PMADS

Id:	acc0726
Group:	2sens
Protein:	Hsp90
Gene Symbol:	HSP90AA1
Protein Id:	P07900
Protein Name:	HS90A_HUMAN
PTM:	acetylation
Site:	lys
Site Sequence:
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	SK-BR-3
Disease Info:
Drug:	trastuzumab
Drug Info:	"Trastuzumab is a humanized monoclonal antibody targeting HER2 (ERBB2/neu) receptors, primarily used in the treatment of HER2-positive metastatic breast cancer and HER2-positive metastatic esophageal cancer. "
Effect:	enhance
Effect Info:	"CBZ treatment induces an increase in Hsp90 acetylation and alpha-tubulin acetylation by inhibiting HDAC, thereby sensitizing tumors to herceptin or 17-AAG."
Note:
Score:	5.0
Pubmed(PMID):	21082217
Sentence Index:	21082217_6-7
Sentence:	"Mechanistically, carbamazepine could enhance the acetylation of alpha-tubulin, indicating its inhibitory effect on HDAC6. Functionally, carbamazepine could synergize with trastuzumab or geldanamycin to promote Her-2 degradation and inhibit breast cancer cell proliferation."

Sequence & Structure:

MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIRYESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPMGRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKEDKEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRNPDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNNIKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKCLELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDYCTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKTLVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIVTSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVKDLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLEGDDDTSRMEEVD

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	3	Terminated	lung adenocarcinoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	3	Completed	multiple myeloma	ClinicalTrials
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	3	Terminated	non-small cell lung carcinoma	ClinicalTrials
HSP90AA1	RETASPIMYCIN	Heat shock protein HSP90 inhibitor	3	Terminated	gastrointestinal stromal tumor	ClinicalTrials
HSP90AA1	RETASPIMYCIN HYDROCHLORIDE	Heat shock protein HSP90 inhibitor	3	Terminated	gastrointestinal stromal tumor	ClinicalTrials
HSP90AA1	CD24FC	Heat shock protein HSP90 inhibitor	3	Completed	COVID-19	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	Hodgkins lymphoma	ClinicalTrials
HSP90AA1	RETASPIMYCIN	Heat shock protein HSP90 inhibitor	2	Terminated	breast carcinoma	ClinicalTrials
HSP90AA1	RETASPIMYCIN HYDROCHLORIDE	Heat shock protein HSP90 inhibitor	2	Terminated	breast carcinoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	cutaneous melanoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	follicular thyroid carcinoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	leukemia	ClinicalTrials
HSP90AA1	LUMINESPIB	Heat shock protein HSP90 inhibitor	2	Terminated	lymphoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	lymphoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	prostate adenocarcinoma	ClinicalTrials
HSP90AA1	RETASPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	prostate adenocarcinoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	papillary thyroid carcinoma	ClinicalTrials
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	2	Completed	prostate adenocarcinoma	ClinicalTrials
HSP90AA1	RETASPIMYCIN HYDROCHLORIDE	Heat shock protein HSP90 inhibitor	2	Completed	prostate adenocarcinoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Terminated	melanoma	ClinicalTrials
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	2	Completed	small cell lung carcinoma	ClinicalTrials
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	2	Completed	melanoma	ClinicalTrials
HSP90AA1	GANETESPIB	Heat shock protein HSP90 inhibitor	2	Terminated	melanoma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	multiple myeloma	ClinicalTrials
HSP90AA1	TANESPIMYCIN	Heat shock protein HSP90 inhibitor	2	Completed	chronic myeloproliferative disorder	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

No intensity data of this site,
show all other sites!

HSP90AA1-Lys180
Cancer	Intensity
BRCA	0.283
COAD
HGSC
ccRCC
GBM	-1.021
HNSC
LUAD	-0.928
LUSC	0.274
non_ccRCC
PDAC
UCEC	1.393

HSP90AA1-Lys206
Cancer	Intensity
BRCA	-1.341
COAD
HGSC
ccRCC
GBM	-0.795
HNSC
LUAD	0.56
LUSC	0.708
non_ccRCC
PDAC
UCEC	0.868

HSP90AA1-Lys234
Cancer	Intensity
BRCA	0.153
COAD
HGSC
ccRCC
GBM	-1.643
HNSC
LUAD	0.737
LUSC	-0.099
non_ccRCC
PDAC
UCEC	0.852

HSP90AA1-Lys313
Cancer	Intensity
BRCA	-0.684
COAD
HGSC
ccRCC
GBM	0.587
HNSC
LUAD	-0.996
LUSC	1.093
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys331
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys346
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-1.152
HNSC
LUAD
LUSC	0.643
non_ccRCC
PDAC
UCEC	0.509

HSP90AA1-Lys360
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

HSP90AA1-Lys363
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

HSP90AA1-Lys391
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	1.153
HNSC
LUAD	-0.53
LUSC	-0.623
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys405
Cancer	Intensity
BRCA	-1.743
COAD
HGSC
ccRCC
GBM	0.35
HNSC
LUAD	0.746
LUSC	0.129
non_ccRCC
PDAC
UCEC	0.517

HSP90AA1-Lys414
Cancer	Intensity
BRCA	0.066
COAD
HGSC
ccRCC
GBM	0.836
HNSC
LUAD	-0.239
LUSC	-1.56
non_ccRCC
PDAC
UCEC	0.897

HSP90AA1-Lys436
Cancer	Intensity
BRCA	-0.19
COAD
HGSC
ccRCC
GBM	-0.833
HNSC
LUAD	-0.257
LUSC	-0.452
non_ccRCC
PDAC
UCEC	1.732

HSP90AA1-Lys449
Cancer	Intensity
BRCA	-0.244
COAD
HGSC
ccRCC
GBM	1.399
HNSC
LUAD	-0.342
LUSC	-1.283
non_ccRCC
PDAC
UCEC	0.471

HSP90AA1-Lys484
Cancer	Intensity
BRCA	-1.309
COAD
HGSC
ccRCC
GBM	0.509
HNSC
LUAD	-0.8
LUSC	0.567
non_ccRCC
PDAC
UCEC	1.033

HSP90AA1-Lys529
Cancer	Intensity
BRCA	-1.644
COAD
HGSC
ccRCC
GBM	0.96
HNSC
LUAD	-0.03
LUSC	0.603
non_ccRCC
PDAC
UCEC	0.11

HSP90AA1-Lys541
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

HSP90AA1-Lys553
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-0.707
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys558
Cancer	Intensity
BRCA	-0.137
COAD
HGSC
ccRCC
GBM	1.258
HNSC
LUAD	-1.389
LUSC	-0.331
non_ccRCC
PDAC
UCEC	0.599

HSP90AA1-Lys565
Cancer	Intensity
BRCA	0.388
COAD
HGSC
ccRCC
GBM	-1.05
HNSC
LUAD	0.501
LUSC	-1.034
non_ccRCC
PDAC
UCEC	1.195

HSP90AA1-Lys568
Cancer	Intensity
BRCA	0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-0.707
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys600
Cancer	Intensity
BRCA	-1.026
COAD
HGSC
ccRCC
GBM	-0.148
HNSC
LUAD	-0.091
LUSC	-0.396
non_ccRCC
PDAC
UCEC	1.661

HSP90AA1-Lys611
Cancer	Intensity
BRCA	-0.908
COAD
HGSC
ccRCC
GBM	1.679
HNSC
LUAD	-0.378
LUSC	0.063
non_ccRCC
PDAC
UCEC	-0.457

HSP90AA1-Lys621
Cancer	Intensity
BRCA	0.776
COAD
HGSC
ccRCC
GBM	1.185
HNSC
LUAD	-0.691
LUSC	-0.039
non_ccRCC
PDAC
UCEC	-1.231

HSP90AA1-Lys635
Cancer	Intensity
BRCA	1.133
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-0.76
LUSC	-0.373
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys656
Cancer	Intensity
BRCA	0.787
COAD
HGSC
ccRCC
GBM	-0.663
HNSC
LUAD	0.921
LUSC	-1.046
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys661
Cancer	Intensity
BRCA	-1.578
COAD
HGSC
ccRCC
GBM	0.255
HNSC
LUAD	-0.286
LUSC	0.991
non_ccRCC
PDAC
UCEC	0.618

HSP90AA1-Lys680
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM	0.538
HNSC
LUAD	-1.175
LUSC	-0.007
non_ccRCC
PDAC
UCEC	1.352

HSP90AA1-Lys681
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	0.707
non_ccRCC
PDAC
UCEC

HSP90AA1-Lys689
Cancer	Intensity
BRCA	-0.067
COAD
HGSC
ccRCC
GBM	1.391
HNSC
LUAD	0.104
LUSC	-1.432
non_ccRCC
PDAC
UCEC	0.003

HSP90AA1-Lys695
Cancer	Intensity
BRCA	-1.297
COAD
HGSC
ccRCC
GBM	-0.702
HNSC
LUAD	0.174
LUSC	1.168
non_ccRCC
PDAC
UCEC	0.656

HSP90AA1-Lys698
Cancer	Intensity
BRCA	-0.204
COAD
HGSC
ccRCC
GBM	-1.32
HNSC
LUAD	0.822
LUSC	1.155
non_ccRCC
PDAC
UCEC	-0.452

HSP90AA1-Lys707
Cancer	Intensity
BRCA	-1.611
COAD
HGSC
ccRCC
GBM	0.488
HNSC
LUAD	1.043
LUSC	-0.153
non_ccRCC
PDAC
UCEC	0.234

HSP90AA1-Lys737
Cancer	Intensity
BRCA	-1.458
COAD
HGSC
ccRCC
GBM	0.204
HNSC
LUAD	1.347
LUSC	0.035
non_ccRCC
PDAC
UCEC	-0.129

HSP90AA1-Lys753
Cancer	Intensity
BRCA	-1.527
COAD
HGSC
ccRCC
GBM	1.263
HNSC
LUAD	0.075
LUSC	-0.065
non_ccRCC
PDAC
UCEC	0.254

HSP90AA1-Lys754
Cancer	Intensity
BRCA	0.557
COAD
HGSC
ccRCC
GBM	-0.382
HNSC
LUAD	-1.212
LUSC
non_ccRCC
PDAC
UCEC	1.037

HSP90AA1-Lys776
Cancer	Intensity
BRCA	-1.666
COAD
HGSC
ccRCC
GBM	0.687
HNSC
LUAD	0.735
LUSC	0.424
non_ccRCC
PDAC
UCEC	-0.18

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
-	-	U	Clear cell renal cell carcinoma	Acetylation	34931765
-	-	U	Alzheimer's disease	Acetylation	29844403
-	-	U	Non-alcoholic fatty liver	Ubiquitination	37633951

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

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb