CDC25A: Cell Division Cycle 25A Phosphatase
Key regulator of cell cycle progression and checkpoint control
Gene Information Card
| Symbol | CDC25A |
|---|---|
| Full Name | Cell Division Cycle 25A |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 993 ncbi.nlm.nih.gov/gene/993 |
| Ensembl ID | ENSG00000164050 |
| UniProt ID | P30304 |
| OMIM ID | 116947 |
| HGNC ID | 1725 |
| Aliases | CDC25A2, MPP2 |
Description
CDC25A is a dual-specificity phosphatase that activates cyclin-dependent kinases (CDKs) by removing inhibitory phosphate residues at Thr14 and Tyr15. It is essential for G1/S and G2/M cell cycle transitions. CDC25A is tightly regulated during the cell cycle and in response to DNA damage, where it is degraded via ubiquitin-proteasome pathways. Overexpression or aberrant activation of CDC25A is frequently observed in various cancers, contributing to unchecked proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of CDC25A leads to increased CDK2 activity and accelerated G1/S transition, promoting tumorigenesis. | PMID: 10646847; COSMIC |
| Colorectal cancer | Elevated CDC25A mRNA and protein levels correlate with poor prognosis and resistance to chemotherapy. | PMID: 11526407; COSMIC |
| Non-small cell lung cancer | CDC25A amplification and overexpression drive cell cycle progression and are associated with advanced stage. | PMID: 14695180; COSMIC |
| Prostate cancer | CDC25A upregulation contributes to androgen-independent growth and metastasis. | PMID: 15604211; COSMIC |
| Hepatocellular carcinoma | CDC25A overexpression promotes hepatocyte proliferation and is linked to aggressive tumor features. | PMID: 18391493; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Bone marrow | 8.2 | Medium |
| Lymph node | 6.7 | Medium |
| Spleen | 5.9 | Low |
| Thymus | 5.1 | Low |
| Colon | 4.3 | Low |
| Breast | 3.8 | Low |
| Lung | 3.5 | Low |
| Liver | 2.1 | Low |
| Brain | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 10.2 | Cervical adenocarcinoma; high expression |
| MCF7 | 8.5 | Breast cancer; moderate expression |
| A549 | 7.1 | Lung adenocarcinoma; moderate expression |
| HCT116 | 6.8 | Colorectal carcinoma; moderate expression |
| HEK293 | 5.4 | Embryonic kidney; low expression |
| K562 | 4.9 | Chronic myeloid leukemia; low expression |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Loss of start codon; likely loss of function |
| c.215C>T (p.Pro72Leu) | Missense | <0.1% | Unknown significance |
| c.487G>A (p.Glu163Lys) | Missense | <0.1% | Unknown significance |
| c.1024C>T (p.Arg342Trp) | Missense | <0.1% | Unknown significance |
| c.1243G>A (p.Gly415Arg) | Missense | <0.1% | Unknown significance |
Mutation functional classification
Loss of Function (LOF)
Rare missense mutations (e.g., p.Met1?) may disrupt protein expression or catalytic activity, impairing cell cycle progression.
Gain of Function (GOF)
Amplification or overexpression of wild-type CDC25A is common in cancers, acting as an oncogenic gain of function.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported in CDC25A.
View complete mutation data:
Gene Ontology (GO)
Pathways
• Cell Cycle (KEGG hsa04110)
• p53 signaling pathway (KEGG hsa04115)
• G1 to S cell cycle control (Reactome R-HSA-69206)
• G2/M DNA damage checkpoint (Reactome R-HSA-69481)
• CDK-mediated phosphorylation and removal of Cdc6 (Reactome R-HSA-69017)
Protein Summary
CDC25A is a 524-amino acid dual-specificity phosphatase (UniProt P30304) that activates CDK1, CDK2, CDK4, and CDK6 by dephosphorylating inhibitory residues. It contains an N-terminal regulatory domain with multiple phosphorylation sites for ubiquitin-mediated degradation and a C-terminal catalytic domain. The protein is predominantly nuclear and is expressed at low levels in most tissues but elevated in proliferating cells and many cancers. Its activity is essential for cell cycle entry and is tightly controlled by checkpoint kinases (e.g., CHK1, CHK2) in response to DNA damage.
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