View source for Phosphatase Subfamily CDC25

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_Rhodanese|Fold CC3]]: [[Phosphatase_Superfamily_CC3|Superfamily CC3]]: [[Phosphatase_Family_CDC25|Family CDC25]]: [[Phosphatase_Subfamily_CDC25|Subfamily CDC25]]

=== Evolution ===
The CDC25 subfamily is found in most 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  [http://pfam.xfam.org/family/M-inducer_phosp 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 [[HMM_PD0128|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 <cite>boutros06, rudolph07, boutros07</cite>. 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 ([http://www.sdbonline.org/sites/fly/genebrief/twine.htm Interactive Fly ]), while in mammals, CDC25A is involved in the G1-S checkpoint (dephosphorylating CDK2, CDK4 and CDK6) <cite>Shen</cite>, and CDC25B and CDC25C are involved at G2-M.

=== Phosphatase domain structure ===
The three human CDC25s have the same structure, with a secondary structure (SS) combination of E1, H1, E2, H2, E3, E4, H3, E5, H4, E6, H5, E7. The strands E1, E2, E4, E5, E6 form a 5-stranded sheet; E3 and E7 form a 2-stranded sheet. 

Human CDC25s and yeast YCH1 share the SS elements of E1, H1, E2, E3, E4, H3, E5, H4, E6, H5, E7. Yeast YCH1 structure differs from human CDC25s in two aspects:
* While human CDC25s have an helix (H2) between E2 and E3, yeast YCH1 has an helix between E4 and H3, which we name H2-YCH1.
* Yeast YCH1 has a helix between H4 and E6, which we name H4'-YCH1.

Note: These SS elements are the same as those reported in human CDC25 structures <cite> Fauman98, Reynolds99 </cite>, but differ from those reported for the YCH1 structure <cite>Yeo09</cite>, where it had a SS elements of EHEEHHEHEH. Our assignments include annotations from DSSP and Stride and validated in structure visualization.

=== References ===
<biblio>
#boutros06 pmid=16488126
#boutros07 pmid=17568790
#Fauman98 pmid=9604936
#Reynolds99 pmid=10543950
#rudolph07 pmid=17328562
#Shen pmid=22263797
#Yeo09 pmid=19382206
</biblio>