CDC7/DBF4 Active Protein

This gene encodes a cell division cycle protein with kinase activity that is critical for the G1/S transition. The yeast homolog is also essential for initiation of DNA replication as cell division occurs. Overexpression of this gene product may be associated with neoplastic transformation for some tumors. Multiple alternatively spliced transcript variants that encode the same protein have been detected. [provided by RefSeq, Aug 2008]

CDC7: 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.

Protein type: CDC7 family; EC 2.7.11.1; Kinase, protein; Other group; Protein kinase, Other; Protein kinase, Ser/Thr (non-receptor)

Chromosomal Location of Human Ortholog: 1p22.1

Cellular Component: cytoplasm; intercellular bridge; nucleoplasm; nucleus

Molecular Function: kinase activity; protein binding; protein kinase activity; protein serine/threonine kinase activity

Biological Process: DNA replication; DNA replication initiation; double-strand break repair via break-induced replication; G1/S transition of mitotic cell cycle; peptidyl-serine phosphorylation; phagocytosis; positive regulation of cell proliferation; regulation of cell shape