| 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. |
| Nomenclature | | HGNC (Hugo) | CHEK2 16627 |
| Entrez_Gene (NCBI) | CHEK2 11200 checkpoint kinase 2 |
| Cards | | Atlas | CHEK2ID312 |
| GeneCards (Weizmann) | CHEK2 |
| Ensembl (Hinxton) | ENSG00000183765 [Gene_View] chr22:29083731-29137822 [Contig_View] CHEK2 [Vega] |
| AceView (NCBI) | CHEK2 |
| Genatlas (Paris) | CHEK2 |
| SOURCE (Stanford) | NM_001005735 NM_001257387 NM_007194 NM_145862 |
| Genomic and cartography | | GoldenPath (UCSC) | CHEK2 - 22q12.1 chr22:29083731-29137822 - 22q12.1 [Description] (hg19-Feb_2009) |
| Ensembl | CHEK2 - 22q12.1 [CytoView] |
| Mapping of homologs : NCBI | CHEK2 [Mapview] |
| OMIM | 114480 176807 259500 604373 609265 |
| Gene and transcription |
| Genbank (Entrez) | AB040105 AF086904 AF096279 AF174135 AF217975 |
| RefSeq transcript (SRS) | NM_001005735 NM_001257387 NM_007194 NM_145862 |
| RefSeq transcript (Entrez) | NM_001005735 NM_001257387 NM_007194 NM_145862 |
| RefSeq genomic (SRS) | AC_000154 NC_000022 NC_018933 NG_008150 NT_011520 NW_001838745 NW_004078112 |
| RefSeq genomic (Entrez) | AC_000154 NC_000022 NC_018933 NG_008150 NT_011520 NW_001838745 NW_004078112 |
| Consensus coding sequences : CCDS (NCBI) | CHEK2 |
| Cluster EST : Unigene | Hs.505297 [ SRS ] Hs.505297 [ NCBI ] |
| CGAP (NCI) | Hs.505297 |
| Alternative Splicing : Fast-db (Paris) | GSHG0020283 |
| Alternative Splicing Gallery | ENSG00000183765 |
| Gene Expression | CHEK2 [ NCBI-GEO ] CHEK2 [ EBI - ARRAY_EXPRESS ] |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | O96017 (SRS) O96017 (Uniprot) |
| NextProt | O96017 |
| With graphics : InterPro | O96017 |
| Splice isoforms : SwissVar | O96017(Swissvar) |
| Domaine pattern : Prosite (SRS) | FHA_DOMAIN (PS50006) PROTEIN_KINASE_ATP (PS00107) PROTEIN_KINASE_DOM (PS50011) PROTEIN_KINASE_ST (PS00108) |
| Domaine pattern : Prosite (Expaxy) | FHA_DOMAIN (PS50006) PROTEIN_KINASE_ATP (PS00107) PROTEIN_KINASE_DOM (PS50011) PROTEIN_KINASE_ST (PS00108) |
| Domains : Interpro (SRS) | FHA_dom Kinase-like_dom Prot_kinase_cat_dom Ser/Thr_dual-sp_kinase_dom Ser/Thr_kinase_AS SMAD_FHA_domain |
| Domains : Interpro (EBI) | FHA_dom Kinase-like_dom Prot_kinase_cat_dom Ser/Thr_dual-sp_kinase_dom Ser/Thr_kinase_AS SMAD_FHA_domain |
| Related proteins : CluSTr | O96017 |
| Domain families : Pfam (SRS) | FHA (PF00498) Pkinase (PF00069) |
| Domain families : Pfam (Sanger) | FHA (PF00498) Pkinase (PF00069) |
| Domain families : Pfam (NCBI) | pfam00498 pfam00069 |
| Domain families : Smart (EMBL) | FHA (SM00240) S_TKc (SM00220) |
| DMDM | 11200 |
| Blocks (Seattle) | O96017 |
| 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 |
| 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 |
| 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 |
| 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 |
| Human Protein Atlas | ENSG00000183765 |
| HPRD | 05084 |
| IPI | IPI00014072 IPI00607851 IPI00423157 IPI00030746 IPI00607753 IPI00607709 IPI00607739 IPI00423149 IPI00607680 IPI00607619 IPI00423156 IPI00423146 IPI00953558 IPI00878704 IPI00982188 IPI00871524 IPI00877689 IPI00878496 IPI00877980 IPI00878892 IPI00878345 IPI00879227 IPI00879419 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | O96017 |
| IntAct (EBI) | O96017 |
| FunCoup | ENSG00000183765 |
| REACTOME | CHEK2 |
| Protein Interaction Database | 11200 |
| BioGRID | CHEK2 |
| InParanoid | O96017 |
| Interologous Interaction database | O96017 |
| IntegromeDB | CHEK2 |
| Polymorphism : SNP, mutations, diseases | | SNP Single Nucleotide Polymorphism (NCBI) | CHEK2 |
| SNP (GeneSNP Utah) | CHEK2 |
| SNP : HGBase | CHEK2 |
| Genetic variants : HAPMAP | CHEK2 |
| Cancer Gene: Census | CHEK2 |
| Somatic Mutations in Cancer : COSMIC | CHEK2 |
| CONAN: Copy Number Analysis | CHEK2 |
| Translocation Breakpoints in Cancer : TICdb | CHEK2 |
| Mutations and Diseases : HGMD | CHEK2 |
| OMIM | 114480 176807 259500 604373 609265 |
| GENETests | 114480 176807 259500 604373 609265 |
| Disease Genetic Association | CHEK2 |
| Huge Navigator |
CHEK2 [HugePedia] CHEK2 [HugeCancerGEM] |
| Genomic Variants | CHEK2 CHEK2 [DGVbeta] |
| snp3D : Map Gene to Disease | 11200 |
| General knowledge |
|---|
| Homologs : HomoloGene | CHEK2 |
| Homology/Alignments : Family Browser (UCSC) | CHEK2 |
| Phylogenetic Trees/Animal Genes : TreeFam | CHEK2 |
| Catalytic activity : Enzyme | 2.7.11.1 [ Enzyme-Expasy ] 2.7.11.1 [ Enzyme-SRS ] 2.7.11.1 [ IntEnz-EBI ] 2.7.11.1 [ BRENDA ] 2.7.11.1 [ KEGG ] |
| Chemical/Protein Interactions : CTD | 11200 |
| Chemical/Pharm GKB Gene | PA404 |
| Clinical trial | CHEK2 |
| Cancer Resource (Charite) | ENSG00000183765 |
| Ontology : AmiGO | cell cycle checkpoint DNA damage checkpoint G2/M transition of mitotic cell cycle chromosome, telomeric region protein serine/threonine kinase activity protein serine/threonine kinase activity protein binding ATP binding nucleoplasm double-strand break repair transcription, DNA-dependent regulation of transcription, DNA-dependent response to DNA damage stimulus response to DNA damage stimulus DNA damage induced protein phosphorylation intrinsic apoptotic signaling pathway in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage response to gamma radiation PML body protein kinase binding ubiquitin protein ligase binding regulation of protein catabolic process signal transduction in response to DNA damage protein homodimerization activity cellular protein catabolic process positive regulation of transcription, DNA-dependent protein autophosphorylation metal ion binding cell division signal transduction involved in intra-S DNA damage checkpoint spindle assembly involved in mitosis replicative senescence |
| Ontology : EGO-EBI | cell cycle checkpoint DNA damage checkpoint G2/M transition of mitotic cell cycle chromosome, telomeric region protein serine/threonine kinase activity protein serine/threonine kinase activity protein binding ATP binding nucleoplasm double-strand break repair transcription, DNA-dependent regulation of transcription, DNA-dependent response to DNA damage stimulus response to DNA damage stimulus DNA damage induced protein phosphorylation intrinsic apoptotic signaling pathway in response to DNA damage intrinsic apoptotic signaling pathway in response to DNA damage response to gamma radiation PML body protein kinase binding ubiquitin protein ligase binding regulation of protein catabolic process signal transduction in response to DNA damage protein homodimerization activity cellular protein catabolic process positive regulation of transcription, DNA-dependent protein autophosphorylation metal ion binding cell division signal transduction involved in intra-S DNA damage checkpoint spindle assembly involved in mitosis replicative senescence |
| 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 |
| Other databases | | Probes |
|---|
| Litterature | | PubMed | 393 Pubmed reference(s) in Entrez |
| PubGene | CHEK2 |
| iHOP | CHEK2 |
| 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 |
| |
| 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 |
| |
| 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, Aittomˆ§ki K, Nevanlinna H |
| Cancer research. 2001 ; 61 (15) : 5718-5722. |
| PMID 11479205 |
| |
| 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 |
| |
| 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 |
| |
| 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. |
| Syrjˆ§koski K, Kuukasjˆ§rvi T, Auvinen A, Kallioniemi OP |
| International journal of cancer. Journal international du cancer. 2004 ; 108 (3) : 475-476. |
| PMID 14648717 |
| |