1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
ATF3_MOUSE	Atf3	physical	17766920
TF65_MOUSE	Rela	physical	17766920
NDUV2_HUMAN	NDUFV2	physical	26496610
RA51D_HUMAN	RAD51D	physical	26496610
FZD1_HUMAN	FZD1	physical	26496610
OFD1_HUMAN	OFD1	physical	26496610
RBCC1_HUMAN	RB1CC1	physical	26496610
SNW1_HUMAN	SNW1	physical	26496610
DGCR8_HUMAN	DGCR8	physical	26496610
BI2L1_HUMAN	BAIAP2L1	physical	26496610
JPH1_HUMAN	JPH1	physical	26496610
YIPF5_HUMAN	YIPF5	physical	26496610
FWCH1_HUMAN	FLYWCH1	physical	26496610

Drug and Disease Associations

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

Regulatory Network of HSF1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry."; Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.; Mol. Cell. Proteomics 8:904-912(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-303 AND SER-307, ANDMASS SPECTROMETRY.	19131326 [Abstract]

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