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FLASH GENE

Symbol

CDC25A

contributors: mct - updated : 10-09-2014

HGNC name	cell division cycle 25 homolog A (S. pombe)
HGNC id	1725

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001789 15 splicing 3717 NP_001780 59 524 - 2000 11139144 NM_201567 14 splicing 3597 NP_963861 54 484 - 2000 11139144 lacking an alternate in-frame exon compared to variant 1 having the same N- and C-termini compared to isoform a

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Reproductive female system uterus cervix   moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular       highly

cell lineage
cell lines
fluid/secretion	predominantly in lymph

at STAGE

cell cycle

cell cycle, interphase, checkpoint, G1S

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a phosphodegron motif
	a rhodanese domain

conjugated

PhosphoP , Other

HOMOLOGY

interspecies	homolog to rattus Cdc25a (86.4 pc)
	homolog to murine Cdc25a (86 pc)

Homologene

FAMILY	MPI phosphatase family
	CDC25 family of phosphatases

CATEGORY

enzyme , protooncogene , receptor membrane phosphatase

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm
text	centrosomal protein

basic FUNCTION	dual specificity (tyr/thr) phosphatase, putative upregulated c-Myc target gene
	acting as a regulator of the cell cycle required for progression from G1 to S phase
	functioning as a dosage-dependent inducer of mitotic progression
	coordinate cell cycle progression through activating dephosphorylation of Cyclin-dependent kinases
	directly dephosphorylating CDC2 and stimulating its kinase activity
	has non-redundant functions in late G2/early M-phase as a major regulator of Cyclin A/kinase complexes
	mainly involved in chromatin condensation and acts after Cdc25B in G2–M phase
	can activate both Cdk1/Cyclin A and Cdk2/Cyclin A complexes in G2–M
	may have an essential function during early embryonic development
	with CSC25B and CDC25C, are implicated at G1/S, during S-phase, at G2/M and during mitosis (are implicated at G1/S, during S-phase, at G2/M and during mitosis
	having effects on breast cancer cell metastasis, independent of cell proliferation and apoptosis
	dual specificity protein phosphatase, exhibiting anti-apoptotic activity
	has an important physiological role in NFKB activity regulation and it may be an important survival mechanism of cancer cells
	FOXM1 controls the cell cycle through its association with CDC25A
	CDC25A normally plays a pivotal role in regulating the G1/S and G2/M transitions by dephosphorylating and activating cyclin/cyclin-dependent kinase (CDK) complexes

CELLULAR PROCESS	cell cycle, division, mitosis
	cell cycle, checkpoint
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

ubiquitinated

INTERACTION

DNA

RNA

small molecule

other,

protein	interacting with CCNB1/cyclin B1
	interacting with YWHAE/14- 3-3 epsilon when phosphorylated
	interacting with CUL1 specifically when CUL1 is neddylated and active
	interacting with BOLL (a decreased CDC25A expression caused by lack or decrease of BOLL may be associated with male infertility)
	interacting with BTRC/BTRCP1 and FBXW11/BTRCP2
	interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage
	TRIB3 is a regulator for adjusting the expression level of CDC25A both in a normal and a genotoxic conditions
	enhancing FOXO1 stability by dephosphorylating CDK2
	stimulates NFKB activity by destabilizing NFKBIA protein through inducing its phosphorylation and ubiquitination
	FOXM1 directly regulates CDC25A gene transcription via direct promoter binding and indirect activation of E2F-dependent pathways
	RPS6KA3 promotes G2/M transition in mammalian cells through activating phosphorylation of CDC25A and CDC25B
	STK38-mediated phosphorylation of CDC25A at Ser-76 and the subsequent degradation of CDC25A are required to promote DNA damage-induced G2/M checkpoint activation

cell & other

REGULATION

activated by

cyclin B

inhibited by	ubiquinated and degraded by the proteasome pathway
	phosphorylated and inactivated by CHEK1

Other	specifically degraded in response to DNA damage
	deubiquitinated by USP17L2
	stimulated by B-type cyclins
	ubiquitinated by CUL1
	phosphorylated by NEK11, phosphorylation that is required for its polyubiquitination and thus degradation

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   associated with spermatogenic failure and failed sperm retrieval in infertile men constitutional     --over   initiates centrosome separation by activation of centrosomal Cdk1/Cyclin B pools tumoral     --over   in breast cancer cells enhances metastasis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast anti-Cdc25A strategy may reveal its therapeutic potential in prevention and treatment of breast cancer cell dissemination digestive liver   pharmacological targeting of CDC25A has therapeutic potential in polycystic liver diseases

ANIMAL & CELL MODELS

CDC25A-deficient embryos exhibit growth retardation and die before E7.5 through an apoptotic pathway