| Id: | acc1083 |
| Group: | 2sens |
| Protein: | JNK |
| Gene Symbol: | MAPK8 |
| Protein Id: | P45983 |
| Protein Name: | MK08_HUMAN |
| PTM: | phosphorylation |
| Site: | Thr183 |
| Site Sequence: | RTAGTSFMMTPYVVTRYYRAP |
| Disease Category: | Cancer |
| Disease: | Leukemia |
| Disease Subtype: | CML |
| Disease Cellline: | CML-iPSCs |
| Disease Info: | |
| Drug: | imatinib |
| Drug Info: | "Imatinib is a tyrosine kinase inhibitor that targets Bcr-Abl and KIT proteins, used in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST)." |
| Effect: | inhibit |
| Effect Info: | "CML-iPSCs confer resistance to imatinib by maintaining the activity of ERK and AKT and the phosphorylation of ERK1/2, AKT, and JNK." |
| Note: | |
| Score: | 5.0 |
| Pubmed(PMID): | 22592606 |
| Sentence Index: | 22592606_4-5 |
| Sentence: | "Remarkably, the CML-iPSCs were resistant to imatinib although they consistently expressed BCR-ABL oncoprotein. In CML-iPSCs, the phosphorylation of ERK1/2, AKT, and JNK, which are essential for the maintenance of both BCR-ABL (+) leukemia cells and iPSCs, were unchanged after imatinib treatment, whereas the phosphorylation of signal transducer and activator of transcription (STAT)5 and CRKL was significantly decreased." |
Sequence & Structure:
MSRSKRDNNFYSVEIGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDLWSVGCIMGEMVCHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRTYVENRPKYAGYSFEKLFPDVLFPADSEHNKLKASQARDLLSKMLVIDASKRISVDEALQHPYINVWYDPSEAEAPPPKIPDKQLDEREHTIEEWKELIYKEVMDLEERTKNGVIRGQPSPLGAAVINGSQHPSSSSSVNDVSSMSTDPTLASDTDSSLEAAAGPLGCCR
Select PDB:
| Target | Drug name | MOA | Phase | Status | Disease | Source |
|---|---|---|---|---|---|---|
| MAPK8 | BENTAMAPIMOD | c-Jun N-terminal kinase, JNK inhibitor | 2 | Completed | endometriosis | ClinicalTrials |
| MAPK8 | TANZISERTIB | c-Jun N-terminal kinase 1 inhibitor | 2 | Terminated | idiopathic pulmonary fibrosis | ClinicalTrials |
| MAPK8 | TANZISERTIB | c-Jun N-terminal kinase 1 inhibitor | 2 | Terminated | lupus erythematosus | ClinicalTrials |
| MAPK8 | CC-401 | c-Jun N-terminal kinase 1 inhibitor | 1 | Terminated | myeloid leukemia | ClinicalTrials |
Note: Only show clinically investigational or approved drugs with protein targets.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTAC| MAPK8-Thr183 | |
|---|---|
| Cancer | Intensity |
| BRCA | |
| COAD | 0.707 |
| HGSC | -0.707 |
| ccRCC | |
| GBM | |
| HNSC | |
| LUAD | |
| LUSC | |
| non_ccRCC | |
| PDAC | |
| UCEC | |
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| T | 183 | D | Chronic myelogenous leukemia/chronic myeloid leukemia | Phosphorylation | 26147002 |
| T | 183 | U | Type 2 diabetes | Phosphorylation | 21931634 |
| T | 183 | U | Pancreatic cancer | Phosphorylation | 37016317 |
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.
