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Beschreibung

Cyclin-dependent kinase 12 (EC 2.7.11.22, EC 2.7.11.23, UniProt Q9NYV4, also known as CDC2-related protein kinase 7, Cdc2-related kinase, arginine/serine-rich, Cell division cycle 2-related protein kinase 7, Cell division protein kinase 12, CrkRS, hCDK12) is encoded by the CDK12 (also known as CRK7, CRKRS, KIAA0904) gene (Gene ID 51755) in human. CDK12 belongs to the CMGC Ser/Thr protein kinase subfamily of cyclin-dependent kinases (CDKs). Originally identified and characterized as an RNA Polymerase II C-terminal domain (CTD) kinase, CDK12 is involved in the 3' end processing of the MYC and c-FOS mRNA transcripts. In addtion, CDK12/CyclinK complex is implicated in the maintenance of genomic stability through the regulation of DNA damage response genes and as a determinant of PARP1/2 inhibitor sensitivity in cancer treatment. Human CDK12 is uncharacteristically large with a molecular weight of >=160 kDa (most CDKs are about 50 kDa) and contains large N- and C-terminal extensions flanking the kinase domain (a.a. 727-1020). These extensions contain multiple stretches of low complexity sequence and RS domains characteristic of splicing factors and regulators believed to mediate protein-protein interactions. As expected of RS domain-containing proteins, CDK12 is found in nuclear speckles representing storage sites for splicing factors.