Gene: CHEK2 - Homo sapiens
Last modified: Dec 09, 2014. Release 1 • Page created: May 19, 2024
Summary
Gene Symbol | : | CHEK2 | ||||||||||||||||
NCBI Gene ID | : | 11200 | ||||||||||||||||
Species | : | Homo sapiens | ||||||||||||||||
Gene Synonyms | : | bA444G7 | CDS1 | cds1 homolog | CDS1, S. POMBE, HOMOLOG OF | checkpoint kinase 2 | CHECKPOINT KINASE 2, S. POMBE, HOMOLOG OF | checkpoint-like protein CHK2 | CHEK2 | CHK2 | CHK2 (checkpoint, S.pombe) homolog | CHK2 checkpoint homolog | CHK2 checkpoint homolog (S. pombe) | hCds1 | HuCds1 | LFS2 | PP1425 | RAD53 | RAD53, S. CEREVISIAE, HOMOLOG OF | RP11-436C9.1 | serine/threonine-protein kinase Chk2 Source: GPSDB |
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Gene Homologs | : | AgaP_AGAP009784 (Anopheles gambiae) | CELE_T08D2.7 (Caenorhabditis elegans) | CHEK2 (Bos taurus) | CHEK2 (Canis lupus familiaris) | chek2 (Danio rerio) | CHEK2 (Gallus gallus) | CHEK2 (Homo sapiens) | CHEK2 (Macaca mulatta) | Chek2 (Mus musculus) | CHEK2 (Pan troglodytes) | Chek2 (Rattus norvegicus) | chk-2 (Caenorhabditis elegans) | lok (Drosophila melanogaster) | MGG_01596 (Magnaporthe oryzae) | NCU02814 (Neurospora crassa) | ||||||||||||||||
Ageing Relevance Analysis | : |
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Ageing Factor Stable ID | : | AF_004801 | ||||||||||||||||
Download | : | XML |
Protein Information
Protein Name | Species | UniProt Accession Number | UniProt Entry Name | Protein Function | Sequence |
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Serine/threonine-protein kinase Chk2 | Homo sapiens | O96017 (UniProtKB/Swiss-Prot) | CHK2_HUMAN (UniProtKB/Swiss-Prot) | Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. | View |
Serine/threonine-protein kinase Chk2 | Homo sapiens | Q9HBS5 (UniProtKB/TrEMBL) | Q9HBS5_HUMAN (UniProtKB/TrEMBL) | View |
Observations
Ageing Phenotype
Data Type 1
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
# | Observation Stable ID | Species | Gene | Other Ageing Factor | Description | PubMed | Source | ||||
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1 | OB_009838 | Homo sapiens |
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CHEK2 is a cell cycle checkpoint regulator and putative tumor suppressor. It blocks cell cycle progression in response to DNA damage. Loss or haploid loss of CHEK2 enables mice lacking BRCA1 to avoid embryonic lethality and display signs of premature ageing at about 18 months of age and develop multiple tumours later in life. Absence of CHEK2 may have attenuated TP53-dependent apoptosis and growth arrest [1838]. In humans, mutations in CHEK2 have been shown to confer susceptibility to multiple tumours and have been associated with Li-Fraumeni syndrome [1859]. | GenAge |
Data Type 2
no ageing phenotype observation—data type 2 available
Homology Analysis
Ageing Relevance:
- yes (Exp. Analysis)
- yes, but no ageing factor assigned (Exp. Analysis)
- no (Exp. Analysis)
- putative (Comp. Analysis)
Legend:
- #EGHG:
- Number of Experimentally Confirmed Ageing-related Genes In Homology Group
# | Observation Stable ID | Homology Group Genes | #EGHG | Description | Source | Homology Source |
---|---|---|---|---|---|---|
1 | OB_008257 | 2 | The HomoloGene homology group 38289 contains 2 genes with experimental evidence for ageing relevance (CHEK2 - Homo sapiens | Chek2 - Mus musculus) and 13 other genes. | AgeFactDB Homology Analysis | HomoloGene homology group 38289 |
Sequences
CHK2_HUMAN | O96017 | Serine/threonine-protein kinase Chk2 (Homo sapiens) from UniProtKB/Swiss-Prot Length: 543 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380 390 400 410 420 430 440 450 460 470 480 490 500 510 520 530 540 CHK2_HUMAN 1 MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL 543
Q9HBS5_HUMAN | Q9HBS5 | Serine/threonine-protein kinase Chk2 (Homo sapiens) from UniProtKB/TrEMBL Length: 322 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 Q9HBS5_HUMAN 1 MSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL 322
References
MeSH Terms: Only a subset of the Medical Subject Headings terms is shown: the Major Topics MeSH terms. They describe one of the main topics discussed in the article denoted by an asterisk on the MeSH term or MeSH/Subheading combination on the PubMed page. MeSH terms that belong to the Ageing MeSH are highlighted in green.
- Chaturvedi P, Eng WK, Zhu Y, Mattern MR, Mishra R, Hurle MR, Zhang X, Annan RS, Lu Q, Faucette LF, Scott GF, Li X, Carr SA, Johnson RK, Winkler JD, Zhou BB:
Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.
Oncogene. 1999; 18: 4047-54.
PubMed (ID: 10435585), doi:10.1038/sj.onc.1202925
MeSH Terms: DNA Damage; DNA Repair/genetics; Protein Kinases; Protein-Serine-Threonine Kinases/physiology; Proteins/physiology; ras-GRF1 - Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DC, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA:
Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.
Science. 1999; 286: 2528-31.
PubMed (ID: 10617473)
MeSH Terms: G2 Phase; Genes, Tumor Suppressor; Germ-Line Mutation; Li-Fraumeni Syndrome/genetics; Protein-Serine-Threonine Kinases/genetics - Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ, Mak TW:
DNA damage-induced activation of p53 by the checkpoint kinase Chk2.
Science. 2000; 287: 1824-7.
PubMed (ID: 10710310)
MeSH Terms: DNA Damage; Interphase; Nuclear Proteins; Protein Kinases; Protein-Serine-Threonine Kinases/metabolism; Tumor Suppressor Protein p53/metabolism - Cybulski C, Górski B, Huzarski T, Masojć B, Mierzejewski M, Debniak T, Teodorczyk U, Byrski T, Gronwald J, Matyjasik J, Zlowocka E, Lenner M, Grabowska E, Nej K, Castaneda J, Medrek K, Szymańska A, Szymańska J, Kurzawski G, Suchy J, Oszurek O, Witek A, Narod SA, Lubiński J:
CHEK2 is a multiorgan cancer susceptibility gene.
Am J Hum Genet. 2004; 75: 1131-5.
PubMed (ID: 15492928), PubMed Central (ID: PMC1182149), doi:10.1086/426403
MeSH Terms: Genetic Predisposition to Disease/genetics; Genetic Variation; Neoplasms/genetics; Protein-Serine-Threonine Kinases/genetics - Nannenga B, Lu X, Dumble M, Van Maanen M, Nguyen TA, Sutton R, Kumar TR, Donehower LA:
Augmented cancer resistance and DNA damage response phenotypes in PPM1D null mice.
Mol Carcinog. 2006; 45: 594-604.
PubMed (ID: 16652371), doi:10.1002/mc.20195
MeSH Terms: Cell Transformation, Neoplastic/genetics; DNA Damage/genetics; Longevity/genetics; Neoplasm Proteins/genetics; Phosphoprotein Phosphatases/genetics - Cao L, Kim S, Xiao C, Wang RH, Coumoul X, Wang X, Li WM, Xu XL, De Soto JA, Takai H, Mai S, Elledge SJ, Motoyama N, Deng CX:
ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency.
EMBO J. 2006; 25: 2167-77.
PubMed (ID: 16675955), PubMed Central (ID: PMC1462967), doi:10.1038/sj.emboj.7601115
MeSH Terms: BRCA1 Protein/metabolism; Cell Cycle Proteins/metabolism; DNA-Binding Proteins/metabolism; Homeostasis; Neoplasms/metabolism; Protein-Serine-Threonine Kinases/metabolism; Tumor Suppressor Protein p53/metabolism; Tumor Suppressor Proteins/metabolism - Buscemi G, Zannini L, Fontanella E, Lecis D, Lisanti S, Delia D:
The shelterin protein TRF2 inhibits Chk2 activity at telomeres in the absence of DNA damage.
Curr Biol. 2009; 19: 874-9.
PubMed (ID: 19375317), doi:10.1016/j.cub.2009.03.064
MeSH Terms: DNA Damage; Protein-Serine-Threonine Kinases/metabolism; Telomere/metabolism; Telomeric Repeat Binding Protein 2/metabolism - Liu J, Cao L, Chen J, Song S, Lee IH, Quijano C, Liu H, Keyvanfar K, Chen H, Cao LY, Ahn BH, Kumar NG, Rovira II, Xu XL, van Lohuizen M, Motoyama N, Deng CX, Finkel T:
Bmi1 regulates mitochondrial function and the DNA damage response pathway.
Nature. 2009; 459: 387-92.
PubMed (ID: 19404261), doi:10.1038/nature08040
MeSH Terms: DNA Damage/genetics; Mitochondria/metabolism; Nuclear Proteins/metabolism; Proto-Oncogene Proteins/metabolism; Repressor Proteins/metabolism
Sources
Ageing-related Data Sources
- AgeFactDB Homology Analysis
- GenAge
Additional Data Sources
- AgeFactDB Pipeline
- GPSDB
- HomoloGene
- NCBI Taxonomy
- PubMed
- UniProtKB/Swiss-Prot
- UniProtKB/TrEMBL