| Id: | acc0886 |
| Group: | 2sens |
| Protein: | FOXO3a |
| Gene Symbol: | FOXO3 |
| Protein Id: | O43524 |
| Protein Name: | FOXO3_HUMAN |
| PTM: | phosphorylation |
| Site: | Thr32 |
| Site Sequence: | EPQSRPRSCTWPLQRPELQAS |
| Disease Category: | Cancer |
| Disease: | Lung Cancer |
| Disease Subtype: | NSCLC |
| Disease Cellline: | A549 |
| Disease Info: | |
| Drug: | Cisplatin |
| Drug Info: | "Cisplatin is a platinum-based chemotherapeutic agent widely used in the treatment of various malignancies, including ovarian, bladder, testicular, and non-small cell lung cancers, by forming DNA cross-links to interfere with replication and repair, thereby inhibiting cancer cell growth and proliferation." |
| Effect: | modulate |
| Effect Info: | "Cisplatin reduces the phosphorylation of PI3K and AKT and significantly inhibits the phosphorylation of FOXO3a, thereby inducing cell apoptosis." |
| Note: | |
| Score: | 4.0 |
| Pubmed(PMID): | 24814195 |
| Sentence Index: | 24814195_5-6 |
| Sentence: | "The results showed that cisplatin inhibited the proliferation of these lung cancer cell lines by inhibiting the PI3K/AKT pathway, with evidence of decreasing phosphorylation of PI3K and AKT under cisplatin treatment, and constitutively activating AKT1 could reduce cisplatin-induced cell apoptosis. More importantly, cisplatin significantly inhibited FOXO3a phosphorylation (at Thr32, AKT phosphorylation site) and induced FOXO3a nuclear accumulation, which in turn increased the expression of FOXO3a-dependent apoptotic protein Bim." |
Sequence & Structure:
MAEAPASPAPLSPLEVELDPEFEPQSRPRSCTWPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGRAGSAMAIGGGGGSGTLGSGLLLEDSARVLAPGGQDPGSGPATAAGGLSGGTQALLQPQQPLPPPQPGAAGGSGQPRKCSSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWIINPDGGKSGKAPRRRAVSMDNSNKYTKSRGRAAKKKAALQTAPESADDSPSQLSKWPGSPTSRSSDELDAWTDFRSRTNSNASTVSGRLSPIMASTELDEVQDDDAPLSPMLYSSSASLSPSVSKPCTVELPRLTDMAGTMNLNDGLTENLMDDLLDNITLPPSQPSPTGGLMQRSSSFPYTTKGSGLGSPTSSFNSTVFGPSSLNSLRQSPMQTIQENKPATFSSMSHYGNQTLQDLLTSDSLSHSDVMMTQSDPLMSQASTAVSAQNSRRNVMLRNDPMMSFAAQPNQGSLVNQNLLHHQHQTQGALGGSRALSNSVSNMGLSESSSLGSAKHQQQSPVSQSMQTLSDSLSGSSLYSTSANLPVMGHEKFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDSLISTQNVVGLNVGNFTGAKQASSQSWVPG
Select PDB:
No data.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTAC| FOXO3-Thr32 | |
|---|---|
| Cancer | Intensity |
| BRCA | |
| COAD | |
| HGSC | |
| ccRCC | |
| GBM | |
| HNSC | |
| LUAD | |
| LUSC | |
| non_ccRCC | |
| PDAC | |
| UCEC | |
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| T | 32 | U | Breast cancer | Phosphorylation | 36797347 |
| T | 32 | U | Non-small cell lung cancer | Phosphorylation | 35459265 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAK | A431 | Dasatinib | 5.9597 | down | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAK | A431 | Gefitinib | 5.4679 | down | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAK | A431 | Gefitinib | 4.9989 | down | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 6.2182 | - | |
| O43524 | FOXO3 | P | Thr32;Ser43 | SCT(ph)WPLQRPELQAS(ph)PAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 4.3461 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 4.4676 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAK | A431 | Dasatinib | 7.2352 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 7.1471 | - | |
| O43524 | FOXO3 | P | Thr32;Ser43 | SCT(ph)WPLQRPELQAS(ph)PAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 8.5156 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Dasatinib | 5.8468 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Gefitinib | 6.093 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAK | A431 | Gefitinib | 6.3386 | - | |
| O43524 | FOXO3 | P | Thr32 | SCT(ph)WPLQRPELQASPAKPSGETAADSMIPEEEDDEDDEDGGGR | A431 | Gefitinib | 5.744 | - |
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: funscoRNo data.
