Protein: Tyrosine-protein phosphatase CDC14 (EC 3.1.3.48) (Q00684)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
Function: Protein phosphatase which antagonizes mitotic cyclin-dependent kinase CDC28, the inactivation of which is essential for exit from mitosis. To access its substrates, is released from nucleolar sequestration during mitosis. Plays an essential in coordinating the nuclear division cycle with cytokinesis through the cytokinesis checkpoint. Involved in chromosome segregation, where it is required for meiosis I spindle dissambly as well as for establishing two consecutive chromosome segregation phases. Allows damaged actomyosin rings to be maintained to facilitate completion of cell division in response to minor perturbation of the cell division machinery. Inhibits transcription of ribosomal genes (rDNA) during anaphase and controls segregation of nucleolus by facilitating condensin targeting to rDNA chromatin in anaphase. Dephosphorylates SIC1, a CDC28 inhibitor, and SWI5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by dephosphorylating the activator of mitotic cyclin degradation, CDH1. Dephosphorylates the microtubule bundling factor ASE1 which is required to define a centered and focused mitotic spindle midzone that can drive continuous spindle elongation. Dephosphorylates the anaphase-promoting complex inhibitor ACM1, leading to its degradation. Facilitates INN1-CYK3 complex formation which promotes cytokinesis through the dephosphorylation of CDC28-phosphosphorylated INN1. Reverts also the inhibitory CDC28 phosphorylation of CHS2 for endoplasmic reticulum export, ensuring that septum formation is contingent upon chromosome separation and exit from mitosis. Additional substrates for CDC14 are the formins BNI1 and BNR1, as well as CDC6, DBP2, DSN1, INCENP, KAR9, MCM3, ORC2, ORC6, SLD2, and SWI6. Activity is inhibited by interaction with NET1 which sequesters it to the nucleolus.
Subcellular location: Nucleus, nucleolus. Cytoplasm. Bud neck. Note=Sequestered in the nucleolus for most of the cell cycle by the nucleolar proteins NET1 and TOF2, and is released into the nucleus and cytoplasm during anaphase. CDC55 maintains CDC14 sequestration in the nucleolus during early meiosis, which is essential for the assembly of the meiosis I spindle. In anaphase, the CDC14 early anaphase release (FEAR) network (including CDC5, ESP1, and SLK19), and the mitotic exit network (including the DBF2-MOB1 complex) coordinately trigger the release of CDC14 from the nucleolus.
Interaction partners:
- Cell division control protein 15
- Mitosis inhibitor protein kinase SWE1
- Cell cycle protein kinase DBF2
- Nucleolar protein NET1
- Mitotic check point protein BUB2
- Cell cycle serine/threonine-protein kinase CDC5/MSD2
- Sporulation-specific protein 12
- NAD-dependent histone deacetylase SIR2
- Kinetochore protein SLK19
- Protein SIC1
Sequence:
MRRSVYLDNTIEFLRGRVYLGAYDYTPEDTDELVFFTVEDAIFYNSFHLDFGPMNIGHLYRFAVIFHEILNDPENANKAVVFYSSASTRQRANAACMLCCYMILVQAWTPHQVLQPLAQVDPPFMPFRDAGYSNADFEITIQDVVYGVWRAKEKGLIDLHSFNLESYEKYEHVEFGDFNVLTPDFIAFASPQEDHPKGYLATKSSHLNQPFKSVLNFFANNNVQLVVRLNSHLYNKKHFEDIGIQHLDLIFEDGTCPDLSIVKNFVGAAETIIKRGGKIAVHCKAGLGRTGCLIGAHLIYTYGFTANECIGFLRFIRPGMVVGPQQHWLYLHQNDFREWKYTTRISLKPSEAIGGLYPLISLEEYRLQKKKLKDDKRVAQNNIEGELRDLTMTPPSNGHGALSARNSSQPSTANNGSNSFKSSAVPQTSPGQPRKGQNGSNTIEDINNNRNPTSHANRKVVIESNNSDDESMQDTNGTSNHYPKVSRKKNDISSASSSRMEDNEPSATNINNAADDTILRQLLPKNRRVTSGRRTTSAAGGIRKISGSIKK