PMADS

Id:	acc2207
Group:	2sens
Protein:	ERK2
Gene Symbol:	MAPK1
Protein Id:	P28482
Protein Name:	MK01_HUMAN
PTM:	phosphorylation
Site:	Tyr187?
Site Sequence:	HDHTGFLTEYVATRWYRAPEI
Disease Category:	Cancer
Disease:	Breast Cancer
Disease Subtype:
Disease Cellline:	MDA-MB-231
Disease Info:
Drug:	VPA
Drug Info:	"VPA (Valproic acid/Sodium valproate): A broad-spectrum antiepileptic drug effective in preventing and treating various types of epileptic seizures, particularly generalized tonic-clonic seizures and absence seizures, while also exhibiting mood-stabilizing properties. "
Effect:	modulate
Effect Info:	"The effect of VPA in inhibiting the Warburg effect is to inactivate ERK1/2 phosphorylation by reducing the expression of HDAC1, thereby inhibiting the growth of breast cancer."
Note:
Score:	4.0
Pubmed(PMID):	34263655
Sentence Index:	34263655_4-5
Sentence:	"In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth."

Sequence & Structure:

MAAAAAAGAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNVNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	2	Terminated	neoplasm	ClinicalTrials
MAPK1	TEMUTERKIB	Mitogen-activated protein kinase; ERK1/ERK2 inhibitor	2	Completed	pancreatic carcinoma	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	2	Recruiting	histiocytic neoplasm	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	2	Active, not recruiting	Uveal Melanoma	ClinicalTrials
MAPK1	TEMUTERKIB	Mitogen-activated protein kinase; ERK1/ERK2 inhibitor	2	Terminated	cancer	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Completed	acute myeloid leukemia	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Completed	myelodysplastic syndrome	ClinicalTrials
MAPK1	TEMUTERKIB	Mitogen-activated protein kinase; ERK1/ERK2 inhibitor	1	Recruiting	acute myeloid leukemia	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Completed	neoplasm	ClinicalTrials ClinicalTrials
MAPK1	MK-8353	MAP kinase ERK2 inhibitor	1	Completed	neoplasm	ClinicalTrials
MAPK1	RAVOXERTINIB	MAP kinase ERK2 inhibitor	1	Completed	neoplasm	ClinicalTrials
MAPK1	MK-8353	MAP kinase ERK2 inhibitor	1	Terminated	neoplasm	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Recruiting	pancreatic carcinoma	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Terminated	pancreatic carcinoma	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	1	Recruiting	metastatic colorectal cancer	ClinicalTrials
MAPK1	KO-947	Mitogen-activated protein kinase; ERK1/ERK2 inhibitor	1	Terminated	cancer	ClinicalTrials
MAPK1	MK-8353	MAP kinase ERK2 inhibitor	1	Completed	colorectal cancer	ClinicalTrials
MAPK1	TEMUTERKIB	Mitogen-activated protein kinase; ERK1/ERK2 inhibitor	0.5	Recruiting	glioblastoma multiforme	ClinicalTrials
MAPK1	ULIXERTINIB	MAP kinase ERK2 inhibitor	0.5	Recruiting	Paraganglioma	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!

MAPK1-Thr181
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.957
GBM	0.466
HNSC	1.279
LUAD	0.285
LUSC
non_ccRCC
PDAC
UCEC	-1.072

MAPK1-Thr185
Cancer	Intensity
BRCA	2.529
COAD	-0.118
HGSC	-0.164
ccRCC	-0.105
GBM	-0.046
HNSC	-0.09
LUAD
LUSC
non_ccRCC	-0.821
PDAC	-0.882
UCEC	-0.302

MAPK1-Tyr187
Cancer	Intensity
BRCA	0.772
COAD	0.273
HGSC	0.701
ccRCC	-0.806
GBM	0.279
HNSC	0.328
LUAD	0.387
LUSC	0.866
non_ccRCC	-2.593
PDAC	0.32
UCEC	-0.527

MAPK10-Thr221
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

MAPK10-Tyr223
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

MAPK13-Ser350
Cancer	Intensity
BRCA	0.145
COAD	0.5
HGSC	1.029
ccRCC	-1.866
GBM
HNSC	0.744
LUAD	-0.887
LUSC	-0.463
non_ccRCC
PDAC
UCEC	0.797

MAPK13-Thr180
Cancer	Intensity
BRCA
COAD	-0.286
HGSC
ccRCC
GBM
HNSC	0.146
LUAD
LUSC	0.689
non_ccRCC	-1.554
PDAC
UCEC	1.005

MAPK13-Thr265
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

MAPK13-Tyr182
Cancer	Intensity
BRCA	0.573
COAD	-1.084
HGSC	1.31
ccRCC
GBM
HNSC	0.115
LUAD	0.311
LUSC	-0.255
non_ccRCC	-1.737
PDAC
UCEC	0.767

MAPK14-Ser143
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	0.707
non_ccRCC
PDAC
UCEC	-0.707

MAPK14-Ser252
Cancer	Intensity
BRCA	-0.822
COAD
HGSC	2.685
ccRCC	-0.234
GBM	-0.193
HNSC	0.262
LUAD	-0.258
LUSC	-0.426
non_ccRCC	0.143
PDAC	-0.484
UCEC	-0.672

MAPK14-Ser32
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC	0.707

MAPK14-Thr175
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.659
GBM
HNSC	-1.151
LUAD	0.492
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr180
Cancer	Intensity
BRCA	2.28
COAD	0.452
HGSC	-1.055
ccRCC	-0.189
GBM	-0.187
HNSC	0.188
LUAD	0.929
LUSC	0.063
non_ccRCC	-0.898
PDAC	-0.317
UCEC	-1.265

MAPK14-Thr185
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr239
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

MAPK14-Thr241
Cancer	Intensity
BRCA
COAD
HGSC	1.02
ccRCC	-0.978
GBM
HNSC
LUAD
LUSC	-0.042
non_ccRCC
PDAC
UCEC

MAPK14-Tyr182
Cancer	Intensity
BRCA	2.374
COAD	-0.005
HGSC	-0.861
ccRCC	0.066
GBM	1.175
HNSC	-0.22
LUAD	0.029
LUSC	-0.105
non_ccRCC	-0.927
PDAC	-0.488
UCEC	-1.039

MAPK15-Ser415
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.152
LUSC	0.644
non_ccRCC
PDAC
UCEC	0.508

MAPK15-Thr97
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-0.697
LUSC	-0.449
non_ccRCC
PDAC
UCEC	1.146

MAPK1IP1L-Ser15
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
Y	187	U	Thyroid cancer/carcinoma	Phosphorylation	17209045
Y	187	U	Triple-negative breast cancer	Phosphorylation	28415597

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