Serine/threonine-protein kinase Chk2

Details

Name
Serine/threonine-protein kinase Chk2
Synonyms
  • 2.7.11.1
  • CDS1
  • Cds1 homolog
  • Checkpoint kinase 2
  • CHK2
  • CHK2 checkpoint homolog
  • hCds1
  • Hucds1
  • RAD53
Gene Name
CHEK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006597|Serine/threonine-protein kinase Chk2
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTL
SSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKS
CEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKR
RPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFER
KTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIV
LELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEE
DCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFIC
LSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEA
LRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCA
AVL
Number of residues
543
Molecular Weight
60914.26
Theoretical pI
5.72
GO Classification
Functions
ATP binding / identical protein binding / metal ion binding / protein homodimerization activity / protein kinase binding / protein serine/threonine kinase activity / ubiquitin protein ligase binding
Processes
cell division / cellular protein catabolic process / cellular response to DNA damage stimulus / DNA damage checkpoint / DNA damage induced protein phosphorylation / DNA repair / double-strand break repair / G2/M transition of mitotic cell cycle / intrinsic apoptotic signaling pathway in response to DNA damage / mitotic spindle assembly / positive regulation of transcription, DNA-templated / protein autophosphorylation / protein phosphorylation / protein stabilization / regulation of protein catabolic process / regulation of transcription, DNA-templated / replicative cell aging / replicative senescence / response to gamma radiation / signal transduction in response to DNA damage / signal transduction involved in intra-S DNA damage checkpoint / transcription, DNA-templated
Components
Golgi apparatus / nucleoplasm / PML body
General Function
Ubiquitin protein ligase binding
Specific 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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0012364|Serine/threonine-protein kinase Chk2 (CHEK2)
ATGTCTCGGGAGTCGGATGTTGAGGCTCAGCAGTCTCATGGCAGCAGTGCCTGTTCACAG
CCCCATGGCAGCGTTACCCAGTCCCAAGGCTCCTCCTCACAGTCCCAGGGCATATCCAGC
TCCTCTACCAGCACGATGCCAAACTCCAGCCAGTCCTCTCACTCCAGCTCTGGGACACTG
AGCTCCTTAGAGACAGTGTCCACTCAGGAACTCTATTCTATTCCTGAGGACCAAGAACCT
GAGGACCAAGAACCTGAGGAGCCTACCCCTGCCCCCTGGGCTCGATTATGGGCCCTTCAG
GATGGATTTGCCAATCTTGAGACAGAGTCTGGCCATGTTACCCAATCTGATCTTGAACTC
CTGCTGTCATCTGATCCTCCTGCCTCAGCCTCCCAAAGTGCTGGGATAAGAGGTGTGAGG
CACCATCCCCGGCCAGTTTGCAGTCTAAAATGTGTGAATGACAACTACTGGTTTGGGAGG
GACAAAAGCTGTGAATATTGCTTTGATGAACCACTGCTGAAAAGAACAGATAAATACCGA
ACATACAGCAAGAAACACTTTCGGATTTTCAGGGAAGTGGGTCCTAAAAACTCTTACATT
GCATACATAGAAGATCACAGTGGCAATGGAACCTTTGTAAATACAGAGCTTGTAGGGAAA
GGAAAACGCCGTCCTTTGAATAACAATTCTGAAATTGCACTGTCACTAAGCAGAAATAAA
GTTTTTGTCTTTTTTGATCTGACTGTAGATGATCAGTCAGTTTATCCTAAGGCATTAAGA
GATGAATACATCATGTCAAAAACTCTTGGAAGTGGTGCCTGTGGAGAGGTAAAGCTGGCT
TTCGAGAGGAAAACATGTAAGAAAGTAGCCATAAAGATCATCAGCAAAAGGAAGTTTGCT
ATTGGTTCAGCAAGAGAGGCAGACCCAGCTCTCAATGTTGAAACAGAAATAGAAATTTTG
AAAAAGCTAAATCATCCTTGCATCATCAAGATTAAAAACTTTTTTGATGCAGAAGATTAT
TATATTGTTTTGGAATTGATGGAAGGGGGAGAGCTGTTTGACAAAGTGGTGGGGAATAAA
CGCCTGAAAGAAGCTACCTGCAAGCTCTATTTTTACCAGATGCTCTTGGCTGTGCAGTAC
CTTCATGAAAACGGTATTATACACCGTGACTTAAAGCCAGAGAATGTTTTACTGTCATCT
CAAGAAGAGGACTGTCTTATAAAGATTACTGATTTTGGGCACTCCAAGATTTTGGGAGAG
ACCTCTCTCATGAGAACCTTATGTGGAACCCCCACCTACTTGGCGCCTGAAGTTCTTGTT
TCTGTTGGGACTGCTGGGTATAACCGTGCTGTGGACTGCTGGAGTTTAGGAGTTATTCTT
TTTATCTGCCTTAGTGGGTATCCACCTTTCTCTGAGCATAGGACTCAAGTGTCACTGAAG
GATCAGATCACCAGTGGAAAATACAACTTCATTCCTGAAGTCTGGGCAGAAGTCTCAGAG
AAAGCTCTGGACCTTGTCAAGAAGTTGTTGGTAGTGGATCCAAAGGCACGTTTTACGACA
GAAGAAGCCTTAAGACACCCGTGGCTTCAGGATGAAGACATGAAGAGAAAGTTTCAAGAT
CTTCTGTCTGAGGAAAATGAATCCACAGCTCTACCCCAGGTTCTAGCCCAGCCTTCTACT
AGTCGAAAGCGGCCCCGTGAAGGGGAAGCCGAGGGTGCCGAGACCACAAAGCGCCCAGCT
GTGTGTGCTGCTGTGTTGTGA
Chromosome Location
22
Locus
22q11|22q12.1
External Identifiers
ResourceLink
UniProtKB IDO96017
UniProtKB Entry NameCHK2_HUMAN
GenBank Gene IDAF086904
GenAtlas IDCHEK2
HGNC IDHGNC:16627
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05149XL844investigationalunknownDetails
DB06486EnzastaurininvestigationalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails