PMADS

Id:	acc0844
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:	Melanoma
Disease Subtype:
Disease Cellline:	A375
Disease Info:
Drug:	trametinib
Drug Info:	"Trametinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2, used for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, either as a single agent or in combination with dabrafenib. "
Effect:	inhibit
Effect Info:	SHR8443 inhibited the phosphorylation of AKT and S6 in tumor tissues and overcame the resistance to RAF/MEK inhibitors.
Note:
Score:	5.0
Pubmed(PMID):	29296217
Sentence Index:	29296217_6-7
Sentence:	"Compared with the well-known PI3K/mTOR inhibitor BEZ235, SHR8443 showed broader and stronger efficacy against carcinoma xenografts, including those resistant to anti-HER2 antibody trastuzumab, in association with the inhibition of AKT and S6 phosphorylation in tumor tissues, and also caused no noticeable toxicity. Thus, our preclinical data show that SHR8443 is a dual PI3K/mTOR inhibitor with pharmaceutical properties favorable for use as an anticancer agent."

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