Chek1(Chk1);

Serine/threonine-protein kinase Chk1;

Checkpoint kinase-1;CHK1 checkpoint homolog;

Rat (Rattus norvegicus). 

Interacts with BRCA1, CLSPN, FBXO6, PPM1D, RAD51, TIMELESS, XPO1/CRM1 and YWHAZ/14-3-3 zeta (By similarity). Interacts with FEM1B.

Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-508' and phosphorylation of CDC25C creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-283' and 'Ser-296' promotes proteolysis of CDC25A. Inhibition of CDC25 activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Binds to and phosphorylates RAD51, which may enhance the association of RAD51 with chromatin and promote DNA repair by homologous recombination. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may affect chromatin assembly during S phase or DNA repair. May also phosphorylate multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and enhances suppression of cellular proliferation. Phosphorylates NEK6 and NEK11. Phosphorylation of CDC25A at Ser-76 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11.

Nucleus Cytoplasm Cytoplasm cytoskeleton centrosome 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.

476

N/A

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rno:140583

Rn.33267

Q91ZN7

PF00069

Q91ZN7