Id: | acc1115 |
Group: | 2sens |
Protein: | MEK1 |
Gene Symbol: | MAP2K1 |
Protein Id: | Q02750 |
Protein Name: | MP2K1_HUMAN |
PTM: | phosphorylation |
Site: | Ser221 |
Site Sequence: | SGQLIDSMANSFVGTRSYMSP |
Disease Category: | Cancer |
Disease: | Lung Cancer |
Disease Subtype: | NSCLC |
Disease Cellline: | PC-9/GR |
Disease Info: | |
Drug: | gefitinib + Lovastatin |
Drug Info: | Gefitinib: - Lovastatin: Lovastatin is a cell-permeable HMG-CoA reductase inhibitor used to lower cholesterol. |
Effect: | modulate |
Effect Info: | "Lovastatin inhibits cholesterol synthesis, making the gefitinib-resistant cell lines sensitive to gefitinib. The combined use has a significant inhibitory effect on the phosphorylation of EGFR, Akt - 1, MEK1/2, and ERK1/2." |
Note: | drug comb |
Score: | 4.0 |
Pubmed(PMID): | 29215723 |
Sentence Index: | 29215723_2-3 |
Sentence: | "In this study, we showed that cholesterol level in lipid rafts in gefitinib resistant non-small cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib sensitive cell line, and depletion of cholesterol increased gefitinib sensitivity. Furthermore, cholesterol-depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt-1, MEK1/2, and ERK1/2 and these were reversed in cholesterol add-back experiments." |
Sequence & Structure:
MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDEQQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFGCQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEFQDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAGV
Select PDB:
Target | Drug name | MOA | Phase | Status | Disease | Source |
---|---|---|---|---|---|---|
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | neoplasm | ATC |
MAP2K1 | SELUMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 4 | - | neoplasm | ATC |
MAP2K1 | COBIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | neoplasm | ATC |
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | Recruiting | neoplasm | ClinicalTrials |
MAP2K1 | COBIMETINIB FUMARATE | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | melanoma | EMA |
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | melanoma | DailyMed EMA |
MAP2K1 | COBIMETINIB FUMARATE | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | metastatic melanoma | DailyMed |
MAP2K1 | TRAMETINIB DIMETHYL SULFOXIDE | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | metastatic melanoma | FDA |
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | metastatic melanoma | FDA |
MAP2K1 | SELUMETINIB SULFATE | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 4 | - | neurofibromatosis | DailyMed |
MAP2K1 | TRAMETINIB DIMETHYL SULFOXIDE | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | thyroid cancer | DailyMed |
MAP2K1 | TRAMETINIB DIMETHYL SULFOXIDE | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 4 | - | lung cancer | DailyMed |
MAP2K1 | SELUMETINIB SULFATE | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 4 | - | neurofibromatosis type 1 | EMA FDA |
MAP2K1 | SELUMETINIB SULFATE | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Recruiting | astrocytoma | ClinicalTrials |
MAP2K1 | SELUMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Recruiting | astrocytoma | ClinicalTrials |
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Completed | cutaneous melanoma | ClinicalTrials |
MAP2K1 | COBIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Withdrawn | melanoma | ClinicalTrials |
MAP2K1 | TRAMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Recruiting | melanoma | ClinicalTrials ClinicalTrials |
MAP2K1 | COBIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Active, not recruiting | melanoma | ClinicalTrials |
MAP2K1 | COBIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Completed | melanoma | ClinicalTrials |
MAP2K1 | COBIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Terminated | melanoma | ClinicalTrials |
MAP2K1 | BINIMETINIB | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | 3 | Active, not recruiting | melanoma | ClinicalTrials ClinicalTrials ClinicalTrials |
MAP2K1 | TRAMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Active, not recruiting | melanoma | ClinicalTrials |
MAP2K1 | TRAMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Completed | melanoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
MAP2K1 | SELUMETINIB | Dual specificity mitogen-activated protein kinase kinase; MEK1/2 inhibitor | 3 | Active, not recruiting | non-small cell lung carcinoma | ClinicalTrials |
Note: Only show clinically investigational or approved drugs with protein targets.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTACNo intensity data of this site,
show all other sites!
MAP2K1-Ser212 | |||||
---|---|---|---|---|---|
Cancer | Intensity | ||||
BRCA | |||||
COAD | 0.336 | ||||
HGSC | -2.466 | ||||
ccRCC | |||||
GBM | 0.491 | ||||
HNSC | 0.463 | ||||
LUAD | 0.347 | ||||
LUSC | 0.32 | ||||
non_ccRCC | 0.267 | ||||
PDAC | |||||
UCEC | 0.243 |
MAP2K1-Ser218 | |||||
---|---|---|---|---|---|
Cancer | Intensity | ||||
BRCA | 1.025 | ||||
COAD | 0.17 | ||||
HGSC | -2.102 | ||||
ccRCC | |||||
GBM | -0.726 | ||||
HNSC | 1.253 | ||||
LUAD | 0.502 | ||||
LUSC | 0.141 | ||||
non_ccRCC | -0.26 | ||||
PDAC | -0.732 | ||||
UCEC | 0.729 |
MAP2K1-Ser222 | |||||
---|---|---|---|---|---|
Cancer | Intensity | ||||
BRCA | 1.754 | ||||
COAD | -0.057 | ||||
HGSC | -2.024 | ||||
ccRCC | |||||
GBM | 0.263 | ||||
HNSC | 0.783 | ||||
LUAD | 0.076 | ||||
LUSC | 0.656 | ||||
non_ccRCC | -0.519 | ||||
PDAC | -0.44 | ||||
UCEC | -0.492 |
MAP2K1-Thr286 | |||||
---|---|---|---|---|---|
Cancer | Intensity | ||||
BRCA | |||||
COAD | |||||
HGSC | |||||
ccRCC | |||||
GBM | 1.485 | ||||
HNSC | -0.682 | ||||
LUAD | -0.348 | ||||
LUSC | -0.455 | ||||
non_ccRCC | |||||
PDAC | |||||
UCEC |
MAP2K1-Thr7 | |
---|---|
Cancer | Intensity |
BRCA | |
COAD | |
HGSC | |
ccRCC | |
GBM | |
HNSC | |
LUAD | -1.121 |
LUSC | |
non_ccRCC | |
PDAC | 0.32 |
UCEC | 0.801 |
PTM-Disease Association:
source: PTMDResidue | Position | State | Disease | Class | PMID |
---|---|---|---|---|---|
- | - | P | Colon cancer/carcinoma | Phosphorylation | 15233637 |
- | - | P | Pancreatic cancer/carcinoma/adenocarcinoma | Phosphorylation | 24209743 |
S | 218 | U | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
S | 222 | U | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
- | - | U | Breast cancer | Phosphorylation | 15193230 |
- | - | U | Crohn's disease | Phosphorylation | 23970928 |
- | - | U | Adenoma | Phosphorylation | 21989899 |
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: DecryptMNo data.
Function score:
source: funscoRNo data.