Chek2
entrez
50883
canonical
uniprot
Q9Z265
canonical
ensembl
ENSMUSG00000029521
resolver
ensp
ENSMUSP00000066679
resolver
enst
ENSMUST00000066160
resolver
genesymbol
Chek2
resolver
genesymbol_syn
Chk2
resolver
genesymbol_syn
Rad53
resolver
uniprot
Q543W6
resolver
uniprot_entry
CHK2_MOUSE
resolver
uniprot_entry
Q543W6_MOUSE
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 (By similarity). {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MKSHHQSHSSTSSKAHDSASCSQSQGGFSQPQGTPSQLHELSQYQGSSSSSTGTVPSSSQSSHSSSGTLSSLETVSTQELCSIPEDQEPEEPGPAPWARLWALQDGFSNLDCVNDNYWFGRDKSCEYCFDGPLLRRTDKYRTYSKKHFRIFREMGPKNCYIVYIEDHSGNGTFVNTELIGKGKRCPLSNNSEIALSLCRNKVFVFFDLTVDDQSVYPKELRDEYIMSKTLGSGACGEVKMAFERKTCQKVAIKIISKRRFALGSSREADTAPSVETEIEILKKLNHPCIIKIKDVFDAEDYYIVLELMEGGELFDRVVGNKRLKEATCKLYFYQMLVAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGQSKILGETSLMRTLCGTPTYLAPEVLVSNGTAGYSRAVDCWSLGVILFICLSGYPPFSEHKTQVSLKDQITSGKYNFIPEVWTDVSEEALDLVKKLLVVDPKARLTTEEALNHPWLQDEYMKKKFQDLLVQEKNSVTLPVAPAQTSSQKRPLELEVEGMPSTKRLSVCGAVL
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]. 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 (By similarity). Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-56' leading to positive regulation of the autophagosme assembly (By similarity). {ECO:0000250|UniProtKB:O96017, ECO:0000269|PubMed:12192050, ECO:0000269|PubMed:25619829}.
uniprot
proteins
mass_dalton
61088
uniprot
proteins
mutagenesis
MUTAGEN 394; /note="Y->C: Does not inhibit cell survival upon DNA damage. Not phosphorylates p53/TP53."; /evidence="ECO:0000269|PubMed:25619829
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylated at Ser-82 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-77 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-77 induces homodimerization. Autophosphorylates at Thr-387 and Thr-391 in the T-loop/activation segment upon dimerization to become fully active. DNA damage-induced autophosphorylation at Ser-383 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-460 also regulates ubiquitination. Phosphorylated by PLK4 (By similarity). {ECO:0000250}.; PTM: Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination (By similarity). {ECO:0000250}.
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
12192050
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
25619829
uniprot
proteins
pubmed
9836640
uniprot
proteins
sequence_length
546
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250}. Nucleus, nucleoplasm. Note=Recruited into PML bodies together with TP53. {ECO:0000250}.
uniprot
proteins