Phosphatase Subfamily CDC25

Phosphatase Classification: Fold CC3: Superfamily CC3: Family CDC25: Subfamily CDC25

Evolution

The CDC25 subfamily is found in a broad of eukaryotes, but absent from most if not all of plants. It has multiple copies in many species, including three in human, two in Drosophila (string and twine) and four in C. elegans, all from apparently independent duplications.

Domain

Human CDC25s have an N-terminal regulatory domain known as M-phase inducer phosphatase domain and a C-terminal phosphatase domain with a rhodanese fold. Both human CDC25s show alternative splicing of the regulatory domain. The N-terminal regulatory domain is classified as tetrapod-specific in Pfam, but has clearly conserved homology with CDC25 genes in Nematostella vectensis. A divergent N-terminal domain is also found in insects and Trichocephalida (an order of nematode), but not in Caenorhabditis species (see technical note of CDC25 N-terminal domain). Thus, the CDC25, N-terminal domain is probably lost in Caenorhabditis.

Catalytic activity and functions

Cdc25 dephosphorylates CDK kinases in many organisms, including yeasts, Drosophila and mammals, and so controls checkpoint progression of the cell cycle. CDC25 structures and functions have been reviewed in detail [1, 2, 3]. CDC25 removes inhibitory phosphates added by Wee1 from a threonine and a tyrosine in the G-loop of CDK1 and other CDKs, activating their cell cycle function. Duplicated CDC25s often have specific subfunctions: in Drosophila, string (stg) is involved in mitosis, and twine (twe) in meiosis (Interactive Fly ), while in mammals, CDC25A is involved in the G1-S checkpoint (dephosphorylating CDK2, CDK4 and CDK6) [4], and CDC25B and CDC25C are involved at G2-M.

References

Error fetching PMID 16488126:
Error fetching PMID 17568790:
Error fetching PMID 17328562:
Error fetching PMID 22263797: