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Names & Taxonomy

Uniprot ID:: O14757
Entry Name:: CHK1_HUMAN
Status:: reviewed
Protein Names:: Serine/threonine-protein kinase Chk1 (EC 2.7.11.1) (CHK1 checkpoint homolog) (Cell cycle checkpoint kinase) (Checkpoint kinase-1)
Gene Names:: CHEK1 CHK1
Gene Names Primary:: CHEK1
Organism:: Homo sapiens (Human)

Structure

Length:: 476
Sequence:: MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINKMLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLKRREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDFSPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRRNNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B.

Function

Function:: Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence . Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest.; Isoform 2: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B.
Active Site:: ACT_SITE 130 130 Proton acceptor.
Gene Ontology Go:: centrosome
chromatin
condensed nuclear chromosome
cytosol
extracellular space
intracellular membrane-bounded organelle
nucleoplasm
nucleus
replication fork
ATP binding
histone kinase activity (H3-T11 specific)
protein kinase activity
protein serine/threonine kinase activity
cellular response to DNA damage stimulus
cellular response to mechanical stimulus
chromatin-mediated maintenance of transcription
DNA damage checkpoint
DNA damage induced protein phosphorylation
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
G2 DNA damage checkpoint
G2/M transition of mitotic cell cycle
histone H3-T11 phosphorylation
negative regulation of mitotic nuclear division
peptidyl-threonine phosphorylation
regulation of cell proliferation
regulation of double-strand break repair via homologous recombination
regulation of histone H3-K9 acetylation
regulation of mitotic centrosome separation
regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
replicative senescence
Gene Ontology Biological Process:: cellular response to DNA damage stimulus
cellular response to mechanical stimulus
chromatin-mediated maintenance of transcription
DNA damage checkpoint
DNA damage induced protein phosphorylation
DNA repair
DNA replication
double-strand break repair
double-strand break repair via homologous recombination
G2/M transition of mitotic cell cycle
G2 DNA damage checkpoint
histone H3-T11 phosphorylation
negative regulation of mitotic nuclear division
peptidyl-threonine phosphorylation
regulation of cell proliferation
regulation of double-strand break repair via homologous recombination
regulation of histone H3-K9 acetylation
regulation of mitotic centrosome separation
regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage
replicative senescence
Gene Ontology Molecular Function:: ATP binding
histone kinase activity (H3-T11 specific)
protein kinase activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:: centrosome
chromatin
condensed nuclear chromosome
cytosol
extracellular space
intracellular membrane-bounded organelle
nucleoplasm
nucleus
replication fork
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Cell cycle
Complete proteome
Cytoplasm
Cytoskeleton
DNA damage
DNA repair
Isopeptide bond
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Interacts With:: P38398; P30307; Q95KV1; Q9HAW4; Q9UJM3; P08238; O00255; Q06609; P06400; Q9HCE7-2; Q9UNS1; P61981

Names & Taxonomy

Structure

Subcellular location

Function

Publication