| Id: | acc0811 |
| Group: | 2sens |
| Protein: | RAF |
| Gene Symbol: | RAF1 |
| Protein Id: | P04049 |
| Protein Name: | RAF1_HUMAN |
| PTM: | phosphorylation |
| Site: | Ser338 |
| Site Sequence: | KIRPRGQRDSSYYWEIEASEV |
| Disease Category: | Cancer |
| Disease: | Glioblastoma |
| Disease Subtype: | |
| Disease Cellline: | U251 |
| Disease Info: | |
| Drug: | berberine |
| Drug Info: | "Berberine is a bioactive alkaloid derived from plants such as *Berberis vulgaris*, with demonstrated hypoglycemic, lipid-lowering, and antimicrobial effects, primarily mediated through AMP-activated protein kinase (AMPK) activation and gut microbiota modulation." |
| Effect: | modulate |
| Effect Info: | "Berberine inhibits the EGFR - RAF - MEK - ERK signaling pathway by reducing the phosphorylation of RAF, MEK, and ERK, thereby inducing senescence in human glioblastoma cells." |
| Note: | |
| Score: | 4.0 |
| Pubmed(PMID): | 25504754 |
| Sentence Index: | 25504754_5-6 |
| Sentence: | "In glioblastoma cells treated with berberine, the level of epidermal growth factor receptor (EGFR) was greatly reduced. Examination of the activities of the kinases downstream of EGFR revealed that the RAF-MEK-ERK signaling pathway was remarkably inhibited, whereas AKT phosphorylation was not altered." |
Sequence & Structure:
MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRVFLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAASLIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKVPTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTFNTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNLSPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF
Select PDB:
| Target | Drug name | MOA | Phase | Status | Disease | Source |
|---|---|---|---|---|---|---|
| RAF1 | REGORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 4 | - | neoplasm | ATC |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 4 | - | renal cell carcinoma | DailyMed |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 4 | - | thyroid carcinoma | DailyMed |
| RAF1 | REGORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 4 | - | colorectal neoplasm | EMA |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Terminated | hepatocellular carcinoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Unknown status | hepatocellular carcinoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Recruiting | hepatocellular carcinoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Withdrawn | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | REGORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | REGORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Recruiting | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | REGORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Terminated | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | hepatocellular carcinoma | ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Terminated | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Unknown status | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Active, not recruiting | hepatocellular carcinoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | hepatocellular carcinoma | ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Not yet recruiting | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Not yet recruiting | hepatocellular carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Active, not recruiting | acute myeloid leukemia | ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Active, not recruiting | acute myeloid leukemia | ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Not yet recruiting | acute myeloid leukemia | ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | clear cell renal carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | carcinoma | ClinicalTrials ClinicalTrials |
| RAF1 | SORAFENIB | Serine/threonine-protein kinase RAF inhibitor | 3 | Unknown status | carcinoma | ClinicalTrials |
| RAF1 | SORAFENIB TOSYLATE | Serine/threonine-protein kinase RAF inhibitor | 3 | Completed | clear cell renal carcinoma | ClinicalTrials |
Note: Only show clinically investigational or approved drugs with protein targets.
Protein Tractability:
source: Open TargetsPTM Intensity:
source: CPTACNo intensity data of this site,
show all other sites!
| RAF1-Ser12 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | 0.172 | ||||||||
| COAD | |||||||||
| HGSC | 2.108 | ||||||||
| ccRCC | -0.682 | ||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | -0.189 | ||||||||
| LUSC | -0.96 | ||||||||
| non_ccRCC | -0.274 | ||||||||
| PDAC | |||||||||
| UCEC | -0.174 | ||||||||
| RAF1-Ser220 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | 0.504 | ||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | 0.648 | ||||||||
| UCEC | -1.152 | ||||||||
| RAF1-Ser222 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | -0.707 | ||||||||
| HGSC | 0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser243 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | -0.637 | ||||||||
| ccRCC | |||||||||
| GBM | 1.153 | ||||||||
| HNSC | -0.516 | ||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser244 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | -0.707 | ||||||||
| ccRCC | |||||||||
| GBM | 0.707 | ||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser259 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | -0.707 | ||||||||
| HGSC | 0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser29 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | -1.443 | ||||||||
| COAD | 1.053 | ||||||||
| HGSC | 1.395 | ||||||||
| ccRCC | -0.971 | ||||||||
| GBM | 0.777 | ||||||||
| HNSC | 0.798 | ||||||||
| LUAD | 0.392 | ||||||||
| LUSC | -0.242 | ||||||||
| non_ccRCC | -1.329 | ||||||||
| PDAC | -0.765 | ||||||||
| UCEC | 0.336 | ||||||||
| RAF1-Ser296 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | -0.707 | ||||||||
| HGSC | 0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser315 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | -0.707 | ||||||||
| HNSC | |||||||||
| LUAD | 0.707 | ||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser316 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | 0.707 | ||||||||
| LUAD | -0.707 | ||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser321 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | 0.09 | ||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | 0.652 | ||||||||
| HNSC | -0.28 | ||||||||
| LUAD | -1.608 | ||||||||
| LUSC | 0.37 | ||||||||
| non_ccRCC | |||||||||
| PDAC | 1.498 | ||||||||
| UCEC | -0.723 | ||||||||
| RAF1-Ser377 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | 0.711 | ||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | 0.944 | ||||||||
| HNSC | |||||||||
| LUAD | -1.519 | ||||||||
| LUSC | 0.311 | ||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | -0.448 | ||||||||
| RAF1-Ser43 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | -0.746 | ||||||||
| COAD | -0.083 | ||||||||
| HGSC | 1.675 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | -0.055 | ||||||||
| UCEC | -0.791 | ||||||||
| RAF1-Ser621 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | -0.707 | ||||||||
| HGSC | 0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser625 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | 0.707 | ||||||||
| GBM | |||||||||
| HNSC | -0.707 | ||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser632 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | -0.621 | ||||||||
| HNSC | 1.154 | ||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | -0.532 | ||||||||
| UCEC | |||||||||
| RAF1-Ser639 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | 0.842 | ||||||||
| HNSC | 0.264 | ||||||||
| LUAD | -1.105 | ||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Ser641 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | 0.613 | ||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | 0.172 | ||||||||
| GBM | 0.609 | ||||||||
| HNSC | -1.065 | ||||||||
| LUAD | -0.714 | ||||||||
| LUSC | 1.845 | ||||||||
| non_ccRCC | -1.422 | ||||||||
| PDAC | -0.294 | ||||||||
| UCEC | 0.256 | ||||||||
| RAF1-Ser642 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | -0.707 | ||||||||
| HGSC | 0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Thr10 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | -1.409 | ||||||||
| GBM | |||||||||
| HNSC | 0.926 | ||||||||
| LUAD | 0.099 | ||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | 0.385 | ||||||||
| RAF1-Thr242 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | |||||||||
| GBM | 0.707 | ||||||||
| HNSC | -0.707 | ||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Thr260 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | 0.707 | ||||||||
| HGSC | -0.707 | ||||||||
| ccRCC | |||||||||
| GBM | |||||||||
| HNSC | |||||||||
| LUAD | |||||||||
| LUSC | |||||||||
| non_ccRCC | |||||||||
| PDAC | |||||||||
| UCEC | |||||||||
| RAF1-Thr330 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer | Intensity | ||||||||
| BRCA | |||||||||
| COAD | |||||||||
| HGSC | |||||||||
| ccRCC | -0.44 | ||||||||
| GBM | -1.329 | ||||||||
| HNSC | 1.788 | ||||||||
| LUAD | 0.033 | ||||||||
| LUSC | -0.602 | ||||||||
| non_ccRCC | 0.907 | ||||||||
| PDAC | 0.367 | ||||||||
| UCEC | -0.723 | ||||||||
| RAF1-Thr641 | |
|---|---|
| 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 |
|---|---|---|---|---|---|
| S | 338 | U | Alzheimer's disease | Phosphorylation | 17064357 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | K562 | Dasatinib | 9.8241 | down | |
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | K562 | Dasatinib | 8.8557 | down | |
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | BT-474 | Pertuzumab | -1.5377 | - | |
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | K562 | Dasatinib | 8.743 | - | |
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | MDA-MB-175 | Pertuzumab | -4.593 | - | |
| P04049 | RAF1 | P | Ser338 | GQRDS(ph)SYYWEIEASEVMLSTR | MDA-MB-175 | Trastuzumab | -0.8503 | - |
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.
