ID:MPIP1_HUMAN DESCRIPTION: RecName: Full=M-phase inducer phosphatase 1; EC=3.1.3.48; AltName: Full=Dual specificity phosphatase Cdc25A; FUNCTION: Tyrosine 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. CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. ENZYME REGULATION: Stimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation. SUBUNIT: Interacts 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. INTERACTION: P04049:RAF1; NbExp=4; IntAct=EBI-747671, EBI-365996; P31946:YWHAB; NbExp=8; IntAct=EBI-747671, EBI-359815; DOMAIN: The 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. PTM: Phosphorylated 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. PTM: Ubiquitinated 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. SIMILARITY: Belongs to the MPI phosphatase family. SIMILARITY: Contains 1 rhodanese domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org//Genes/CDC25AID40004ch3p21.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdc25a/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P30304
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC007401 - Homo sapiens cell division cycle 25 homolog A (S. pombe), mRNA (cDNA clone MGC:1786 IMAGE:2989279), complete cds. BC018642 - Homo sapiens cell division cycle 25 homolog A (S. pombe), mRNA (cDNA clone MGC:16244 IMAGE:3687561), complete cds. M81933 - Human cdc25A mRNA, complete cds. JD312832 - Sequence 293856 from Patent EP1572962. JD445879 - Sequence 426903 from Patent EP1572962. JD377557 - Sequence 358581 from Patent EP1572962. JD396913 - Sequence 377937 from Patent EP1572962. AK290554 - Homo sapiens cDNA FLJ76018 complete cds, highly similar to Homo sapiens cell division cycle 25A (CDC25A), transcript variant 1, mRNA. JD261925 - Sequence 242949 from Patent EP1572962. JD326515 - Sequence 307539 from Patent EP1572962. JD066161 - Sequence 47185 from Patent EP1572962. JD535099 - Sequence 516123 from Patent EP1572962. AY137580 - Homo sapiens cell division cycle protein 25A splice variant 2 (CDC25A) mRNA, complete cds; alternatively spliced. EU812118 - Homo sapiens CDC25A2-CAG isoform (CDC25A) mRNA, complete cds. FJ866789 - Homo sapiens CDC25 isoform A1-CAG mRNA, complete cds. KJ890878 - Synthetic construct Homo sapiens clone ccsbBroadEn_00272 CDC25A gene, encodes complete protein. DQ890753 - Synthetic construct clone IMAGE:100003383; FLH165680.01X; RZPDo839F05160D cell division cycle 25A (CDC25A) gene, encodes complete protein. DQ892919 - Synthetic construct clone IMAGE:100005549; FLH190824.01X; RZPDo839E0576D cell division cycle 25A (CDC25A) gene, encodes complete protein. DQ896168 - Synthetic construct Homo sapiens clone IMAGE:100010628; FLH190820.01L; RZPDo839E0566D cell division cycle 25A (CDC25A) gene, encodes complete protein. AB590275 - Synthetic construct DNA, clone: pFN21AE1308, Homo sapiens CDC25A gene for cell division cycle 25 homolog A, without stop codon, in Flexi system. AF277722 - Homo sapiens cell division cycle 25A splice variant 2 (CDC25A) mRNA, partial cds. CU675643 - Synthetic construct Homo sapiens gateway clone IMAGE:100019776 5' read CDC25A mRNA. JD338320 - Sequence 319344 from Patent EP1572962. JD368691 - Sequence 349715 from Patent EP1572962. JD211119 - Sequence 192143 from Patent EP1572962. JD462637 - Sequence 443661 from Patent EP1572962. JD523481 - Sequence 504505 from Patent EP1572962. JD541045 - Sequence 522069 from Patent EP1572962. JD043936 - Sequence 24960 from Patent EP1572962. JD537730 - Sequence 518754 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_rbPathway - RB Tumor Suppressor/Checkpoint Signaling in response to DNA damage h_g2Pathway - Cell Cycle: G2/M Checkpoint h_cellcyclePathway - Cyclins and Cell Cycle Regulation h_cdc25Pathway - cdc25 and chk1 Regulatory Pathway in response to DNA damage h_ptc1Pathway - Sonic Hedgehog (SHH) Receptor Ptc1 Regulates cell cycle h_srcRPTPPathway - Activation of Src by Protein-tyrosine phosphatase alpha h_g1Pathway - Cell Cycle: G1/S Check Point
Reactome (by CSHL, EBI, and GO)
Protein P30304 (Reactome details) participates in the following event(s):
R-HSA-69598 Ubiquitination of phosphorylated Cdc25A R-HSA-69604 Phosphorylation of Cdc25A at Ser-123 by Chk1 R-HSA-69608 Phosphorylation of Cdc25A at Ser-123 by Chk2 R-HSA-8863014 p25-bound CDK5 phosphorylates CDC25A R-HSA-170159 Translocation of Cdc25 to the nucleus R-HSA-69199 Dephosphorylation of Cyclin E:Cdk2 complexes by Cdc25A R-HSA-170158 Dephosphorylation of nuclear Cyclin A:phospho-Cdc2 complexes R-HSA-170153 Dephosphorylation of nuclear Cyclin B1:phospho-Cdc2 (Thr 14, Tyr15) complexes by Cdc25 phosphatases R-HSA-174110 Cdc25A mediated dephosphorylation of Cyclin A:phospho-Cdk2 R-HSA-5696600 USP17 deubiquitinates RCE1, CDC25A, DDX58, IFIH1 R-HSA-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A R-HSA-176187 Activation of ATR in response to replication stress R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex R-HSA-156711 Polo-like kinase mediated events R-HSA-69610 p53-Independent DNA Damage Response R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-69481 G2/M Checkpoints R-HSA-8863678 Neurodegenerative Diseases R-HSA-69206 G1/S Transition R-HSA-69242 S Phase R-HSA-1538133 G0 and Early G1 R-HSA-69275 G2/M Transition R-HSA-69613 p53-Independent G1/S DNA damage checkpoint R-HSA-69620 Cell Cycle Checkpoints R-HSA-1643685 Disease R-HSA-453279 Mitotic G1-G1/S phases R-HSA-69278 Cell Cycle (Mitotic) R-HSA-453274 Mitotic G2-G2/M phases R-HSA-5689880 Ub-specific processing proteases R-HSA-69615 G1/S DNA Damage Checkpoints R-HSA-1640170 Cell Cycle R-HSA-5688426 Deubiquitination R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
