PMADS

Id:	acc1535
Group:	2sens
Protein:	HSP27
Gene Symbol:	HSPB1
Protein Id:	P04792
Protein Name:	HSPB1_HUMAN
PTM:	phosphorylation
Site:	Ser15
Site Sequence:	VPFSLLRGPSWDPFRDWYPHS
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:	Ductal carcinoma
Disease Cellline:	JIMT-1
Disease Info:
Drug:	TZMB
Drug Info:	-
Effect:	inhibit
Effect Info:	"The combined use of TZMB and the HSP27 functional inhibitor J2 significantly reduces the phosphorylation of HSP27 at S15/78, attenuates HER2 and its downstream signals, and enhances the sensitivity of TZMB - resistant cells and the JIMT1 xenograft mouse model to TZMB."
Note:
Score:	5.0
Pubmed(PMID):	32545363
Sentence Index:	32545363_5-6
Sentence:	"By extensively utilizing TZMB-refractory breast cancer cell lines transduced with diverse phosphovariants of HSP27, our study newly revealed that specific phosphorylation of HSP27 at S15 promoted its S78 phosphorylation and served as key mediator to promote direct interactions that increase the stability of HER2 and protein kinase B (AKT). This phosphorylation promoted nuclear translocation of HER2, enhancing the distinct nuclear function of HER2 that promoted AKT activation and cyclin D1 expression."

Sequence & Structure:

MTERRVPFSLLRGPSWDPFRDWYPHSRLFDQAFGLPRLPEEWSQWLGGSSWPGYVRPLPPAAIESPAVAAPAYSRALSRQLSSGVSEIRHTADRWRVSLDVNHFAPDELTVKTKDGVVEITGKHEERQDEHGYISRCFTRKYTLPPGVDPTQVSSSLSPEGTLTVEAPMPKLATQSNEITIPVTFESRAQLGGPEAAKSDETAAK

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	2	Unknown status	squamous cell lung carcinoma	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	2	Completed	pancreatic carcinoma	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	2	Completed	non-small cell lung carcinoma	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	2	Completed	prostate cancer	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	2	Terminated	prostate cancer	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	1	Completed	neoplasm	ClinicalTrials
HSPB1	APATORSEN	Heat shock protein beta-1 (HSP27) mRNA antisense inhibitor	1	Unknown status	urinary bladder cancer	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

HSPB1-Ser15
Cancer	Intensity
BRCA	1.131
COAD	0.266
HGSC	0.504
ccRCC	-1.22
GBM	0.362
HNSC	0.495
LUAD	0.979
LUSC	0.929
non_ccRCC	-1.325
PDAC	-1.655
UCEC	-0.466

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	15	N	Dilated cardiomyopathy	Phosphorylation	34477462
S	15	P	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	22012255

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

Protein	Gene	PTM	Position	Modified sequence	Cell	Drug	pEC50	Regulation
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Dactolisib	7.0386	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Dactolisib	6.1671	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	PD325901	8.1361	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Staursporin	7.7495	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	BT-474	Lapatinib	6.5032	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	HeLa	CUDC101	4.5058	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	HeLa	Curcumin	4.2586	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	HeLa	Curcumin	4.25	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	8.5138	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.8	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.4001	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.0921	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	6.9555	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	6.389	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.4801	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.3997	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	6.7534	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	6.5452	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.7445	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.7014	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.6158	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.0533	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.7054	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.6617	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	RPMI8226	BTZ	7.5674	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	7.3704	up
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Afatinib	5.7204	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Afatinib	6.5325	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Afatinib	6.0041	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Afatinib	6.5034	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Afatinib	5.4989	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Dasatinib	6.1463	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Dasatinib	6.2189	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Dasatinib	5.8113	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Dasatinib	5.4376	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Dasatinib	6.564	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Dasatinib	5.683	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	7.0751	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	6.6265	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	PC-9	Lapatinib	6.5724	down
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Afatinib	8.3291	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Afatinib	6.5223	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Afatinib	5.4981	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Dasatinib	8.6231	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Dasatinib	6.1505	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Dasatinib	5.7707	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Dasatinib	5.7395	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Dasatinib	5.6263	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Gefitinib	9.2446	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Gefitinib	4.001	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Gefitinib	6.9723	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Gefitinib	6.9156	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Gefitinib	7.4712	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Gefitinib	6.9889	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A431	Imatinib	6.7762	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A431	Imatinib	3.4319	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A459	MK2206	8.5251	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A459	MK2206	8.3863	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A459	MK2206	5.7602	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A459	Selumetinib	5.2463	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A459	Selumetinib	6.3664	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A459	SelumetinibMK2206-3to1	8.4613	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	AZD8055	7.8265	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	AZD8055	7.4392	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Dasatinib	6.8512	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Dasatinib	6.2356	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	MK2206	5.7652	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	MK2206	5.2513	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Nintedanib	10.6855	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	PD325901	8.1353	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	PD325901	7.0465	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	PD325901	6.587	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Pictilisib	7.7413	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Refametinib	7.5088	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Refametinib	7.2842	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Staursporin	7.8365	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	A549	Tideglusib	10.9418	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	A549	Tideglusib	8.7447	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-1.6613	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-3.2566	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	ARH-77	Rituximab	-3.4003	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-4.2413	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-3.4711	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	ARH-77	Rituximab	-3.296	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-3.7576	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-3.4781	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	ARH-77	Rituximab	-1.2107	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	ARH-77	Rituximab	-3.1815	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	ARH-77	Rituximab	-3.7376	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	BT-474	Lapatinib	6.7577	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	BT-474	Pertuzumab	-3.7582	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	BT-474	Pertuzumab	-4.2656	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	BT-474	Trastuzumab	-2.2243	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	BT-474	Trastuzumab	-2.7376	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	HeLa	A485	5.6142	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	HeLa	A486	7.7147	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	HeLa	A486	3.1907	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	HeLa	Romidepsin	12.1532	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	HeLa	Romidepsin	12.0383	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Cytarabine	6.7877	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Cytarabine	6.3666	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	9.1492	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	9.1344	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	9.0807	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	9.0772	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	10.0727	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	10.0126	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	9.52	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	9.4952	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	4.5651	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Dasatinib	4.4624	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	4	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Dasatinib	4	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Imatinib	5.5879	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	K562	Imatinib	5.4147	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	K562	Paclitaxel	5.1484	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	KYSE-520	SHP099	5.4432	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	KYSE-520	SHP099	4.0277	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	MDA-MB-175	Lapatinib	7.0175	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	MDA-MB-175	Pertuzumab	-1.23	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	MDA-MB-175	Pertuzumab	-4.2682	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	MDA-MB-175	Trastuzumab	-0.7219	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	MDA-MB-175	Trastuzumab	-2.2413	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	PC-9	AZD4547	5.2512	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	PC-9	AZD4547	7.5602	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	PC-9	GeftinibAZD4547-1to80	9.4301	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	PC-9	LapatinibAZD4547	10.5242	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	6.4557	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	RPMI8226	BTZ	6.4312	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	SK-BR-3	Lapatinib	7.252	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	SK-BR-3	Lapatinib	6.1733	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	SK-BR-3	Pertuzumab	0.9056	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	SK-BR-3	Pertuzumab	-0.9196	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFR	SK-BR-3	Trastuzumab	-2.0088	-
P04792	HSPB1	P	Ser15	GPS(ph)WDPFRDWYPHSR	SK-BR-3	Trastuzumab	-2.9615	-

pEC50 Note: pEC50 is the negative logarithm of EC50 (half-maximal effective concentration, dosage unit Mol), calculated as pEC50 = -log10(EC50), which quantifies the potency of a drug or compound.

Function score:

source: funscoR

No data.

Cross Links:

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