CHEK2
entrez
11200
canonical
uniprot
O96017
canonical
ensembl
ENSG00000183765
resolver
ensp
ENSP00000329012
resolver
ensp
ENSP00000372023
resolver
ensp
ENSP00000384835
resolver
ensp
ENSP00000385747
resolver
ensp
ENSP00000390244
resolver
ensp
ENSP00000483777
resolver
ensp
ENSP00000598746
resolver
ensp
ENSP00000735025
resolver
enst
ENST00000402731
resolver
genesymbol
CHEK2
resolver
genesymbol_syn
CDS1
resolver
genesymbol_syn
CHK2
resolver
genesymbol_syn
RAD53
resolver
hgnc
HGNC:16627
resolver
uniprot
A0A7P0MUT5
resolver
uniprot
A8K3Y9
resolver
uniprot
B7ZBF3
resolver
uniprot
B7ZBF4
resolver
uniprot
B7ZBF5
resolver
uniprot
Q6QA03
resolver
uniprot
Q6QA04
resolver
uniprot
Q6QA05
resolver
uniprot
Q6QA06
resolver
uniprot
Q6QA07
resolver
uniprot
Q6QA08
resolver
uniprot
Q6QA10
resolver
uniprot
Q6QA11
resolver
uniprot
Q6QA12
resolver
uniprot
Q6QA13
resolver
uniprot
Q9HBS5
resolver
uniprot
Q9HCQ8
resolver
uniprot
Q9UGF0
resolver
uniprot
Q9UGF1
resolver
uniprot_entry
A0A7P0MUT5_HUMAN
resolver
uniprot_entry
CHK2_HUMAN
resolver
uniprot_sec
A8K3Y9
resolver
uniprot_sec
B7ZBF3
resolver
uniprot_sec
B7ZBF4
resolver
uniprot_sec
B7ZBF5
resolver
uniprot_sec
Q6QA03
resolver
uniprot_sec
Q6QA04
resolver
uniprot_sec
Q6QA05
resolver
uniprot_sec
Q6QA06
resolver
uniprot_sec
Q6QA07
resolver
uniprot_sec
Q6QA08
resolver
uniprot_sec
Q6QA10
resolver
uniprot_sec
Q6QA11
resolver
uniprot_sec
Q6QA12
resolver
uniprot_sec
Q6QA13
resolver
uniprot_sec
Q9HBS5
resolver
uniprot_sec
Q9HCQ8
resolver
uniprot_sec
Q9UGF0
resolver
uniprot_sec
Q9UGF1
resolver
activity_regulation
ACTIVITY REGULATION: Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68. {ECO:0000269|PubMed:15342622}.
uniprot
proteins
amino_acid_sequence
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL
uniprot
proteins
disease_involvement
DISEASE: Tumor predisposition syndrome 4 (TPDS4) [MIM:609265]: A disorder characterized by an increased risk for developing various types of benign and/or malignant neoplasms that arise at an accelerated rate and in different organs. {ECO:0000269|PubMed:11719428}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:12533788}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones. {ECO:0000269|PubMed:11746983}. Note=The gene represented in this entry may be involved in disease pathogenesis.; DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:12094328, ECO:0000269|PubMed:12454775, ECO:0000269|PubMed:12610780, ECO:0000269|PubMed:15818573, ECO:0000269|PubMed:21618645, ECO:0000269|PubMed:25619829}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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] (PubMed:37943659). 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). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659). {ECO:0000250|UniProtKB:Q9Z265, ECO:0000269|PubMed:10097108, ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12717439, ECO:0000269|PubMed:12810724, ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:17101782, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:20364141, ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25619829, ECO:0000269|PubMed:37943659, ECO:0000269|PubMed:9836640, ECO:0000269|PubMed:9889122}.; FUNCTION: (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity. {ECO:0000269|PubMed:32001251}.
uniprot
proteins
mass_dalton
60915
uniprot
proteins
mutagenesis
MUTAGEN 68; /note="T->A: Loss of activation and phosphorylation."; /evidence="ECO:0000269|PubMed:11901158, ECO:0000269|PubMed:15342622"; MUTAGEN 73; /note="S->A: Impaired activation, phosphorylation by ATM and G2/M transition checkpoint."; /evidence="ECO:0000269|PubMed:16481012"; MUTAGEN 347; /note="D->A: Loss of kinase activity and of the ability to phosphorylate CDC25A."; /evidence="ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:9836640"; MUTAGEN 368; /note="D->N: Loss of autophosphorylation activity."; /evidence="ECO:0000269|PubMed:15342622"; MUTAGEN 379; /note="S->A: Abrogates autophosphorylation at Ser-379 and prevents ubiquitination."; /evidence="ECO:0000269|PubMed:18644861"; MUTAGEN 383; /note="T->A: Loss of phosphorylation in response to ionizing radiation."; /evidence="ECO:0000269|PubMed:11390408"; MUTAGEN 387; /note="T->A: Loss of phosphorylation in response to ionizing radiation."; /evidence="ECO:0000269|PubMed:11390408"; MUTAGEN 456; /note="S->A: Increased ubiquitination and degradation by the proteasome."; /evidence="ECO:0000269|PubMed:17715138
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylated at Ser-73 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-68 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-68 induces homodimerization. Autophosphorylates at Thr-383 and Thr-387 in the T-loop/activation segment upon dimerization to become fully active and phosphorylate its substrates like for instance CDC25C. DNA damage-induced autophosphorylation at Ser-379 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-456 also regulates ubiquitination. Phosphorylated by PLK4. {ECO:0000269|PubMed:10973490, ECO:0000269|PubMed:11390408, ECO:0000269|PubMed:15342622, ECO:0000269|PubMed:16311512, ECO:0000269|PubMed:16481012, ECO:0000269|PubMed:17715138, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:19164942}.; PTM: Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
CHK2 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10097108
uniprot
proteins
pubmed
10591208
uniprot
proteins
pubmed
10617473
uniprot
proteins
pubmed
10724175
uniprot
proteins
pubmed
10973490
uniprot
proteins
pubmed
11298456
uniprot
proteins
pubmed
11390408
uniprot
proteins
pubmed
11461078
uniprot
proteins
pubmed
11719428
uniprot
proteins
pubmed
11746983
uniprot
proteins
pubmed
11901158
uniprot
proteins
pubmed
12049740
uniprot
proteins
pubmed
12052256
uniprot
proteins
pubmed
12094328
uniprot
proteins
pubmed
12364621
uniprot
proteins
pubmed
12402044
uniprot
proteins
pubmed
12454775
uniprot
proteins
pubmed
12533788
uniprot
proteins
pubmed
12607004
uniprot
proteins
pubmed
12610780
uniprot
proteins
pubmed
12717439
uniprot
proteins
pubmed
12810724
uniprot
proteins
pubmed
14612911
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15087378
uniprot
proteins
pubmed
15095295
uniprot
proteins
pubmed
15239132
uniprot
proteins
pubmed
15279791
uniprot
proteins
pubmed
15342622
uniprot
proteins
pubmed
15361853
uniprot
proteins
pubmed
15461802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15492928
uniprot
proteins
pubmed
15498874
uniprot
proteins
pubmed
15535844
uniprot
proteins
pubmed
15649950
uniprot
proteins
pubmed
15810020
uniprot
proteins
pubmed
15818573
uniprot
proteins
pubmed
16163388
uniprot
proteins
pubmed
16311512
uniprot
proteins
pubmed
16481012
uniprot
proteins
pubmed
16794575
uniprot
proteins
pubmed
17101782
uniprot
proteins
pubmed
17380128
uniprot
proteins
pubmed
17715138
uniprot
proteins
pubmed
18317453
uniprot
proteins
pubmed
18644861
uniprot
proteins
pubmed
18728393
uniprot
proteins
pubmed
19164942
uniprot
proteins
pubmed
19782031
uniprot
proteins
pubmed
20364141
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21618645
uniprot
proteins
pubmed
22266820
uniprot
proteins
pubmed
24825908
uniprot
proteins
pubmed
25361978
uniprot
proteins
pubmed
25619829
uniprot
proteins
pubmed
32001251
uniprot
proteins
pubmed
37943659
uniprot
proteins
pubmed
9836640
uniprot
proteins
pubmed
9889122
uniprot
proteins
sequence_length
543
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. Note=Isoform 10 is present throughout the cell.; SUBCELLULAR LOCATION: [Isoform 4]: Nucleus.; SUBCELLULAR LOCATION: [Isoform 7]: Nucleus.; SUBCELLULAR LOCATION: [Isoform 9]: Nucleus.; SUBCELLULAR LOCATION: [Isoform 12]: Nucleus.; SUBCELLULAR LOCATION: Nucleus, PML body. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53.
uniprot
proteins