WEE1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000086 G2/M transition of mitotic cell cycle	TAS Reactome:R-HSA-69275	MODIFY	Summary: WEE1 restrains, rather than executes, the G2/M transition. Reason: WEE1 phosphorylates CDK1 Tyr15 to hold cyclin B1-CDK1 inactive, so its role is negative regulation of the G2/M transition, which the gene already carries by IDA and IBA. Proposed replacements: negative regulation of G2/M transition of mitotic cell cycle Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2
GO:0000278 mitotic cell cycle	IEA GO_REF:0000002	MODIFY	Summary: Correct but very general; the specific supported process is negative regulation of G2/M. Reason: The InterPro-based mapping is true but uninformative. The experimentally supported, more specific process already on this gene is negative regulation of the G2/M transition through inhibitory CDK1 Tyr15 phosphorylation. Proposed replacements: negative regulation of G2/M transition of mitotic cell cycle Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2
GO:0000287 magnesium ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Magnesium is the catalytic cofactor of the kinase domain. Reason: UniProt records two Mg2+ ions per subunit from the human WEE1 kinase-domain crystal structure. The term is accurate but describes a cofactor of the core kinase activity, not a separate function. Supporting Evidence: file:human/WEE1/WEE1-uniprot.txt Note=Binds 2 magnesium ions per subunit. {ECO:0000269\|PubMed:15837193}
GO:0004672 protein kinase activity	IEA GO_REF:0000120	MODIFY	Summary: Generic protein kinase activity; the demonstrated activity is tyrosine-directed. Reason: Human WEE1 phosphorylates CDK1 exclusively on Tyr15 and not Thr14, so the specific supported term is protein tyrosine kinase activity, already carried by this gene with direct evidence. The generic term is also what PAINT placed at the family root (PTN000113601), which spans eIF2-alpha Ser/Thr kinases. Proposed replacements: protein tyrosine kinase activity Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:15837193 Although Wee1A is functionally a tyrosine kinase, in sequence and structure it most closely resembles serine/threonine kinases such as Chk1 and cAMP kinases
GO:0004713 protein tyrosine kinase activity	EXP PMID:8348613 Human wee1 maintains mitotic timing by protecting the nucleu...	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	IDA PMID:7743995 Regulation of the human WEE1Hu CDK tyrosine 15-kinase during...	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	IDA PMID:8428596 Human Wee1 kinase inhibits cell division by phosphorylating ...	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	TAS PMID:7774574 Cell cycle regulation of human WEE1.	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-170070	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-170156	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-174164	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-69195	ACCEPT	Summary: WEE1 phosphorylates the inhibitory Tyr15 of cyclin-bound CDKs. Reason: Purified human WEE1 phosphorylates cyclin-bound CDK1 on Tyr15 but not Thr14, endogenous WEE1 phosphorylates several cyclin-associated CDKs on Tyr15, and a Lys114 (ATP-site lysine) mutant loses both kinase and mitotic-inhibitor activity. Antibody depletion shows WEE1 supplies most CDK1-Tyr15 kinase activity in HeLa lysates. The structural resemblance of the WEE1 kinase domain to Ser/Thr kinases does not change its demonstrated tyrosine specificity. The IBA is placed at PTN008510964, seeded by human WEE1, Drosophila Wee1 and Xenopus Wee2-A; human WEE1 is a descendant and has its own direct evidence, so the inheritance is sound. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7774574 Antibody depletion experiments demonstrate that WEE1 accounts for most of the activity that phosphorylates CDC2 on Tyr15 in an in vitro assay of HeLa cell lysates
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: WEE1 is a soluble, non-receptor protein tyrosine kinase (EC 2.7.10.2). Reason: WEE1 has no transmembrane segment, is a nuclear protein, and directly phosphorylates CDK1 Tyr15; this is the most specific accurate molecular function term for its catalytic activity. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0005515 protein binding	IPI PMID:15070733 M-phase kinases induce phospho-dependent ubiquitination of s...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: PLK1 phosphorylates WEE1 Ser53 to create a beta-TrCP phosphodegron; WEE1 is the substrate. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes. Supporting Evidence: PMID:15070733 recognition of Wee1A by beta-TrCP depended on phosphorylation
GO:0005515 protein binding	IPI PMID:15070733 M-phase kinases induce phospho-dependent ubiquitination of s...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: FBXW11 (beta-TrCP2) recognises phosphorylated WEE1 for SCF-mediated ubiquitination; WEE1 is the substrate. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes. Supporting Evidence: PMID:15070733 recognition of Wee1A by beta-TrCP depended on phosphorylation
GO:0005515 protein binding	IPI PMID:15070733 M-phase kinases induce phospho-dependent ubiquitination of s...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: BTRC (beta-TrCP1) recognises phosphorylated WEE1 for SCF-mediated ubiquitination; WEE1 is the substrate. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes. Supporting Evidence: PMID:15070733 recognition of Wee1A by beta-TrCP depended on phosphorylation
GO:0005515 protein binding	IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 zeta binds phosphorylated WEE1 as a client in proteomic screens. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:15778465 Targeted proteomic analysis of 14-3-3 sigma, a p53 effector ...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 sigma binds phosphorylated WEE1 as a client in proteomic screens. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: FBXW11 (beta-TrCP2) recognises phosphorylated WEE1 for SCF-mediated ubiquitination; WEE1 is the substrate. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: PLK1 phosphorylates WEE1 Ser53 to create a beta-TrCP phosphodegron; WEE1 is the substrate. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 zeta binds phosphorylated WEE1 as a client in proteomic screens. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 sigma binds phosphorylated WEE1 as a client in proteomic screens. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 epsilon binds phosphorylated WEE1 as a client in a proteomic screen. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	REMOVE	Summary: Generic protein binding; the interaction regulates WEE1 rather than defining a WEE1 activity. Reason: 14-3-3 zeta binds phosphorylated WEE1 as a client in proteomic screens. Bare protein binding (GO:0005515) is uninformative and is removed under the repository protein-binding policy; removal does not mean the reported interaction is false. No more informative molecular function on the WEE1 side is supported, because WEE1 is the phosphorylated substrate or client in these complexes.
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP is the phosphate donor for WEE1 catalysis. Reason: Accurate and implied by the kinase reaction (the Lys114 ATP-site mutant is inactive), but a substrate-binding description of the core kinase activity rather than an independent function. Supporting Evidence: PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: WEE1 is a nuclear protein and acts on CDK1 in the nucleus. Reason: Heald et al. showed human WEE1 is nuclear and protects the nucleus from cytoplasmically activated CDK1; UniProt records nuclear localization from this study. The IBA from PTN000113601 is seeded by human WEE1 itself and many family members, which is expected and not circular. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005634 nucleus	IDA PMID:8348613 Human wee1 maintains mitotic timing by protecting the nucleu...	ACCEPT	Summary: WEE1 is a nuclear protein and acts on CDK1 in the nucleus. Reason: Heald et al. showed human WEE1 is nuclear and protects the nucleus from cytoplasmically activated CDK1; UniProt records nuclear localization from this study. The IBA from PTN000113601 is seeded by human WEE1 itself and many family members, which is expected and not circular. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: WEE1 is a nuclear protein and acts on CDK1 in the nucleus. Reason: Heald et al. showed human WEE1 is nuclear and protects the nucleus from cytoplasmically activated CDK1; UniProt records nuclear localization from this study. The IBA from PTN000113601 is seeded by human WEE1 itself and many family members, which is expected and not circular. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005634 nucleus	TAS PMID:8348613 Human wee1 maintains mitotic timing by protecting the nucleu...	ACCEPT	Summary: WEE1 is a nuclear protein and acts on CDK1 in the nucleus. Reason: Heald et al. showed human WEE1 is nuclear and protects the nucleus from cytoplasmically activated CDK1; UniProt records nuclear localization from this study. The IBA from PTN000113601 is seeded by human WEE1 itself and many family members, which is expected and not circular. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-156699	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-170070	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-170156	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-174164	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-69195	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9929535	ACCEPT	Summary: WEE1 acts on soluble cyclin-CDK complexes in the nucleoplasm. Reason: Reactome places the WEE1 reactions on cyclin-CDK complexes in the nucleoplasm; this is consistent with the experimentally established nuclear localization and is a specific, accurate location. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis file:human/WEE1/WEE1-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269\|PubMed:8348613}
GO:0005730 nucleolus	IDA GO_REF:0000052	UNDECIDED	Summary: HPA nucleolar signal is not supported by the primary localization studies. Reason: The primary studies establish nuclear WEE1, and McGowan and Russell (PMID:7774574, full text, as summarised in the deep-research report) describe transfected WEE1 as excluded from nucleoli, which conflicts with this antibody-based HPA call. Without access to the HPA images and antibody validation the row cannot be resolved; it is not removed because it is an experimental annotation. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0005737 cytoplasm	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: Cytoplasmic activity is a family-level inference not borne out for WEE1. Reason: The IBA comes from the PTHR11042 root node PTN000113601, whose cytoplasm seeds are dominated by eIF2-alpha kinases, PKMYT1 and other members; human WEE1 is not among the cytoplasm seeds although it seeds the nucleus assertion at the same node. The Ensembl Compara IEA is a projection from mouse Wee1. Human WEE1 is experimentally nuclear, and its defining function is to oppose CDK1 that is activated in the cytoplasm from inside the nucleus. A transient cytoplasmic pool (e.g. during synthesis) is not excluded, but 'active in cytoplasm' over-states the evidence. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000113601 · PTHR11042 root node SUPPORTS SOURCE BUT NOT TARGET Cytoplasm seeds are other family members (eIF2-alpha kinases, PKMYT1, WEE2 and others); human WEE1 seeds only the nucleus assertion at this node. UniProtKB:P47817 · Xenopus Wee2-A (SF75 paralog) SUPPORTS SOURCE BUT NOT TARGET Oocyte WEE2 lineage, a different PANTHER subfamily from WEE1 (SF72). Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase
GO:0005737 cytoplasm	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Cytoplasmic activity is a family-level inference not borne out for WEE1. Reason: The IBA comes from the PTHR11042 root node PTN000113601, whose cytoplasm seeds are dominated by eIF2-alpha kinases, PKMYT1 and other members; human WEE1 is not among the cytoplasm seeds although it seeds the nucleus assertion at the same node. The Ensembl Compara IEA is a projection from mouse Wee1. Human WEE1 is experimentally nuclear, and its defining function is to oppose CDK1 that is activated in the cytoplasm from inside the nucleus. A transient cytoplasmic pool (e.g. during synthesis) is not excluded, but 'active in cytoplasm' over-states the evidence. Supporting Evidence: PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis PMID:8348613 The human wee1 kinase appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from this cytoplasmically activated cdc2 kinase
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IBA GO_REF:0000033	ACCEPT	Summary: WEE1 negatively regulates mitotic entry by inhibiting CDK1. Reason: Overexpressed WEE1 blocks cell division in a kinase-dependent manner, and WEE1 Tyr15 phosphorylation holds cyclin B1-CDK1 inactive until G2/M, when WEE1 is inactivated and degraded. The IBA at PTN008510965 (Euteleostomi) is seeded by human WEE1 itself, which is expected. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2 PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IDA PMID:7743995 Regulation of the human WEE1Hu CDK tyrosine 15-kinase during...	ACCEPT	Summary: WEE1 negatively regulates mitotic entry by inhibiting CDK1. Reason: Overexpressed WEE1 blocks cell division in a kinase-dependent manner, and WEE1 Tyr15 phosphorylation holds cyclin B1-CDK1 inactive until G2/M, when WEE1 is inactivated and degraded. The IBA at PTN008510965 (Euteleostomi) is seeded by human WEE1 itself, which is expected. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2 PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IDA PMID:8348613 Human wee1 maintains mitotic timing by protecting the nucleu...	ACCEPT	Summary: WEE1 negatively regulates mitotic entry by inhibiting CDK1. Reason: Overexpressed WEE1 blocks cell division in a kinase-dependent manner, and WEE1 Tyr15 phosphorylation holds cyclin B1-CDK1 inactive until G2/M, when WEE1 is inactivated and degraded. The IBA at PTN008510965 (Euteleostomi) is seeded by human WEE1 itself, which is expected. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2 PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IDA PMID:8428596 Human Wee1 kinase inhibits cell division by phosphorylating ...	ACCEPT	Summary: WEE1 negatively regulates mitotic entry by inhibiting CDK1. Reason: Overexpressed WEE1 blocks cell division in a kinase-dependent manner, and WEE1 Tyr15 phosphorylation holds cyclin B1-CDK1 inactive until G2/M, when WEE1 is inactivated and degraded. The IBA at PTN008510965 (Euteleostomi) is seeded by human WEE1 itself, which is expected. Supporting Evidence: PMID:8428596 purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected PMID:8428596 Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function PMID:7743995 WEE1Hu plays a role in inhibiting mitosis before M phase by phosphorylating cyclin B1-Cdc2 PMID:8348613 the human wee1-like tyrosine kinase is a nuclear protein that ensures the completion of DNA replication prior to mitosis
GO:0045740 positive regulation of DNA replication	TAS Reactome:R-HSA-69656	MODIFY	Summary: Wrong direction: WEE1 restrains, rather than promotes, DNA replication initiation. Reason: The Reactome pathway mapped to this term (Cyclin A:Cdk2-associated events at S phase entry) includes WEE1 only as the kinase that inhibits Cyclin A:CDK2 through Tyr15 phosphorylation. Direct human-cell evidence shows that loss of WEE1 activity increases replication initiation, causing replication stress. The sign of the annotation should be corrected to negative regulation of DNA replication initiation. Proposed replacements: negative regulation of DNA-templated DNA replication initiation Supporting Evidence: Reactome:R-HSA-69656 Prior to S phase entry, the activity of Cyclin A:Cdk2 complexes is negatively regulated through Tyr 15 phosphorylation of Cdk2 PMID:22907750 elevation of CDK activity by inhibition of WEE1 kinase rapidly increases initiation of replication PMID:20194642 WEE1 depletion rapidly induced DNA damage in S phase in newly replicated DNA
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle	TAS Reactome:R-HSA-69195	KEEP AS NON CORE	Summary: WEE1 can inhibit CDK2 and thereby restrain S-phase entry. Reason: Endogenous WEE1 phosphorylates several cyclin-associated CDKs, including CDK2 complexes, on Tyr15, and Reactome curates WEE1 phosphorylation of cyclin E:CDK2 as inhibiting S-phase entry. WEE1 levels and activity are highest in S and G2, so this is a secondary context relative to the G2/M role. Supporting Evidence: PMID:7743995 the endogenous WEE1Hu phosphorylated several cyclin-associated CDKs on Y15 Reactome:R-HSA-69195 WEE1 phosphorylates CDK2, inhibiting entry into S-phase

Gene Description

Existing Annotations Review

Core Functions

Non-receptor tyrosine kinase that phosphorylates CDK1 Tyr15 in cyclin B1-CDK1 within the nucleus, holding CDK1 inactive and restraining entry into mitosis.

Phosphorylates CDK2 Tyr15 during S phase, limiting replication-origin firing and preventing replication stress.

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