| Id: | acc1706 |
| Group: | 2sens |
| Protein: | SHP2 |
| Gene Symbol: | NR0B2 |
| Protein Id: | Q15466 |
| Protein Name: | NR0B2_HUMAN |
| PTM: | phosphorylation |
| Site: | Tyr62 |
| Site Sequence: | HRTCREALDVLAKTVAFLRNL |
| Disease Category: | Cancer |
| Disease: | Leukemia |
| Disease Subtype: | AML |
| Disease Cellline: | MV4-11 |
| Disease Info: | |
| Drug: | SHP099 |
| Drug Info: | "SHP099 is a potent, selective, and orally active allosteric inhibitor of SHP2 (Src homology 2-containing protein tyrosine phosphatase 2) with an IC50 of 70 nM, which stabilizes the autoinhibited conformation of SHP2 by binding to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thereby suppressing RAS-ERK signaling pathway and inhibiting proliferation of receptor tyrosine kinase-driven cancer cells. " |
| Effect: | resist |
| Effect Info: | Phosphorylation of SHP2 at the Tyr62 site confers acquired resistance to the SHP2 allosteric inhibitor SHP099. |
| Note: | |
| Score: | 5.0 |
| Pubmed(PMID): | 35311954 |
| Sentence Index: | 35311954_5-6 |
| Sentence: | "Label-free and isobaric labeling quantitative mass spectrometry-based phosphoproteomics of these resistant models demonstrated that AML cells can restore phosphorylated ERK (pERK) in the presence of SHP099, thus developing adaptive resistance. Mechanistically, SHP2 inhibition induced tyrosine phosphorylation and feedback-driven activation of the FLT3 receptor, which in turn phosphorylated SHP2 on tyrosine 62." |
Sequence & Structure:
MSTSQPGACPCQGAASRPAILYALLSSSLKAVPRPRSRCLCRQHRPVQLCAPHRTCREALDVLAKTVAFLRNLPSFWQLPPQDQRRLLQGCWGPLFLLGLAQDAVTFEVAEAPVPSILKKILLEEPSSSGGSGQLPDRPQPSLAAVQWLQCCLESFWSLELSPKEYACLKGTILFNPDVPGLQAASHIGHLQQEAHWVLCEVLEPWCPAAQGRLTRVLLTASTLKSIPTSLLGDLFFRPIIGDVDIAGLLGDMLLLR
Select PDB:
No data.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTACNo data.
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| - | - | C | CADASIL | Ubiquitination | 20516075 |
| - | - | U | Glioma | Ubiquitination | 34195079 |
| - | - | U | Colorectal cancer | Ubiquitination | 30918473 |
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.
