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Identification
HMDB Protein ID HMDBP08919
Secondary Accession Numbers
  • 14648
Name M-phase inducer phosphatase 1
Synonyms
  1. Dual specificity phosphatase Cdc25A
Gene Name CDC25A
Protein Type Enzyme
Biological Properties
General Function Involved in protein tyrosine phosphatase activity
Specific 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.
Pathways
  • Cell cycle
  • Progesterone-mediated oocyte maturation
Reactions
Protein tyrosine phosphate + Water → protein tyrosine + Phosphoric acid details
GO Classification
Biological Process
cell division
G2/M transition of mitotic cell cycle
cell proliferation
S phase of mitotic cell cycle
G1/S transition of mitotic cell cycle
DNA replication
cell cycle checkpoint
regulation of cyclin-dependent protein kinase activity
cellular response to UV
mitosis
peptidyl-tyrosine dephosphorylation
Cellular Component
cytosol
nucleoplasm
Component
cell part
intracellular
Function
phosphoprotein phosphatase activity
protein tyrosine phosphatase activity
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
phosphoric ester hydrolase activity
phosphatase activity
Molecular Function
protein tyrosine phosphatase activity
Process
phosphorus metabolic process
phosphate metabolic process
m phase
dephosphorylation
m phase of mitotic cell cycle
protein amino acid dephosphorylation
metabolic process
cellular process
cellular metabolic process
cell cycle process
cell cycle phase
Cellular Location
  1. Cytoplasmic
Gene Properties
Chromosome Location 3
Locus 3p21
SNPs CDC25A
Gene Sequence
>1575 bp
ATGGAACTGGGCCCGGAGCCCCCGCACCGCCGCCGCCTGCTCTTCGCCTGCAGCCCCCCT
CCCGCGTCGCAGCCCGTCGTGAAGGCGCTATTTGGCGCTTCAGCCGCCGGGGGACTGTCG
CCTGTCACCAACCTGACCGTCACTATGGACCAGCTGCAGGGTCTGGGCAGTGATTATGAG
CAACCACTGGAGGTGAAGAACAACAGTAATCTGCAGAGAATGGGCTCCTCCGAGTCAACA
GATTCAGGTTTCTGTCTAGATTCTCCTGGGCCATTGGACAGTAAAGAAAACCTTGAAAAT
CCTATGAGAAGAATACATTCCCTACCTCAGAAGCTGTTGGGATGTAGTCCAGCTCTGAAG
AGGAGCCATTCTGATTCTCTTGACCATGACATCTTTCAGCTCATCGACCCAGATGAGAAC
AAGGAAAATGAAGCCTTTGAGTTTAAGAAGCCAGTAAGACCTGTATCTCGTGGCTGCCTG
CACTCTCATGGACTCCAGGAGGGTAAAGATCTCTTCACACAGAGGCAGAACTCTGCCCCA
GCTCGGATGCTTTCCTCAAATGAAAGAGATAGCAGTGAACCAGGGAATTTCATTCCTCTT
TTTACACCCCAGTCACCTGTGACAGCCACTTTGTCTGATGAGGATGATGGCTTCGTGGAC
CTTCTCGATGGAGAGAATCTGAAGAATGAGGAGGAGACCCCCTCGTGCATGGCAAGCCTC
TGGACAGCTCCTCTCGTCATGAGAACTACAAACCTTGACAACCGATGCAAGCTGTTTGAC
TCCCCTTCCCTGTGTAGCTCCAGCACTCGGTCAGTGTTGAAGAGACCAGAACGATCTCAA
GAGGAGTCTCCACCTGGAAGTACAAAGAGGAGGAAGAGCATGTCTGGGGCCAGCCCCAAA
GAGTCAACTAATCCAGAGAAGGCCCATGAGACTCTTCATCAGTCTTTATCCCTGGCATCT
TCCCCCAAAGGAACCATTGAGAACATTTTGGACAATGACCCAAGGGACCTTATAGGAGAC
TTCTCCAAGGGTTATCTCTTTCATACAGTTGCTGGGAAACATCAGGATTTAAAATACATC
TCTCCAGAAATTATGGCATCTGTTTTGAATGGCAAGTTTGCCAACCTCATTAAAGAGTTT
GTTATCATCGACTGTCGATACCCATATGAATACGAGGGAGGCCACATCAAGGGTGCAGTG
AACTTGCACATGGAAGAAGAGGTTGAAGACTTCTTATTGAAGAAGCCCATTGTACCTACT
GATGGCAAGCGTGTCATTGTTGTGTTTCACTGCGAGTTTTCTTCTGAGAGAGGTCCCCGC
ATGTGCCGGTATGTGAGAGAGAGAGATCGCCTGGGTAATGAATACCCCAAACTCCACTAC
CCTGAGCTGTATGTCCTGAAGGGGGGATACAAGGAGTTCTTTATGAAATGCCAGTCTTAC
TGTGAGCCCCCTAGCTACCGGCCCATGCACCACGAGGACTTTAAAGAAGACCTGAAGAAG
TTCCGCACCAAGAGCCGGACCTGGGCAGGGGAGAAGAGCAAGAGGGAGATGTACAGTCGT
CTGAAGAAGCTCTGA
Protein Properties
Number of Residues 524
Molecular Weight 59086.235
Theoretical pI 6.944
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>M-phase inducer phosphatase 1
MELGPEPPHRRRLLFACSPPPASQPVVKALFGASAAGGLSPVTNLTVTMDQLQGLGSDYE
QPLEVKNNSNLQRMGSSESTDSGFCLDSPGPLDSKENLENPMRRIHSLPQKLLGCSPALK
RSHSDSLDHDIFQLIDPDENKENEAFEFKKPVRPVSRGCLHSHGLQEGKDLFTQRQNSAP
ARMLSSNERDSSEPGNFIPLFTPQSPVTATLSDEDDGFVDLLDGENLKNEEETPSCMASL
WTAPLVMRTTNLDNRCKLFDSPSLCSSSTRSVLKRPERSQEESPPGSTKRRKSMSGASPK
ESTNPEKAHETLHQSLSLASSPKGTIENILDNDPRDLIGDFSKGYLFHTVAGKHQDLKYI
SPEIMASVLNGKFANLIKEFVIIDCRYPYEYEGGHIKGAVNLHMEEEVEDFLLKKPIVPT
DGKRVIVVFHCEFSSERGPRMCRYVRERDRLGNEYPKLHYPELYVLKGGYKEFFMKCQSY
CEPPSYRPMHHEDFKEDLKKFRTKSRTWAGEKSKREMYSRLKKL
GenBank ID Protein 42490758
UniProtKB/Swiss-Prot ID P30304
UniProtKB/Swiss-Prot Entry Name MPIP1_HUMAN
PDB IDs
GenBank Gene ID NM_001789.2
GeneCard ID CDC25A
GenAtlas ID CDC25A
HGNC ID HGNC:1725
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Zhao H, Watkins JL, Piwnica-Worms H: Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14795-800. Epub 2002 Oct 24. [PubMed:12399544 ]
  3. Sorensen CS, Syljuasen RG, Falck J, Schroeder T, Ronnstrand L, Khanna KK, Zhou BB, Bartek J, Lukas J: Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell. 2003 Mar;3(3):247-58. [PubMed:12676583 ]
  4. Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, Harper JW: SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 2003 Dec 15;17(24):3062-74. Epub 2003 Dec 17. [PubMed:14681206 ]
  5. Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH, Fesik S, Zhang H: Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem. 2003 Jun 13;278(24):21767-73. Epub 2003 Apr 3. [PubMed:12676925 ]
  6. Hassepass I, Voit R, Hoffmann I: Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint. J Biol Chem. 2003 Aug 8;278(32):29824-9. Epub 2003 May 20. [PubMed:12759351 ]
  7. Chen MS, Ryan CE, Piwnica-Worms H: Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol. 2003 Nov;23(21):7488-97. [PubMed:14559997 ]
  8. Galaktionov K, Beach D: Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins. Cell. 1991 Dec 20;67(6):1181-94. [PubMed:1836978 ]
  9. Wegener S, Hampe W, Herrmann D, Schaller HC: Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C. Eur J Cell Biol. 2000 Nov;79(11):810-5. [PubMed:11139144 ]
  10. Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta GF: Dual mode of degradation of Cdc25 A phosphatase. EMBO J. 2002 Sep 16;21(18):4875-84. [PubMed:12234927 ]
  11. Pereg Y, Liu BY, O'Rourke KM, Sagolla M, Dey A, Komuves L, French DM, Dixit VM: Ubiquitin hydrolase Dub3 promotes oncogenic transformation by stabilizing Cdc25A. Nat Cell Biol. 2010 Apr;12(4):400-6. doi: 10.1038/ncb2041. Epub 2010 Mar 14. [PubMed:20228808 ]
  12. Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, Saper MA: Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998 May 15;93(4):617-25. [PubMed:9604936 ]