CDC25B (M-phase inducer phosphatase 2) is a dual-specificity phosphatase (EC 3.1.3.48) that activates cyclin-dependent kinases by removing inhibitory phosphates at Thr14 and Tyr15. Its primary substrate is CDK1-cyclin B, and it functions as a "starter phosphatase" that initiates mitotic entry at the centrosome during the G2/M transition. CDC25B contains a conserved C-terminal catalytic domain with the HCX5R motif (catalytic Cys473) and a divergent N-terminal regulatory domain. The enzyme is regulated by phosphorylation-dependent 14-3-3 protein binding (which controls nucleocytoplasmic shuttling), checkpoint kinases (CHEK1, MAPKAPK2), and redox-dependent inactivation via an intramolecular disulfide bond between Cys473 and Cys426. CDC25B localizes to the centrosome and spindle poles during mitosis and shuttles between nucleus and cytoplasm during interphase. It is overexpressed in many cancers and is considered a proto-oncogene.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B shuttles between nucleus and cytoplasm. 14-3-3 binding sequesters it in the cytoplasm during interphase, but it translocates to the nucleus as part of its activation cycle. Multiple studies confirm nuclear localization. Reason: IBA annotation is well supported. CDC25B is known to shuttle between nucleus and cytoplasm, with nuclear localization being part of its functional cycle for activating CDK1-cyclin B complexes (PMID:15173315, PMID:12764136). UniProt subcellular location also describes centrosomal and spindle pole localization, both of which require transit through the nucleus/cytoplasm. Supporting Evidence: PMID:15173315 Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B PMID:12764136 14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B is present in the cytoplasm, where it is sequestered by 14-3-3 proteins during interphase. It also functions at the centrosome, which is in the cytoplasm. Reason: IBA annotation is well supported. CDC25B localizes to cytoplasm during interphase via 14-3-3 binding and functions at the centrosome (a cytoplasmic structure) during the G2/M transition (PMID:15128871, PMID:15908796). Supporting Evidence: PMID:15173315 Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B |
| GO:0000086 G2/M transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B is a key regulator of the G2/M transition, functioning as a "starter phosphatase" that initiates activation of CDK1-cyclin B at the centrosome. Reason: This is one of the most well-established functions of CDC25B. The IBA annotation reflects the conserved core function across species. Multiple primary studies confirm CDC25B drives G2/M transition through dephosphorylation of CDK1 (PMID:20360007, PMID:1836978, PMID:17332740). Supporting Evidence: PMID:20360007 Overexpression of Cdc25A or Cdc25B promotes earlier assembly and activation of Cdk1-cyclin B complexes, whereas repression of these phosphatases by short hairpin RNA has a reverse effect PMID:1836978 cdc25A and cdc25B display endogenous tyrosine phosphatase activity that is stimulated several-fold, in the absence of cdc2, by stoichiometric addition of either cyclin B1 or B2 |
| GO:0004725 protein tyrosine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B is a dual-specificity phosphatase that removes phosphates from both phosphotyrosine and phosphothreonine residues on CDKs. The protein tyrosine phosphatase activity annotation captures the tyrosine phosphatase component. Reason: IBA annotation is correct. CDC25B dephosphorylates Tyr15 (and Thr14) on CDK1. The original characterization demonstrated endogenous tyrosine phosphatase activity (PMID:1836978). EC 3.1.3.48 classifies it as a protein-tyrosine-phosphatase. While CDC25B is technically a dual-specificity phosphatase, the protein tyrosine phosphatase activity term is appropriate since it does remove phosphotyrosine. Supporting Evidence: PMID:1836978 cdc25A and cdc25B display endogenous tyrosine phosphatase activity |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B positively regulates the G2/M transition by dephosphorylating and activating CDK1-cyclin B complexes. This is the core evolved function. Reason: This annotation accurately captures CDC25B's role as a positive regulator of mitotic entry. CDC25B dephosphorylation of CDK1 promotes G2/M transition (PMID:20360007, PMID:1836978). Supporting Evidence: PMID:20360007 Overexpression of Cdc25A or Cdc25B promotes earlier assembly and activation of Cdk1-cyclin B complexes |
| GO:0110032 positive regulation of G2/MI transition of meiotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: CDC25B has been implicated in meiotic cell cycle regulation. UniProt lists GO annotations for oocyte maturation and female meiosis I (IEA from Ensembl), consistent with a conserved role in meiotic G2/M transition. Reason: IBA annotations have undergone phylogenetic review and are generally at the right level of specificity. CDC25B is known to function in oocyte maturation and meiotic cell cycle entry in vertebrates, consistent with this annotation. UniProt lists IEA annotations for female meiosis I and oocyte maturation based on Ensembl data. |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: CDC25B localizes to spindle poles during mitosis, as demonstrated by immunofluorescence with phospho-specific antibodies. Reason: This IEA annotation is confirmed by direct experimental evidence. UniProt explicitly lists spindle pole as a subcellular location based on PMID:15908796. The IDA annotation for the same term (below) provides the experimental backing. Supporting Evidence: PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis |
| GO:0004721 phosphoprotein phosphatase activity | IEA GO_REF:0000043 | ACCEPT | Summary: CDC25B has phosphoprotein phosphatase activity, dephosphorylating CDK1 at inhibitory Thr14 and Tyr15 residues. Reason: This IEA annotation from UniProt keyword mapping is correct. CDC25B is classified as EC 3.1.3.48, a protein-tyrosine-phosphatase, and its function is to dephosphorylate CDK1. This broader term encompasses the more specific protein tyrosine phosphatase activity also annotated. Supporting Evidence: PMID:20360007 dephosphorylation is catalyzed by the dual specific Cdc25 phosphatases |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate IEA annotation for protein tyrosine phosphatase activity from combined automated methods. Reason: Same term as the IBA annotation above; this IEA confirms via automated methods what is well established experimentally. CDC25B is classified as EC 3.1.3.48 and has demonstrated tyrosine phosphatase activity (PMID:1836978). |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: CDC25B localizes to the centrosome, where it initiates activation of CDK1-cyclin B at the G2/M transition. Reason: IEA annotation is well supported by experimental data. UniProt lists centrosome as a subcellular location with experimental evidence from PMID:15128871, PMID:15311285, and PMID:15908796. CDC25B functions as a "starter phosphatase" at the centrosome. Supporting Evidence: PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: CDC25B is a phosphatase (hydrolase) that cleaves phosphoester bonds on CDK substrates. Reason: This is a very broad parent term for the more specific phosphatase activities also annotated. While not very informative on its own, it is not incorrect as phosphatases are hydrolases. The IEA from keyword mapping is acceptable as a broader classification. |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: CDC25B is involved in cell division through its role in activating CDK1-cyclin B for mitotic entry and its requirement for cytokinesis. Reason: This IEA from UniProt keyword mapping is correct. CDC25B promotes cell division through its role at G2/M transition and its requirement for abscission during cytokinesis (PMID:17332740). This broad term encompasses both functions. Supporting Evidence: PMID:17332740 PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B |
| GO:1902751 positive regulation of cell cycle G2/M phase transition | IEA GO_REF:0000002 | ACCEPT | Summary: CDC25B positively regulates the G2/M phase transition by dephosphorylating CDK1. Reason: This IEA annotation from InterPro mapping is correct and consistent with the IBA and IDA annotations for GO:0010971 (positive regulation of G2/M transition of mitotic cell cycle). This is the core function of CDC25B. |
| GO:0005515 protein binding | IPI PMID:10713667 Specific interaction between 14-3-3 isoforms and the human C... | MODIFY | Summary: PMID:10713667 demonstrates specific interaction between 14-3-3 isoforms (particularly zeta and eta) and CDC25B. This is a functionally significant interaction regulating CDC25B localization and activity. Reason: The interaction with 14-3-3 proteins is well documented and functionally significant, but "protein binding" is too vague per curation guidelines. The interaction with 14-3-3 proteins should be annotated with a more specific term. CDC25B binds 14-3-3 via phosphoserine motifs, and this regulates its subcellular localization and activity. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:10713667 CDC25 dual-specificity phosphatases are essential regulators that activate cyclin-dependent kinases (CDKs) at critical stages of the cell cycle... a specific, strong interaction between CDC25B and 14-3-3zeta and eta isoforms is revealed by a deletion of 288 residues in the amino-terminal region of CDC25B |
| GO:0005515 protein binding | IPI PMID:12764136 14-3-3 acts as an intramolecular bridge to regulate cdc25B l... | MODIFY | Summary: PMID:12764136 shows 14-3-3 acts as an intramolecular bridge to regulate CDC25B localization and activity. This is a specific 14-3-3 binding interaction. Reason: Should use a more specific term than protein binding. This study demonstrates 14-3-3 binding to CDC25B. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12764136 14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity |
| GO:0005515 protein binding | IPI PMID:12766774 Dual phosphorylation controls Cdc25 phosphatases and mitotic... | MODIFY | Summary: PMID:12766774 describes dual phosphorylation controlling Cdc25 phosphatases and mitotic entry, likely involving checkpoint kinase-dependent 14-3-3 binding. Reason: Protein binding is too vague. The context from the title suggests phosphorylation- dependent interactions controlling CDC25 function, likely 14-3-3 binding. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:12766774 Dual phosphorylation controls Cdc25 phosphatases and mitotic entry |
| GO:0005515 protein binding | IPI PMID:12871587 Interaction of 14-3-3 with Bid during seizure-induced neuron... | UNDECIDED | Summary: PMID:12871587 is about interaction of 14-3-3 with Bid during seizure-induced neuronal death. The relevance to CDC25B is unclear from the abstract. Reason: This paper is primarily about 14-3-3 interaction with Bid in neuronal death contexts. It is not clear how this directly supports a CDC25B protein binding annotation. Unable to verify relevance without full text access. Supporting Evidence: PMID:12871587 Interaction of 14-3-3 with Bid during seizure-induced neuronal death |
| GO:0005515 protein binding | IPI PMID:15173315 Binding of 14-3-3beta but not 14-3-3sigma controls the cytop... | MODIFY | Summary: PMID:15173315 demonstrates 14-3-3beta binding to CDC25B controls cytoplasmic localization. This is a specific and functionally relevant interaction. Reason: Should use a more specific term. This study specifically examines 14-3-3 binding to CDC25B and its effects on subcellular localization. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:15173315 Binding of 14-3-3beta but not 14-3-3sigma controls the cytoplasmic localization of CDC25B |
| GO:0005515 protein binding | IPI PMID:15629715 MAPKAP kinase-2 is a cell cycle checkpoint kinase that regul... | MODIFY | Summary: PMID:15629715 shows MAPKAPK2 phosphorylates CDC25B at Ser323, creating a 14-3-3 binding site. The interaction demonstrated is between CDC25B and its upstream kinase MAPKAPK2 and downstream binding partner 14-3-3. Reason: Protein binding is too vague. The CDC25B interaction described involves both kinase binding (MAPKAPK2) and 14-3-3 binding. The 14-3-3 binding is the more specific annotation. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:15629715 MAPKAP kinase-2 is directly responsible for Cdc25B/C phosphorylation and 14-3-3 binding in vitro and in response to UV-induced DNA damage within mammalian cells |
| GO:0005515 protein binding | IPI PMID:16672277 Amino acids C-terminal to the 14-3-3 binding motif in CDC25B... | MODIFY | Summary: PMID:16672277 examines amino acids C-terminal to the 14-3-3 binding motif in CDC25B that affect 14-3-3 binding efficiency. Specific 14-3-3 interaction study. Reason: This is specifically about 14-3-3 binding to CDC25B and should be annotated with the more specific term. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:16672277 Amino acids C-terminal to the 14-3-3 binding motif in CDC25B affect the efficiency of 14-3-3 binding |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: PMID:26496610 is a large-scale interactome study. Protein binding from high-throughput studies is generally uninformative without specific partner context. Reason: High-throughput interactome study. Protein binding annotations from such studies do not provide specific functional information about CDC25B interactions. Supporting Evidence: PMID:26496610 A human interactome in three quantitative dimensions organized by stoichiometries and abundances |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: PMID:28514442 is a large-scale interactome mapping study. Reason: High-throughput interactome study providing uninformative protein binding annotation. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: PMID:32296183 is a large-scale binary interactome mapping study. Reason: High-throughput interactome study. Generic protein binding annotation is not informative for functional annotation. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: PMID:33961781 is a large-scale proteome-scale interactome study. Reason: High-throughput interactome study. Generic protein binding is uninformative. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: PMID:35271311 (OpenCell) is a large-scale endogenous tagging and interactome study. Reason: High-throughput study. Generic protein binding is not informative for CDC25B functional annotation. Supporting Evidence: PMID:35271311 Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: PMID:36931259 describes a chaperone-like role for 14-3-3 proteins. The interaction with CDC25B is a known 14-3-3 client interaction. Reason: Should use the more specific 14-3-3 protein binding term. CDC25B is a well-known 14-3-3 client protein. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human cells |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: PMID:40205054 is a large-scale multimodal cell map study. Reason: High-throughput study. Generic protein binding is not informative. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics |
| GO:0005515 protein binding | IPI PMID:7644510 14-3-3 proteins associate with cdc25 phosphatases. | MODIFY | Summary: PMID:7644510 is one of the original studies demonstrating 14-3-3 association with cdc25 phosphatases via yeast two-hybrid screen. This is a functionally significant interaction. Reason: Should use the more specific 14-3-3 protein binding term. This foundational paper identified 14-3-3 epsilon and beta as CDC25B-interacting proteins. Proposed replacements: 14-3-3 protein binding Supporting Evidence: PMID:7644510 Two members of the 14-3-3 protein family have been isolated in a yeast two-hybrid screen designed to identify proteins that interact with the human cdc25A and cdc25B phosphatases |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for nuclear localization, consistent with the IBA annotation above. Reason: Consistent with the IBA annotation and known biology of CDC25B nuclear-cytoplasmic shuttling. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for cytoplasmic localization, consistent with the IBA annotation above. Reason: Consistent with the IBA annotation and known cytoplasmic localization of CDC25B during interphase via 14-3-3 sequestration. |
| GO:0000086 G2/M transition of mitotic cell cycle | TAS Reactome:R-HSA-69275 | ACCEPT | Summary: TAS annotation from Reactome G2/M Transition pathway. CDC25B is a central component of this pathway. Reason: Reactome correctly includes CDC25B in the G2/M transition pathway. This is the core biological process for CDC25B. |
| GO:0004721 phosphoprotein phosphatase activity | TAS Reactome:R-HSA-170153 | ACCEPT | Summary: TAS from Reactome pathway for dephosphorylation of nuclear Cyclin B1:phospho-Cdc2 complexes by Cdc25 phosphatases. Reason: Correctly annotates CDC25B's phosphoprotein phosphatase activity in the context of dephosphorylating CDK1-cyclin B complexes in the nucleus. |
| GO:0004721 phosphoprotein phosphatase activity | TAS Reactome:R-HSA-170161 | ACCEPT | Summary: TAS from Reactome pathway for dephosphorylation of cytoplasmic Cyclin B1/B2: phospho-Cdc2 complexes specifically by CDC25B. Reason: Correctly annotates CDC25B's phosphoprotein phosphatase activity. Reactome R-HSA-170161 specifically names CDC25B as the phosphatase for cytoplasmic CDK1-cyclin B dephosphorylation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9929935 | ACCEPT | Summary: TAS from Reactome pathway CCNA:CDK1 phosphorylates CDC25B, placing CDC25B in the nucleoplasm. Reason: CDC25B is phosphorylated by Cyclin A:CDK1 complexes in the nucleus, consistent with nucleoplasmic localization during parts of its functional cycle. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:20360007 Cdc25 phosphatases are required for timely assembly of CDK1-... | ACCEPT | Summary: PMID:20360007 directly demonstrates that CDC25B has phosphoprotein phosphatase activity, dephosphorylating CDK1 to promote assembly and activation of CDK1-cyclin B complexes at G2/M. Reason: Direct experimental demonstration (IDA) of CDC25B phosphatase activity. The study shows overexpression of CDC25B promotes CDK1-cyclin B assembly and activation while knockdown inhibits it (PMID:20360007). Supporting Evidence: PMID:20360007 Overexpression of Cdc25A or Cdc25B promotes earlier assembly and activation of Cdk1-cyclin B complexes, whereas repression of these phosphatases by short hairpin RNA has a reverse effect, leading to a substantial decrease in amounts of cyclin B-bound Cdk1 in G(2) and mitosis |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IDA PMID:20360007 Cdc25 phosphatases are required for timely assembly of CDK1-... | ACCEPT | Summary: PMID:20360007 directly demonstrates CDC25B positively regulates G2/M transition through effects on CDK1-cyclin B complex assembly and activation. Reason: Direct experimental evidence (IDA) confirming CDC25B's role as a positive regulator of G2/M transition. Overexpression accelerates G2/M while knockdown delays it (PMID:20360007). Supporting Evidence: PMID:20360007 Cdc25A and Cdc25B, but not Cdc25C phosphatases have an effect on timing and efficiency of cyclin-kinase complex formation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863007 | ACCEPT | Summary: TAS from Reactome pathway for p25-bound CDK5 phosphorylation of CDC25B, placing CDC25B in the cytosol. Reason: CDC25B is present in the cytosol as part of its nucleocytoplasmic shuttling and centrosomal localization cycle. Reactome places it in the cytosol for CDK5-mediated phosphorylation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-170120 | ACCEPT | Summary: TAS from Reactome for translocation of Cdc25B to the cytoplasm, implying nucleoplasmic origin. Reason: CDC25B translocates from nucleus to cytoplasm, consistent with nucleoplasmic localization before translocation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-170153 | ACCEPT | Summary: TAS from Reactome for dephosphorylation of nuclear Cyclin B1:phospho-Cdc2 complexes, placing CDC25B in nucleoplasm. Reason: CDC25B dephosphorylates CDK1-cyclin B complexes in the nucleus, consistent with nucleoplasmic localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-170159 | ACCEPT | Summary: TAS from Reactome for translocation of Cdc25 to the nucleus. Reason: CDC25B translocates to the nucleus as part of its activation cycle. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926524 | ACCEPT | Summary: TAS from Reactome for MITF-M-dependent CDC25B gene expression, placing CDC25B in the nucleoplasm. Reason: Consistent with nucleoplasmic localization of CDC25B. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170120 | ACCEPT | Summary: TAS from Reactome for translocation of Cdc25B to the cytoplasm. Reason: CDC25B translocates to the cytoplasm/cytosol during its regulation cycle, where it is sequestered by 14-3-3 proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170159 | ACCEPT | Summary: TAS from Reactome for translocation of Cdc25 to the nucleus, implying cytosolic origin before translocation. Reason: CDC25B is in the cytosol before translocating to the nucleus. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-170161 | ACCEPT | Summary: TAS from Reactome for dephosphorylation of cytoplasmic Cyclin B1/B2: phospho-Cdc2 complexes by CDC25B. Reason: CDC25B dephosphorylates CDK1-cyclin B complexes in the cytosol, consistent with its centrosomal activation function. |
| GO:0006468 protein phosphorylation | IDA PMID:17332740 Rho GTPases regulate PRK2/PKN2 to control entry into mitosis... | REMOVE | Summary: CRITICAL MISANNOTATION: CDC25B is a PHOSPHATASE (EC 3.1.3.48), NOT a kinase. UniProt states it "Directly dephosphorylates CDK1 and stimulates its kinase activity." PMID:17332740 describes CDC25B as "the phosphatase required for activation of mitotic cyclin/Cdk1 complexes" - it dephosphorylates CDK1 to activate it. Annotating a phosphatase to "protein phosphorylation" is incorrect. Reason: CDC25B is a phosphatase that removes phosphate groups from CDK1. The paper PMID:17332740 describes PRK2/PKN2 as the kinase that phosphorylates CDC25B, and CDC25B as the phosphatase downstream. The annotation of CDC25B to "protein phosphorylation" (GO:0006468) confuses the fact that CDC25B is a substrate of phosphorylation with CDC25B performing phosphorylation. CDC25B performs dephosphorylation, not phosphorylation. Supporting Evidence: PMID:17332740 PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B, the phosphatase required for activation of mitotic cyclin/Cdk1 complexes at the G2/M transition |
| GO:0032467 positive regulation of cytokinesis | IMP PMID:17332740 Rho GTPases regulate PRK2/PKN2 to control entry into mitosis... | KEEP AS NON CORE | Summary: PMID:17332740 demonstrates that CDC25B is required for abscission during cytokinesis in an ECT2-dependent manner, supporting a role in positive regulation of cytokinesis. Reason: While the core function of CDC25B is G2/M transition regulation, the role in cytokinesis is a secondary function demonstrated by IMP evidence. The paper shows PRK2 controls exit from cytokinesis through CDC25B and ECT2 (PMID:17332740). UniProt also notes CDC25B is "Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner." This is a real but non-core function. Supporting Evidence: PMID:17332740 PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B |
| GO:0045931 positive regulation of mitotic cell cycle | IMP PMID:17332740 Rho GTPases regulate PRK2/PKN2 to control entry into mitosis... | ACCEPT | Summary: PMID:17332740 shows CDC25B positively regulates mitotic cell cycle entry via PRK2-dependent phosphorylation and activation. Reason: This annotation is correct. CDC25B promotes entry into mitosis by activating CDK1-cyclin B complexes. The paper demonstrates PRK2 phosphorylates and activates CDC25B for mitotic entry (PMID:17332740). This is consistent with the core function of CDC25B. Supporting Evidence: PMID:17332740 PRK2 is required for abscission of the midbody at the end of the cell division cycle and for phosphorylation and activation of Cdc25B, the phosphatase required for activation of mitotic cyclin/Cdk1 complexes at the G2/M transition |
| GO:0000086 G2/M transition of mitotic cell cycle | TAS PMID:12400006 Human pEg3 kinase associates with and phosphorylates CDC25B ... | ACCEPT | Summary: PMID:12400006 describes pEg3 kinase associating with and phosphorylating CDC25B, with implications for G2/M cell cycle regulation. Reason: CDC25B's role in G2/M transition is well established. This paper provides additional evidence by showing pEg3 kinase regulates CDC25B at the G2/M boundary (PMID:12400006). Supporting Evidence: PMID:12400006 CDC25B is one of the three CDC25 phosphatase genes identified in human. It is thought to regulate the G2/M progression by dephosphorylating and activating the CDK/cyclin complexes |
| GO:0000922 spindle pole | IDA PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome an... | ACCEPT | Summary: PMID:15908796 demonstrates by immunofluorescence with phospho-specific antibodies that CDC25B phosphorylated at Ser169 by pEg3 localizes to spindle poles during mitosis. Reason: Direct experimental evidence (IDA) for spindle pole localization. The study uses phosphoepitope-specific antibodies to show the phosphorylated form of CDC25B at spindle poles during mitosis (PMID:15908796). UniProt also lists spindle pole as a confirmed subcellular location. Supporting Evidence: PMID:15908796 using phosphoepitope-specific antibodies we show that serine 169 is phosphorylated in vivo, that this phosphorylated form of CDC25B accumulates during mitosis, and is localized to the centrosomes |
| GO:0005813 centrosome | IDA PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome an... | ACCEPT | Summary: PMID:15908796 directly demonstrates CDC25B localization to the centrosome during mitosis, confirmed by phospho-specific antibodies for Ser169. Reason: Direct experimental evidence (IDA) for centrosomal localization. CDC25B functions as a "starter phosphatase" at the centrosome, and this is one of the key localization sites for its G2/M function. UniProt confirms centrosome as a subcellular location with multiple supporting references. Supporting Evidence: PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome and the spindle poles at mitosis |
| GO:0019901 protein kinase binding | IPI PMID:12400006 Human pEg3 kinase associates with and phosphorylates CDC25B ... | ACCEPT | Summary: PMID:12400006 demonstrates that pEg3 (MELK) kinase physically associates with CDC25B in vitro and in vivo, and phosphorylates CDC25B at Ser323. Reason: CDC25B binds multiple protein kinases including pEg3/MELK (PMID:12400006), AURKA (PMID:15128871), CHEK1 (PMID:15311285), and MAPKAPK2 (PMID:15629715). These are functionally significant interactions as CDC25B is a substrate of these kinases. Protein kinase binding is an appropriate term. Supporting Evidence: PMID:12400006 pEg3 is also able to specifically associate with CDC25B in vitro and in vivo |
| GO:0019901 protein kinase binding | IPI PMID:15908796 CDC25B phosphorylated by pEg3 localizes to the centrosome an... | ACCEPT | Summary: PMID:15908796 confirms pEg3 kinase interaction with CDC25B, showing phosphorylation-dependent localization effects. Reason: Confirms protein kinase binding between pEg3/MELK and CDC25B. The study shows pEg3 phosphorylates CDC25B at Ser169 and this interaction controls centrosomal localization (PMID:15908796). Supporting Evidence: PMID:15908796 we study the phosphorylation of CDC25B at mitosis by the kinase pEg3, a member of the KIN1/PAR-1/MARK family |
| GO:0000278 mitotic cell cycle | TAS PMID:1836978 Specific activation of cdc25 tyrosine phosphatases by B-type... | ACCEPT | Summary: PMID:1836978 is the original characterization of CDC25B showing it has tyrosine phosphatase activity activated by B-type cyclins and is involved in the mitotic cell cycle. Reason: Foundational paper establishing CDC25B as a mitotic cell cycle regulator. The study shows CDC25B is activated by cyclin B1/B2 and functions in mitotic regulation (PMID:1836978). Supporting Evidence: PMID:1836978 cdc25A and cdc25B display endogenous tyrosine phosphatase activity that is stimulated several-fold, in the absence of cdc2, by stoichiometric addition of either cyclin B1 or B2 but not A or D1 |
| GO:0004725 protein tyrosine phosphatase activity | TAS PMID:1836978 Specific activation of cdc25 tyrosine phosphatases by B-type... | ACCEPT | Summary: PMID:1836978 demonstrates endogenous tyrosine phosphatase activity of CDC25B that is stimulated by B-type cyclins. Reason: The original study demonstrating CDC25B has tyrosine phosphatase activity. This is the core enzymatic activity of CDC25B (PMID:1836978). Supporting Evidence: PMID:1836978 cdc25A and cdc25B display endogenous tyrosine phosphatase activity |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:8276402 Chromosome mapping of human CDC25A and CDC25B phosphatases. | MARK AS OVER ANNOTATED | Summary: PMID:8276402 maps CDC25A and CDC25B chromosomal locations and discusses their potential as oncogenes due to their role in promoting cell division. No direct experimental evidence for cell proliferation regulation is provided. Reason: PMID:8276402 is a chromosome mapping study that only mentions the potential role of CDC25B as an oncogene based on its function in cell division. It does not directly demonstrate positive regulation of cell population proliferation. While CDC25B overexpression is associated with cancer, this is a pleiotropic effect rather than a core functional annotation. Supporting Evidence: PMID:8276402 the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division |
| GO:0000278 mitotic cell cycle | TAS PMID:9188863 Alternative splicing of the human CDC25B tyrosine phosphatas... | ACCEPT | Summary: PMID:9188863 identifies alternative splice variants of CDC25B and shows their cell cycle regulation in G2 phase. Reason: The study confirms CDC25B expression is cell cycle regulated, peaking in G2, and that the variants function as mitotic inducers (PMID:9188863). Supporting Evidence: PMID:9188863 In primary fibroblasts and in HeLa cells the CDC25B expression is cell cycle regulated, reaching a maximum in G2-phase |
| GO:0004725 protein tyrosine phosphatase activity | TAS PMID:9188863 Alternative splicing of the human CDC25B tyrosine phosphatas... | ACCEPT | Summary: PMID:9188863 confirms CDC25B splice variants have tyrosine phosphatase activity with different levels of activity. Reason: The study demonstrates all three CDC25B splice variants have phosphatase activity (PMID:9188863), confirming the protein tyrosine phosphatase annotation. Supporting Evidence: PMID:9188863 In vitro, CDC25B1 phosphatase is slightly more active than CDC25B2 and B3 |
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