Phosphatase Subfamily CDC14
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily CDC14
CDC14 subfamily consists of cell cycle genes widely found in eukaryotes with the exception of higher plants.
Evolution
CDC14 is found in most eukaryotes with the exception of higher plants. Most vertebrates express two paralogs typically designated CDC14A and CDC14B (see unpublished data from gOrtholog).
Domain
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.
Yeast CDC14 has a nucleolar targeting sequence at C-terminal (517-551), which functions as a nuclear localization signal (NLS) in vivo and also binds to Kap121p (also known as Pse1p), an essential nuclear import carrier (karyopherin/importin) in yeast, in a Gsp1p-GTP-dependent manner in vitro [1]. In human, Kap121 (Pse1) ortholog can be found (IPO5), but human CDC14s has nucleolar targeting sequence at N-terminal instead of C-terminal and it is unclear whether IPO5 binds to this region [2].
Function
Unlike the budding yeast enzyme, Cdc14 orthologs of most other species are not required for mitotic exit [3, 4]. 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 [3, 4].
References
- 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 |
- 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 |
- 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 |
- 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 |
