Human Gene CDC25A (ENST00000351231.7) from GENCODE V44
Description: Homo sapiens cell division cycle 25A (CDC25A), transcript variant 2, mRNA. (from RefSeq NM_201567) RefSeq Summary (NM_201567): CDC25A is a member of the CDC25 family of phosphatases. CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by removing two phosphate groups. CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. CDC25A is an oncogene, although its exact role in oncogenesis has not been demonstrated. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]. Gencode Transcript: ENST00000351231.7 Gencode Gene: ENSG00000164045.12 Transcript (Including UTRs) Position: hg38 chr3:48,157,146-48,188,356 Size: 31,211 Total Exon Count: 14 Strand: - Coding Region Position: hg38 chr3:48,158,945-48,187,947 Size: 29,003 Coding Exon Count: 14
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.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04110 - Cell cycle hsa04914 - Progesterone-mediated oocyte maturation
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
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