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MGP000483

UniProt Annotations

Entry Information
Gene Namecell division cycle 25A
Protein EntryMPIP1_HUMAN
UniProt IDP30304
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=CDC25A1; IsoId=P30304-1; Sequence=Displayed; Name=2; Synonyms=CDC25A2; IsoId=P30304-2; Sequence=VSP_000860;
Catalytic ActivityProtein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
DomainThe phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-79 and Ser-82 appear to be essential for this interaction. {ECO:0000269|PubMed:12234927}.
Enzyme RegulationStimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation.
FunctionTyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro.
InteractionP04049:RAF1; NbExp=4; IntAct=EBI-747671, EBI-365996; P31946:YWHAB; NbExp=8; IntAct=EBI-747671, EBI-359815; P63104:YWHAZ; NbExp=2; IntAct=EBI-747671, EBI-347088;
PtmPhosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-279, Ser-293 and Thr-507 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-124, Ser-279, and Ser-293 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and Thr-507 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-76, Ser-124, Ser- 178, Ser-279 and Ser-293 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-76 by CHEK1 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11. Phosphorylation by NEK11 is required for BTRC-mediated polyubiquitination and degradation. Phosphorylation by PIM1 leads to an increase in phosphatase activity. Phosphorylated by PLK3 following DNA damage, leading to promote its ubiquitination and degradation. {ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:20228808, ECO:0000269|PubMed:21376736}.
PtmUbiquitinated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase leading to its degradation by the proteasome. Ubiquitinated by a SCF complex containing BTRC and FBXW11 during S phase leading to its degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads to its stabilization. {ECO:0000269|PubMed:20228808}.
SimilarityBelongs to the MPI phosphatase family. {ECO:0000305}.
SimilarityContains 1 rhodanese domain. {ECO:0000255|PROSITE- ProRule:PRU00173}.
SubunitInteracts with CCNB1/cyclin B1. Interacts with YWHAE/14- 3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage. Interacts with PIM1. Interacts with CHEK2; mediates CDC25A phosphorylation and degradation in response to infrared-induced DNA damages. {ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:16356754}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/CDC25AID40004ch3p21.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdc25a/";
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