| Description | 61 kDa. Isoform a: 543 amino acids; isoform b: 514 amino acids. Contains FHA and ser/thr kinase domains. Molecular studies of Chk2 typically do not distinguish between the different isoforms. |
| Expression | All tissues tested. |
| Localisation | nuclear |
| Function | Chk2 plays a role in the DNA damage signal cascade, especially in response to double-strand breaks. After detection of DNA damage, Chk2 is phosphorylated on Thr-68 by ATM and ATR. Thus activated, Chk2 targets p53 for phosphorylation on Ser20, releasing p53 from its inhibitor MDM2 and allowing transcriptional activation of genes responsible for cell cycle arrest, such as p21waf1/cip1, as well as initiation of apoptosis. In S phase, Chk2 phosphorylates Cdc25A on Ser123, targeting it for degradation and making it unavailable for the activation of cdk2, thus inhibiting the advance of S phase. In G2 phase, Chk2 phosphorylates Ser216 of Cdc25C, blocking entry into mitosis. Chk2 is also involved in the regulation of BRCA1. Under normal conditions the two proteins are associated; after irradiation Chk2 phosphorylates Ser988 of BRCA1. This step is required for their dissociation, and the liberated BRCA1 participates directly in DNA repair and cell cycle arrest. Finally, Chk2 can provoke apoptosis independently of p53, for example via phosphorylation of PML. |
| Homology | 26 % identical to the Rad53 S. cereviscea homolog. The FHA and kinase domains are particularly conserved. |
| DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. |
| Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY |
| Oncogene. 1999 ; 18 (55) : 7883-7899. |
| PMID 10630641 |
| |
| Contribution of the CHEK2 1100delC variant to risk of multiple colorectal adenoma and carcinoma. |
| Lipton L, Fleischmann C, Sieber OM, Thomas HJ, Hodgson SV, Tomlinson IP, Houlston RS |
| Cancer letters. 2003 ; 200 (2) : 149-152. |
| PMID 14568168 |
| |
| Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. |
| Matsuoka S, Huang M, Elledge SJ |
| Science (New York, N.Y.). 1998 ; 282 (5395) : 1893-1897. |
| PMID 9836640 |
| |
| Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors. |
| Miller CW, Ikezoe T, Krug U, Hofmann WK, Tavor S, Vegesna V, Tsukasaki K, Takeuchi S, Koeffler HP |
| Genes, chromosomes & cancer. 2002 ; 33 (1) : 17-21. |
| PMID 11746983 |
| |
| Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility. |
| Schutte M, Seal S, Barfoot R, Meijers-Heijboer H, Wasielewski M, Evans DG, Eccles D, Meijers C, Lohman F, Klijn J, van den Ouweland A, Futreal PA, Nathanson KL, Weber BL, Easton DF, Stratton MR, Breast Cancer Linkage Consortium, Rahman N |
| American journal of human genetics. 2003 ; 72 (4) : 1023-1028. |
| PMID 12610780 |
| |
| CHEK2 1100delC is not a risk factor for male breast cancer population. |
| Syrjäkoski K, Kuukasjä T, Auvinen A, Kallioniemi OP |
| International journal of cancer. Journal international du cancer. 2004 ; 108 (3) : 475-476. |
| PMID 14648717 |
| |
| p53, CHK2, and CHK1 genes in Finnish families with Li-Fraumeni syndrome: further evidence of CHK2 in inherited cancer predisposition. |
| Vahteristo P, Tamminen A, Karvinen P, Eerola H, Eklund C, Aaltonen LA, Blomqvist C, Aittomäki K, Nevanlinna H |
| Cancer research. 2001 ; 61 (15) : 5718-5722. |
| PMID 11479205 |
| |
| Nomenclature |
|---|
| HGNC (Hugo) | CHEK2 16627 |
| LRG (Locus Reference Genomic) | LRG_302 |
| Cards |
|---|
| Atlas | CHEK2ID312 |
| Entrez_Gene (NCBI) | CHEK2 11200 checkpoint kinase 2 |
| Aliases | CDS1; CHK2; HuCds1; LFS2; |
| PP1425; RAD53; hCds1 |
| GeneCards (Weizmann) | CHEK2 |
| Ensembl hg19 (Hinxton) | ENSG00000183765 [Gene_View] |
| Ensembl hg38 (Hinxton) | ENSG00000183765 [Gene_View] chr22:28687743-28741834 [Contig_View] CHEK2 [Vega] |
| ICGC DataPortal | ENSG00000183765 |
| TCGA cBioPortal | CHEK2 |
| AceView (NCBI) | CHEK2 |
| Genatlas (Paris) | CHEK2 |
| WikiGenes | 11200 |
| SOURCE (Princeton) | CHEK2 |
| Genetics Home Reference (NIH) | CHEK2 |
| Genomic and cartography |
|---|
| GoldenPath hg38 (UCSC) | CHEK2 - chr22:28687743-28741834 - 22q12.1 [Description] (hg38-Dec_2013) |
| GoldenPath hg19 (UCSC) | CHEK2 - 22q12.1 [Description] (hg19-Feb_2009) |
| Ensembl | CHEK2 - 22q12.1 [CytoView hg19] CHEK2 - 22q12.1 [CytoView hg38] |
| Mapping of homologs : NCBI | CHEK2 [Mapview hg19] CHEK2 [Mapview hg38] |
| OMIM | 114480 176807 259500 604373 609265 |
| Gene and transcription |
|---|
| Genbank (Entrez) | ############################################################################################################################################################################################################################################################### |
| RefSeq transcript (Entrez) | NM_001005735 NM_001257387 NM_001349956 NM_007194 NM_145862 |
| RefSeq genomic (Entrez) | |
| Consensus coding sequences : CCDS (NCBI) | CHEK2 |
| Cluster EST : Unigene | Hs.505297 [ NCBI ] |
| CGAP (NCI) | Hs.505297 |
| Alternative Splicing Gallery | ENSG00000183765 |
| Gene Expression | CHEK2 [ NCBI-GEO ] CHEK2 [ EBI - ARRAY_EXPRESS ]
CHEK2 [ SEEK ] CHEK2 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | CHEK2 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevisible | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 11200 |
| GTEX Portal (Tissue expression) | CHEK2 |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | O96017 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
| NextProt | O96017 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | O96017 |
| Splice isoforms : SwissVar | O96017 |
| Catalytic activity : Enzyme | 2.7.11.1 [ Enzyme-Expasy ] 2.7.11.12.7.11.1 [ IntEnz-EBI ] 2.7.11.1 [ BRENDA ] 2.7.11.1 [ KEGG ] |
| PhosPhoSitePlus | O96017 |
| Domaine pattern : Prosite (Expaxy) | FHA_DOMAIN (PS50006) PROTEIN_KINASE_DOM (PS50011) PROTEIN_KINASE_ST (PS00108) |
| Domains : Interpro (EBI) | Ca/CaM-dep_Ca-dep_prot_Kinase FHA_dom Kinase-like_dom Prot_kinase_dom Ser/Thr_kinase_AS SMAD_FHA_domain |
| Domain families : Pfam (Sanger) | FHA (PF00498) Pkinase (PF00069) |
| Domain families : Pfam (NCBI) | pfam00498 pfam00069 |
| Domain families : Smart (EMBL) | FHA (SM00240) S_TKc (SM00220) |
| Conserved Domain (NCBI) | CHEK2 |
| DMDM Disease mutations | 11200 |
| Blocks (Seattle) | CHEK2 |
| PDB (SRS) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| PDB (PDBSum) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| PDB (IMB) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| PDB (RSDB) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| Structural Biology KnowledgeBase | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| SCOP (Structural Classification of Proteins) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| CATH (Classification of proteins structures) | 1GXC 2CN5 2CN8 2W0J 2W7X 2WTC 2WTD 2WTI 2WTJ 2XBJ 2XK9 2XM8 2XM9 2YCF 2YCQ 2YCR 2YCS 2YIQ 2YIR 2YIT 3I6U 3I6W 3VA4 4A9R 4A9S 4A9T 4A9U 4BDA 4BDB 4BDC 4BDD 4BDE 4BDF 4BDG 4BDH 4BDI 4BDJ 4BDK |
| Superfamily | O96017 |
| Human Protein Atlas | ENSG00000183765 |
| Peptide Atlas | O96017 |
| HPRD | 05084 |
| IPI | ############################################################################################################################################################################################################################################################### |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | O96017 |
| IntAct (EBI) | O96017 |
| FunCoup | ENSG00000183765 |
| BioGRID | CHEK2 |
| STRING (EMBL) | CHEK2 |
| ZODIAC | CHEK2 |
| Ontologies - Pathways |
|---|
| QuickGO | O96017 |
| Ontology : AmiGO | DNA damage checkpoint G2/M transition of mitotic cell cycle chromosome, telomeric region replicative cell aging positive regulation of protein phosphorylation protein serine/threonine kinase activity protein serine/threonine kinase activity protein binding ATP binding nucleoplasm nucleoplasm Golgi apparatus double-strand break repair transcription, DNA-templated regulation of transcription, DNA-templated protein phosphorylation cellular response to DNA damage stimulus cellular response to DNA damage stimulus cellular response to DNA damage stimulus DNA damage induced protein phosphorylation DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator intrinsic apoptotic signaling pathway in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage PML body peptidyl-serine phosphorylation peptidyl-threonine phosphorylation protein kinase binding ubiquitin protein ligase binding cellular response to drug regulation of protein catabolic process signal transduction in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator identical protein binding protein homodimerization activity regulation of apoptotic process cellular protein catabolic process positive regulation of transcription, DNA-templated protein autophosphorylation metal ion binding protein stabilization cell division negative regulation of cell cycle arrest cellular response to gamma radiation signal transduction involved in intra-S DNA damage checkpoint mitotic spindle assembly replicative senescence regulation of signal transduction by p53 class mediator response to glycoside cellular response to bisphenol A negative regulation of DNA damage checkpoint positive regulation of anoikis |
| Ontology : EGO-EBI | DNA damage checkpoint G2/M transition of mitotic cell cycle chromosome, telomeric region replicative cell aging positive regulation of protein phosphorylation protein serine/threonine kinase activity protein serine/threonine kinase activity protein binding ATP binding nucleoplasm nucleoplasm Golgi apparatus double-strand break repair transcription, DNA-templated regulation of transcription, DNA-templated protein phosphorylation cellular response to DNA damage stimulus cellular response to DNA damage stimulus cellular response to DNA damage stimulus DNA damage induced protein phosphorylation DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator intrinsic apoptotic signaling pathway in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage PML body peptidyl-serine phosphorylation peptidyl-threonine phosphorylation protein kinase binding ubiquitin protein ligase binding cellular response to drug regulation of protein catabolic process signal transduction in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator identical protein binding protein homodimerization activity regulation of apoptotic process cellular protein catabolic process positive regulation of transcription, DNA-templated protein autophosphorylation metal ion binding protein stabilization cell division negative regulation of cell cycle arrest cellular response to gamma radiation signal transduction involved in intra-S DNA damage checkpoint mitotic spindle assembly replicative senescence regulation of signal transduction by p53 class mediator response to glycoside cellular response to bisphenol A negative regulation of DNA damage checkpoint positive regulation of anoikis |
| Pathways : BIOCARTA | Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility [Genes] Cell Cycle: G2/M Checkpoint [Genes] ATM Signaling Pathway [Genes] Regulation of cell cycle progression by Plk3 [Genes] |
| Pathways : KEGG | Cell cycle p53 signaling pathway HTLV-I infection |
| REACTOME | O96017 [protein] |
| REACTOME Pathways | R-HSA-69601 [pathway] |
| NDEx Network | CHEK2 |
| Atlas of Cancer Signalling Network | CHEK2 |
| Wikipedia pathways | CHEK2 |
| Orthology - Evolution |
|---|
| OrthoDB | 11200 |
| GeneTree (enSembl) | ENSG00000183765 |
| Phylogenetic Trees/Animal Genes : TreeFam | CHEK2 |
| HOVERGEN | O96017 |
| HOGENOM | O96017 |
| Homologs : HomoloGene | CHEK2 |
| Homology/Alignments : Family Browser (UCSC) | CHEK2 |
| Gene fusions - Rearrangements |
|---|
| Fusion : Mitelman | AHI1/CHEK2 [6q23.3/22q12.1] [t(6;22)(q23;q12)] |
| Fusion : Mitelman | CHEK2/PARVB [22q12.1/22q13.31] [inv(22)(q12q13)] |
| Fusion : Mitelman | PPP2R2A/CHEK2 [8p21.2/22q12.1] [t(8;22)(p21;q12)] |
| Fusion: TCGA | AHI1 6q23.3 CHEK2 22q12.1 BRCA |
| Fusion : TICdb | PPP2R2A [8p21.2] - CHEK2 [22q12.1] |
| Polymorphisms : SNP and Copy number variants |
|---|
| NCBI Variation Viewer | CHEK2 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | CHEK2 |
| dbVar | CHEK2 |
| ClinVar | CHEK2 |
| 1000_Genomes | CHEK2 |
| Exome Variant Server | CHEK2 |
| ExAC (Exome Aggregation Consortium) | CHEK2 (select the gene name) |
| Genetic variants : HAPMAP | 11200 |
| Genomic Variants (DGV) | CHEK2 [DGVbeta] |
| DECIPHER | CHEK2 [patients] [syndromes] [variants] [genes] |
| CONAN: Copy Number Analysis | CHEK2 |
| Mutations |
|---|
| ICGC Data Portal | CHEK2 |
| TCGA Data Portal | CHEK2 |
| Broad Tumor Portal | CHEK2 |
| OASIS Portal | CHEK2 [ Somatic mutations - Copy number] |
| Cancer Gene: Census | CHEK2 |
| Somatic Mutations in Cancer : COSMIC | CHEK2 [overview] [genome browser] [tissue] [distribution] |
| Mutations and Diseases : HGMD | CHEK2 |
| intOGen Portal | CHEK2 |
| LOVD (Leiden Open Variation Database) | Whole genome datasets |
| LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
| LOVD (Leiden Open Variation Database) | Zhejiang University Center for Genetic and Genomic Medicine (ZJU-CGGM) |
| BioMuta | search CHEK2 |
| DgiDB (Drug Gene Interaction Database) | CHEK2 |
| DoCM (Curated mutations) | CHEK2 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | CHEK2 (select a term) |
| intoGen | CHEK2 |
| NCG5 (London) | CHEK2 |
| Cancer3D | CHEK2(select the gene name) |
| Impact of mutations | [PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
|---|
| OMIM | 114480 176807 259500 604373 609265 |
| Orphanet | 196 903 3384 3758 |
| Medgen | CHEK2 |
| Genetic Testing Registry | CHEK2
|
| NextProt | O96017 [Medical] |
| TSGene | 11200 |
| GENETests | CHEK2 |
| Target Validation | CHEK2 |
| Huge Navigator |
CHEK2 [HugePedia] |
| snp3D : Map Gene to Disease | 11200 |
| BioCentury BCIQ | CHEK2 |
| ClinGen | CHEK2 |
| Clinical trials, drugs, therapy |
|---|
| Chemical/Protein Interactions : CTD | 11200 |
| Chemical/Pharm GKB Gene | PA404 |
| Clinical trial | CHEK2 |
| Miscellaneous |
|---|
| canSAR (ICR) | CHEK2 (select the gene name) |
| Probes |
|---|
| Litterature |
|---|
| PubMed | 499 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | CHEK2 |
| EVEX | CHEK2 |
| GoPubMed | CHEK2 |
| iHOP | CHEK2 |
