Difference between revisions of "Phosphatase Family CDC25"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Superfamily_CDC25|Superfamily CDC25]]: [[Phosphatase_Family_CDC25|Family CDC25]]
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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_Rhodanese|Fold CC3 (Rhodanese)]]: [[Phosphatase_Superfamily_CC3|Superfamily CC3 (Rhodanese)]]: [[Phosphatase_Family_CDC25|Family CDC25]]
  
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== Function ==
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CDC25 consists of two subfamilies, '''[[Phosphatase_Subfamily_CDC25|CDC25]]''' and '''[[Phosphatase_Subfamily_Acr2|Acr2]]'''. CDC25 is is an important phosphatase of cyclin-dependent kinases ([http://kinase.com/wiki/index.php/Kinase_Family_CDK CDKs]), the function role of Acr2 is uncertain: it has arsenate reductase activity but may also be a protein phosphatase.
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CDC25 activates cyclin-dependent kinases ([http://kinase.com/wiki/index.php/Kinase_Family_CDK CDKs]) by dephosphorylating two sites within their ATP binding loop. CDKs regulate key transitions between cell cycle phases, and are key components of the checkpoint pathways involved in DNA damage. Thus, it is not suppressing to find it overexpressed in many human cancers <cite>Boutros07</cite>.
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CDC25 has a phosphatase domain belonging to the rhodanese fold in the C-terminus <cite>fauman98 reynolds99</cite>, and a less-conserved N-terminal regulatory region <cite>forrest01</cite>, which can be phosphorylated and ubiquitinated.
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CDC25 and Acr2 are found in a largely exclusive clades. CDC25 is found in most animals, but is absent from plants, while Acr2 is found in plants but not animals. Most fungi and many protists have both.
  
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== Evolution ==
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=== Phosphatase domain structure ===
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CDC25s can be found through the unikonts (fungi, animal, amoebazoans), and in a few other eukaryotes. Within plants, they are only found in the alga Ostreococcus, but not Chalmydomonas, and are absent from land plants. In excavates, they are found in Trichomonas, but not Giardia, Leishmania, or Trypanosomes.
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==== Compare the structures of CDC25 and Acr2 subfamilies ====
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We compared the structures of three human CDC25s of CDC25 subfamily and yeast YCH1 of Acr2 subfamily.  
  
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Plants contain a phosphatase called Arc2. It is a dubious CDC25. While it shows the phosphatase activity towards CDKs in vitro, its overexpression or knock-out have no obvious cell cycle phenotype <cite>Boudolf06</cite>. Arc2 can also be found in fungi, Amoebozoans, Heterokonts, Excavates. In several cases, Arc2 and CDC25 are mutually exclusive: in algae, Arc2 is in Chlamydomonas but not Ostreococcus, and Arc2 is absent from holozoans.  
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The three human CDC25s have generally the same structure, which have 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; the strands E3 and E7 form a 2-stranded sheet.  
  
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Based upon their phylogenetic profiles, the possible history is the basal eukaryotes have both of the two genes, and got lost in some branches. While some organisms have both of the genes, both are lost in Alveolates. It is interesting taking account of its function in cell cycle regulation and checkpoint of DNA damage.
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The human CDC25s and yeast YCH1 share the SS elements of E1, H1, E2, E3, E4, H3, E5, H4, E6, H5, E7. But,  yeast YCH1 structure is different from human CDC25s in two aspects:
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* While human CDC25s have an helix (H2) between E2 and E3, yeast YCH1 has an helix between E4 and H3. We named the SS elements as H2-YCH1.
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* Yeast YCH1 has a helix between H4 and E6. We name it as H4'-YCH1.
  
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Note: We have the same SS annotation of CDC25 in the papers reported CDC25 structures <cite> Fauman98, Reynolds99 </cite>, but we have the SS annotation of YCH1 different from the paper reported its structure <cite>Yeo09</cite>, where it had a SS elements of EHEEHHEHEH. We obtained the original annotations from DSSP and Stride programs and validated them in structure visualization.
  
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== References ==
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==== Compare the structures of human CDC25s and Arabidopsis  Acr2 ====
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Arabidopsis Acr2 has a solution NMR structure (PDB [http://www.rcsb.org/pdb/explore/explore.do?structureId=1T3K 1T3K]). It lacks H1, E3 and E7. It also has slight difference in H3 localization.
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=== References ===
 
<biblio>
 
<biblio>
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#forrest01 pmid=11466620
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#Fauman98 pmid=9604936
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#reynolds99 pmid=10543950
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#Reynolds99 pmid=10543950
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#fauman98 pmid=9604936
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#Yeo09 pmid=19382206
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#Boutros07 pmid=17568790
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#Boudolf06 pmid=16949857
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</biblio>
 
</biblio>

Latest revision as of 00:45, 20 November 2015

Phosphatase Classification: Fold CC3 (Rhodanese): Superfamily CC3 (Rhodanese): Family CDC25

CDC25 consists of two subfamilies, CDC25 and Acr2. CDC25 is is an important phosphatase of cyclin-dependent kinases (CDKs), the function role of Acr2 is uncertain: it has arsenate reductase activity but may also be a protein phosphatase.

CDC25 and Acr2 are found in a largely exclusive clades. CDC25 is found in most animals, but is absent from plants, while Acr2 is found in plants but not animals. Most fungi and many protists have both.

Phosphatase domain structure

Compare the structures of CDC25 and Acr2 subfamilies

We compared the structures of three human CDC25s of CDC25 subfamily and yeast YCH1 of Acr2 subfamily.

The three human CDC25s have generally the same structure, which have 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; the strands E3 and E7 form a 2-stranded sheet.

The human CDC25s and yeast YCH1 share the SS elements of E1, H1, E2, E3, E4, H3, E5, H4, E6, H5, E7. But, yeast YCH1 structure is different 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. We named the SS elements as H2-YCH1.
  • Yeast YCH1 has a helix between H4 and E6. We name it as H4'-YCH1.

Note: We have the same SS annotation of CDC25 in the papers reported CDC25 structures [1, 2], but we have the SS annotation of YCH1 different from the paper reported its structure [3], where it had a SS elements of EHEEHHEHEH. We obtained the original annotations from DSSP and Stride programs and validated them in structure visualization.

Compare the structures of human CDC25s and Arabidopsis Acr2

Arabidopsis Acr2 has a solution NMR structure (PDB 1T3K). It lacks H1, E3 and E7. It also has slight difference in H3 localization.

References

  1. Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, and Saper MA. Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998 May 15;93(4):617-25. DOI:10.1016/s0092-8674(00)81190-3 | PubMed ID:9604936 | HubMed [Fauman98]
  2. Reynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, and Watenpaugh KD. Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol. 1999 Oct 29;293(3):559-68. DOI:10.1006/jmbi.1999.3168 | PubMed ID:10543950 | HubMed [Reynolds99]
  3. Yeo HK and Lee JY. Crystal structure of Saccharomyces cerevisiae Ygr203w, a homolog of single-domain rhodanese and Cdc25 phosphatase catalytic domain. Proteins. 2009 Aug 1;76(2):520-4. DOI:10.1002/prot.22420 | PubMed ID:19382206 | HubMed [Yeo09]
All Medline abstracts: PubMed | HubMed
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