Id: acc0757
Group: 2sens
Protein: ERK1
Gene Symbol: MAPK3
Protein Id: P27361
Protein Name: MK03_HUMAN
PTM: phosphorylation
Site: Tyr204
Site Sequence: HDHTGFLTEYVATRWYRAPEI
Disease Category: Cancer
Disease: Leukemia
Disease Subtype: CLL
Disease Cellline:
Disease Info:
Drug: acalabrutinib
Drug Info: "Acalabrutinib is a second-generation Bruton's tyrosine kinase (BTK) inhibitor, approved for the treatment of adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL), and it is administered orally as capsules or tablets, developed and marketed by AstraZeneca Pharmaceuticals. "
Effect: modulate
Effect Info: "Acalabrutinib targets and reduces the phosphorylation of PLCgamma2 and ERK, and significantly inhibits the proliferation of CLL cells."
Note:
Score: 4.0
Pubmed(PMID): 27903679
Sentence Index:
Sentence:

Sequence & Structure:

MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAYDHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYIVQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDLKICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSDSKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target Drug name MOA Phase Status Disease Source
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Terminated neoplasm ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 2 Completed pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Recruiting histiocytic neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 2 Active, not recruiting Uveal Melanoma ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 2 Terminated cancer ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed acute myeloid leukemia ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed myelodysplastic syndrome ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 1 Recruiting acute myeloid leukemia ClinicalTrials
MAPK3 RAVOXERTINIB MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Completed neoplasm ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Terminated neoplasm ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Recruiting pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Terminated pancreatic carcinoma ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 inhibitor 1 Recruiting metastatic colorectal cancer ClinicalTrials
MAPK3 KO-947 Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 1 Terminated cancer ClinicalTrials
MAPK3 MK-8353 MAP kinase ERK1 inhibitor 1 Completed colorectal cancer ClinicalTrials
MAPK3 TEMUTERKIB Mitogen-activated protein kinase; ERK1/ERK2 inhibitor 0.5 Recruiting glioblastoma multiforme ClinicalTrials
MAPK3 ULIXERTINIB MAP kinase ERK1 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
MAPK3-Tyr204
Cancer Intensity
BRCA 1.299
COAD 0.294
HGSC 1.686
ccRCC -0.456
GBM 0.155
HNSC 0.082
LUAD -0.027
LUSC 0.328
non_ccRCC -0.355
PDAC -1.055
UCEC -1.949

PTM-Disease Association:

source: PTMD
Residue Position State Disease Class PMID
Y 204 D Acute lymphocytic leukemia Phosphorylation 26073130
Y 204 D Head and neck squamous cell carcinoma Phosphorylation 21281788
Y 204 U Breast cancer Phosphorylation 31944568
Y 204 U Acute myelogenous leukemia Phosphorylation 26073130
Y 204 U Alzheimer's disease Phosphorylation 35847683
Y 204 U Glioma Phosphorylation 33820494
Y 204 U Pulmonary emphysema Phosphorylation 14764579
Y 204 U Triple-negative breast cancer Phosphorylation 28415597
Y 204 U Tuberous sclerosis complex Phosphorylation 17671177

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
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Lapatinib 6.5402 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Lapatinib 7.4061 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Pertuzumab -4.6099 down
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Pertuzumab -1.9536 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR BT-474 Trastuzumab -1.9524 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR MDA-MB-175 Trastuzumab 5 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Lapatinib 6.25 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Pertuzumab -1.7417 -
P27361 MAPK3 P Tyr204 IADPEHDHTGFLTEY(ph)VATR SK-BR-3 Trastuzumab -0.8941 -

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: