| Id: | acc3246 |
| Group: | 2sens |
| Protein: | Chk1 |
| Gene Symbol: | CHEK1 |
| Protein Id: | O14757 |
| Protein Name: | CHK1_HUMAN |
| PTM: | phosphorylation |
| Site: | Ser345 |
| Site Sequence: | DKLVQGISFSQPTCPDHMLLN |
| Disease Category: | Cancer |
| Disease: | Cancer |
| Disease Subtype: | |
| Disease Cellline: | HeLa |
| Disease Info: | |
| Drug: | Hyperthermia? |
| Drug Info: | "Hyperthermia is not a drug. It refers to a condition where the body's temperature rises above normal, such as in fever or due to external heat sources." |
| Effect: | decrease |
| Effect Info: | "Hyperthermia induces the activation of the ATR - Chk1 pathway, enhances the phosphorylation of Chk1 at the Ser345 site in human cancer cells (HeLa), thereby promoting the tolerance of (tumor) cells to heat stress." |
| Note: | Non-conventional drugs |
| Score: | 4.5 |
| Pubmed(PMID): | 23383325 |
| Sentence Index: | 23383325_2-3 |
| Sentence: | "Heat treatment per se activates DNA damage responses mediated by the ATR-Chk1 and ATM-Chk2 pathways but it is not fully understood how these DNA damage responses are activated and affect heat tolerance. By performing a genetic analysis of human HeLa cells and chicken B lymphoma DT40 cells, we found that heat-induced Chk1 Ser345 phosphorylation by ATR was largely dependent on Rad9, Rad17, TopBP1 and Claspin." |
Sequence & Structure:
MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINKMLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLKRREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDFSPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRRNNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
Select PDB:
| Target | Drug name | MOA | Phase | Status | Disease | Source |
|---|---|---|---|---|---|---|
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Terminated | lymphoma | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | small cell lung carcinoma | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | small cell lung carcinoma | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Terminated | melanoma | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | pancreatic carcinoma | ClinicalTrials |
| CHEK1 | RABUSERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | non-small cell lung carcinoma | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | peritoneum cancer | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | fallopian tube cancer | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Unknown status | kidney cancer | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | cancer | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | ovarian cancer | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Terminated | ovarian cancer | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Terminated | breast cancer | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 2 | Completed | ovarian cancer | ClinicalTrials |
| CHEK1 | XL-844 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Terminated | chronic lymphocytic leukemia | ClinicalTrials |
| CHEK1 | SCH-900776 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | Hodgkins lymphoma | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | acute myeloid leukemia | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | acute erythroleukemia | ClinicalTrials |
| CHEK1 | PREXASERTIB | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | myelodysplastic syndrome | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | myelodysplastic syndrome | ClinicalTrials ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | acute monocytic leukemia | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | acute myelomonocytic leukemia | ClinicalTrials |
| CHEK1 | SCH-900776 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Terminated | acute lymphoblastic leukemia | ClinicalTrials |
| CHEK1 | SCH-900776 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Terminated | acute myeloid leukemia | ClinicalTrials |
| CHEK1 | UCN-01 | Serine/threonine-protein kinase Chk1 inhibitor | 1 | Completed | acute promyelocytic leukemia | 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!
| CHEK1-Ser286 | |||||
|---|---|---|---|---|---|
| Cancer | Intensity | ||||
| BRCA | -0.573 | ||||
| COAD | |||||
| HGSC | -0.61 | ||||
| ccRCC | |||||
| GBM | |||||
| HNSC | -0.303 | ||||
| LUAD | |||||
| LUSC | |||||
| non_ccRCC | |||||
| PDAC | |||||
| UCEC | 1.486 | ||||
| CHEK1-Ser296 | |||||
|---|---|---|---|---|---|
| Cancer | Intensity | ||||
| BRCA | |||||
| COAD | 0.707 | ||||
| HGSC | -0.707 | ||||
| ccRCC | |||||
| GBM | |||||
| HNSC | |||||
| LUAD | |||||
| LUSC | |||||
| non_ccRCC | |||||
| PDAC | |||||
| UCEC | |||||
| CHEK1-Ser301 | |||||
|---|---|---|---|---|---|
| Cancer | Intensity | ||||
| BRCA | |||||
| COAD | 0.707 | ||||
| HGSC | -0.707 | ||||
| ccRCC | |||||
| GBM | |||||
| HNSC | |||||
| LUAD | |||||
| LUSC | |||||
| non_ccRCC | |||||
| PDAC | |||||
| UCEC | |||||
| CHEK1-Ser317 | |||||
|---|---|---|---|---|---|
| Cancer | Intensity | ||||
| BRCA | |||||
| COAD | 0.707 | ||||
| HGSC | -0.707 | ||||
| ccRCC | |||||
| GBM | |||||
| HNSC | |||||
| LUAD | |||||
| LUSC | |||||
| non_ccRCC | |||||
| PDAC | |||||
| UCEC | |||||
| CHEK1-Ser331 | |
|---|---|
| Cancer | Intensity |
| BRCA | |
| COAD | 0.941 |
| HGSC | -1.05 |
| ccRCC | |
| GBM | |
| HNSC | 0.11 |
| LUAD | |
| LUSC | |
| non_ccRCC | |
| PDAC | |
| UCEC | |
PTM-Disease Association:
source: PTMD| Residue | Position | State | Disease | Class | PMID |
|---|---|---|---|---|---|
| S | 345 | D | Riddle syndrome | Phosphorylation | 17940005 |
| S | 345 | U | Colorectal cancer | Phosphorylation | 32357935 |
| S | 345 | U | Head and neck squamous cell carcinoma | Phosphorylation | 21281788 |
| S | 345 | U | Multiple myeloma | Phosphorylation | 35190641 |
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.
