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.

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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