| Id: | acc3002 |
| Group: | 2sens |
| Protein: | AKT |
| Gene Symbol: | AKT1 |
| Protein Id: | P31749 |
| Protein Name: | AKT1_HUMAN |
| PTM: | phosphorylation |
| Site: | Thr308 |
| Site Sequence: | GIKDGATMKTFCGTPEYLAPE |
| Disease Category: | Cancer |
| Disease: | Breast Cancer |
| Disease Subtype: | ER+ |
| Disease Cellline: | T47D |
| Disease Info: | |
| Drug: | Everolimus? |
| Drug Info: | Everolimus is an immunosuppressant and mTOR inhibitor used in the treatment of various cancers and to prevent organ transplant rejection. |
| Relation: |
AKT-Thr308
UP
＋
Everolimus?
➜
Breast Cancer
Aggravate
|
| Effect: | resist |
| Effect Info: | "After everolimus treatment, the p-AKT level in the highly sensitive cell line ZR-75-1 was unaffected, while the p-AKT level in the low-sensitive cell line T47D increased." |
| Note: | |
| Score: | 5.0 |
| Pubmed(PMID): | 29476223 |
| Sentence Index: | 29476223_8-9 |
| Sentence: | "MCF-7, T47D and HCC1500 had activating mutations in PIK3CA gene, while loss-of-activity PTEN mutations were detected in sensitive cell lines, including ZR-75-1, which showed no changes or minimal increase in the amount of p-AKT(Ser473/Thr308) and p-ERK1/2(Thr202/Tyr204) induced by everolimus compared to the resistant cell line T47D in which phosphorylation of AKT and ERK was increased. CONCLUSIONS: Cellular levels of p-AKT(Ser473/Thr308) and p-ERK1/2(Thr202/Tyr204), activating mutations of PIK3CA and inactivating mutations of PTEN may predict response to everolimus in breast cancer cells; these findings have potential applications for treatment personalization of everolimus in breast cancer patients." |
Sequence & Structure:
MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA
Select PDB:
| Target | Drug name | MOA | Phase | Status | Disease | Source |
|---|---|---|---|---|---|---|
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Completed | metastatic prostate cancer | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Active, not recruiting | breast neoplasm | ClinicalTrials |
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Completed | triple-negative breast cancer | ClinicalTrials |
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Recruiting | cancer | ClinicalTrials |
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Active, not recruiting | breast cancer | ClinicalTrials |
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Completed | breast cancer | ClinicalTrials |
| AKT1 | IPATASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Terminated | breast cancer | ClinicalTrials |
| AKT1 | AFURESERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Recruiting | breast cancer | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Active, not recruiting | breast cancer | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Recruiting | breast cancer | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Recruiting | prostate cancer | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 3 | Active, not recruiting | prostate cancer | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | hepatocellular carcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | head and neck squamous cell carcinoma | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 2 | Active, not recruiting | neoplasm of mature B-cells | ClinicalTrials |
| AKT1 | UPROSERTIB | Serine/threonine-protein kinase AKT inhibitor | 2 | Terminated | acute myeloid leukemia | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 2 | Active, not recruiting | adenocarcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | breast carcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Terminated | breast carcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | adenosquamous lung carcinoma | ClinicalTrials |
| AKT1 | UPROSERTIB | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | breast carcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | bronchoalveolar adenocarcinoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Completed | diffuse large B-cell lymphoma | ClinicalTrials |
| AKT1 | MK-2206 | Serine/threonine-protein kinase AKT inhibitor | 2 | Terminated | diffuse large B-cell lymphoma | ClinicalTrials |
| AKT1 | CAPIVASERTIB | Serine/threonine-protein kinase AKT inhibitor | 2 | Terminated | gastric adenocarcinoma | ClinicalTrials |
Note: Only show clinically investigational or approved drugs with protein targets.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTAC| AKT1-Thr308 | |
|---|---|
| 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 | 308 | D | Ovarian cancer/carcinoma | Phosphorylation | 20153512 |
| T | 308 | D | Type 2 diabetes | Phosphorylation | 15919790 ; 15919790 |
| T | 308 | D | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
| T | 308 | D | Diabetes mellitus | Phosphorylation | 17272402 ; 20938636 ; 15919790 |
| T | 308 | P | Non-small cell lung cancer/carcinoma | Phosphorylation | 23091605 |
| T | 308 | U | Chronic lymphocytic leukemia | Phosphorylation | 16940331 |
| T | 308 | U | Melanoma | Phosphorylation | 19996208 |
| T | 308 | U | Multiple myeloma | Phosphorylation | 37781194 |
| T | 308 | U | Neuroblastoma | Phosphorylation | 17234785 |
| T | 308 | U | Pancreatic cancer/carcinoma/adenocarcinoma | Phosphorylation | 26676747 |
| T | 308 | U | Rhabdomyosarcoma | Phosphorylation | 17848913 |
| T | 308 | U | Breast cancer | Phosphorylation | 33571243 |
| T | 308 | U | Acute myeloid leukemia/acute myelogenous leukemia | Phosphorylation | 12750723 |
| T | 308 | U | Cholangiocarcinoma | Phosphorylation | 37752233 |
| T | 308 | U | Lymphocytic leukemia | Phosphorylation | 20576813 |
| T | 308 | U | Obesity | Phosphorylation | 35413055 |
| T | 308 | U | Sjogren's syndrome | Phosphorylation | 34948236 |
| T | 308 | U | Endometrial cancer | Phosphorylation | 35253622 |
| T | 308 | U | Esophageal squamous cell carcinoma | Phosphorylation | 36995521 |
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.
