M-phase inducer phosphatase-1 (dual-specificity phosphatase Cdc25A, CDC25A)

Function: - tyrosine protein phosphatase - dosage-dependent inducer of mitotic progression - directly dephosphorylates CDC2 & stimulates its kinase activity - dephosphorylates CDK2 in complex with cyclin E, in vitro - stimulated by B-type cyclins - interacts with CCNB1/cyclin B - interacts with YWHAE/14-3-3 epsilon when phosphorylated - interacts with CUL1 specifically when CUL1 is neddylated & active - interacts with BTRC/BTRCP1 & FBXW11/BTRCP2 - interactions with CUL1, BTRC & FBXW11 are enhanced upon DNA damage - phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-279, Ser-293 & Thr-507 during checkpoint mediated cell cycle arrest - phosphorylated by CHEK2 on Ser-124, Ser-279, & Ser-293 during checkpoint mediated cell cycle arrest - phosphorylation on Ser-178 & Thr-507 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A - phosphorylation on Ser-76, Ser-124, Ser-178, Ser-279 & Ser-293 may also promote ubiquitin-dependent proteolysis of CDC25A - ubiquitinated - association with the F-box proteins BTRC & FBXW11 targets the protein for ubiquitination by CUL1 & proteolysis by the ubiquitin-dependent proteasome pathway protein tyrosine phosphate + H₂O protein tyrosine + phosphate Structure: - phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated; phosphorylation sites at Ser-79 & Ser-82 appear to be essential for this interaction - belongs to the MPI phosphatase family - contains 1 rhodanese domain Alternative splicing: named isoforms=2

Properties

SIZE: entity length = 524 aa MW = 59 kD COMPARTMENT: cell nucleus CELL-CYCLE: G2 MOTIF: Phosphodegron {74-84} MOTIF: Ser phosphorylation site {S76} Ser phosphorylation site {S124} Ser phosphorylation site {S178} Ser phosphorylation site {S279} Ser phosphorylation site {S293} Rhodanese {376-482} MOTIF: cysteine residue {C431} Thr phosphorylation site {T507} STATE: active state

Database Correlations

OMIM 116947 UniProt P30304 Entrez Gene 993 ENZYME 3.1.3.48