CHEK2
Summary: In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| checkpoint kinase 2 | MIM:604373 | Ensembl:ENSG00000183765 | HGNC:HGNC:16627 | PA404 | 22q12.1 |
GO terms in CHEK2
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| CC | IDA | GO:0000781 | chromosome, telomeric region |
| CC | IBA | GO:0005634 | nucleus |
| CC | IDA | GO:0005654 | nucleoplasm |
| CC | TAS | GO:0005654 | nucleoplasm |
| CC | IBA | GO:0005737 | cytoplasm |
| CC | IDA | GO:0005794 | Golgi apparatus |
| CC | IDA | GO:0016605 | PML body |
| BP | TAS | GO:0000077 | DNA damage checkpoint |
| BP | IMP | GO:0000086 | G2/M transition of mitotic cell cycle |
| BP | IMP | GO:0001302 | replicative cell aging |
| BP | IEA | GO:0001934 | positive regulation of protein phosphorylation |
| BP | IMP | GO:0006302 | double-strand break repair |
| BP | IEA | GO:0006351 | transcription, DNA-templated |
| BP | IDA | GO:0006355 | regulation of transcription, DNA-templated |
| BP | IDA | GO:0006468 | protein phosphorylation |
| BP | IDA | GO:0006974 | cellular response to DNA damage stimulus |
| BP | IMP | GO:0006974 | cellular response to DNA damage stimulus |
| BP | TAS | GO:0006974 | cellular response to DNA damage stimulus |
| BP | IMP | GO:0006975 | DNA damage induced protein phosphorylation |
| BP | TAS | GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest |
| BP | IEA | GO:0006978 | DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator |
| BP | IDA | GO:0008630 | intrinsic apoptotic signaling pathway in response to DNA damage |
| BP | IMP | GO:0008630 | intrinsic apoptotic signaling pathway in response to DNA damage |
| BP | IMP | GO:0042176 | regulation of protein catabolic process |
| BP | IBA | GO:0042770 | signal transduction in response to DNA damage |
| BP | IDA | GO:0042770 | signal transduction in response to DNA damage |
| BP | IEA | GO:0042771 | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator |
| BP | IBA | GO:0042981 | regulation of apoptotic process |
| BP | IMP | GO:0044257 | cellular protein catabolic process |
| BP | IBA | GO:0044773 | mitotic DNA damage checkpoint |
| BP | IDA | GO:0045893 | positive regulation of transcription, DNA-templated |
| BP | IDA | GO:0046777 | protein autophosphorylation |
| BP | IDA | GO:0050821 | protein stabilization |
| BP | IEA | GO:0051301 | cell division |
| BP | IEA | GO:0071157 | negative regulation of cell cycle arrest |
| BP | IEA | GO:0071480 | cellular response to gamma radiation |
| BP | IMP | GO:0072428 | signal transduction involved in intra-S DNA damage checkpoint |
| BP | IMP | GO:0090307 | mitotic spindle assembly |
| BP | NAS | GO:0090399 | replicative senescence |
| BP | TAS | GO:1901796 | regulation of signal transduction by p53 class mediator |
| BP | IEA | GO:1903416 | response to glycoside |
| BP | IEA | GO:1903926 | cellular response to bisphenol A |
| BP | IEA | GO:2000002 | negative regulation of DNA damage checkpoint |
| BP | IEA | GO:2000210 | positive regulation of anoikis |
| MF | IBA | GO:0004674 | protein serine/threonine kinase activity |
| MF | IDA | GO:0004674 | protein serine/threonine kinase activity |
| MF | TAS | GO:0004674 | protein serine/threonine kinase activity |
| MF | IPI | GO:0005515 | protein binding |
| MF | IEA | GO:0005524 | ATP binding |
| MF | TAS | GO:0016301 | kinase activity |
| MF | IPI | GO:0019901 | protein kinase binding |
| MF | IPI | GO:0031625 | ubiquitin protein ligase binding |
| MF | IPI | GO:0042802 | identical protein binding |
| MF | IDA | GO:0042803 | protein homodimerization activity |
| MF | IEA | GO:0046872 | metal ion binding |
Gene expression in normal tissue: CHEK2
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in CHEK2
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-3700989 | Transcriptional Regulation by TP53 |
| reactome | R-HSA-5633007 | Regulation of TP53 Activity |
| reactome | R-HSA-5693532 | DNA Double-Strand Break Repair |
| reactome | R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks |
| reactome | R-HSA-5693606 | DNA Double Strand Break Response |
| reactome | R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation |
| reactome | R-HSA-6804757 | Regulation of TP53 Degradation |
| reactome | R-HSA-6804760 | Regulation of TP53 Activity through Methylation |
| reactome | R-HSA-6806003 | Regulation of TP53 Expression and Degradation |
| reactome | R-HSA-69473 | G2/M DNA damage checkpoint |
| reactome | R-HSA-69481 | G2/M Checkpoints |
| reactome | R-HSA-69541 | Stabilization of p53 |
| reactome | R-HSA-69563 | p53-Dependent G1 DNA Damage Response |
| reactome | R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint |
| reactome | R-HSA-69601 | Ubiquitin Mediated Degradation of Phosphorylated Cdc25A |
| reactome | R-HSA-69610 | p53-Independent DNA Damage Response |
| reactome | R-HSA-69613 | p53-Independent G1/S DNA damage checkpoint |
| reactome | R-HSA-69615 | G1/S DNA Damage Checkpoints |
| reactome | R-HSA-69620 | Cell Cycle Checkpoints |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-73894 | DNA Repair |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-75035 | Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex |
| biocarta | atmpathway | atm signaling pathway |
| biocarta | atrbrcapathway | role of brca1 brca2 and atr in cancer susceptibility |
| biocarta | g2pathway | cell cycle: g2/m checkpoint |
| biocarta | plk3pathway | regulation of cell cycle progression by plk3 |
| kegg | hsa04110 | Cell cycle - Homo sapiens (human) |
| kegg | hsa04115 | p53 signaling pathway - Homo sapiens (human) |
| kegg | hsa04218 | Cellular senescence - Homo sapiens (human) |
| kegg | hsa05166 | HTLV-I infection - Homo sapiens (human) |
| pid | atm_pathway | ATM pathway |
| pid | foxm1pathway | FOXM1 transcription factor network |
| pid | p53regulationpathway | p53 pathway |
| pid | plk3_pathway | PLK3 signaling events |
| pharmgkb | PA165374494 | Busulfan Pathway, Pharmacodynamics |
| wikipathways | WP1530 | miRNA Regulation of DNA Damage Response |
| wikipathways | WP179 | Cell Cycle |
| wikipathways | WP3878 | ATM Signaling Network in Development and Disease |
| wikipathways | WP3982 | miRNA regulation of p53 pathway in prostate cancer |
| wikipathways | WP707 | DNA Damage Response |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD433 | Lexibulin | 4 |
| iGMDRD313 | Axitinib | 1 |
| iGMDRD151 | CHM-1 | 3 |
| iGMDRD420 | Leucascandrolide A | 3 |
| iGMDRD1008 | SR-II-138A | 3 |
| iGMDRD772 | BRD4770 | 6 |
| iGMDRD971 | PARP inhibitor | 2 |
| iGMDRD587 | CHEMBL585951 | 1 |
| iGMDRD446 | LY 2183240 | 4 |
| iGMDRD66 | Doxorubicin | 1 |
| iGMDRD61 | Kinetin riboside | 3 |
| iGMDRD466 | Chaetocin | 3 |
| iGMDRD634 | SCHEMBL2608041 | 3 |
| iGMDRD380 | Pifithrin-alpha | 3 |
| iGMDRD235 | SNS-032 | 1 |
| iGMDRD247 | Blebbistatin | 2 |
| iGMDRD138 | PX 12 | 3 |
| iGMDRD802 | 4-methylfasudil | 3 |
| iGMDRD801 | 2,4-dideoxy-DC-45-A2 | 3 |
| iGMDRD318 | PAC-1 | 6 |
| iGMDRD52 | Rotenone | 3 |
| iGMDRD145 | Omacetaxine mepesuccinate | 1 |
| iGMDRD506 | Fedratinib | 1 |
| iGMDRD577 | BIX01294 | 3 |
| iGMDRD391 | OSU-03012 | 1 |
| iGMDRD146 | Elesclomol | 2 |
| iGMDRD690 | PRIMA-1MET | 3 |
| iGMDRD291 | AC1NS4S0 | 1 |
| iGMDRD131 | Erlotinib | 2 |
| iGMDRD64 | Parbendazole | 3 |
| iGMDRD60 | Quinoclamine | 3 |
| iGMDRD225 | AC1MD3YP | 1 |
| iGMDRD268 | Cerulenin | 3 |
| iGMDRD23 | Gossypol | 6 |
| iGMDRD451 | Serdemetan | 3 |
| iGMDRD262 | KU-55933 | 1 |
| iGMDRD607 | Ubistatin B | 6 |
| iGMDRD148 | Pifithrin-mu | 3 |
| iGMDRD532 | Olaparib | 3 |
| iGMDRD594 | AZD-8055 | 1 |
| iGMDRD523 | Cyanoquinoline, 11 | 3 |
| iGMDRD79 | Gemcitabine | 3 |
| iGMDRD232 | FTI-277 | 1 |
| iGMDRD292 | NSC87877 | 1 |
| iGMDRD219 | Bax channel blocker | 2 |
| iGMDRD123 | Isoevodiamine | 1 |
| iGMDRD605 | AZD6482 | 1 |
| iGMDRD154 | NSC23766 | 1 |
| iGMDRD132 | (-)-gallocatechin-3-O-gallate | 3 |
| iGMDRD121 | GMX1778 | 4 |
| iGMDRD289 | Parthenolide | 6 |
| iGMDRD434 | BMS-536924 | 2 |
| iGMDRD311 | Dacinostat | 1 |
| iGMDRD481 | Dactolisib | 1 |
| iGMDRD504 | Obatoclax | 1 |
| iGMDRD213 | SMR000068650 | 3 |
| iGMDRD871 | BRD6368 | 3 |
| iGMDRD119 | Temsirolimus | 1 |
| iGMDRD286 | Nsc 632839 | 3 |
| iGMDRD329 | Merck60 | 6 |
| iGMDRD263 | AACOCF3 | 3 |
| iGMDRD42 | Vorinostat | 1 |
| iGMDRD322 | FK 866 | 1 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in CHEK2
CLASSFICATION
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