General Information of the Protein
Protein ID
PT00851
Protein Name
Serine/threonine-protein kinase Chk2
Secondarily
Protein Name
CHK2 checkpoint homolog
Cds1 homolog
Checkpoint kinase 2
Gene Name
CHEK2
Secondarily
Gene Name
CDS1
CHK2
RAD53
Sequence
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
CAMK protein kinase group
>
CAMK protein kinase RAD53 family
Function
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. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978).
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Uniprot ID
Primary ID:
O96017

Secondarily ID:
A8K3Y9
B7ZBF3
B7ZBF4
B7ZBF5
Q6QA03
Q6QA04
Q6QA05
Q6QA06
Q6QA07
Q6QA08
Q6QA10
Q6QA11
Q6QA12
Q6QA13
Q9HBS5
Q9HCQ8
Q9UGF0
Q9UGF1
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Ensembl ID
ENSG00000183765
HGNC ID
HGNC:16627
Subcellular Location
Nucleus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000013 , Sf9
Compound ID Compound Name Compound Formula
CP0382724
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide
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C49H54BF2N7O7
 1
1
Kd = 147 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0004106
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.1^{2,6}.0^{7,28}.0^{8,13}.0^{15,19}.0^{20,27}.0^{21,26}]nonacosa-8(13),9,11,14(28),15(19),20(27),21(26),22,24-nonaen-16-one
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C28H26N4O3
 8
1 IC50 = 3.34 nM
2 IC50 = 4.86 nM
3 IC50 = 5.72 nM
4 IC50 = 6.7 nM
5 IC50 = 9.21 nM
6 IC50 = 27 nM
7 IC50 = 27000 nM
8 Kd = 74 nM
CP0128439
2-Amino-N-(2-aminoethyl)-5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)nicotinamide
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C14H16N4O3S
 1
1 IC50 = 28 nM
CP0069794
4-(2-Amino-5-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)pyridin-3-yl)benzamide
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C18H15N3O3S
 1
1 IC50 = 92 nM
CP0128477
4-(2-Amino-5-(benzo[d][1,3]dioxol-4-yl)pyridin-3-yl)benzamide
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C19H15N3O3
 1
1 IC50 = 210 nM
Clinical Information about the Protein
Target 1 ( Serine/threonine-protein kinase Chk2 (RAD53) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Clinical Trial Drug(s) 1 Clinical Trial Drug  1
1 E7850 Phase 2
Solid tumour/cancer
Investigative Drug(s) 1 Investigative Drug  1
1 CCT-241533 Investigative
Solid tumour/cancer