Id: acc2054
Group: 2sens
Protein: ERK2
Gene Symbol: MAPK1
Protein Id: P28482
Protein Name: MK01_HUMAN
PTM: phosphorylation
Site: Thr185
Site Sequence: PDHDHTGFLTEYVATRWYRAP
Disease Category: Cancer
Disease: Lung Cancer
Disease Subtype: NSCLC wt EGFR
Disease Cellline: Calu-6
Disease Info:
Drug: AZD6244
Drug Info: AZD6244 (Selumetinib) is a selective MEK1/MEK2 inhibitor developed by AstraZeneca for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas and certain advanced cancers such as non-small cell lung cancer.
Effect: modulate
Effect Info: Treatment with AZD6244 inhibited ERK phosphorylation in both sensitive and drug-resistant cells.
Note:
Score: 4.0
Pubmed(PMID): 19783898
Sentence Index:
Sentence:

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
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

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
- - A Colon cancer/carcinoma Phosphorylation 23786838
- - D Colorectal cancer Phosphorylation 36526622
- - D Squamous cell carcinoma of the larynx Phosphorylation 16865246
- - D Pulmonary carcinoid Phosphorylation 15956248
- - D Myelodysplasia Phosphorylation 12529294
- - P Bladder cancer Phosphorylation 24375195
- - P Non-small cell lung cancer/carcinoma Phosphorylation 24096476
- - P Acute myeloid leukemia/acute myelogenous leukemia Phosphorylation 23840454
- - P Liver cancer Phosphorylation 23693078
- - P Colon cancer/carcinoma Phosphorylation 23183114
- - P Thyroid cancer/carcinoma Phosphorylation 11299771
- - P Astrocytoma/astrocytoma glioblastoma Phosphorylation 17327470
- - P Rhabdomyosarcoma Phosphorylation 14633723
- - P Brain cancer Phosphorylation 12388552
- - U Lung cancer/carcinoma Phosphorylation 24286320
- - U Bipolar disorder Phosphorylation 24075327
- - U Glioblastoma Phosphorylation 36493392
- - U Crohn's disease Phosphorylation 23970928
- - U Neuroblastoma Phosphorylation 15972965
- - U Adenoma Phosphorylation 21989899
- - U Breast cancer/tumor/carcinoma Phosphorylation 10216485
- - U Prostate cancer/carcinoma/adenocarcinoma Phosphorylation 9927031
- - U Glioblastoma Phosphorylation 23115159
- - U Pancreatic cancer Phosphorylation 21678462
- - U Clear cell renal cell carcinoma Phosphorylation 36966163
- - U Lymphoma Phosphorylation 23620775
S 41 U Choriocarcinoma Phosphorylation 11466319
- - U Clear cell renal cell carcinoma Phosphorylation 37454877
- - U Osteosarcoma Phosphorylation 31383289
- - U Ovarian cancer/carcinoma Phosphorylation 23285101
Y 204 U Pulmonary emphysema Phosphorylation 14764579
Y 187 U Triple-negative breast cancer Phosphorylation 28415597
Y 187 U Thyroid cancer/carcinoma Phosphorylation 17209045
Y 204 U Hepatocellular carcinoma Phosphorylation 36230524
T 202 U Pulmonary emphysema Phosphorylation 14764579

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 Experiment
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR BT-474 Lapatinib 6.6659 down
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR KYSE-520 SHP099 6.0769 down
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR MDA-MB-175 Lapatinib 7.3575 down
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR K562 Imatinib 7.1978 -
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR MDA-MB-175 Trastuzumab 5 -
P28482 MAPK1 P Thr185;Tyr187 VADPDHDHTGFLT(ph)EY(ph)VATR MDA-MB-175 Trastuzumab -1.6811 -
P28482 MAPK1 P Thr185;Tyr187 VADPDHDHTGFLT(ph)EY(ph)VATR PC-9 AZD4547 7.2923 -
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR SK-BR-3 Lapatinib 4.7264 -
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR SK-BR-3 Pertuzumab -1.769 -
P28482 MAPK1 P Thr185 VADPDHDHTGFLT(ph)EYVATR SK-BR-3 Trastuzumab -0.9986 -
P28482 MAPK1 P Thr185;Tyr187 VADPDHDHTGFLT(ph)EY(ph)VATR SK-BR-3 Trastuzumab -1.2287 -

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: