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 Most vertebrates express two paralogs typically designated CDC14A and CDC14B (see unpublished data from gOrtholog).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

The CDC14 subfamily has two tandem structural equivalent domains linked by an alpha helix. Both domains have a DSP fold and only the second domain is catalytic active. CDC14 also has a conserved nuclear export sequence (NES) at C-terminal.

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.

Yeast CDC14 has a C-terminal sequence (517-551), which not only functions as a nuclear localization signal (NLS) in vivo but 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 CDC14A and CDC14B have NLSs 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].

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 [5].

References

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