DegronMD - Q00613(HSF1)

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 insults' damage (PubMed:1871105, PubMed:11447121, PubMed:1986252, PubMed:7760831, PubMed:7623826, PubMed:8946918, PubMed:8940068, PubMed:9341107, PubMed:9121459, PubMed:9727490, PubMed:9499401, PubMed:9535852, PubMed:12659875, PubMed:12917326, PubMed:15016915, PubMed:25963659, PubMed:26754925, PubMed:18451878). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form (PubMed:9727490, PubMed:11583998, PubMed:16278218). 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:1871105, PubMed:1986252, PubMed:8455624, PubMed:7935471, PubMed:7623826, PubMed:8940068, PubMed:9727490, PubMed:9499401, PubMed:10359787, PubMed:11583998, PubMed:12659875, PubMed:16278218, PubMed:25963659, PubMed:26754925). 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). 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 (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). Plays also 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: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}. View more >>

GO - Biological processes (BP): cellular response to angiotensin [GO:1904385]; cellular response to cadmium ion [GO:0071276]; cellular response to copper ion [GO:0071280]; cellular response to diamide [GO:0072738]; cellular response to estradiol stimulus [GO:0071392]; cellular response to gamma radiation [GO:0071480]; cellular response to heat [GO:0034605]; cellular response to hydrogen peroxide [GO:0070301]; cellular response to L-glutamine [GO:1904845]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to nitroglycerin [GO:1904843]; cellular response to potassium ion [GO:0035865]; cellular response to sodium arsenite [GO:1903936]; cellular response to unfolded protein [GO:0034620]; cellular response to xenobiotic stimulus [GO:0071466]; defense response [GO:0006952]; DNA repair [GO:0006281]; MAPK cascade [GO:0000165]; mRNA processing [GO:0006397]; mRNA transcription [GO:0009299]; mRNA transport [GO:0051028]; negative regulation of cardiac muscle cell apoptotic process [GO:0010667]; negative regulation of double-strand break repair via nonhomologous end joining [GO:2001033]; negative regulation of gene expression [GO:0010629]; negative regulation of inclusion body assembly [GO:0090084]; negative regulation of neuron death [GO:1901215]; negative regulation of protein-containing complex assembly [GO:0031333]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of apoptotic DNA fragmentation [GO:1902512]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of cold-induced thermogenesis [GO:0120162]; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280]; positive regulation of DNA-binding transcription factor activity [GO:0051091]; positive regulation of gene expression [GO:0010628]; positive regulation of inclusion body assembly [GO:0090261]; positive regulation of macrophage differentiation [GO:0045651]; positive regulation of microtubule binding [GO:1904528]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of mRNA polyadenylation [GO:1900365]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription from RNA polymerase II promoter in response to heat stress [GO:0061408]; positive regulation of tyrosine phosphorylation of STAT protein [GO:0042531]; protein-containing complex assembly [GO:0065003]; regulation of cellular response to heat [GO:1900034]; regulation of transcription by RNA polymerase II [GO:0006357]; response to activity [GO:0014823]; response to hypobaric hypoxia [GO:1990910]; response to nutrient [GO:0007584]; response to psychosocial stress [GO:1990911]; response to testosterone [GO:0033574] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P425S	TCGA-27-1833	GBM	TCGA	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.6752
p.P425S	DO12976	GBM	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.6752
p.E286K	TCGA-A5-A2K7	UCEC	TCGA	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2778
p.R207G	TCGA-A6-2681	COAD	TCGA	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.1111
p.S221Y	TCGA-B5-A11E	UCEC	TCGA	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation altering degron motif	0.712
p.P365Q	TCGA-BQ-7049	KIRP	TCGA	PPTST	DEG_SPOP_SBC_1	365:369	Mutation altering degron motif	0.7035
p.P365Q	TCGA-CV-7238	HNSC	TCGA	PPTST	DEG_SPOP_SBC_1	365:369	Mutation altering degron motif	0.7035
p.E300Q	TCGA-CF-A1HS	BLCA	TCGA	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.1111
p.P420L	TCGA-CM-6165	COAD	TCGA	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.6471
p.P420L	DO9900	COAD	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.6471
p.P430H	TCGA-D3-A2JC	SKCM	TCGA	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.25
p.P430H	DO47578	SKCM	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.25
p.P288L	TCGA-D3-A5GL	SKCM	TCGA	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation altering degron motif	0.7582
p.R296C	TCGA-DU-6392	LGG	TCGA	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.P364S	TCGA-EB-A5SG	SKCM	TCGA	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.3056
p.P239H	TCGA-EE-A2GH	SKCM	TCGA	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1389
p.A254T	TCGA-F1-A448	STAD	TCGA	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.2222
p.A254T	ACH-000179	Lung Cancer	CCLE	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.2222
p.K208N	TCGA-GN-A26C	SKCM	TCGA	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation blocking ubiquitination signal	0.5833
p.S250C	TCGA-GV-A3JZ	BLCA	TCGA	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation altering degron motif	0.7541
p.Y247C	TCGA-W5-AA30	CHOL	TCGA	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation altering degron motif	0.5976
p.S421L	DO48409	BLCA	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7667
p.A286T	DO49970	CESC	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2778
p.R419C	DO223703	COAD	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.8301
p.R419C	ACH-000961	Endometrial/Uterine Cancer	CCLE	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.8301
p.R231C	DO227976	COCA	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.0556
p.R231C	DO22237	LGG	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.0556
p.A427V	DO234219	ESAD	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.6936
p.P239L	DO234251	ESAD	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1389
p.P239L	ACH-001369	Ovarian Cancer	CCLE	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1389
p.P239L	ACH-002279	Neuroblastoma	CCLE	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1389
p.R295W	DO233913	GACA	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.25
p.R295W	DO232199	RT	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.25
p.R295W	ACH-000965	Endometrial/Uterine Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.25
p.P300Q	DO15246	HNSC	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.1111
p.P300Q	DO20853	KIRP	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.1111
p.R222K	DO225404	LAML	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.3056
p.A437S	DO228900	LICA	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.0556
p.S428I	DO228986	LICA	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.3056
p.D373Y	DO229015	LICA	ICGC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.2222
p.S435N	DO231821	LINC	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.1111
p.R417W	DO45299	LIRI	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.2778
p.S298P	DO228236	MALY	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation substituting flanking lysine	0.2778
p.S298P	DO46366	OV	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation substituting flanking lysine	0.2778
p.T292A	DO232852	NACA	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation altering degron motif	0.7139
p.T290P	DO232863	NACA	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation altering degron motif	0.7031
p.S238G	DO35442	PACA	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1111
p.G288S	DO232765	PBCA	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation altering degron motif	0.6993
p.L365M	DO232761	PBCA	ICGC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation altering degron motif	0.711
p.A278T	DO232224	PBCA	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.0556
p.R252H	DO36358	PRAD	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.2778
p.R252H	DO51795	STAD	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.2778
p.S255F	DO37886	SKCM	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1944
p.P211L	DO37430	SKCM	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.2222
p.P223L	DO47430	SKCM	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.2778
p.P299S	DO48726	SKCM	ICGC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.1389
p.T258I	DO37996	SKCM	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.1111
p.S419G	DO229257	THCA	ICGC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.8104
p.R244G	DO229268	THCA	ICGC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.2778
p.E221K	DO41271	UCEC	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation altering degron motif	0.7022
p.M212V	DO43779	UCEC	ICGC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.25
p.S421W	SIDM01004	Chronic Myelogenous Leukemia	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7874
p.S421W	KCL-22	haematopoietic and lymphoid tissue	COSMIC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7874
p.S419R	SIDM01004	Chronic Myelogenous Leukemia	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.8538
p.S419R	KCL-22	haematopoietic and lymphoid tissue	COSMIC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.8538
p.E371K	SIDM01722	Non-Cancerous	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.2778
p.E371K	SIDM00174	Head and Neck Carcinoma	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.2778
p.V424M	SIDM00845	Burkitt's Lymphoma	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7208
p.V424M	SIDM01652	Non-Cancerous	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7208
p.V424M	SIDM00187	Kidney Carcinoma	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.7208
p.G236S	SIDM01040	Ovarian Carcinoma	GDSC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.0556
p.G236S	SIDM00487	Colorectal Carcinoma	GDSC	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.0556
p.G236S	ACH-000658	Myeloma	CCLE	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.0556
p.T411S	SIDM01007	T-Lymphoblastic Leukemia	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.1111
p.T411S	KARPAS-45	haematopoietic and lymphoid tissue	COSMIC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.1111
p.R360Q	SIDM00315	Glioblastoma	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.R360Q	SIDM00808	Burkitt's Lymphoma	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.R360Q	SIDM01254	Burkitt's Lymphoma	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.R360W	SIDM01088	Endometrial Carcinoma	GDSC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.R360W	RL95-2	endometrium	COSMIC	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.V422L	SIDM00145	T-Lymphoblastic Leukemia	GDSC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.5654
p.V422L	ACH-001127	Leukemia	CCLE	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.5654
p.V422L	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation altering degron motif	0.5654
p.R296H	SIDM01246	Ewing's Sarcoma	GDSC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.R296H	SIDM00634	Ewing's Sarcoma	GDSC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.R296H	ACH-000039	Bone Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.R296H	ACH-002160	Bone Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.R296H	MC-IXC	autonomic ganglia	COSMIC	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.2222
p.R227Q	SIDM00150	Colorectal Carcinoma	GDSC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.1667
p.R227Q	KM12	large intestine	COSMIC	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation rewiring degron network	0.1667
p.P208L	ACH-000899	Skin Cancer	CCLE	DSGSAHS	DEG_SCF_TRCP1_1	215:221	Mutation blocking ubiquitination signal	0.5833
p.R287M	ACH-000994	Endometrial/Uterine Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.3056
p.G428S	ACH-001061	Colon/Colorectal Cancer	CCLE	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.3056
p.P243L	ACH-001274	Sarcoma	CCLE	AYSSS	DEG_SPOP_SBC_1	246:250	Mutation rewiring degron network	0.25
p.V280I	ACH-001517	Endometrial/Uterine Cancer	CCLE	PLSSS	DEG_SPOP_SBC_1	288:292	Mutation rewiring degron network	0.1111
p.T374S	ACH-002256	Leukemia	CCLE	PPTST	DEG_SPOP_SBC_1	365:369	Mutation rewiring degron network	0.1944
p.M429V	HN	upper aerodigestive tract	COSMIC	SPSVTVPDM	DEG_COP1_1	419:427	Mutation rewiring degron network	0.2778

Kaplan plot for HSF1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

HSF1

UniProt ID: Q00613

Entrez ID: 3297

Protein name: Heat shock factor protein 1 (HSF 1) (Heat shock transcription factor 1) (HSTF 1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HSF1 in