SpermatogenesisOnline 1.0
 

Tag Content
SG ID
SG00000584 
UniProt Accession
Theoretical PI
6.49  
Molecular Weight
59087 Da  
Genbank Nucleotide ID
Genbank Protein ID
Gene Name
CDC25A 
Gene Synonyms/Alias
 
Protein Name
M-phase inducer phosphatase 1 
Protein Synonyms/Alias
EC=3.1.3.48 Dual specificity phosphatase Cdc25A; 
Organism
Homo sapiens (Human) 
NCBI Taxonomy ID
9606 
Chromosome Location
chr:3;48198636-48229892;-1
View in Ensembl genome browser  
Function in Stage
Function in Cell Type
Description
BOULE is a possible fundamental mediator of meiotic transition in the human. 
The information of related literatures
1. C. M. Luetjens, E. Y. Xu, R. A. Rejo Pera, A. Kamischke, E. Nieschlag and J. Gromoll (2004) Association of meiotic arrest with lack of BOULE protein expression in infertile men. J Clin Endocrinol Metab 89(4): 1926-33. 

Abstract
Spermatogenesis is a complex developmental process of mitotic and meiotic cell divisions that ultimately results in production of haploid spermatozoa. Recent studies in flies demonstrate that the BOULE gene encodes a key factor of meiosis in male germ cells, regulating the expression of twine, a cdc25 phosphatase, which promotes progression through meiosis. In this study, we investigated whether a common mechanism underlies the block of germ cell maturation observed in idiopathic and nonidiopathic azoospermic patients with meiotic arrest. We examined, by immunohistochemistry, BOULE and CDC25A phosphatase protein, the human homolog of twine, expression in 47 men with meiotic arrest, mixed atrophy, or normal spermatogenesis. The presence of genetic alterations within the BOULE gene was investigated by single-stranded conformation polymorphism. BOULE protein expression in men with complete spermatogenesis can be restricted to stages from leptotene up to stages of late spermatocytes, whereas CDC25A expression ranges from leptotene spermatocytes to elongating spermatids. Although spermatocytes were present in all testicular biopsies with meiotic arrest (28 testes), BOULE protein expression was completely lacking. In addition, in nearly all biopsies in which BOULE was absent, CDC25A was concomitantly lacking. However, no mutations or polymorphisms in the BOULE gene were identified, which could explain the lack of BOULE or CDC25A expression. These results indicate that a major group of infertile men with meiotic arrest lack BOULE protein and its putative target, CDC25A expression. The spermatogenic failure seems to arise from factor(s) upstream of BOULE, which are possibly involved in regulating transcription and/or translation of BOULE. Thus, the spermatogenic damage leading to meiotic arrest is independent of the etiology and indicates that BOULE is a possible fundamental mediator of meiotic transition in the human. PMID: [15070965] 

2. Y. M. Lin, C. L. Chung and Y. S. Cheng (2009) Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis. J Clin Endocrinol Metab 94(7): 2650-7. 

Abstract
CONTEXT PMID: [19417033] 

3. Y. S. Cheng, P. L. Kuo, Y. N. Teng, T. Y. Kuo, C. L. Chung, Y. H. Lin, R. W. Liao, J. S. Lin and Y. M. Lin (2006) Association of spermatogenic failure with decreased CDC25A expression in infertile men. Hum Reprod 21(9): 2346-52. 

Abstract
BACKGROUND PMID: [16720623] 

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Figures for illustrating the function of this protein/gene
Ref: C. M. Luetjens, E. Y. Xu, R. A. Rejo Pera, A. Kamischke, E. Nieschlag and J. Gromoll (2004) Association of meiotic arrest with lack of BOULE protein expression in infertile men. J Clin Endocrinol Metab 89(4): 1926-33. PMID: [15070965]
Ref: Y. M. Lin, C. L. Chung and Y. S. Cheng (2009) Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis. J Clin Endocrinol Metab 94(7): 2650-7. PMID: [19417033]
Ref: Y. S. Cheng, P. L. Kuo, Y. N. Teng, T. Y. Kuo, C. L. Chung, Y. H. Lin, R. W. Liao, J. S. Lin and Y. M. Lin (2006) Association of spermatogenic failure with decreased CDC25A expression in infertile men. Hum Reprod 21(9): 2346-52. PMID: [16720623]
Ref: Y. S. Cheng, P. L. Kuo, Y. N. Teng, T. Y. Kuo, C. L. Chung, Y. H. Lin, R. W. Liao, J. S. Lin and Y. M. Lin (2006) Association of spermatogenic failure with decreased CDC25A expression in infertile men. Hum Reprod 21(9): 2346-52. PMID: [16720623]
Function
Tyrosine protein phosphatase which functions as adosage-dependent inducer of mitotic progression. Directlydephosphorylates CDK1 and stimulates its kinase activity. Alsodephosphorylates CDK2 in complex with cyclin E, in vitro. 
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Subcellular Location
 
Tissue Specificity
 
Gene Ontology
GO IDGO termEvidence
GO:0005829 C:cytosol TAS:Reactome.
GO:0005654 C:nucleoplasm TAS:Reactome.
GO:0004725 F:protein tyrosine phosphatase activity IEA:EC.
GO:0000075 P:cell cycle checkpoint TAS:Reactome.
GO:0051301 P:cell division IEA:UniProtKB-KW.
GO:0008283 P:cell proliferation TAS:UniProtKB.
GO:0034644 P:cellular response to UV IDA:UniProtKB.
GO:0006260 P:DNA replication TAS:Reactome.
GO:0000082 P:G1/S transition of mitotic cell cycle TAS:Reactome.
GO:0000086 P:G2/M transition of mitotic cell cycle TAS:Reactome.
GO:0007067 P:mitosis IEA:UniProtKB-KW.
GO:0035335 P:peptidyl-tyrosine dephosphorylation IEA:GOC.
GO:0000079 P:regulation of cyclin-dependent protein kinase activity TAS:UniProtKB.
GO:0000084 P:S phase of mitotic cell cycle TAS:Reactome.
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Interpro
IPR000751;    MPI_Phosphatase.
IPR001763;    Rhodanese-like_dom.
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Pfam
PF06617;    M-inducer_phosp;    1.
PF00581;    Rhodanese;    1.
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SMART
SM00450;    RHOD;    1.
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PROSITE
PS50206;    RHODANESE_3;    1.
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PRINTS
PR00716;    MPIPHPHTASE.;   
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Created Date
18-Oct-2012 
Record Type
Experiment identified 
Protein sequence Annotation
CHAIN         1    524       M-phase inducer phosphatase 1.
                             /FTId=PRO_0000198641.
DOMAIN      376    482       Rhodanese.
MOTIF        74     84       Phosphodegron.
MOTIF       141    143       KEN box.
ACT_SITE    431    431
MOD_RES      76     76       Phosphoserine; by CHEK1.
MOD_RES      79     79       Phosphoserine; by NEK11.
MOD_RES      82     82       Phosphoserine; by NEK11.
MOD_RES      88     88       Phosphoserine; by NEK11.
MOD_RES     124    124       Phosphoserine; by CHEK1 and CHEK2.
MOD_RES     178    178       Phosphoserine; by CHEK1.
MOD_RES     279    279       Phosphoserine; by CHEK1 and CHEK2.
MOD_RES     293    293       Phosphoserine; by CHEK1 and CHEK2.
MOD_RES     507    507       Phosphothreonine; by CHEK1.
MOD_RES     513    513       Phosphoserine; by PLK3.
MOD_RES     519    519       Phosphoserine; by PLK3.
VAR_SEQ     144    183       Missing (in isoform 2).
                             /FTId=VSP_000860.
VARIANT      88     88       S -> F (in dbSNP:rs3731499).
                             /FTId=VAR_020932.
VARIANT     182    182       R -> G (in dbSNP:rs6771386).
                             /FTId=VAR_023532.
VARIANT     182    182       R -> W (in dbSNP:rs6771386).
                             /FTId=VAR_023533.
MUTAGEN      76     76       S->A: Abolishes ubiquitination and
                             impairs CHEK1-dependent degradation
                             following checkpoint activation.
MUTAGEN      79     79       S->A: Abrogates interactions with BTRC
                             and FBXW11 and prevents ubiquitination.
MUTAGEN      81     81       D->A: Abrogates interactions with BTRC
                             and FBXW11 and prevents ubiquitination.
MUTAGEN      82     82       S->A: Abrogates interactions with BTRC
                             and FBXW11 and prevents ubiquitination.
MUTAGEN     124    124       S->A: Abrogates phosphorylation by CHEK2
                             and infrared-induced degradation.
                             Increases basal stability and impairs
                             CHEK1-dependent degradation following
                             checkpoint activation; when associated
                             with A-178; A-279 and A-293.
MUTAGEN     141    143       KEN->AAA: Prevents ubiquitination and
                             subsequent degradation by the APC/C
                             ubiquitin ligase complex.
MUTAGEN     178    178       S->A: Increases basal stability and
                             impairs CHEK1-dependent degradation
                             following checkpoint activation; when
                             associated with A-124; A-279 and A-293.
                             Abrogates 14-3-3 protein binding.
MUTAGEN     279    279       S->A: Increases basal stability and
                             impairs CHEK1-dependent degradation
                             following checkpoint activation; when
                             associated with A-124; A-178 and A-293.
MUTAGEN     293    293       S->A: Increases basal stability and
                             impairs CHEK1-dependent degradation
                             following checkpoint activation; when
                             associated with A-124; A-178 and A-279.
MUTAGEN     431    431       C->S: Abolishes phosphatase activity.
MUTAGEN     507    507       T->A: Abrogates 14-3-3 protein binding;
                             increases binding to cyclin B1.
MUTAGEN     513    513       S->A: Increased stability following IR
                             treatment.
MUTAGEN     513    513       S->D: Mimicks phosphorylation state,
                             leading to promote degradation following
                             IR treatment.
MUTAGEN     514    514       K->L: Abrogates binding to CCNB1; when
                             associated with L-520.
MUTAGEN     519    519       S->A: Increased stability following IR
                             treatment.
MUTAGEN     519    519       S->D: Mimicks phosphorylation state,
                             leading to promote degradation following
                             IR treatment.
MUTAGEN     520    520       R->L: Abrogates binding to CCNB1; when
                             associated with L-514.
CONFLICT      6     10       EPPHR -> SPAP (in Ref. 1; AAA58415).
CONFLICT    180    181       PA -> QL (in Ref. 1; AAA58415).
STRAND      341    344
HELIX       362    369
TURN        370    376
STRAND      377    384
HELIX       388    392
HELIX       405    411
TURN        412    414
STRAND      423    430
STRAND      432    436
HELIX       437    451
STRAND      463    466
HELIX       469    477
HELIX       478    480
STRAND      481    484
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Nucleotide Sequence
Length: 2419 bp   Go to nucleotide: FASTA
Protein Sequence
Length: 524 bp   Go to amino acid: FASTA
The verified Protein-Protein interaction information
UniProt
 Gene Symbol Ref Databases
YWHABBioGRID 
YWHAZHPRD 
_BioGRID 
_BioGRID 
_BioGRID 
CCNA1HPRD 
CCNB1HPRD 
CCNE1HPRD 
CDK1HPRD 
CDKN3HPRD 
CHEK1HPRD 
CHEK2HPRD 
YWHAZHPRD 
EGFRHPRD 
BTRCHPRD 
FBXW11HPRD 
MAP3K5HPRD 
MAPKAPK2IntAct 
MAPK14BioGRID 
YWHABHPRD 
YWHAEHPRD 
YWHAQMINT 
YWHAZMINT 
ARHPRD 
_BioGRID 
CCNB1BioGRID 
CCNE1BioGRID 
CDK2HPRD 
CHEK1BioGRID 
CUL1BioGRID 
CUX1HPRD 
EGFRBioGRID 
BTRCBioGRID 
FBXW11BioGRID 
MAP3K5BioGRID 
NAA10HPRD 
CDK2deltaTBioGRID 
BTRCBioGRID 
ARD1AMINT 
_HPRD 
_HPRD 
RAF1HPRD 
HRASDIP 
SMAD3HPRD 
UBCBioGRID 
NAA10IntAct 
PIM1HPRD 
UBBHPRD 
BTRCHPRD 
HRASHPRD 
_BioGRID 
RAF1BioGRID 
HRASHPRD 
ROCK1HPRD 
SMAD3BioGRID 
UBBHPRD 
UBCBioGRID 
Other Protein-Protein interaction resources
String database  
View Microarray data
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