Chk2 Recombinant Rabbit Monoclonal Antibody [SC604] (ET1610-52)

UNIPROT #

O96017

PROTEIN NAME

Chk2

SYNONYMS

CDS 1 antibody;Cds1 antibody;Cds1 homolog antibody;Checkpoint kinase 2 antibody;Checkpoint like protein CHK2 antibody;CHEK 2 antibody;Chek2 antibody;Chk 2 antibody;CHK2 checkpoint homolog (S. pombe) antibody;CHK2 checkpoint homolog antibody;CHK2_HUMAN antibody;hCds1 antibody;HuCds 1 antibody;LFS 2 antibody;LFS2 antibody;PP1425 antibody;RAD 53 antibody;RAD53 antibody;Rad53 homolog antibody;Serine/threonine protein kinase Chk2 antibody;Serine/threonine-protein kinase Chk2 antibody

SEQUENCE SIMILARITIES

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.

TISSUE SPECIFICITY

High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.

POST-TRANSLATIONAL MODIFICATION

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.; Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination.

SUBCELLULAR LOCATION

Nucleus.

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.