Id: acc1310
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: Thyroid Cancer
Disease Subtype:
Disease Cellline: LOXIMVI
Disease Info:
Drug: AMG655
Drug Info: -
Effect: increase
Effect Info: "B-Raf and MEK inhibitors downregulate the expression of DR5 by inhibiting ERK phosphorylation, thereby reducing the sensitivity of cancer cells to apoptosis induced by TRAIL or DR5 agonistic antibodies and decreasing the sensitivity of cancer cells to T cell-mediated killing."
Note:
Score: 5.0
Pubmed(PMID): 25867065
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: