an evolutionarily conserved serine/threonine protein kinase of the CDC7 family. Predominantly localized in the nucleus, it plays a pivotal role in linking cell cycle regulation to genome duplication, being essential for the firing of DNA replication origins. Plays an essential role in initiating DNA replication at replication origins by phosphorylating the MCM2 and MCM4 subunits of the MCM2-7 helicase complex. The human protein requires phosphorylation by CDK1 at T376 and binding to activator of S-phase kinase (ASK)/DBF4B to be fully activated. The interaction between Cdc7 and DBFK subunits facilitates ATP binding and substrate recognition by the Cdc7 kinase. Although CDC7 expression levels appear to be constant throughout the cell cycle, the expression levels of DBF4B is cell cycle-regulated. Thus, the CDC7 activity is activated during S phase in eukaryotes. The Cdc7/ DBF4B complex regulates initiation of DNA replication by phosphorylating chromatin-bound mini-chromosome maintenance protein 2 (MCM2). Impaired Cdc7 kinase activity leads to S-phase arrest. Plays a role in the TGF-beta regulation of smooth muscle cell (SMC) differentiation. Interacts with Smad3 to facilitate Smad3 binding to SMC marker promoter, leading to the activation of SMC marker gene transcription. Note: This description may include information from UniProtKB.
Protein type: EC 18.104.22.168; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Protein kinase, Other; Other group; CDC7 family
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.