Difference between revisions of "Phosphatase Subfamily CDC14"

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[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_CDC14|Subfamily CDC14]]
 
[[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_CC1|Fold CC1]]:  [[Phosphatase_Superfamily_CC1|Superfamily CC1]]: [[Phosphatase_Family_DSP|Family DSP]]: [[Phosphatase_Subfamily_CDC14|Subfamily CDC14]]
  
CDC14 subfamily consists of cell cycle genes widely found in eukaryotes with the exception of higher plants.  
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CDC14 is a cell cycle phosphatase that dephosphorylates cyclin dependent kinases (CDKs).
  
 
=== Evolution ===
 
=== Evolution ===
CDC14 is found in most eukaryotes with the exception of higher plants. Most vertebrates express two paralogs typically designated CDC14A and CDC14B (see [http://resdev.gene.com/gOrtholog/view/cluster/MC0000760/overview unpublished data from gOrtholog]).  
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CDC14 is found in most eukaryotes with the exception of higher plants. Vertebrates have two members, CDC14A and CDC14B. Many primates have an additional CDC14C <cite>Rosso</cite>, though its functional relevance in human is not clear, as it may be a pseudogene.
  
=== Domain ===
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=== Domain Architecture ===
CDC14 has two tandem structural equivalent domains linked by an alpha helix. Both domains have a DSP fold and the second domain is catalytic active. CDC14 also has a conserved nuclear export sequence (NES) at C-terminal; human CDC14s has nucleolar targeting sequence at N-terminal <cite>Gray03</cite>.
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CDC14 has twin DSP phosphatase domains, separated by an alpha helix. The N-terminal domain is a [[pseudophosphatase]]. CDC14 also has a conserved nuclear export sequence (NES) at the C terminus.
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C. elegans cdc-14 has multiple isoforms and the longest one has a THAP domain at C-terminal. The [[Protein_Domain#THAP|THAP domain]] is a DNA-binding domain similar to P element transposase. However, the domain combination is dubious. ESTs suggest that the the THAP domain may belong to another gene.
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Yeast CDC14 has a C-terminal  sequence (517-551), which acts as a nuclear localization signal (NLS) in vivo and binds to Kap121p (also known as Pse1p), a nuclear import carrier (karyopherin/importin), in a Gsp1p-GTP-dependent manner in vitro <cite>Kobayashi15</cite>. In human, Kap121 (Pse1) ortholog can be found (IPO5), but human CDC14A and CDC14B have NLSs at N-terminal instead of C-terminal and it is unclear whether IPO5 binds to this region <cite>Gray03</cite>.
  
 
=== Function ===
 
=== Function ===
Unlike the budding yeast enzyme, Cdc14 orthologs of most other species are not required for mitotic exit <cite>Mocciaro10, Bremmer12</cite>. In vertebrates, there are conflicting reports on the functions of the Cdc14 isoforms, but there is evidence for involvement in regulating mitotic entry, centrosome duplication, DNA repair, and cytokinesis <cite>Mocciaro10, Bremmer12</cite>.  
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Yeast cdc14 is required for mitotic exit, though this is not seen in most other species <cite>Mocciaro10, Bremmer12</cite>. In vertebrates, there are conflicting reports on the functions of the Cdc14 isoforms, but there is evidence for involvement in regulating mitotic entry, centrosome duplication, DNA repair, and cytokinesis <cite>Mocciaro10, Bremmer12</cite>.
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Human CDC14A and CDC14B show functional redundancy in double-strand breaks repair <cite>Lin15</cite>, and their unique functions are not well understood.
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===== Yeast CDC14 =====
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Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. Iqg1, an IQGAP family member, is an essential protein in Saccharomyces cerevisiae required for assembly and contraction of the actomyosin ring. It has a calponin homology domain (CHD) that mediates the localization of F-actin to the ring which only occurs after anaphase <cite>Miller15</cite>.
  
 
=== References ===
 
=== References ===
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#Bremmer12 pmid=22117071
 
#Bremmer12 pmid=22117071
 
#Gray03 pmid=12853468
 
#Gray03 pmid=12853468
 +
#Kobayashi15 pmid=26022122
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#Lin15 pmid=26283732
 
#Mocciaro10 pmid=20720150
 
#Mocciaro10 pmid=20720150
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#Miller15 pmid=26085509
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#Rosso pmid=18547142
 
</biblio>
 
</biblio>

Latest revision as of 19:33, 1 April 2017

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily CDC14

CDC14 is a cell cycle phosphatase that dephosphorylates cyclin dependent kinases (CDKs).

Evolution

CDC14 is found in most eukaryotes with the exception of higher plants. Vertebrates have two members, CDC14A and CDC14B. Many primates have an additional CDC14C [1], though its functional relevance in human is not clear, as it may be a pseudogene.

Domain Architecture

CDC14 has twin DSP phosphatase domains, separated by an alpha helix. The N-terminal domain is a pseudophosphatase. CDC14 also has a conserved nuclear export sequence (NES) at the C terminus.

C. elegans cdc-14 has multiple isoforms and the longest one has a THAP domain at C-terminal. The THAP domain is a DNA-binding domain similar to P element transposase. However, the domain combination is dubious. ESTs suggest that the the THAP domain may belong to another gene.

Yeast CDC14 has a C-terminal sequence (517-551), which acts as a nuclear localization signal (NLS) in vivo and binds to Kap121p (also known as Pse1p), a nuclear import carrier (karyopherin/importin), in a Gsp1p-GTP-dependent manner in vitro [2]. In human, Kap121 (Pse1) ortholog can be found (IPO5), but human CDC14A and CDC14B have NLSs at N-terminal instead of C-terminal and it is unclear whether IPO5 binds to this region [3].

Function

Yeast cdc14 is required for mitotic exit, though this is not seen in most other species [4, 5]. In vertebrates, there are conflicting reports on the functions of the Cdc14 isoforms, but there is evidence for involvement in regulating mitotic entry, centrosome duplication, DNA repair, and cytokinesis [4, 5].

Human CDC14A and CDC14B show functional redundancy in double-strand breaks repair [6], and their unique functions are not well understood.

Yeast CDC14

Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. Iqg1, an IQGAP family member, is an essential protein in Saccharomyces cerevisiae required for assembly and contraction of the actomyosin ring. It has a calponin homology domain (CHD) that mediates the localization of F-actin to the ring which only occurs after anaphase [7].

References

  1. Rosso L, Marques AC, Weier M, Lambert N, Lambot MA, Vanderhaeghen P, and Kaessmann H. Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein. PLoS Biol. 2008 Jun 10;6(6):e140. DOI:10.1371/journal.pbio.0060140 | PubMed ID:18547142 | HubMed [Rosso]
  2. Kobayashi J, Hirano H, and Matsuura Y. Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p. Biochem Biophys Res Commun. 2015 Jul 31;463(3):309-14. DOI:10.1016/j.bbrc.2015.05.060 | PubMed ID:26022122 | HubMed [Kobayashi15]
  3. Gray CH, Good VM, Tonks NK, and Barford D. The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase. EMBO J. 2003 Jul 15;22(14):3524-35. DOI:10.1093/emboj/cdg348 | PubMed ID:12853468 | HubMed [Gray03]
  4. Mocciaro A and Schiebel E. Cdc14: a highly conserved family of phosphatases with non-conserved functions?. J Cell Sci. 2010 Sep 1;123(Pt 17):2867-76. DOI:10.1242/jcs.074815 | PubMed ID:20720150 | HubMed [Mocciaro10]
  5. Bremmer SC, Hall H, Martinez JS, Eissler CL, Hinrichsen TH, Rossie S, Parker LL, Hall MC, and Charbonneau H. Cdc14 phosphatases preferentially dephosphorylate a subset of cyclin-dependent kinase (Cdk) sites containing phosphoserine. J Biol Chem. 2012 Jan 13;287(3):1662-9. DOI:10.1074/jbc.M111.281105 | PubMed ID:22117071 | HubMed [Bremmer12]
  6. Lin H, Ha K, Lu G, Fang X, Cheng R, Zuo Q, and Zhang P. Cdc14A and Cdc14B Redundantly Regulate DNA Double-Strand Break Repair. Mol Cell Biol. 2015 Nov;35(21):3657-68. DOI:10.1128/MCB.00233-15 | PubMed ID:26283732 | HubMed [Lin15]
  7. Miller DP, Hall H, Chaparian R, Mara M, Mueller A, Hall MC, and Shannon KB. Dephosphorylation of Iqg1 by Cdc14 regulates cytokinesis in budding yeast. Mol Biol Cell. 2015 Aug 15;26(16):2913-26. DOI:10.1091/mbc.E14-12-1637 | PubMed ID:26085509 | HubMed [Miller15]
All Medline abstracts: PubMed | HubMed