ID MPIP1_HUMAN Reviewed; 524 AA. AC P30304; Q8IZH5; Q96IL3; Q9H2F2; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 2. DT 27-MAR-2024, entry version 214. DE RecName: Full=M-phase inducer phosphatase 1; DE EC=3.1.3.48 {ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:14559997, ECO:0000305|PubMed:20360007}; DE AltName: Full=Dual specificity phosphatase Cdc25A; GN Name=CDC25A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ACTIVITY REGULATION, AND RP VARIANT GLY-182. RX PubMed=1836978; DOI=10.1016/0092-8674(91)90294-9; RA Galaktionov K.I., Beach D.; RT "Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: RT evidence for multiple roles of mitotic cyclins."; RL Cell 67:1181-1194(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Varmeh-Ziaie S., Manfredi J.J.; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-88. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 37-234 (ISOFORM 2). RX PubMed=11139144; DOI=10.1078/0171-9335-00115; RA Wegener S., Hampe W., Herrmann D., Schaller H.C.; RT "Alternative splicing in the regulatory region of the human phosphatases RT CDC25A and CDC25C."; RL Eur. J. Cell Biol. 79:810-815(2000). RN [6] RP INTERACTION WITH CHEK2, PHOSPHORYLATION AT SER-124 BY CHEK2, AND RP MUTAGENESIS OF SER-124. RX PubMed=11298456; DOI=10.1038/35071124; RA Falck J., Mailand N., Syljuaasen R.G., Bartek J., Lukas J.; RT "The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA RT synthesis."; RL Nature 410:842-847(2001). RN [7] RP UBIQUITINATION BY THE APC/C UBIQUITIN LIGASE COMPLEX, DOMAIN KEN BOX MOTIF, RP AND MUTAGENESIS OF 141-LYS--ASN-143. RX PubMed=12234927; DOI=10.1093/emboj/cdf491; RA Donzelli M., Squatrito M., Ganoth D., Hershko A., Pagano M., Draetta G.F.; RT "Dual mode of degradation of Cdc25 A phosphatase."; RL EMBO J. 21:4875-4884(2002). RN [8] RP PHOSPHORYLATION AT SER-124, AND MUTAGENESIS OF SER-124. RX PubMed=12399544; DOI=10.1073/pnas.182557299; RA Zhao H., Watkins J.L., Piwnica-Worms H.; RT "Disruption of the checkpoint kinase 1/cell division cycle 25A pathway RT abrogates ionizing radiation-induced S and G2 checkpoints."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14795-14800(2002). RN [9] RP PHOSPHORYLATION AT SER-124; SER-178; SER-279 AND SER-293, AND MUTAGENESIS RP OF SER-124; SER-178; SER-279 AND SER-293. RX PubMed=12676583; DOI=10.1016/s1535-6108(03)00048-5; RA Soerensen C.S., Syljuaesen R.G., Falck J., Schroeder T., Roennstrand L., RA Khanna K.K., Zhou B.-B., Bartek J., Lukas J.; RT "Chk1 regulates the S phase checkpoint by coupling the physiological RT turnover and ionizing radiation-induced accelerated proteolysis of RT Cdc25A."; RL Cancer Cell 3:247-258(2003). RN [10] RP INTERACTION WITH BTRC; CUL1 AND FBXW11, PHOSPHODEGRON MOTIF, RP PHOSPHORYLATION AT SER-76 AND SER-124, UBIQUITINATION, AND MUTAGENESIS OF RP SER-76; SER-79; ASP-81 AND SER-82. RX PubMed=14681206; DOI=10.1101/gad.1157503; RA Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W.; RT "SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein RT phosphatase."; RL Genes Dev. 17:3062-3074(2003). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, PHOSPHORYLATION, AND MUTAGENESIS RP OF CYS-431. RX PubMed=12676925; DOI=10.1074/jbc.m300229200; RA Xiao Z., Chen Z., Gunasekera A.H., Sowin T.J., Rosenberg S.H., Fesik S., RA Zhang H.; RT "Chk1 mediates S and G2 arrests through Cdc25A degradation in response to RT DNA-damaging agents."; RL J. Biol. Chem. 278:21767-21773(2003). RN [12] RP PHOSPHORYLATION AT SER-76; SER-124 AND SER-178, AND MUTAGENESIS OF SER-76; RP SER-124 AND SER-178. RX PubMed=12759351; DOI=10.1074/jbc.m302704200; RA Hassepass I., Voit R., Hoffmann I.; RT "Phosphorylation at serine 75 is required for UV-mediated degradation of RT human Cdc25A phosphatase at the S-phase checkpoint."; RL J. Biol. Chem. 278:29824-29829(2003). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, INTERACTION WITH CCNB1 AND RP YWHAE, PHOSPHORYLATION AT SER-178 AND THR-507, AND MUTAGENESIS OF SER-178; RP CYS-431; THR-507; LYS-514 AND ARG-520. RX PubMed=14559997; DOI=10.1128/mcb.23.21.7488-7497.2003; RA Chen M.-S., Ryan C.E., Piwnica-Worms H.; RT "Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase RT through 14-3-3 binding."; RL Mol. Cell. Biol. 23:7488-7497(2003). RN [14] RP ACTIVITY REGULATION. RX PubMed=16356754; DOI=10.1016/j.biocel.2005.10.010; RA Bachmann M., Kosan C., Xing P.X., Montenarh M., Hoffmann I., Moroy T.; RT "The oncogenic serine/threonine kinase Pim-1 directly phosphorylates and RT activates the G2/M specific phosphatase Cdc25C."; RL Int. J. Biochem. Cell Biol. 38:430-443(2006). RN [15] RP PHOSPHORYLATION AT SER-79; SER-82 AND SER-88. RX PubMed=19734889; DOI=10.1038/ncb1969; RA Melixetian M., Klein D.K., Soerensen C.S., Helin K.; RT "NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint."; RL Nat. Cell Biol. 11:1247-1253(2009). RN [16] RP PHOSPHORYLATION AT SER-82 AND SER-88. RX PubMed=20090422; DOI=10.4161/cc.9.3.10513; RA Soerensen C.S., Melixetian M., Klein D.K., Helin K.; RT "NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling."; RL Cell Cycle 9:450-455(2010). RN [17] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20360007; DOI=10.1074/jbc.m109.096552; RA Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I.; RT "Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at RT the G2/M transition."; RL J. Biol. Chem. 285:16978-16990(2010). RN [18] RP DEUBIQUITINATION BY USP17L2. RX PubMed=20228808; DOI=10.1038/ncb2041; RA Pereg Y., Liu B.Y., O'Rourke K.M., Sagolla M., Dey A., Komuves L., RA French D.M., Dixit V.M.; RT "Ubiquitin hydrolase Dub3 promotes oncogenic transformation by stabilizing RT Cdc25A."; RL Nat. Cell Biol. 12:400-406(2010). RN [19] RP PHOSPHORYLATION AT SER-513 AND SER-519 BY PLK3, UBIQUITINATION, AND RP MUTAGENESIS OF SER-513 AND SER-519. RX PubMed=21376736; DOI=10.1016/j.mrfmmm.2011.02.006; RA Myer D.L., Robbins S.B., Yin M., Boivin G.P., Liu Y., Greis K.D., RA Bahassi el M., Stambrook P.J.; RT "Absence of polo-like kinase 3 in mice stabilizes Cdc25A after DNA damage RT but is not sufficient to produce tumors."; RL Mutat. Res. 714:1-10(2011). RN [20] RP INTERACTION WITH HSP90AB1. RX PubMed=22843495; DOI=10.1093/hmg/dds303; RA Giessrigl B., Krieger S., Rosner M., Huttary N., Saiko P., Alami M., RA Messaoudi S., Peyrat J.F., Maciuk A., Gollinger M., Kopf S., Kazlauskas E., RA Mazal P., Szekeres T., Hengstschlaeger M., Matulis D., Jaeger W., RA Krupitza G.; RT "Hsp90 stabilizes Cdc25A and counteracts heat shock-mediated Cdc25A RT degradation and cell-cycle attenuation in pancreatic carcinoma cells."; RL Hum. Mol. Genet. 21:4615-4627(2012). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107 AND SER-321, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 336-496. RX PubMed=9604936; DOI=10.1016/s0092-8674(00)81190-3; RA Fauman E.B., Cogswell J.P., Lovejoy B., Rocque W.J., Holmes W., RA Montana V.G., Piwnica-Worms H., Rink M.J., Saper M.A.; RT "Crystal structure of the catalytic domain of the human cell cycle control RT phosphatase, Cdc25A."; RL Cell 93:617-625(1998). CC -!- FUNCTION: Tyrosine protein phosphatase which functions as a dosage- CC dependent inducer of mitotic progression (PubMed:1836978, CC PubMed:12676925, PubMed:14559997, PubMed:20360007). Directly CC dephosphorylates CDK1 and stimulates its kinase activity CC (PubMed:20360007). Also dephosphorylates CDK2 in complex with cyclin-E, CC in vitro (PubMed:20360007). {ECO:0000269|PubMed:12676925, CC ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:1836978, CC ECO:0000269|PubMed:20360007}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620; EC=3.1.3.48; CC Evidence={ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:14559997, CC ECO:0000305|PubMed:20360007}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685; CC Evidence={ECO:0000305|PubMed:20360007}; CC -!- ACTIVITY REGULATION: Stimulated by B-type cyclins (PubMed:1836978). CC Stimulated by PIM1-mediated phosphorylation (PubMed:16356754). CC {ECO:0000269|PubMed:16356754, ECO:0000269|PubMed:1836978}. CC -!- SUBUNIT: Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3 CC epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 CC is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. CC Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage. CC Interacts with CHEK2; mediates CDC25A phosphorylation and degradation CC in response to infrared-induced DNA damages. Interacts with HSP90AB1; CC prevents heat shock-mediated CDC25A degradation and contributes to cell CC cycle progression (PubMed:22843495). {ECO:0000269|PubMed:11298456, CC ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, CC ECO:0000269|PubMed:16356754, ECO:0000269|PubMed:22843495}. CC -!- INTERACTION: CC P30304; Q9BSU3: NAA11; NbExp=3; IntAct=EBI-747671, EBI-2585120; CC P30304; P04049: RAF1; NbExp=4; IntAct=EBI-747671, EBI-365996; CC P30304; P31946: YWHAB; NbExp=10; IntAct=EBI-747671, EBI-359815; CC P30304; P27348: YWHAQ; NbExp=3; IntAct=EBI-747671, EBI-359854; CC P30304; P63104: YWHAZ; NbExp=2; IntAct=EBI-747671, EBI-347088; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=CDC25A1; CC IsoId=P30304-1; Sequence=Displayed; CC Name=2; Synonyms=CDC25A2; CC IsoId=P30304-2; Sequence=VSP_000860; CC -!- DOMAIN: The phosphodegron motif mediates interaction with specific F- CC box proteins when phosphorylated. Putative phosphorylation sites at CC Ser-79 and Ser-82 appear to be essential for this interaction. CC {ECO:0000269|PubMed:12234927}. CC -!- PTM: Phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-279, Ser- CC 293 and Thr-507 during checkpoint mediated cell cycle arrest. Also CC phosphorylated by CHEK2 on Ser-124, Ser-279, and Ser-293 during CC checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and CC Thr-507 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CC CDC25A. Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-279 and Ser- CC 293 may also promote ubiquitin-dependent proteolysis of CDC25A by the CC SCF complex. Phosphorylation of CDC25A at Ser-76 by CHEK1 primes it for CC subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11. CC Phosphorylation by NEK11 is required for BTRC-mediated CC polyubiquitination and degradation. Phosphorylation by PIM1 leads to an CC increase in phosphatase activity. Phosphorylated by PLK3 following DNA CC damage, leading to promote its ubiquitination and degradation. CC {ECO:0000269|PubMed:11298456, ECO:0000269|PubMed:12399544, CC ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, CC ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:14559997, CC ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:19734889, CC ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:20228808, CC ECO:0000269|PubMed:21376736}. CC -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) CC ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase CC leading to its degradation by the proteasome. Ubiquitinated by a SCF CC complex containing BTRC and FBXW11 during S phase leading to its CC degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads CC to its stabilization. {ECO:0000269|PubMed:20228808}. CC -!- SIMILARITY: Belongs to the MPI phosphatase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40004/CDC25A"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdc25a/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M81933; AAA58415.1; -; mRNA. DR EMBL; AY137580; AAN11305.1; -; mRNA. DR EMBL; AF527417; AAM77917.1; -; Genomic_DNA. DR EMBL; BC007401; AAH07401.1; -; mRNA. DR EMBL; BC018642; AAH18642.1; -; mRNA. DR EMBL; AF277722; AAG41884.1; -; mRNA. DR CCDS; CCDS2760.1; -. [P30304-1] DR CCDS; CCDS2761.1; -. [P30304-2] DR PIR; A41648; A41648. DR RefSeq; NP_001780.2; NM_001789.2. [P30304-1] DR RefSeq; NP_963861.1; NM_201567.1. [P30304-2] DR RefSeq; XP_011532618.1; XM_011534316.1. DR PDB; 1C25; X-ray; 2.30 A; A=337-496. DR PDBsum; 1C25; -. DR AlphaFoldDB; P30304; -. DR SMR; P30304; -. DR BioGRID; 107428; 142. DR DIP; DIP-166N; -. DR ELM; P30304; -. DR IntAct; P30304; 48. DR MINT; P30304; -. DR STRING; 9606.ENSP00000303706; -. DR BindingDB; P30304; -. DR ChEMBL; CHEMBL3775; -. DR DrugCentral; P30304; -. DR DEPOD; CDC25A; -. DR GlyCosmos; P30304; 1 site, 1 glycan. DR GlyGen; P30304; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P30304; -. DR PhosphoSitePlus; P30304; -. DR BioMuta; CDC25A; -. DR DMDM; 50403734; -. DR EPD; P30304; -. DR jPOST; P30304; -. DR MassIVE; P30304; -. DR MaxQB; P30304; -. DR PaxDb; 9606-ENSP00000303706; -. DR PeptideAtlas; P30304; -. DR ProteomicsDB; 54652; -. [P30304-1] DR ProteomicsDB; 54653; -. [P30304-2] DR Antibodypedia; 1619; 1902 antibodies from 47 providers. DR DNASU; 993; -. DR Ensembl; ENST00000302506.8; ENSP00000303706.3; ENSG00000164045.12. [P30304-1] DR Ensembl; ENST00000351231.7; ENSP00000343166.3; ENSG00000164045.12. [P30304-2] DR GeneID; 993; -. DR KEGG; hsa:993; -. DR MANE-Select; ENST00000302506.8; ENSP00000303706.3; NM_001789.3; NP_001780.2. DR UCSC; uc003csh.2; human. [P30304-1] DR AGR; HGNC:1725; -. DR CTD; 993; -. DR DisGeNET; 993; -. DR GeneCards; CDC25A; -. DR HGNC; HGNC:1725; CDC25A. DR HPA; ENSG00000164045; Tissue enhanced (bone marrow, lymphoid tissue, testis). DR MIM; 116947; gene. DR neXtProt; NX_P30304; -. DR OpenTargets; ENSG00000164045; -. DR PharmGKB; PA26259; -. DR VEuPathDB; HostDB:ENSG00000164045; -. DR eggNOG; KOG3772; Eukaryota. DR GeneTree; ENSGT00940000160737; -. DR HOGENOM; CLU_014464_0_1_1; -. DR InParanoid; P30304; -. DR OMA; NSAPAQM; -. DR OrthoDB; 12481at2759; -. DR PhylomeDB; P30304; -. DR TreeFam; TF101056; -. DR BRENDA; 3.1.3.48; 2681. DR PathwayCommons; P30304; -. DR Reactome; R-HSA-1362277; Transcription of E2F targets under negative control by DREAM complex. DR Reactome; R-HSA-156711; Polo-like kinase mediated events. DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition. DR Reactome; R-HSA-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models. DR SignaLink; P30304; -. DR SIGNOR; P30304; -. DR BioGRID-ORCS; 993; 65 hits in 1186 CRISPR screens. DR ChiTaRS; CDC25A; human. DR EvolutionaryTrace; P30304; -. DR GeneWiki; CDC25A; -. DR GenomeRNAi; 993; -. DR Pharos; P30304; Tchem. DR PRO; PR:P30304; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P30304; Protein. DR Bgee; ENSG00000164045; Expressed in secondary oocyte and 135 other cell types or tissues. DR ExpressionAtlas; P30304; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0008283; P:cell population proliferation; TAS:UniProtKB. DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0045740; P:positive regulation of DNA replication; TAS:Reactome. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0110032; P:positive regulation of G2/MI transition of meiotic cell cycle; IBA:GO_Central. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0009314; P:response to radiation; IDA:UniProtKB. DR CDD; cd01530; Cdc25; 1. DR Gene3D; 3.40.250.10; Rhodanese-like domain; 1. DR InterPro; IPR000751; MPI_Phosphatase. DR InterPro; IPR001763; Rhodanese-like_dom. DR InterPro; IPR036873; Rhodanese-like_dom_sf. DR PANTHER; PTHR10828:SF46; M-PHASE INDUCER PHOSPHATASE 1; 1. DR PANTHER; PTHR10828; M-PHASE INDUCER PHOSPHATASE DUAL SPECIFICITY PHOSPHATASE CDC25; 1. DR Pfam; PF06617; M-inducer_phosp; 1. DR Pfam; PF00581; Rhodanese; 1. DR PRINTS; PR00716; MPIPHPHTASE. DR SMART; SM00450; RHOD; 1. DR SUPFAM; SSF52821; Rhodanese/Cell cycle control phosphatase; 1. DR PROSITE; PS50206; RHODANESE_3; 1. DR Genevisible; P30304; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Cell division; Hydrolase; KW Mitosis; Phosphoprotein; Protein phosphatase; Reference proteome; KW Ubl conjugation. FT CHAIN 1..524 FT /note="M-phase inducer phosphatase 1" FT /id="PRO_0000198641" FT DOMAIN 376..482 FT /note="Rhodanese" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173" FT REGION 264..317 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 74..84 FT /note="Phosphodegron" FT MOTIF 141..143 FT /note="KEN box" FT COMPBIAS 274..288 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 431 FT /evidence="ECO:0000305|PubMed:12676925, FT ECO:0000305|PubMed:14559997" FT MOD_RES 76 FT /note="Phosphoserine; by CHEK1" FT /evidence="ECO:0000269|PubMed:12759351, FT ECO:0000269|PubMed:14681206" FT MOD_RES 79 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000269|PubMed:19734889" FT MOD_RES 82 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000269|PubMed:19734889, FT ECO:0000269|PubMed:20090422" FT MOD_RES 88 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000269|PubMed:19734889, FT ECO:0000269|PubMed:20090422" FT MOD_RES 107 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 124 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000269|PubMed:11298456, FT ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12676583, FT ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:14681206" FT MOD_RES 178 FT /note="Phosphoserine; by CHEK1" FT /evidence="ECO:0000269|PubMed:12676583, FT ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:14559997" FT MOD_RES 279 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000269|PubMed:12676583" FT MOD_RES 293 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000269|PubMed:12676583" FT MOD_RES 321 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 507 FT /note="Phosphothreonine; by CHEK1" FT /evidence="ECO:0000269|PubMed:14559997" FT MOD_RES 513 FT /note="Phosphoserine; by PLK3" FT /evidence="ECO:0000269|PubMed:21376736" FT MOD_RES 519 FT /note="Phosphoserine; by PLK3" FT /evidence="ECO:0000269|PubMed:21376736" FT VAR_SEQ 144..183 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11139144, ECO:0000303|Ref.2" FT /id="VSP_000860" FT VARIANT 88 FT /note="S -> F (in dbSNP:rs3731499)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020932" FT VARIANT 182 FT /note="R -> G (in dbSNP:rs6771386)" FT /evidence="ECO:0000269|PubMed:1836978" FT /id="VAR_023532" FT VARIANT 182 FT /note="R -> W (in dbSNP:rs6771386)" FT /id="VAR_023533" FT MUTAGEN 76 FT /note="S->A: Abolishes ubiquitination and impairs FT CHEK1-dependent degradation following checkpoint FT activation." FT /evidence="ECO:0000269|PubMed:12759351, FT ECO:0000269|PubMed:14681206" FT MUTAGEN 79 FT /note="S->A: Abrogates interactions with BTRC and FBXW11 FT and prevents ubiquitination." FT /evidence="ECO:0000269|PubMed:14681206" FT MUTAGEN 81 FT /note="D->A: Abrogates interactions with BTRC and FBXW11 FT and prevents ubiquitination." FT /evidence="ECO:0000269|PubMed:14681206" FT MUTAGEN 82 FT /note="S->A: Abrogates interactions with BTRC and FBXW11 FT and prevents ubiquitination." FT /evidence="ECO:0000269|PubMed:14681206" FT MUTAGEN 124 FT /note="S->A: Abrogates phosphorylation by CHEK2 and FT infrared-induced degradation. Increases basal stability and FT impairs CHEK1-dependent degradation following checkpoint FT activation; when associated with A-178; A-279 and A-293." FT /evidence="ECO:0000269|PubMed:11298456, FT ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12676583, FT ECO:0000269|PubMed:12759351" FT MUTAGEN 141..143 FT /note="KEN->AAA: Prevents ubiquitination and subsequent FT degradation by the APC/C ubiquitin ligase complex." FT /evidence="ECO:0000269|PubMed:12234927" FT MUTAGEN 178 FT /note="S->A: Increases basal stability and impairs FT CHEK1-dependent degradation following checkpoint FT activation; when associated with A-124; A-279 and A-293. FT Abrogates 14-3-3 protein binding." FT /evidence="ECO:0000269|PubMed:12676583, FT ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:14559997" FT MUTAGEN 279 FT /note="S->A: Increases basal stability and impairs FT CHEK1-dependent degradation following checkpoint FT activation; when associated with A-124; A-178 and A-293." FT /evidence="ECO:0000269|PubMed:12676583" FT MUTAGEN 293 FT /note="S->A: Increases basal stability and impairs FT CHEK1-dependent degradation following checkpoint FT activation; when associated with A-124; A-178 and A-279." FT /evidence="ECO:0000269|PubMed:12676583" FT MUTAGEN 431 FT /note="C->S: Abolishes phosphatase activity." FT /evidence="ECO:0000269|PubMed:12676925, FT ECO:0000269|PubMed:14559997" FT MUTAGEN 507 FT /note="T->A: Abrogates 14-3-3 protein binding; increases FT binding to cyclin B1." FT /evidence="ECO:0000269|PubMed:14559997" FT MUTAGEN 513 FT /note="S->A: Increased stability following IR treatment." FT /evidence="ECO:0000269|PubMed:21376736" FT MUTAGEN 513 FT /note="S->D: Mimicks phosphorylation state, leading to FT promote degradation following IR treatment." FT /evidence="ECO:0000269|PubMed:21376736" FT MUTAGEN 514 FT /note="K->L: Abrogates binding to CCNB1; when associated FT with L-520." FT /evidence="ECO:0000269|PubMed:14559997" FT MUTAGEN 519 FT /note="S->A: Increased stability following IR treatment." FT /evidence="ECO:0000269|PubMed:21376736" FT MUTAGEN 519 FT /note="S->D: Mimicks phosphorylation state, leading to FT promote degradation following IR treatment." FT /evidence="ECO:0000269|PubMed:21376736" FT MUTAGEN 520 FT /note="R->L: Abrogates binding to CCNB1; when associated FT with L-514." FT /evidence="ECO:0000269|PubMed:14559997" FT CONFLICT 6..10 FT /note="EPPHR -> SPAP (in Ref. 1; AAA58415)" FT /evidence="ECO:0000305" FT CONFLICT 180..181 FT /note="PA -> QL (in Ref. 1; AAA58415)" FT /evidence="ECO:0000305" FT STRAND 341..344 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 362..369 FT /evidence="ECO:0007829|PDB:1C25" FT TURN 370..376 FT /evidence="ECO:0007829|PDB:1C25" FT STRAND 377..384 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 388..392 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 405..411 FT /evidence="ECO:0007829|PDB:1C25" FT TURN 412..414 FT /evidence="ECO:0007829|PDB:1C25" FT STRAND 423..430 FT /evidence="ECO:0007829|PDB:1C25" FT STRAND 432..436 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 437..451 FT /evidence="ECO:0007829|PDB:1C25" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 469..477 FT /evidence="ECO:0007829|PDB:1C25" FT HELIX 478..480 FT /evidence="ECO:0007829|PDB:1C25" FT STRAND 481..484 FT /evidence="ECO:0007829|PDB:1C25" SQ SEQUENCE 524 AA; 59087 MW; B2F6B792D4E6122B CRC64; MELGPEPPHR RRLLFACSPP PASQPVVKAL FGASAAGGLS PVTNLTVTMD QLQGLGSDYE QPLEVKNNSN LQRMGSSEST DSGFCLDSPG PLDSKENLEN PMRRIHSLPQ KLLGCSPALK RSHSDSLDHD IFQLIDPDEN KENEAFEFKK PVRPVSRGCL HSHGLQEGKD LFTQRQNSAP ARMLSSNERD SSEPGNFIPL FTPQSPVTAT LSDEDDGFVD LLDGENLKNE EETPSCMASL WTAPLVMRTT NLDNRCKLFD SPSLCSSSTR SVLKRPERSQ EESPPGSTKR RKSMSGASPK ESTNPEKAHE TLHQSLSLAS SPKGTIENIL DNDPRDLIGD FSKGYLFHTV AGKHQDLKYI SPEIMASVLN GKFANLIKEF VIIDCRYPYE YEGGHIKGAV NLHMEEEVED FLLKKPIVPT DGKRVIVVFH CEFSSERGPR MCRYVRERDR LGNEYPKLHY PELYVLKGGY KEFFMKCQSY CEPPSYRPMH HEDFKEDLKK FRTKSRTWAG EKSKREMYSR LKKL //