Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000307 cyclin-dependent protein kinase holoenzyme complex	IBA GO_REF:0000033	ACCEPT	Summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex. Reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically conserved. Supporting Evidence: PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0000086 G2/M transition of mitotic cell cycle	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: G2/M transition of mitotic cell cycle: cyclin A/CDK2 modulates entry into mitosis. Reason: CDK2 contributes to G2 progression and the timing of cyclin B/CDK1 activation, but the G2/M transition is principally CDK1-driven and CDK2 is dispensable for mitosis; non-core. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004672 protein kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Protein kinase activity (broad parent term, IEA from InterPro/UniRule). Reason: Correct but general; the specific cyclin-dependent serine/threonine kinase activity (GO:0004693) is the appropriate leaf term and is separately annotated. Acceptable as a broader IEA mapping. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding, the phosphate donor for CDK2 catalysis. Reason: Required for kinase catalysis; CDK2 crystal structures resolve bound ATP. Supporting Evidence: PMID:21565702 high-resolution crystal structures of a CDK2/Cyclin A transition state complex bound to ADP, substrate peptide, and MgF(3)(-).
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Cytoplasmic localization of CDK2. While CDK2 acts predominantly in the nucleus, a cytoplasmic cyclin A2/CDK2 pool appears at the S/G2 transition and contributes to mitotic entry. Reason: CDK2 shuttles between nucleus and cytoplasm and has cytoplasmic/compartmentalized pools; directly observed. At the S/G2 transition cyclin A2/CDK2 redistributes partly to the cytoplasm, where it can activate PLK1 via the activator Bora, illustrating a compartment-specific output for CDK2. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. file:human/CDK2/CDK2-deep-research-falcon.md Cytoplasmic cyclin A2-CDK2 activates the mitotic kinase PLK1 through phosphorylation of the PLK1 activator Bora
GO:0005768 endosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Endosomal localization of a compartmentalized CDK2 pool linked to insulin internalization. Reason: Specific minor pool; peripheral to canonical cell-cycle function. Supporting Evidence: PMID:21262353 Compartmentalized CDK2 is connected with SHP-1 and β-catenin and regulates insulin internalization.
GO:0005813 centrosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication. Reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication. Directly observed (IDA/HPA) and by orthology. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0006338 chromatin remodeling	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Chromatin remodeling, derived (IEA, GO_REF:0000108) from histone-kinase activity context. Reason: CDK2 influences chromatin via phosphorylation of SUV39H1, EZH2 and CSB/ERCC6, but the broad 'chromatin remodeling' BP from an automated mapping is non-core; the specific substrate-level processes are separately annotated. Supporting Evidence: PMID:29203878 ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice.
GO:0015030 Cajal body	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cajal body localization, where cyclin E/CDK2 phosphorylates NPAT to activate histone gene transcription. Reason: Directly observed localization tied to a specific S-phase function (NPAT phosphorylation). Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. CDK2 is a proline-directed kinase, preferring serine/threonine residues followed by proline (S/T-P motif). Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. CDK2 substrate selection follows a proline-directed (S/T-P) consensus, supported by an analog-sensitive in situ nuclear phosphorylation screen and a kinome-wide specificity atlas. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15. file:human/CDK2/CDK2-deep-research-falcon.md 156 of 166 CDK2-specific thiophosphopeptides (93%) contained at least one S/T-P site, confirming this strong selectivity
GO:0005515 protein binding	IPI PMID:10330164 Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions wi...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:10330164 Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator.
GO:0005515 protein binding	IPI PMID:11463386 Phosphoprotein-protein interactions revealed by the crystal ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and EP300, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:11463386 Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2.
GO:0005515 protein binding	IPI PMID:12244298 Structure-based design of a potent purine-based cyclin-depen...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:12244298 Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
GO:0005515 protein binding	IPI PMID:12941338 Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-n...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:12941338 Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2.
GO:0005515 protein binding	IPI PMID:15178429 NIRF induces G1 arrest and associates with Cdk2.	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15178429 NIRF induces G1 arrest and associates with Cdk2.
GO:0005515 protein binding	IPI PMID:15189033 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor age...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and UHRF2 (NIRF), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15189033 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents.
GO:0005515 protein binding	IPI PMID:15232106 Self-assembling protein microarrays.	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15232106 Self-assembling protein microarrays.
GO:0005515 protein binding	IPI PMID:15239650 N2-substituted O6-cyclohexylmethylguanine derivatives: poten...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15239650 N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2.
GO:0005515 protein binding	IPI PMID:15530371 The crystal structure of human CDK7 and its protein recognit...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15530371 CDK7, a member of the cyclin-dependent protein kinase family, regulates the activities of other CDKs through phosphorylation on their activation segment and hence contributes to control of the eukaryotic cell cycle.
GO:0005515 protein binding	IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division.
GO:0005515 protein binding	IPI PMID:16061792 Association of the human papillomavirus type 16 E7 oncoprote...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16061792 Among the proteins identified are previously described cellular targets of E7 including pRB, p107, p130, several E2F and DP family members, cyclin A, cyclin E, CDC2, and CDK2 ( Fig.
GO:0005515 protein binding	IPI PMID:16209941 Structural basis of the Cks1-dependent recognition of p27(Ki...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16209941 The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many common cancers.
GO:0005515 protein binding	IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16326706 Here, we show that TIMP-2 mediates G1 growth arrest in human endothelial cells through de novo synthesis of the cyclin-dependent kinase inhibitor p27Kip1.
GO:0005515 protein binding	IPI PMID:16327805 Dichotomous but stringent substrate selection by the dual-fu...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16327805 Cdk7 performs two essential but distinct functions as a CDK-activating kinase (CAK) required for cell-cycle progression and as the RNA polymerase II (Pol II) CTD kinase of general transcription factor IIH.
GO:0005515 protein binding	IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells.
GO:0005515 protein binding	IPI PMID:16765349 Increased p21 expression and complex formation with cyclin E...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16765349 Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced pre-B lymphoma cell apoptosis.
GO:0005515 protein binding	IPI PMID:16962592 Honokiol causes the p21WAF1-mediated G(1)-phase arrest of th...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and HPV E7 (xeno), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:16962592 Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells.
GO:0005515 protein binding	IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:17053782 Entry of cells into the cell division cycle requires the coordinated activation of cyclin-dependent kinases (cdks) and the deactivation of cyclin kinase inhibitors.
GO:0005515 protein binding	IPI PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directl...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:17254966 Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases.
GO:0005515 protein binding	IPI PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:17254967 p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.
GO:0005515 protein binding	IPI PMID:17418410 HIF-2alpha promotes hypoxic cell proliferation by enhancing ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:17418410 The HIFs can alter cell cycle progression through putative transcriptional targets such as Cyclin D1 ( Baba et al., 2003 ) and indirect modulation of p21 and p27 ( Gardner et al., 2001 ; Green et al., 2001 ; Koshiji et al., 2004 ).
GO:0005515 protein binding	IPI PMID:17698606 SCAPER, a novel cyclin A-interacting protein that regulates ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:17698606 SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression.
GO:0005515 protein binding	IPI PMID:18177895 Role of intrinsic flexibility in signal transduction mediate...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:18177895 p27(Kip1) (p27), which controls eukaryotic cell division through interactions with cyclin-dependent kinases (Cdks), integrates and transduces promitogenic signals from various nonreceptor tyrosine kinases by orchestrating its own phosphorylation, ubiquitination and degradation.
GO:0005515 protein binding	IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:19470470 p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1 pathways.
GO:0005515 protein binding	IPI PMID:20098747 Expanding the substantial interactome of NEMO using protein ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:20098747 Of the novel interactors, more than 30% were kinases, while at least 25% were involved in signal transduction.
GO:0005515 protein binding	IPI PMID:20871633 p38 phosphorylates Rb on Ser567 by a novel, cell cycle-indep...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:20871633 Cyclin-dependent kinases (Cdks) promote cell division by phosphorylating and reversibly inactivating Rb by a hierarchical series of phosphorylation events and sequential conformational changes.
GO:0005515 protein binding	IPI PMID:21092281 HTLV-I p30 inhibits multiple S phase entry checkpoints, decr...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:21092281 HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression.
GO:0005515 protein binding	IPI PMID:21423803 Role of T198 modification in the regulation of p27(Kip1) pro...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:21423803 Recently, it has been demonstrated that the tumor suppression function of p27 resides not only in the ability to inhibit Cyclins/CDKs complexes through its N-terminal domain but also in the capacity to modulate cell motility through its C-terminal portion.
GO:0005515 protein binding	IPI PMID:21565702 Briefly bound to activate: transient binding of a second cat...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:21565702 Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis.
GO:0005515 protein binding	IPI PMID:21952639 NIRF constitutes a nodal point in the cell cycle network and...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:21952639 Here, we show that the ubiquitin ligase NIRF (also known as UHRF2), which induces G1 arrest, interacts with multiple cell cycle proteins including cyclins (A2, B1, D1 and E1), p53 and pRB, and ubiquitinates cyclins D1 and E1.
GO:0005515 protein binding	IPI PMID:22810586 Interpreting cancer genomes using systematic host network pe...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:22810586 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
GO:0005515 protein binding	IPI PMID:22940584 The molecular basis for substrate specificity of the nuclear...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:22940584 For these experiments, SAP155 or CDC5L were first phosphorylated with recombinant CycA2/CDK2, which resulted in six (CDC5L) or nine (SAP155) phosphorylated residues, as verified by MS.
GO:0005515 protein binding	IPI PMID:23082202 The stomatin-like protein SLP-1 and Cdk2 interact with the F...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:23082202 The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein Fbw7-γ.
GO:0005515 protein binding	IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and SCAPER, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:23455922 We systematically investigated the reproducibility of a standardized AP-MS workflow by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human kinases.
GO:0005515 protein binding	IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:23602568 The protein interaction landscape of the human CMGC kinase group.
GO:0005515 protein binding	IPI PMID:23853094 Foxp3 protein stability is regulated by cyclin-dependent kin...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:23853094 Foxp3 protein stability is regulated by cyclin-dependent kinase 2.
GO:0005515 protein binding	IPI PMID:24218572 CDK10/cyclin M is a protein kinase that controls ETS2 degrad...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and IKBKG (NEMO), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:24218572 CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome.
GO:0005515 protein binding	IPI PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding a...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and RB1, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:24358021 Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.
GO:0005515 protein binding	IPI PMID:25218637 RASSF1A-LATS1 signalling stabilizes replication forks by res...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:25218637 RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:25241761 Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and Ccna2 (cyclin A2, mouse), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and UHRF2 (NIRF), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and HPV E7 (xeno), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. 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...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2, xeno), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:28514442 kinases) are enriched more than by chance, suggesting that such proteins are highly interactive (Extended Data Fig.
GO:0005515 protein binding	IPI PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid tec...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and FBXW7, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:29997244 LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.
GO:0005515 protein binding	IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and STOML1, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:30833792 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.
GO:0005515 protein binding	IPI PMID:31467278 Maximizing binary interactome mapping with a minimal number ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:31467278 CMV cytomegalovirus, HSV-TK herpes simplex virus-thymidine kinase, UAS upstream activating sequence, IRES internal ribosome entry site.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:34591612 A protein interaction landscape of breast cancer.	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCND1 (cyclin D1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:34591612 The BPIFA1-PIK3CA interaction we identified and the inhibition of WT PIK3CA kinase activity by BPIFA1 in vitro suggests that BPIFA1 may also directly modulate PI3K/AKT via PPI, which warrants a structural study of the complex.
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:34591642 Additionally, we observe mutation-enriched interactions between the human epidermal growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0005515 protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:37398436 Notably, such a classification strategy has been successfully used to predict kinase substrates from phosphoproteomics data (Yang et al, 2019; Kim et al, 2021), or to classify cell types from single cell RNA-sequencing (Abdelaal et al, 2019).
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics.
GO:0005515 protein binding	IPI PMID:7630397 Mechanism of CDK activation revealed by the structure of a c...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CKS1B, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:7630397 Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
GO:0005515 protein binding	IPI PMID:8242750 Cdi1, a human G1 and S phase protein phosphatase that associ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and EP300, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8242750 Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2.
GO:0005515 protein binding	IPI PMID:8521818 In vitro assembly of a functional human CDK7-cyclin H comple...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and MAPK15 (ERK8), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8521818 In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein.
GO:0005515 protein binding	IPI PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.
GO:0005515 protein binding	IPI PMID:8756328 Structural basis of cyclin-dependent kinase activation by ph...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8756328 Structural basis of cyclin-dependent kinase activation by phosphorylation.
GO:0005515 protein binding	IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8756624 Cyclin-binding motifs are essential for the function of p21CIP1.
GO:0005515 protein binding	IPI PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins.
GO:0000287 magnesium ion binding	IEA GO_REF:0000107	ACCEPT	Summary: Magnesium ion binding; CDK2 binds two Mg2+ ions required for catalysis. Reason: Mg2+ is an essential catalytic cofactor; a second transiently bound Mg2+ activates catalysis. Supporting Evidence: PMID:21565702 Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis.
GO:0000307 cyclin-dependent protein kinase holoenzyme complex	IEA GO_REF:0000107	ACCEPT	Summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex. Reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically conserved. Supporting Evidence: PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0000781 chromosome, telomeric region	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: chromosome, telomeric region localization, transferred by orthology (IEA) from the mouse ortholog. Reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional information; kept as non-core. Supporting Evidence: PMID:28216226 Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
GO:0000793 condensed chromosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: condensed chromosome localization, transferred by orthology (IEA) from the mouse ortholog. Reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional information; kept as non-core. Supporting Evidence: PMID:28216226 Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
GO:0000805 X chromosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: X chromosome localization, transferred by orthology (IEA) from the mouse ortholog. Reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional information; kept as non-core. Supporting Evidence: PMID:28216226 Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
GO:0000806 Y chromosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Y chromosome localization, transferred by orthology (IEA) from the mouse ortholog. Reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional information; kept as non-core. Supporting Evidence: PMID:28216226 Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000107	ACCEPT	Summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent kinase activity). Reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific cyclin-dependent term is also annotated. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005634 nucleus	IEA GO_REF:0000107	ACCEPT	Summary: Nuclear localization of CDK2. Reason: CDK2 acts on nuclear substrates; nuclear localization directly observed (IDA) and inferred by orthology. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005635 nuclear envelope	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Nuclear envelope localization (IEA by orthology). Reason: Low-specificity orthology-transferred localization; not a primary functional site. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005667 transcription regulator complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transcription regulator complex membership (IEA by orthology). Reason: CDK2 regulates transcriptional programs (E2F via RB1; histone genes via NPAT) but is not itself a core transcription-complex subunit; broad orthology transfer. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0008284 positive regulation of cell population proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Positive regulation of cell proliferation, consistent with CDK2's proliferative role. Reason: Real but high-level/indirect consequence of CDK2 cell-cycle activity; non-core. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0016301 kinase activity	IEA GO_REF:0000107	ACCEPT	Summary: Kinase activity (broad parent term, IEA by orthology). Reason: Correct but very general; specific kinase MF terms are separately annotated. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0030332 cyclin binding	IEA GO_REF:0000107	ACCEPT	Summary: Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory activating subunits of the holoenzyme. Reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A binding drives the activating conformational change. Supporting Evidence: PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0097123 cyclin A1-CDK2 complex	IEA GO_REF:0000107	ACCEPT	Summary: Part of the cyclin A1-CDK2 complex, the germ-cell (cyclin A1) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:7630397 Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
GO:0097124 cyclin A2-CDK2 complex	IEA GO_REF:0000107	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:7630397 Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
GO:0097134 cyclin E1-CDK2 complex	IEA GO_REF:0000107	ACCEPT	Summary: Part of the cyclin E1-CDK2 complex, the G1/S (cyclin E1) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:7630397 Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
GO:0097135 cyclin E2-CDK2 complex	IEA GO_REF:0000107	ACCEPT	Summary: Part of the cyclin E2-CDK2 complex, the G1/S (cyclin E2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:7630397 Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
GO:0097472 cyclin-dependent protein kinase activity	IEA GO_REF:0000107	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0007346 regulation of mitotic cell cycle	TAS Reactome:R-HSA-68911	ACCEPT	Summary: Regulation of the mitotic cell cycle (Reactome TAS). Reason: Accurate higher-level process; CDK2 is a central cell-cycle regulator at G1/S and S/G2. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0045740 positive regulation of DNA replication	TAS Reactome:R-HSA-69656	ACCEPT	Summary: Positive regulation of DNA replication by cyclin-CDK2 (Reactome TAS). Reason: Consistent with CDK2's core S-phase-promoting activity. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0090398 cellular senescence	TAS Reactome:R-HSA-2559583	KEEP AS NON CORE	Summary: Cellular senescence: cyclin E/CDK2-mediated MYC phosphorylation suppresses Ras-induced senescence (Reactome TAS). Reason: Specific, context-dependent role; peripheral to the core cell-cycle kinase function. Supporting Evidence: PMID:9054499 Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
GO:1905784 regulation of anaphase-promoting complex-dependent catabolic process	TAS Reactome:R-HSA-176408	KEEP AS NON CORE	Summary: Regulation of APC/C-dependent catabolism: CDK2 activates USP37 to antagonize APC/C-CDH1 and promote S-phase entry. Reason: Specific mechanistic role at the G1/S boundary; peripheral to core MF. Supporting Evidence: PMID:21596315 Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	TAS Reactome:R-HSA-174079	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	TAS Reactome:R-HSA-187520	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	TAS Reactome:R-HSA-187959	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	TAS Reactome:R-HSA-188390	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	TAS Reactome:R-HSA-3788705	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005813 centrosome	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication. Reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication. Directly observed (IDA/HPA) and by orthology. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0036064 ciliary basal body	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: Ciliary basal body localization (HPA immunofluorescence). Reason: Basal body is closely related to the centriole/centrosome where CDK2 localizes; peripheral to core function. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0000082 G1/S transition of mitotic cell cycle	NAS PMID:15838514 Cyclin E in normal and neoplastic cell cycles.	ACCEPT	Summary: G1/S transition of mitotic cell cycle, the canonical CDK2 function (cyclin E/CDK2). Reason: Core biological role: cyclin E/CDK2 drives G1/S by phosphorylating RB1, NPAT and other substrates to launch the E2F program and DNA synthesis. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0000082 G1/S transition of mitotic cell cycle	NAS PMID:9840943 Cyclin E2, a novel human G1 cyclin and activating partner of...	ACCEPT	Summary: G1/S transition of mitotic cell cycle, the canonical CDK2 function (cyclin E/CDK2). Reason: Core biological role: cyclin E/CDK2 drives G1/S by phosphorylating RB1, NPAT and other substrates to launch the E2F program and DNA synthesis. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0097123 cyclin A1-CDK2 complex	NAS PMID:12244298 Structure-based design of a potent purine-based cyclin-depen...	ACCEPT	Summary: Part of the cyclin A1-CDK2 complex, the germ-cell (cyclin A1) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:12244298 Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
GO:0097124 cyclin A2-CDK2 complex	IPI PMID:12244298 Structure-based design of a potent purine-based cyclin-depen...	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:12244298 Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
GO:0097134 cyclin E1-CDK2 complex	IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C...	ACCEPT	Summary: Part of the cyclin E1-CDK2 complex, the G1/S (cyclin E1) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:8756624 Cyclin-binding motifs are essential for the function of p21CIP1.
GO:0097135 cyclin E2-CDK2 complex	IPI PMID:15232106 Self-assembling protein microarrays.	ACCEPT	Summary: Part of the cyclin E2-CDK2 complex, the G1/S (cyclin E2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:15232106 Self-assembling protein microarrays.
GO:0106310 protein serine kinase activity	EXP PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0106310 protein serine kinase activity	EXP PMID:24670654 Cell-cycle-regulated activation of Akt kinase by phosphoryla...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0106310 protein serine kinase activity	EXP PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in con...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0106310 protein serine kinase activity	EXP PMID:28216226 NBS1 phosphorylation status dictates repair choice of dysfun...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0106310 protein serine kinase activity	EXP PMID:28666995 Structural basis of divergent cyclin-dependent kinase activa...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0106310 protein serine kinase activity	EXP PMID:9030781 Biochemical and cellular effects of roscovitine, a potent an...	ACCEPT	Summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2 catalyzes. Reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple EXP/IDA studies of CDK2 substrate phosphorylation. Supporting Evidence: PMID:1396589 Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	IDA PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in con...	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0120186 negative regulation of protein localization to chromatin	IDA PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in con...	KEEP AS NON CORE	Summary: Negative regulation of protein localization to chromatin: CDK2 phosphorylation of SUV39H1 promotes its dissociation from chromatin. Reason: Specific mechanistic outcome of SUV39H1 phosphorylation; non-core. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
GO:0120261 regulation of heterochromatin organization	IDA PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in con...	KEEP AS NON CORE	Summary: Regulation of heterochromatin organization via CDK2 phosphorylation of SUV39H1 at Ser391. Reason: Specific, directly demonstrated function controlling heterochromatin replication; non-core. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
GO:0097472 cyclin-dependent protein kinase activity	IDA PMID:24670654 Cell-cycle-regulated activation of Akt kinase by phosphoryla...	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	IDA PMID:28216226 NBS1 phosphorylation status dictates repair choice of dysfun...	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0043247 telomere maintenance in response to DNA damage	IDA PMID:28216226 NBS1 phosphorylation status dictates repair choice of dysfun...	KEEP AS NON CORE	Summary: Telomere maintenance in response to DNA damage: cyclin A/CDK2 phosphorylates NBN/NBS1 to dictate dysfunctional-telomere repair choice. Reason: Specific, directly demonstrated (IDA) DNA-damage-response role; non-core. Supporting Evidence: PMID:28216226 Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:11953320 Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-...	ACCEPT	Summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent kinase activity). Reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific cyclin-dependent term is also annotated. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0043687 post-translational protein modification	IDA PMID:11746698 Intrinsic structural disorder and sequence features of the c...	KEEP AS NON CORE	Summary: Post-translational protein modification (broad), from CDK2 substrate phosphorylation. Reason: Correct but very general parent of protein phosphorylation; non-core given more specific terms exist. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
GO:0031453 positive regulation of heterochromatin formation	IDA PMID:20935635 Cyclin-dependent kinases regulate epigenetic gene silencing ...	KEEP AS NON CORE	Summary: Positive regulation of heterochromatin formation: CDK2 phosphorylates EZH2 to maintain H3K27me3 and epigenetic silencing. Reason: Specific chromatin/epigenetic function via EZH2; peripheral to core cell-cycle role. Supporting Evidence: PMID:20935635 Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2.
GO:0006468 protein phosphorylation	IMP PMID:29203878 ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1...	ACCEPT	Summary: Protein phosphorylation: CDK2 phosphorylates numerous Ser/Thr substrates. In situ nuclear phosphoproteomics with analog-sensitive CDK2 defined a broad nuclear substrate landscape extending beyond canonical cell-cycle targets to chromatin modifiers, DNA-repair and transcription regulators. Reason: Direct readout of CDK2's catalytic function on protein substrates; well supported. An analog-sensitive in situ nuclear phosphorylation screen identified ~117 candidate nuclear CDK2 substrates (~43% of them previously known CDK substrates), validating the breadth of CDK2's phosphorylation activity. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression. file:human/CDK2/CDK2-deep-research-falcon.md identified 117 candidate nuclear CDK2 substrates, of which approximately 43% were previously known CDK substrates
GO:0097124 cyclin A2-CDK2 complex	IDA PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inh...	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:8684460 Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.
GO:0004674 protein serine/threonine kinase activity	IGI PMID:26996940 Regulation of Microtubule Assembly by Tau and not by Pin1.	ACCEPT	Summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent kinase activity). Reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific cyclin-dependent term is also annotated. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005515 protein binding	IPI PMID:28666995 Structural basis of divergent cyclin-dependent kinase activa...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:28666995 Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins.
GO:0097472 cyclin-dependent protein kinase activity	IDA PMID:28666995 Structural basis of divergent cyclin-dependent kinase activa...	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005515 protein binding	IPI PMID:23781148 Overexpression of DOC-1R inhibits cell cycle G1/S transition...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CKS1B, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:23781148 Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.
GO:0006468 protein phosphorylation	IDA PMID:12944431 DOC1R: a MAP kinase substrate that control microtubule organ...	ACCEPT	Summary: Protein phosphorylation: CDK2 phosphorylates numerous Ser/Thr substrates. Reason: Direct readout of CDK2's catalytic function on protein substrates; well supported. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
GO:0030332 cyclin binding	IDA PMID:23781148 Overexpression of DOC-1R inhibits cell cycle G1/S transition...	ACCEPT	Summary: Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory activating subunits of the holoenzyme. Reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A binding drives the activating conformational change. Supporting Evidence: PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0000307 cyclin-dependent protein kinase holoenzyme complex	IDA PMID:1312467 Cyclin A is required at two points in the human cell cycle.	ACCEPT	Summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex. Reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically conserved. Supporting Evidence: PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0097124 cyclin A2-CDK2 complex	IDA PMID:1312467 Cyclin A is required at two points in the human cell cycle.	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0097472 cyclin-dependent protein kinase activity	IDA PMID:1312467 Cyclin A is required at two points in the human cell cycle.	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0030332 cyclin binding	IPI PMID:1312467 Cyclin A is required at two points in the human cell cycle.	ACCEPT	Summary: Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory activating subunits of the holoenzyme. Reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A binding drives the activating conformational change. Supporting Evidence: PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0005654 nucleoplasm	IDA PMID:8245034 Structural and functional characterization of the HPV16 E7 p...	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0019904 protein domain specific binding	IPI PMID:8876165 Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2...	KEEP AS NON CORE	Summary: Protein domain-specific binding, from CDK2 interactions with the CDK-inhibitor domains of p21/CDKN1A and p27/CDKN1B. Reason: Reflects docking of CIP/KIP inhibitor domains onto the cyclin-CDK2 surface; valid but peripheral to CDK2's core catalytic function. Supporting Evidence: PMID:8876165 Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity.
GO:0097124 cyclin A2-CDK2 complex	IDA PMID:8876165 Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2...	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:8876165 Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity.
GO:0019904 protein domain specific binding	IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis...	KEEP AS NON CORE	Summary: Protein domain-specific binding, from CDK2 interactions with the CDK-inhibitor domains of p21/CDKN1A and p27/CDKN1B. Reason: Reflects docking of CIP/KIP inhibitor domains onto the cyclin-CDK2 surface; valid but peripheral to CDK2's core catalytic function. Supporting Evidence: PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding.
GO:0030332 cyclin binding	IPI PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis...	ACCEPT	Summary: Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory activating subunits of the holoenzyme. Reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A binding drives the activating conformational change. Supporting Evidence: PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0097124 cyclin A2-CDK2 complex	IDA PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanis...	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:15024385 p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding.
GO:0097124 cyclin A2-CDK2 complex	IDA PMID:11746698 Intrinsic structural disorder and sequence features of the c...	ACCEPT	Summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme. Reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural context for CDK2 function. Supporting Evidence: PMID:11746698 The cell cycle inhibitor p57Kip2 induces cell cycle arrest by inhibiting the activity of cyclin-dependent kinases.
GO:0005515 protein binding	IPI PMID:2227411 Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-ass...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:2227411 Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.
GO:0005515 protein binding	IPI PMID:8601310 Crystal structure and mutational analysis of the human CDK2 ...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:8601310 Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.
GO:0007099 centriole replication	IMP PMID:26297806 Centriolar satellites assemble centrosomal microcephaly prot...	KEEP AS NON CORE	Summary: Centriole replication: CDK2 is recruited by centriolar-satellite microcephaly proteins to promote centriole duplication. Reason: Specific, well-supported (IMP) function but peripheral to the core G1/S kinase role. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0005515 protein binding	IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15107404 Mutation of Ser 193 to Ala also abolishes the ability of C/EBPalpha to cause growth arrest because of a lack of interactions with cdk2 and E2F-Rb complexes.
GO:0018105 peptidyl-serine phosphorylation	IDA PMID:23184662 Phosphorylation of eukaryotic elongation factor 2 (eEF2) by ...	ACCEPT	Summary: Peptidyl-serine phosphorylation of CDK2 substrates. Reason: Specific catalytic-outcome term consistent with CDK2 serine-kinase activity. Supporting Evidence: PMID:24728993 CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.
GO:0005515 protein binding	IPI PMID:19150984 Identification and functional analysis of a novel cyclin e/c...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:19150984 Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17.
GO:0005829 cytosol	TAS Reactome:R-HSA-157906	KEEP AS NON CORE	Summary: Cytosolic localization (Reactome pathway annotation). Reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative sites for CDK2 function. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005829 cytosol	TAS Reactome:R-HSA-174054	KEEP AS NON CORE	Summary: Cytosolic localization (Reactome pathway annotation). Reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative sites for CDK2 function. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005829 cytosol	TAS Reactome:R-HSA-174273	KEEP AS NON CORE	Summary: Cytosolic localization (Reactome pathway annotation). Reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative sites for CDK2 function. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005829 cytosol	TAS Reactome:R-HSA-69191	KEEP AS NON CORE	Summary: Cytosolic localization (Reactome pathway annotation). Reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative sites for CDK2 function. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005829 cytosol	TAS Reactome:R-HSA-9858566	KEEP AS NON CORE	Summary: Cytosolic localization (Reactome pathway annotation). Reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative sites for CDK2 function. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1363303	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1363306	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1363311	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-1363314	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-157906	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-174079	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-174110	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-174164	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-174273	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-176298	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-176318	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187520	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187552	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187574	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187575	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187916	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187934	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187937	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187948	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187949	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-187959	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-188350	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-188371	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-188386	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-188390	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3788705	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-3788708	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-4088024	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5684081	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5684096	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6793661	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6805109	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-68916	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-68917	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-68918	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-68944	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-69005	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-69195	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-69199	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-69562	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9624120	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9686521	ACCEPT	Summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1, NPAT, etc.). Reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations to nucleoplasm are appropriate; duplicates across pathways are acceptable. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0000086 G2/M transition of mitotic cell cycle	NAS PMID:1653904 Isolation of the human cdk2 gene that encodes the cyclin A- ...	KEEP AS NON CORE	Summary: G2/M transition of mitotic cell cycle: cyclin A/CDK2 modulates entry into mitosis. Reason: CDK2 contributes to G2 progression and the timing of cyclin B/CDK1 activation, but the G2/M transition is principally CDK1-driven and CDK2 is dispensable for mitosis; non-core. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0005634 nucleus	IDA PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma...	ACCEPT	Summary: Nuclear localization of CDK2. Reason: CDK2 acts on nuclear substrates; nuclear localization directly observed (IDA) and inferred by orthology. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0005737 cytoplasm	IDA PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma...	ACCEPT	Summary: Cytoplasmic localization of CDK2. Reason: CDK2 shuttles between nucleus and cytoplasm and has cytoplasmic/compartmentalized pools; directly observed. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0008284 positive regulation of cell population proliferation	IDA PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma...	KEEP AS NON CORE	Summary: Positive regulation of cell proliferation, consistent with CDK2's proliferative role. Reason: Real but high-level/indirect consequence of CDK2 cell-cycle activity; non-core. Supporting Evidence: PMID:10767298 Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.
GO:0030332 cyclin binding	IDA PMID:1653904 Isolation of the human cdk2 gene that encodes the cyclin A- ...	ACCEPT	Summary: Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory activating subunits of the holoenzyme. Reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A binding drives the activating conformational change. Supporting Evidence: PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0005515 protein binding	IPI PMID:15611625 Identification and comparative analysis of multiple mammalia...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:15611625 In addition to their activation via binding to cyclins, cyclin-dependent kinases (CDKs) can be activated via binding to a novel cell cycle regulator termed Speedy/Ringo, which shows no apparent similarity to cyclins.
GO:0005515 protein binding	IPI PMID:19829063 Identification and characterization of CAC1 as a novel CDK2-...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:19829063 Identification and characterization of CAC1 as a novel CDK2-associated cullin.
GO:0005768 endosome	IDA PMID:21262353 Compartmentalized CDK2 is connected with SHP-1 and beta-cate...	KEEP AS NON CORE	Summary: Endosomal localization of a compartmentalized CDK2 pool linked to insulin internalization. Reason: Specific minor pool; peripheral to canonical cell-cycle function. Supporting Evidence: PMID:21262353 Compartmentalized CDK2 is connected with SHP-1 and β-catenin and regulates insulin internalization.
GO:0005813 centrosome	TAS PMID:19238148 Cell cycle, CDKs and cancer: a changing paradigm.	KEEP AS NON CORE	Summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication. Reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication. Directly observed (IDA/HPA) and by orthology. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0006260 DNA replication	TAS PMID:19238148 Cell cycle, CDKs and cancer: a changing paradigm.	ACCEPT	Summary: DNA replication: cyclin E/A-CDK2 promotes origin firing and S-phase progression. Reason: Core role; CDK2 activity initiates and sustains DNA synthesis during S phase. Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0015030 Cajal body	IDA PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin...	KEEP AS NON CORE	Summary: Cajal body localization, where cyclin E/CDK2 phosphorylates NPAT to activate histone gene transcription. Reason: Directly observed localization tied to a specific S-phase function (NPAT phosphorylation). Supporting Evidence: PMID:10995387 Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
GO:0031571 mitotic G1 DNA damage checkpoint signaling	TAS PMID:21319273 An important role for CDK2 in G1 to S checkpoint activation ...	KEEP AS NON CORE	Summary: Mitotic G1 DNA-damage checkpoint signaling; p21/CDKN1A inactivation of cyclin E/CDK2 enforces G1/S arrest. Reason: Specific checkpoint role downstream of DNA damage; peripheral to core kinase function. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0051298 centrosome duplication	TAS PMID:19238148 Cell cycle, CDKs and cancer: a changing paradigm.	KEEP AS NON CORE	Summary: Centrosome duplication: cyclin E/CDK2 phosphorylates NPM1 to license centrosome duplication. Reason: Well-established but specific non-core CDK2 function coordinated with S phase. Supporting Evidence: PMID:26297806 Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.
GO:0051321 meiotic cell cycle	TAS PMID:19238148 Cell cycle, CDKs and cancer: a changing paradigm.	KEEP AS NON CORE	Summary: Meiotic cell cycle: CDK2 is essential for meiosis (telomere attachment / meiotic progression). Reason: Genetically CDK2 is essential for meiosis though dispensable for mitosis; a real but tissue/context-restricted function, hence non-core for the general gene summary. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0071732 cellular response to nitric oxide	TAS PMID:20079829 Cdk2 nitrosylation and loss of mitochondrial potential media...	KEEP AS NON CORE	Summary: Cellular response to nitric oxide: CDK2 is S-nitrosylated, contributing to NO-dependent cell-cycle effects. Reason: Context-specific signaling response; peripheral to core function. Supporting Evidence: PMID:19238148 Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity	IDA PMID:21596315 Deubiquitinase USP37 is activated by CDK2 to antagonize APC(...	ACCEPT	Summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining, well-established molecular function, active only when bound to a cyclin partner. Reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that activate the kinase, and Thr160 activation-loop phosphorylation is required for activity. Supporting Evidence: PMID:1396589 Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity. PMID:7630397 CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.
GO:0005515 protein binding	IPI PMID:21596315 Deubiquitinase USP37 is activated by CDK2 to antagonize APC(...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:21596315 Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.
GO:0007265 Ras protein signal transduction	IEP PMID:9054499 Oncogenic ras provokes premature cell senescence associated ...	KEEP AS NON CORE	Summary: Ras protein signal transduction (IEP), associated with Ras-induced senescence where CDK2/cyclin E activity counteracts senescence via MYC. Reason: IEP/correlative association observed in the context of oncogenic Ras-induced senescence; CDK2 is not a canonical Ras-pathway transducer, so this is a peripheral, context-dependent link. Supporting Evidence: PMID:9054499 Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.
GO:0000307 cyclin-dependent protein kinase holoenzyme complex	IDA PMID:8692841 Isolation and characterization of two human transcription fa...	ACCEPT	Summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex. Reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically conserved. Supporting Evidence: PMID:1312467 Cyclin A is required at two points in the human cell cycle.
GO:0035173 histone kinase activity	IDA PMID:8692841 Isolation and characterization of two human transcription fa...	MARK AS OVER ANNOTATED	Summary: contributes_to histone kinase activity, assigned from a CAK/TFIIH-context study (PMID:8692841) in which CDK2-cyclin/CAK preparations phosphorylate histone H1. Reason: Histone H1 is a classic generic in vitro CDK substrate, but bona fide histone kinase activity is not a defining or physiologically primary CDK2 function. The contributes_to qualifier reflects activity within a complex preparation. Marked as over-annotation rather than removed. Supporting Evidence: PMID:8692841 Recent studies have shown that TFIIH copurifies with the cyclin-dependent kinase (cdk)-activating kinase complex (CAK) that includes cdk7, cyclin H, and p36/MAT1.
GO:0005515 protein binding	IPI PMID:11980914 Human Speedy: a novel cell cycle regulator that enhances pro...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:11980914 Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2.
GO:0005515 protein binding	IPI PMID:12839962 Human Spy1 promotes survival of mammalian cells following DN...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:12839962 Speedy (Spy1) is a novel cell cycle regulator that binds and activates cdk2, and was originally identified as a suppressor of Rad1 deficiency in Schizosaccharomyces pombe.
GO:0005515 protein binding	IPI PMID:12361598 CP110, a cell cycle-dependent CDK substrate, regulates centr...	KEEP AS NON CORE	Summary: Experimental physical interaction (IPI) between CDK2 and SCML2, captured by IntAct/curators as the generic term 'protein binding'. Reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21, CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332) and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather than removed because the underlying interaction data are sound. Supporting Evidence: PMID:12361598 Centrosome duplication and separation are linked inextricably to certain cell cycle events, in particular activation of cyclin-dependent kinases (CDKs).

Core Functions

CDK2 is a cyclin-dependent serine/threonine protein kinase that, in complex with cyclin E (G1/S) or cyclin A (S/G2), phosphorylates substrates to drive the G1/S transition and DNA replication.

Molecular Function:

cyclin-dependent protein serine/threonine kinase activity

Directly Involved In:

G1/S transition of mitotic cell cycle DNA replication

Cellular Locations:

nucleoplasm

In Complex:

cyclin-dependent protein kinase holoenzyme complex

Supporting Evidence:

PMID:1396589
Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating that phosphorylation at this site (as in CDC2) is required for kinase activity.
PMID:10995387
Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.

CDK2 binds cyclin partners; cyclin binding is obligatory for kinase activation, inducing the conformational change that aligns the active site.

Molecular Function:

cyclin binding

In Complex:

cyclin-dependent protein kinase holoenzyme complex

Supporting Evidence:

PMID:7630397
CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active site residues and relieving the steric blockade at the entrance of the catalytic cleft.

References

file:human/CDK2/CDK2-deep-research-falcon.md

Falcon deep research report for CDK2

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

GO annotation based on curation of immunofluorescence data (HPA)

GO_REF:0000107

Automatic annotation by orthology (Ensembl Compara)

GO_REF:0000108

GO annotations based on automatic mapping of inter-ontology links (GOC)

GO_REF:0000116

GO annotation based on RHEA mapping of catalytic activity

GO_REF:0000120

Automatic annotation of UniProtKB entries (UniRule/ARBA)

PMID:10330164

Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator.

PMID:10767298

Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.

PMID:10995387

Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.

PMID:11463386

Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2.

PMID:11746698

Intrinsic structural disorder and sequence features of the cell cycle inhibitor p57Kip2.

PMID:11953320

Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation.

PMID:11980914

Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2.

PMID:12244298

Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.

PMID:12361598

CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells.

PMID:12839962

Human Spy1 promotes survival of mammalian cells following DNA damage.

PMID:12941338

Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2.

PMID:12944431

DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes.

PMID:1312467

Cyclin A is required at two points in the human cell cycle.

PMID:1396589

Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.

PMID:15024385

p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding.

PMID:15107404

Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity.

PMID:15178429

NIRF induces G1 arrest and associates with Cdk2.

PMID:15189033

3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding.

PMID:15232106

Self-assembling protein microarrays.

PMID:15239650

N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2.

PMID:15530371

The crystal structure of human CDK7 and its protein recognition properties.

PMID:15611625

Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins.

PMID:15838514

Cyclin E in normal and neoplastic cell cycles.

PMID:15890360

Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division.

PMID:16061792

Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600.

PMID:16209941

Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.

PMID:16326706

Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells.

PMID:16327805

Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics.

PMID:16431923

The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells.

PMID:1653904

Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase.

PMID:16765349

Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced pre-B lymphoma cell apoptosis.

PMID:16962592

Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells.

PMID:17053782

C-terminal phosphorylation controls the stability and function of p27kip1.

PMID:17254966

Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases.

PMID:17254967

p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.

PMID:17418410

HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.

PMID:17698606

SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression.

PMID:18177895

Role of intrinsic flexibility in signal transduction mediated by the cell cycle regulator, p27 Kip1.

PMID:19150984

Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17.

PMID:19238148

Cell cycle, CDKs and cancer: a changing paradigm.

PMID:19470470

RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility.

PMID:19829063

Identification and characterization of CAC1 as a novel CDK2-associated cullin.

PMID:20079829

Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-dependent biphasic effect on HL-60 cell cycle.

PMID:20098747

Expanding the substantial interactome of NEMO using protein microarrays.

PMID:20871633

p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis.

PMID:20935635

Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2.

PMID:21092281

HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression.

PMID:21262353

Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization.

PMID:21319273

An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells.

PMID:21423803

Role of T198 modification in the regulation of p27(Kip1) protein stability and function.

PMID:21565702

Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis.

PMID:21596315

Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.

PMID:21952639

NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor.

PMID:2227411

Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

PMID:22810586

Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.

PMID:22940584

The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme.

PMID:23082202

The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein Fbw7-γ.

PMID:23184662

Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase.

PMID:23455922

Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS.

PMID:23602568

The protein interaction landscape of the human CMGC kinase group.

PMID:23781148

Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation.

PMID:23853094

Foxp3 protein stability is regulated by cyclin-dependent kinase 2.

PMID:24218572

CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome.

PMID:24358021

Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes.

PMID:24670654

Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus.

PMID:24728993

CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression.

PMID:25218637

RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2.

PMID:25241761

Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25852190

Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.

PMID:26297806

Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:26996940

Regulation of Microtubule Assembly by Tau and not by Pin1.

PMID:28216226

NBS1 phosphorylation status dictates repair choice of dysfunctional telomeres.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:28666995

Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins.

PMID:29203878

ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice.

PMID:29997244

LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells.

PMID:30833792

A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.

PMID:31467278

Maximizing binary interactome mapping with a minimal number of assays.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34591612

A protein interaction landscape of breast cancer.

PMID:34591642

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:37398436

AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:7630397

Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.

PMID:8242750

Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2.

PMID:8245034

Structural and functional characterization of the HPV16 E7 protein expressed in bacteria.

PMID:8521818

In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein.

PMID:8601310

Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.

PMID:8684460

Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex.

PMID:8692841

Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.

PMID:8756328

Structural basis of cyclin-dependent kinase activation by phosphorylation.

PMID:8756624

Cyclin-binding motifs are essential for the function of p21CIP1.

PMID:8876165

Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity.

PMID:9030781

Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5.

PMID:9054499

Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a.

PMID:9840943

Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins.

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Suggested Experiments

Experiment: Perform analog-sensitive (as-CDK2) chemical-genetic phosphoproteomics with cyclin E- versus cyclin A-synchronized cells to map partner-specific substrate repertoires in vivo.

Hypothesis: Cyclin E/CDK2 versus cyclin A/CDK2 phosphorylate distinct, partner-specified substrate sets at G1/S versus S/G2.

Type: phosphoproteomics

Experiment: Use separation-of-function CDK2 alleles and germ-cell-specific conditional knockouts to dissect meiosis-specific substrates and phenotypes.

Hypothesis: CDK2's essential meiotic function (e.g., telomere attachment) is mechanistically separable from its mitotic G1/S role.

Type: genetic separation-of-function analysis

Deep Research

Falcon

(CDK2-deep-research-falcon.md)

Comprehensive Research Report: CDK2 Gene Functional Annotation Falcon Edison Scientific Literature 20 citations 1 artifacts 2026-06-20T05:14:46.460996

Edison artifact artifact-00 (text/markdown)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

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Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: CDK2 Gene Functional Annotation

Gene/Protein Identity Verification

The gene CDK2 (UniProt accession P24941) encodes cyclin-dependent kinase 2 in Homo sapiens, a member of the CMGC serine/threonine protein kinase superfamily (pellarin2025cyclindependentproteinkinases pages 2-4). This identity has been confirmed through extensive recent literature demonstrating that human CDK2 is a well-characterized cell cycle regulator with conserved kinase domain structure and cyclin-binding properties (pluta2024cyclin‐dependentkinasesmasters pages 3-5, pellarin2025cyclindependentproteinkinases pages 2-4). The protein functions as described in the UniProt annotation as a catalytically active kinase when bound to cyclin partners, distinguishing it from related but functionally distinct CDK family members.

Primary Enzymatic Function and Catalytic Mechanism

Biochemical Reaction Catalyzed

CDK2 functions as an ATP-dependent serine/threonine protein kinase that catalyzes the phosphotransfer reaction from ATP to hydroxyl groups on serine or threonine residues of protein substrates (chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 1-2). The primary biochemical activity involves transferring the γ-phosphate of ATP to specific S/T residues on target proteins, thereby modulating their activity, stability, localization, or protein-protein interaction capabilities during cell cycle progression (fagundes2021cyclinecdk2dna pages 2-3).

Activation Mechanism

CDK2 requires a multistep activation process to achieve catalytic competence (fagundes2021cyclinecdk2dna pages 2-3, zhang2024cdk2andcdk4 pages 1-2). The kinase is inactive as a monomer and must first bind to regulatory cyclin proteins—principally cyclin E1, cyclin E2, or cyclin A—through an interface between the cyclin box domain of the cyclin and the PSTAIRE helix of CDK2 (fagundes2021cyclinecdk2dna pages 2-3). This interaction induces conformational changes in CDK2 that expose the catalytic site and reorient the activation loop (T-loop). Full catalytic activation subsequently requires phosphorylation of threonine 160 (Thr160) in the activation loop by CDK-activating kinase (CAK), which stabilizes the active kinase conformation (fagundes2021cyclinecdk2dna pages 2-3, pluta2024cyclin‐dependentkinasesmasters pages 3-5).

Recent structural and computational analyses have revealed that CDK2, when activated by cyclin E or cyclin A, adopts a catalytically competent conformation more readily than the related kinase CDK4 (zhang2024cdk2andcdk4 pages 1-2). This difference in conformational dynamics and catalytic efficiency correlates with the distinct cell cycle timing requirements of these kinases—CDK2 mediates the relatively brief G1/S transition and S phase progression, whereas CDK4 operates during the longer G1 phase (zhang2024cdk2andcdk4 pages 1-2).

Substrate Specificity

CDK2 exhibits strict substrate specificity for a proline-directed phosphorylation motif (johnson2023anatlasof pages 1-2, chi2020anovellandscape pages 2-3). Specifically, CDK2 preferentially phosphorylates serine or threonine residues that are immediately followed by proline (S/T-P motif). In a comprehensive in situ phosphorylation study using analog-sensitive CDK2 in isolated nuclei, 156 of 166 CDK2-specific thiophosphopeptides (93%) contained at least one S/T-P site, confirming this strong selectivity (chi2020anovellandscape pages 2-3).

A 2023 kinome-wide substrate specificity atlas that profiled 303 serine/threonine kinases found that CDK2 substrate recognition is shaped by both positive selectivity for specific residues and negative selectivity against charged or other residues at defined positions flanking the phosphorylation site (johnson2023anatlasof pages 1-2). Beyond the core S/T-P motif recognized by the kinase catalytic pocket, substrate recruitment is further enhanced by protein-protein interaction domains on the cyclin partners. For example, cyclin E contains MRAIL and VDCLE regions that facilitate binding to RLX-containing proteins and pocket proteins such as the retinoblastoma (Rb) family members (fagundes2021cyclinecdk2dna pages 2-3).

Subcellular Localization

CDK2 functions primarily in the nucleus, where it carries out the majority of its cell cycle regulatory roles (chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3, fagundes2021cyclinecdk2dna pages 2-3). Nuclear localization is essential for CDK2's ability to phosphorylate key substrates such as the retinoblastoma protein (Rb), E2F transcription factors, and numerous chromatin-associated proteins involved in DNA replication and transcription regulation. The nuclear localization of cyclin E, the primary G1/S activator of CDK2, contributes to maintaining CDK2 in the nuclear compartment during late G1 and S phase (fagundes2021cyclinecdk2dna pages 2-3).

Notably, recent work has identified a regulated shift in cyclin A2-CDK2 localization at the S/G2 transition (fagundes2021cyclinecdk2dna pages 2-3). At this cell cycle stage, cyclin A2 transitions from being exclusively nuclear to appearing in both nuclear and cytoplasmic compartments. Cytoplasmic cyclin A2-CDK2 activates the mitotic kinase PLK1 through phosphorylation of the PLK1 activator Bora, demonstrating that CDK2 can execute distinct functions in different cellular compartments depending on the cell cycle phase and cyclin partner (fagundes2021cyclinecdk2dna pages 2-3).

Signaling and Biochemical Pathways

The CDK-Rb-E2F Pathway and G1/S Transition

CDK2 occupies a central position in the cyclin-dependent kinase-retinoblastoma-E2F (CDK-Rb-E2F) pathway that controls commitment to DNA replication and progression through the G1/S transition (rubin2020integratingoldand pages 1-3, kim2022cdk46initiatesrb pages 1-2, hume2020aunifiedmodel pages 1-2, matthews2022cellcyclecontrol pages 1-4). This pathway integrates external mitogenic signals and internal cell cycle checkpoints to determine whether cells enter the cell cycle or exit to quiescence.

During early and mid-G1 phase, mitogenic signaling activates CDK4 and CDK6 in complex with D-type cyclins (rubin2020integratingoldand pages 1-3). CDK4/6-cyclin D complexes initiate phosphorylation of Rb protein, causing partial inactivation that begins to relieve E2F transcriptional repression (kim2022cdk46initiatesrb pages 1-2, rubin2020integratingoldand pages 1-3). As E2F activity increases, it drives transcription of cyclin E genes (CCNE1 and CCNE2), leading to accumulation of cyclin E protein in late G1 (fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2).

Cyclin E then binds to and activates CDK2, forming cyclin E-CDK2 complexes that drive the G1/S transition (kim2022cdk46initiatesrb pages 1-2, fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2). Cyclin E-CDK2 completes hyperphosphorylation of Rb at multiple serine and threonine sites including T373, S795, S807, and S811, fully disrupting Rb-E2F repressive complexes and maximally activating E2F-dependent transcription (janostiak2022understandingretinoblastomaposttranslational pages 2-4, kim2022cdk46initiatesrb pages 1-2). This creates a positive feedback loop: active CDK2 drives stronger E2F activity, which promotes further cyclin E and cyclin A expression, sustaining and amplifying CDK2 activity (kim2022cdk46initiatesrb pages 1-2, rubin2020integratingoldand pages 1-3).

Recent Paradigm Updates

Recent single-cell studies have substantially revised the classical irreversible "restriction point" model of G1/S control (cornwell2023lossofcdk46 pages 1-2, kim2022cdk46initiatesrb pages 1-2). Contrary to the long-held view that CDK2 activation creates an autonomous, mitogen-independent feedback loop, new evidence demonstrates that CDK2 activity and Rb phosphorylation depend on continuous upstream mitogen signaling and CDK4/6 activity throughout interphase, not just at the G1/S boundary (cornwell2023lossofcdk46 pages 1-2). When mitogens are removed or CDK4/6 is inhibited, even cells in S or G2 phase can lose CDK2 activity and undergo cell cycle exit with dephosphorylated Rb, indicating that the decision to proliferate remains reversible until cells complete mitosis (cornwell2023lossofcdk46 pages 1-2). These findings reveal that CDK2 functions as a phase-specific amplifier and executor of the proliferative decision rather than an autonomous switch, and that maintenance of CDK2 activity requires continued support from the upstream mitogenic pathway (rubin2020integratingoldand pages 1-3, cornwell2023lossofcdk46 pages 1-2, matthews2022cellcyclecontrol pages 1-4).

Coordination with DNA Replication and S Phase Progression

Beyond Rb phosphorylation and E2F activation, cyclin E-CDK2 and cyclin A-CDK2 complexes directly regulate the DNA replication machinery (fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2). CDK2 phosphorylates components of the pre-replication complex, including CDC6 and other licensing factors, facilitating the initiation of DNA replication at origins (fagundes2021cyclinecdk2dna pages 2-3). During S phase, cyclin A replaces cyclin E as the predominant CDK2 partner, and cyclin A-CDK2 activity coordinates S phase progression, ensuring proper timing of replication events and preventing re-replication (fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2).

CDK2 also regulates histone biosynthesis to support chromatin assembly during DNA replication. It phosphorylates NPAT (nuclear protein, coactivator of histone transcription) and HIRA, proteins involved in the transcription and processing of replication-dependent histones, thereby coupling histone production to the S phase program (fagundes2021cyclinecdk2dna pages 2-3).

Substrate Specificity and Key Protein Substrates

Retinoblastoma Protein (Rb)

The retinoblastoma tumor suppressor protein (Rb, encoded by RB1) is the canonical and best-characterized substrate of CDK2 (janostiak2022understandingretinoblastomaposttranslational pages 2-4, kim2022cdk46initiatesrb pages 1-2, hume2020aunifiedmodel pages 1-2). CDK2 phosphorylates Rb at multiple sites, with extensively validated sites including T373, S795, S807, and S811 (janostiak2022understandingretinoblastomaposttranslational pages 2-4). Phosphorylation of these residues disrupts the interaction between Rb and E2F transcription factors, converting Rb from a transcriptional repressor to an inactive state and enabling E2F-driven gene expression programs essential for S phase entry and progression (janostiak2022understandingretinoblastomaposttranslational pages 2-4, kim2022cdk46initiatesrb pages 1-2). The extent and pattern of Rb phosphorylation—moving from monophosphorylated forms in early G1 to hyperphosphorylated forms in late G1 and S phase—serve as molecular markers of cell cycle position and commitment (hume2020aunifiedmodel pages 1-2).

Cyclin-Dependent Kinase Inhibitors

CDK2 phosphorylates members of the Cip/Kip family of CDK inhibitors, particularly p27KIP1 (fagundes2021cyclinecdk2dna pages 2-3). Phosphorylation of p27 by cyclin E-CDK2 promotes p27 degradation and contributes to the progressive increase in CDK2 activity during late G1, creating another positive feedback mechanism that reinforces commitment to S phase entry (fagundes2021cyclinecdk2dna pages 2-3).

Transcription Factors and Coactivators

CDK2 regulates transcriptional programs by phosphorylating transcription factors and coactivators beyond the Rb-E2F axis. Validated substrates include E2F5, which is directly phosphorylated by CDK2, and CBP/p300, transcriptional coactivators whose phosphorylation modulates chromatin accessibility and gene expression (fagundes2021cyclinecdk2dna pages 2-3).

DNA Replication and Histone Regulation

CDK2 substrates involved in DNA replication include CDC6, a component of the pre-replication complex, and CDC25A, a phosphatase that further amplifies CDK activity (fagundes2021cyclinecdk2dna pages 2-3). For histone regulation, CDK2 phosphorylates NPAT, the master regulator of replication-dependent histone gene transcription, thereby ensuring coordinated histone synthesis during S phase (fagundes2021cyclinecdk2dna pages 2-3).

Centrosome Cycle Regulation

CDK2 controls centrosome duplication by phosphorylating centrosome-associated proteins including nucleophosmin (NPM), CP110, and MPS1 (monopolar spindle 1) (fagundes2021cyclinecdk2dna pages 2-3). These phosphorylation events coordinate centrosome duplication with DNA replication, ensuring that cells complete both processes before entering mitosis.

Expanded Nuclear Substrate Landscape

A comprehensive in situ phosphorylation study using analog-sensitive CDK2 in isolated nuclei identified 117 candidate nuclear CDK2 substrates, of which approximately 43% were previously known CDK substrates, providing strong validation of the approach (chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3). Importantly, this study revealed many previously unidentified substrates enriched in chromatin-associated functions, including:

LSD1 (lysine-specific demethylase 1): A histone demethylase involved in epigenetic regulation
DOT1L (DOT1-like histone methyltransferase): A histone methyltransferase that modifies chromatin structure
Rad54: A DNA repair and recombination protein

These findings expand CDK2's functional repertoire beyond canonical cell cycle regulation to include direct roles in chromatin modification, transcriptional regulation, DNA repair, and RNA metabolism (chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3). The identification of these chromatin-associated substrates was likely facilitated by the use of physiological nuclear contexts that preserved CDK2's normal regulatory mechanisms and substrate accessibility.

Regulatory Mechanisms

Positive Regulation

CDK2 activity is positively regulated through multiple interconnected mechanisms (fagundes2021cyclinecdk2dna pages 2-3, kim2022cdk46initiatesrb pages 1-2, rubin2020integratingoldand pages 1-3):

Cyclin accumulation: Mitogenic signaling drives expression of cyclin E and cyclin A through the CDK4/6-Rb-E2F pathway, providing the essential regulatory subunits for CDK2 activation.
Activating phosphorylation: CAK phosphorylates Thr160 in the CDK2 activation loop, which is required for full catalytic activity.
Positive feedback loops: CDK2-mediated phosphorylation of Rb enhances E2F activity, which drives further cyclin E/A expression; CDK2 phosphorylation of p27 promotes its degradation, removing inhibitory constraints.
Upstream pathway support: Recent evidence indicates that sustained CDK4/6 activity is required to maintain CDK2 activation throughout interphase by sequestering CDK inhibitors and sustaining the mitogenic state (cornwell2023lossofcdk46 pages 1-2).

Negative Regulation

CDK2 is subject to multiple inhibitory mechanisms that prevent premature or inappropriate activation (fagundes2021cyclinecdk2dna pages 2-3, pluta2024cyclin‐dependentkinasesmasters pages 3-5, cornwell2023lossofcdk46 pages 1-2):

Cip/Kip CDK inhibitors: p21CIP1 and p27KIP1 bind to cyclin-CDK2 complexes and block both CAK-mediated activation and substrate phosphorylation.
Cyclin degradation: Cyclin E is targeted for ubiquitin-mediated proteolysis by the SCF^FBW7 E3 ubiquitin ligase complex following phosphorylation at specific CDC phosphodegron sites, leading to rapid CDK2 inactivation as cells complete S phase (fagundes2021cyclinecdk2dna pages 2-3).
Loss of mitogenic support: Withdrawal of mitogens or inhibition of upstream CDK4/6 activity leads to redistribution of Cip/Kip inhibitors to CDK2, collapse of CDK2 activity, and reversal of Rb phosphorylation, demonstrating the conditional nature of CDK2 activation (cornwell2023lossofcdk46 pages 1-2).
Checkpoint-mediated inhibition: DNA damage checkpoint pathways induce p21 expression through p53, inhibiting CDK2 and blocking cell cycle progression until damage is repaired (hume2020aunifiedmodel pages 1-2).

Current Expert Perspectives and Recent Developments (2023-2025)

Recent research has substantially refined our understanding of CDK2's role in cell cycle control, moving beyond simple linear pathway models to appreciate the dynamic, context-dependent nature of CDK2 function (rubin2020integratingoldand pages 1-3, cornwell2023lossofcdk46 pages 1-2, matthews2022cellcyclecontrol pages 1-4).

A major conceptual advance is the recognition that catalytic efficiency and activity thresholds, rather than simple biochemical binding specificity, are the primary determinants of how cyclin-CDK2 complexes drive cell cycle progression (zhang2024cdk2andcdk4 pages 1-2, kim2022cdk46initiatesrb pages 1-2). Structural and computational studies have shown that CDK2 is optimized for rapid activation and high catalytic throughput during the brief G1/S transition, contrasting with the slower activation kinetics of CDK4 during the extended G1 phase (zhang2024cdk2andcdk4 pages 1-2).

The 2023 discovery that cell cycle commitment is fully reversible until mitosis, contingent on continuous mitogen signaling and CDK4/6-CDK2 coordination, has fundamentally challenged the restriction point paradigm (cornwell2023lossofcdk46 pages 1-2). This work demonstrates that CDK2 activity depends on sustained upstream support rather than functioning as an autonomous bistable switch, with important implications for understanding cancer cell responses to CDK4/6 inhibitors in clinical use.

High-throughput proteomic approaches have revealed an unexpectedly broad substrate network for CDK2, extending well beyond canonical cell cycle targets to include chromatin modifiers, DNA repair proteins, and transcriptional regulators (johnson2023anatlasof pages 1-2, chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3). These findings suggest that CDK2 coordinates multiple cellular processes—DNA replication, chromatin remodeling, transcription, and genome maintenance—to ensure coordinated S phase progression.

Finally, recent structural studies have provided detailed molecular views of CDK2 activation mechanisms and substrate recognition, including the 2024 cryo-EM structure of the CDK2-cyclin A-CDC25A complex (zhang2024cdk2andcdk4 pages 1-2). These structures are informing the design of more selective CDK2 inhibitors that target allosteric sites or protein-protein interfaces rather than the conserved ATP-binding pocket.

Summary Table

A comprehensive summary of CDK2 properties is provided in the following reference table:

Table: This table summarizes the core structural, enzymatic, pathway, localization, and regulatory properties of human CDK2, with emphasis on experimentally supported functions and recent mechanistic interpretations. It is useful as a compact functional annotation reference grounded in the cited literature.

Conclusions

CDK2 (UniProt P24941) is a serine/threonine protein kinase that serves as a central regulator of the mammalian cell cycle, specifically controlling the G1/S transition and S phase progression through coordinated phosphorylation of a broad network of substrates. The primary enzymatic function is ATP-dependent phosphorylation of serine/threonine residues in proline-directed (S/T-P) motifs on substrate proteins. CDK2 requires binding to cyclin E or cyclin A regulatory subunits and activating phosphorylation at Thr160 for full catalytic activity.

The protein functions predominantly in the nucleus, where it phosphorylates key substrates including the retinoblastoma protein (Rb), CDK inhibitors, transcription factors, DNA replication machinery components, histone regulatory proteins, and chromatin-associated factors. Through these substrates, CDK2 executes critical roles in the CDK-Rb-E2F pathway, drives S phase entry and progression, coordinates DNA replication with histone biosynthesis and centrosome duplication, and links cell cycle progression to chromatin regulation and DNA repair.

Recent evidence has substantially revised classical models of CDK2 function, demonstrating that CDK2 activity is maintained by continuous upstream mitogen and CDK4/6 support rather than functioning as an autonomous feedback loop, that cell cycle commitment remains reversible until mitosis, and that CDK2 regulates a much broader substrate network than previously appreciated. These findings establish CDK2 as a context-dependent amplifier and executor of the proliferative decision whose activity is finely tuned by catalytic efficiency, substrate accessibility, regulatory feedback loops, and integration with upstream signaling pathways.

References

(pellarin2025cyclindependentproteinkinases pages 2-4): Ilenia Pellarin, Alessandra Dall'Acqua, Andrea Favero, I. Segatto, Valentina Rossi, Nicole Crestan, Javad Karimbayli, B. Belletti, and Gustavo Baldassarre. Cyclin-dependent protein kinases and cell cycle regulation in biology and disease. Signal Transduction and Targeted Therapy, Jan 2025. URL: https://doi.org/10.1038/s41392-024-02080-z, doi:10.1038/s41392-024-02080-z. This article has 323 citations and is from a peer-reviewed journal.
(pluta2024cyclin‐dependentkinasesmasters pages 3-5): Aleksandra J. Pluta, Cécilia Studniarek, Shona Murphy, and Chris J. Norbury. Cyclin‐dependent kinases: masters of the eukaryotic universe. Wiley Interdisciplinary Reviews. RNA, Sep 2024. URL: https://doi.org/10.1002/wrna.1816, doi:10.1002/wrna.1816. This article has 57 citations and is from a peer-reviewed journal.
(chi2020anovellandscape pages 1-2): Yong Chi, John H. Carter, Jherek Swanger, Alexander V. Mazin, Robert L. Moritz, and Bruce E. Clurman. A novel landscape of nuclear human cdk2 substrates revealed by in situ phosphorylation. Science Advances, Apr 2020. URL: https://doi.org/10.1126/sciadv.aaz9899, doi:10.1126/sciadv.aaz9899. This article has 47 citations and is from a highest quality peer-reviewed journal.
(fagundes2021cyclinecdk2dna pages 1-2): Rafaela Fagundes and Leonardo K. Teixeira. Cyclin e/cdk2: dna replication, replication stress and genomic instability. Frontiers in Cell and Developmental Biology, Nov 2021. URL: https://doi.org/10.3389/fcell.2021.774845, doi:10.3389/fcell.2021.774845. This article has 311 citations.
(fagundes2021cyclinecdk2dna pages 2-3): Rafaela Fagundes and Leonardo K. Teixeira. Cyclin e/cdk2: dna replication, replication stress and genomic instability. Frontiers in Cell and Developmental Biology, Nov 2021. URL: https://doi.org/10.3389/fcell.2021.774845, doi:10.3389/fcell.2021.774845. This article has 311 citations.
(zhang2024cdk2andcdk4 pages 1-2): Wengang Zhang, Yonglan Liu, Hyunbum Jang, and Ruth Nussinov. Cdk2 and cdk4: cell cycle functions evolve distinct, catalysis-competent conformations, offering drug targets. JACS Au, 4:1911-1927, May 2024. URL: https://doi.org/10.1021/jacsau.4c00138, doi:10.1021/jacsau.4c00138. This article has 38 citations and is from a peer-reviewed journal.
(johnson2023anatlasof pages 1-2): Jared L. Johnson, Tomer M. Yaron, Emily M. Huntsman, Alexander Kerelsky, Junho Song, Amit Regev, Ting-Yu Lin, Katarina Liberatore, Daniel M. Cizin, Benjamin M. Cohen, Neil Vasan, Yilun Ma, Konstantin Krismer, Jaylissa Torres Robles, Bert van de Kooij, Anne E. van Vlimmeren, Nicole Andrée-Busch, Norbert F. Käufer, Maxim V. Dorovkov, Alexey G. Ryazanov, Yuichiro Takagi, Edward R. Kastenhuber, Marcus D. Goncalves, Benjamin D. Hopkins, Olivier Elemento, Dylan J. Taatjes, Alexandre Maucuer, Akio Yamashita, Alexei Degterev, Mohamed Uduman, Jingyi Lu, Sean D. Landry, Bin Zhang, Ian Cossentino, Rune Linding, John Blenis, Peter V. Hornbeck, Benjamin E. Turk, Michael B. Yaffe, and Lewis C. Cantley. An atlas of substrate specificities for the human serine/threonine kinome. Nature, 613:759-766, Jan 2023. URL: https://doi.org/10.1038/s41586-022-05575-3, doi:10.1038/s41586-022-05575-3. This article has 763 citations and is from a highest quality peer-reviewed journal.
(chi2020anovellandscape pages 2-3): Yong Chi, John H. Carter, Jherek Swanger, Alexander V. Mazin, Robert L. Moritz, and Bruce E. Clurman. A novel landscape of nuclear human cdk2 substrates revealed by in situ phosphorylation. Science Advances, Apr 2020. URL: https://doi.org/10.1126/sciadv.aaz9899, doi:10.1126/sciadv.aaz9899. This article has 47 citations and is from a highest quality peer-reviewed journal.
(rubin2020integratingoldand pages 1-3): Seth M. Rubin, Julien Sage, and Jan M. Skotheim. Integrating old and new paradigms of g1/s control. Molecular Cell, 80:183-192, Oct 2020. URL: https://doi.org/10.1016/j.molcel.2020.08.020, doi:10.1016/j.molcel.2020.08.020. This article has 323 citations and is from a highest quality peer-reviewed journal.
(kim2022cdk46initiatesrb pages 1-2): Sungsoo Kim, Alessandra Leong, Minah Kim, and Hee Won Yang. Cdk4/6 initiates rb inactivation and cdk2 activity coordinates cell-cycle commitment and g1/s transition. Scientific Reports, Oct 2022. URL: https://doi.org/10.1038/s41598-022-20769-5, doi:10.1038/s41598-022-20769-5. This article has 117 citations and is from a peer-reviewed journal.
(hume2020aunifiedmodel pages 1-2): Samuel Hume, Grigory L Dianov, and Kristijan Ramadan. A unified model for the g1/s cell cycle transition. Nucleic Acids Research, 48:12483-12501, Nov 2020. URL: https://doi.org/10.1093/nar/gkaa1002, doi:10.1093/nar/gkaa1002. This article has 245 citations and is from a highest quality peer-reviewed journal.
(matthews2022cellcyclecontrol pages 1-4): Helen K. Matthews, Cosetta Bertoli, and Robertus A. M. de Bruin. Cell cycle control in cancer. Nature Reviews Molecular Cell Biology, 23:74-88, Sep 2022. URL: https://doi.org/10.1038/s41580-021-00404-3, doi:10.1038/s41580-021-00404-3. This article has 1864 citations and is from a domain leading peer-reviewed journal.
(janostiak2022understandingretinoblastomaposttranslational pages 2-4): Radoslav Janostiak, Ariadna Torres-Sanchez, Francesc Posas, and Eulàlia de Nadal. Understanding retinoblastoma post-translational regulation for the design of targeted cancer therapies. Cancers, 14:1265, Feb 2022. URL: https://doi.org/10.3390/cancers14051265, doi:10.3390/cancers14051265. This article has 43 citations.
(cornwell2023lossofcdk46 pages 1-2): James A. Cornwell, Adrijana Crncec, Marwa M. Afifi, Kristina Tang, Ruhul Amin, and Steven D. Cappell. Loss of cdk4/6 activity in s/g2 phase leads to cell cycle reversal. Nature, 619:363-370, Jul 2023. URL: https://doi.org/10.1038/s41586-023-06274-3, doi:10.1038/s41586-023-06274-3. This article has 103 citations and is from a highest quality peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

pellarin2025cyclindependentproteinkinases pages 2-4
chi2020anovellandscape pages 2-3
johnson2023anatlasof pages 1-2
rubin2020integratingoldand pages 1-3
janostiak2022understandingretinoblastomaposttranslational pages 2-4
hume2020aunifiedmodel pages 1-2
chi2020anovellandscape pages 1-2
matthews2022cellcyclecontrol pages 1-4
https://doi.org/10.1038/s41392-024-02080-z,
https://doi.org/10.1002/wrna.1816,
https://doi.org/10.1126/sciadv.aaz9899,
https://doi.org/10.3389/fcell.2021.774845,
https://doi.org/10.1021/jacsau.4c00138,
https://doi.org/10.1038/s41586-022-05575-3,
https://doi.org/10.1016/j.molcel.2020.08.020,
https://doi.org/10.1038/s41598-022-20769-5,
https://doi.org/10.1093/nar/gkaa1002,
https://doi.org/10.1038/s41580-021-00404-3,
https://doi.org/10.3390/cancers14051265,
https://doi.org/10.1038/s41586-023-06274-3,

📚 Additional Documentation

Notes

(CDK2-notes.md)

CDK2 (P24941) — Research Notes

Human cyclin-dependent kinase 2 (CDK2 / CDKN2 / p33). 298 aa Ser/Thr protein kinase,
CMGC group, CDC2/CDKX subfamily. EC 2.7.11.22. Gene on chromosome 12.

Core molecular function (kinase + cyclin partners)

CDK2 is a proline-directed Ser/Thr protein kinase that is catalytically inactive as a
monomer and is activated by binding a cyclin partner. The crystal structure of the
cyclin A–CDK2–ATP complex showed: "CyclinA binds to one side of CDK2's catalytic cleft,
inducing large conformational changes in its PSTAIRE helix and T-loop. These changes
activate the kinase by realigning active site residues and relieving the steric blockade
at the entrance of the catalytic cleft" PMID:7630397.
Full activation additionally requires CAK (CDK7/cyclin H/MAT1)-mediated phosphorylation
of the activation (T-) loop at Thr160. Phosphorylation at Thr-14 or Tyr-15 inactivates;
phosphorylation at Thr-160 activates: "the two major phosphorylation sites are Tyr15 (Y15)
and Thr160 (T160)" and activity is governed by these PMID:1396589. UniProt ACTIVITY
REGULATION: "Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while
phosphorylation at Thr-160 activates it."
Catalytic activity (UniProt): L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] +
ADP + H+ (RHEA:17989); and the threonyl reaction; EC=2.7.11.22. Requires Mg2+ cofactor —
binds 2 Mg2+ ions PMID:21565702.
Cyclin partners: cyclin E1/E2 (CCNE1/CCNE2) at G1/S; cyclin A2 (CCNA2; cyclin A1/CCNA1 in
germ cells) at S/G2. Identified originally as the cyclin A- and adenovirus E1A-associated
p33 kinase PMID:1653904. Cyclin A is required at two points in the human cell cycle
(S-phase entry and mitosis) PMID:1312467. Cyclin E2 is a G1 cyclin and activating partner
of CDK2 and CDK3 PMID:9840943. Atypical activator Speedy/RINGO (SPDYA) can activate CDK2
independent of T-loop phosphorylation [PMID:28666995, "Interaction with SPDYA promotes
kinase activation via a conformation change that alleviates obstruction of the
substrate-binding cleft by the T-loop"].

Inhibitors

CIP/KIP family CDK inhibitors CDKN1A (p21) and CDKN1B (p27) bind and inhibit cyclin–CDK2.
Crystal structure of p27Kip1 bound to cyclin A–CDK2: "p27Kip1 binds the complex as an
extended structure interacting with both cyclin A and Cdk2" PMID:8684460. p21 cyclin-binding
(Cy/RXL) motifs essential for function PMID:8756624; p21 structural disorder mediates
binding PMID:8876165; p27 binds via sequential folding mechanism PMID:15024385.
KAP/CDKN3 (Cdi1) is a phosphatase that dephosphorylates pThr160 [PMID:8242750, PMID:11463386].

Cell-cycle substrates / biological roles

RB1: cyclin E/CDK2 phosphorylates RB1, releasing E2F (Reactome R-HSA-188390); part of the
G1/S transition that drives the E2F transcriptional program and initiation of DNA synthesis.
NPAT (p220): cyclin E/CDK2 phosphorylates NPAT in Cajal bodies to promote replication-dependent
histone gene transcription at G1/S [PMID:10995387, "Cyclin E/Cdk2 acts at the G1/S-phase
transition to promote the E2F transcriptional program and the initiation of DNA synthesis"].
DNA replication: phosphorylates CDC6, ORC1, NPM1; promotes origin firing and centrosome
duplication. Centrosome duplication & NPM1 (Cell 2000). Centriole duplication: CDK2 recruited
by centriolar satellite microcephaly proteins PMID:26297806.
USP37: CDK2 phosphorylates and activates USP37 to antagonize APC/C-CDH1 and promote S-phase
entry PMID:21596315.
EZH2: CDK1/CDK2 phosphorylate EZH2 at Thr350 to maintain H3K27me3 and epigenetic gene
silencing PMID:20935635.
SUV39H1: CDK2 phosphorylates Suv39H1 at Ser391, causing dissociation from chromatin and
regulating heterochromatin replication [PMID:24728993, "CDK2 phosphorylates Suv39H1 at Ser391
... results in preferential dissociation from chromatin"].
NBN/NBS1: cyclin A/CDK2 phosphorylation status dictates telomere repair choice; telomere
maintenance in response to DNA damage PMID:28216226.
ERCC6/CSB: cyclin A-CDK2 phosphorylates CSB at S158, required for its chromatin remodeling
in DSB repair pathway choice [PMID:29203878, "cell cycle-dependent phosphorylation on S158
by cyclin A-CDK2"].
eEF2 (Thr57) by cyclin A-CDK2, regulating eEF2K inhibition PMID:23184662.
BRCA2 phosphorylation regulating homologous recombination [PMID:15800615 (UniProt)].
AKT1/2 C-terminal phosphorylation promoting activation PMID:24670654.
MYC phosphorylation to suppress Ras-induced senescence [PMID:19966300 (UniProt)].
DNA-damage checkpoint roles: G1/S checkpoint and DNA damage response in human ESCs
PMID:21319273; p53-independent G2/M checkpoint (UniProt).

Localization

Nucleus and cytoplasm; centrosome (late G2, cyclin A/CDK2); Cajal body (NPAT phosphorylation);
endosome (compartmentalized CDK2 with SHP-1/beta-catenin, insulin internalization
PMID:21262353). UniProt: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome;
Nucleus, Cajal body; Cytoplasm; Endosome.

Knockout / redundancy notes

Cdk2-null mice are viable; CDK2 is dispensable for mitotic cell cycle but essential for meiosis
(UniProt FUNCTION: "essential for meiosis, but dispensable for mitosis"). CDK1 can compensate
for CDK2 in the mitotic cycle (Malumbres & Barbacid review PMID:19238148). This argues the
most defensible CORE function is the MF (kinase activity, cyclin binding) plus the canonical
G1/S and DNA replication roles; many downstream BP annotations are real but non-core/context.

Annotation strategy

MF kinase terms (GO:0004693 cyclin-dependent protein Ser/Thr kinase activity; GO:0004674;
GO:0106310 protein serine kinase; GO:0097472) — ACCEPT as core; well supported.
GO:0030332 cyclin binding — ACCEPT core; defining feature.
GO:0005515 protein binding — bare term; KEEP_AS_NON_CORE (uninformative but valid IPI;
guidance says avoid endorsing as core; do not REMOVE valid experimental IPI).
GO:0005524 ATP binding, GO:0000287 magnesium ion binding — ACCEPT (required for catalysis).
Cyclin–CDK2 complex CC terms (GO:0000307; GO:0097123/4 A1/A2; GO:0097134/5 E1/E2) — ACCEPT.
G1/S, DNA replication, positive regulation of DNA replication — ACCEPT/core.
G2/M, regulation of mitotic cell cycle, APC/C regulation, senescence, centrosome/centriole
duplication, telomere maintenance, heterochromatin/chromatin remodeling, NO response, Ras
signaling (IEP), insulin/endosome — KEEP_AS_NON_CORE (real but peripheral/context-specific).
IEA chromosome location terms transferred from mouse ortholog (telomeric region, condensed
chromosome, X/Y chromosome) — KEEP_AS_NON_CORE; over-broad CC transfers, low specificity.
protein binding (bare) GO:0005515 — avoid as core.
protein domain specific binding GO:0019904 (p21/p27 docking) — KEEP_AS_NON_CORE.
histone kinase activity GO:0035173 contributes_to (PMID:8692841, CAK/TFIIH context) —
this is about CAK complex H1 kinase activity; MARK_AS_OVER_ANNOTATED (CDK2 is not a bona fide
histone H1 kinase as a primary function; weak).
Ras protein signal transduction GO:0007265 IEP (PMID:9054499) — IEP/senescence context;
KEEP_AS_NON_CORE (correlative).

📄 View Raw YAML

id: P24941
gene_symbol: CDK2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'CDK2 (cyclin-dependent kinase 2) is a 298-residue serine/threonine protein kinase of the
  CMGC group, CDC2/CDKX subfamily (EC 2.7.11.22). It is catalytically inactive as a monomer and is activated
  by binding a cyclin partner: cyclin E1/E2 at the G1/S transition and cyclin A2 (cyclin A1 in germ cells)
  during S and G2 phases. Full activation requires CDK-activating kinase (CDK7/cyclin H/MAT1, CAK)-mediated
  phosphorylation of the activation-loop residue Thr160; activity is inhibited by Wee1/Myt1 phosphorylation
  of Thr14/Tyr15 (reversed by CDC25 phosphatases) and by binding of the CIP/KIP inhibitors p21/CDKN1A
  and p27/CDKN1B. Cyclin-CDK2 phosphorylates numerous nuclear substrates to drive the G1/S transition
  and DNA replication, including RB1 (releasing E2F), NPAT (activating replication-dependent histone gene
  transcription in Cajal bodies), CDC6, and NPM1 (licensing centrosome duplication). CDK2 also phosphorylates
  substrates linking it to DNA-damage and telomere responses (BRCA2, NBN/NBS1, ERCC6/CSB), epigenetic
  silencing (EZH2, SUV39H1), and S-phase control (USP37). Although CDK2 is a central S-phase kinase, knockout
  studies show it is dispensable for the mitotic cell cycle (CDK1 compensates) but essential for meiosis.
  CDK2 localizes mainly to the nucleus/nucleoplasm and also to centrosomes, Cajal bodies, and the cytoplasm,
  and is a prominent anticancer drug target.'
alternative_products:
- name: '1'
  id: P24941-1
- name: 2 (CDK2deltaT)
  id: P24941-2
  sequence_note: VSP_041998
existing_annotations:
- term:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex.
    action: ACCEPT
    reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically
      conserved.
    supported_by:
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: 'G2/M transition of mitotic cell cycle: cyclin A/CDK2 modulates entry into mitosis.'
    action: KEEP_AS_NON_CORE
    reason: CDK2 contributes to G2 progression and the timing of cyclin B/CDK1 activation, but the G2/M
      transition is principally CDK1-driven and CDK2 is dispensable for mitosis; non-core.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Protein kinase activity (broad parent term, IEA from InterPro/UniRule).
    action: ACCEPT
    reason: Correct but general; the specific cyclin-dependent serine/threonine kinase activity (GO:0004693)
      is the appropriate leaf term and is separately annotated. Acceptable as a broader IEA mapping.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: ATP binding, the phosphate donor for CDK2 catalysis.
    action: ACCEPT
    reason: Required for kinase catalysis; CDK2 crystal structures resolve bound ATP.
    supported_by:
    - reference_id: PMID:21565702
      supporting_text: high-resolution crystal structures of a CDK2/Cyclin A transition state complex
        bound to ADP, substrate peptide, and MgF(3)(-).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization of CDK2. While CDK2 acts predominantly in the nucleus, a cytoplasmic
      cyclin A2/CDK2 pool appears at the S/G2 transition and contributes to mitotic entry.
    action: ACCEPT
    reason: CDK2 shuttles between nucleus and cytoplasm and has cytoplasmic/compartmentalized pools; directly
      observed. At the S/G2 transition cyclin A2/CDK2 redistributes partly to the cytoplasm, where it
      can activate PLK1 via the activator Bora, illustrating a compartment-specific output for CDK2.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
    - reference_id: file:human/CDK2/CDK2-deep-research-falcon.md
      supporting_text: Cytoplasmic cyclin A2-CDK2 activates the mitotic kinase PLK1 through phosphorylation
        of the PLK1 activator Bora
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Endosomal localization of a compartmentalized CDK2 pool linked to insulin internalization.
    action: KEEP_AS_NON_CORE
    reason: Specific minor pool; peripheral to canonical cell-cycle function.
    supported_by:
    - reference_id: PMID:21262353
      supporting_text: Compartmentalized CDK2 is connected with SHP-1 and β-catenin and regulates insulin
        internalization.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication.
    action: KEEP_AS_NON_CORE
    reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication.
      Directly observed (IDA/HPA) and by orthology.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0006338
    label: chromatin remodeling
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Chromatin remodeling, derived (IEA, GO_REF:0000108) from histone-kinase activity context.
    action: KEEP_AS_NON_CORE
    reason: CDK2 influences chromatin via phosphorylation of SUV39H1, EZH2 and CSB/ERCC6, but the broad
      'chromatin remodeling' BP from an automated mapping is non-core; the specific substrate-level processes
      are separately annotated.
    supported_by:
    - reference_id: PMID:29203878
      supporting_text: ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway
        choice.
- term:
    id: GO:0015030
    label: Cajal body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cajal body localization, where cyclin E/CDK2 phosphorylates NPAT to activate histone gene
      transcription.
    action: KEEP_AS_NON_CORE
    reason: Directly observed localization tied to a specific S-phase function (NPAT phosphorylation).
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes. CDK2 is a proline-directed kinase, preferring serine/threonine residues followed by
      proline (S/T-P motif).
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation. CDK2 substrate selection follows a proline-directed
      (S/T-P) consensus, supported by an analog-sensitive in situ nuclear phosphorylation screen and a
      kinome-wide specificity atlas.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
    - reference_id: file:human/CDK2/CDK2-deep-research-falcon.md
      supporting_text: 156 of 166 CDK2-specific thiophosphopeptides (93%) contained at least one S/T-P
        site, confirming this strong selectivity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10330164
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:10330164
      supporting_text: Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain
        of the p300 coactivator.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11463386
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and EP300, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:11463386
      supporting_text: Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated
        phosphatase in complex with phosphoCDK2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12244298
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:12244298
      supporting_text: Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12941338
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:12941338
      supporting_text: Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine
        inhibitors of cyclin-dependent kinases 1 and 2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15178429
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15178429
      supporting_text: NIRF induces G1 arrest and associates with Cdk2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15189033
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and UHRF2 (NIRF), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15189033
      supporting_text: 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15232106
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15232106
      supporting_text: Self-assembling protein microarrays.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15239650
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15239650
      supporting_text: 'N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent
        kinases 1 and 2.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15530371
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15530371
      supporting_text: CDK7, a member of the cyclin-dependent protein kinase family, regulates the activities
        of other CDKs through phosphorylation on their activation segment and hence contributes to control
        of the eukaryotic cell cycle.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15890360
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15890360
      supporting_text: Molecular basis for the specificity of p27 toward cyclin-dependent kinases that
        regulate cell division.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16061792
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16061792
      supporting_text: Among the proteins identified are previously described cellular targets of E7 including
        pRB, p107, p130, several E2F and DP family members, cyclin A, cyclin E, CDC2, and CDK2 ( Fig.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16209941
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16209941
      supporting_text: The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central
        role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many
        common cancers.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16326706
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16326706
      supporting_text: Here, we show that TIMP-2 mediates G1 growth arrest in human endothelial cells
        through de novo synthesis of the cyclin-dependent kinase inhibitor p27Kip1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16327805
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16327805
      supporting_text: Cdk7 performs two essential but distinct functions as a CDK-activating kinase (CAK)
        required for cell-cycle progression and as the RNA polymerase II (Pol II) CTD kinase of general
        transcription factor IIH.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16431923
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16431923
      supporting_text: The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits
        the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian
        cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16765349
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16765349
      supporting_text: Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced
        pre-B lymphoma cell apoptosis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16962592
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and HPV E7 (xeno), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:16962592
      supporting_text: Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through
        inducing p38 mitogen activated protein kinase in vascular smooth muscle cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17053782
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:17053782
      supporting_text: Entry of cells into the cell division cycle requires the coordinated activation
        of cyclin-dependent kinases (cdks) and the deactivation of cyclin kinase inhibitors.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17254966
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:17254966
      supporting_text: Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic
        tyrosine kinases.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17254967
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:17254967
      supporting_text: p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17418410
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:17418410
      supporting_text: The HIFs can alter cell cycle progression through putative transcriptional targets
        such as Cyclin D1 ( Baba et al., 2003 ) and indirect modulation of p21 and p27 ( Gardner et al.,
        2001 ; Green et al., 2001 ; Koshiji et al., 2004 ).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17698606
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:17698606
      supporting_text: SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18177895
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:18177895
      supporting_text: p27(Kip1) (p27), which controls eukaryotic cell division through interactions with
        cyclin-dependent kinases (Cdks), integrates and transduces promitogenic signals from various nonreceptor
        tyrosine kinases by orchestrating its own phosphorylation, ubiquitination and degradation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19470470
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:19470470
      supporting_text: p90 ribosomal S6 kinase (RSK1) is an effector of both Ras/MEK/MAPK and PI3K/PDK1
        pathways.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20098747
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:20098747
      supporting_text: Of the novel interactors, more than 30% were kinases, while at least 25% were involved
        in signal transduction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20871633
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:20871633
      supporting_text: Cyclin-dependent kinases (Cdks) promote cell division by phosphorylating and reversibly
        inactivating Rb by a hierarchical series of phosphorylation events and sequential conformational
        changes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21092281
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:21092281
      supporting_text: HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2
        interactions and delays cell cycle progression.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21423803
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:21423803
      supporting_text: Recently, it has been demonstrated that the tumor suppression function of p27 resides
        not only in the ability to inhibit Cyclins/CDKs complexes through its N-terminal domain but also
        in the capacity to modulate cell motility through its C-terminal portion.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21565702
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:21565702
      supporting_text: 'Briefly bound to activate: transient binding of a second catalytic magnesium activates
        the structure and dynamics of CDK2 kinase for catalysis.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21952639
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:21952639
      supporting_text: Here, we show that the ubiquitin ligase NIRF (also known as UHRF2), which induces
        G1 arrest, interacts with multiple cell cycle proteins including cyclins (A2, B1, D1 and E1),
        p53 and pRB, and ubiquitinates cyclins D1 and E1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22810586
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:22810586
      supporting_text: Interpreting cancer genomes using systematic host network perturbations by tumour
        virus proteins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22940584
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:22940584
      supporting_text: For these experiments, SAP155 or CDC5L were first phosphorylated with recombinant
        CycA2/CDK2, which resulted in six (CDC5L) or nine (SAP155) phosphorylated residues, as verified
        by MS.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23082202
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:23082202
      supporting_text: The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein Fbw7-γ.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23455922
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and SCAPER, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:23455922
      supporting_text: We systematically investigated the reproducibility of a standardized AP-MS workflow
        by performing a rigorous interlaboratory comparative analysis of the interactomes of 32 human
        kinases.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23602568
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:23602568
      supporting_text: The protein interaction landscape of the human CMGC kinase group.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23853094
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:23853094
      supporting_text: Foxp3 protein stability is regulated by cyclin-dependent kinase 2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24218572
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and IKBKG (NEMO), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:24218572
      supporting_text: CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient
        in STAR syndrome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24358021
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and RB1, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:24358021
      supporting_text: Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21
        complexes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25218637
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:25218637
      supporting_text: RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated
        phosphorylation of BRCA2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:25241761
      supporting_text: Using an in situ proximity ligation assay to systematically profile endogenous
        protein-protein interactions in a pathway network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and Ccna2 (cyclin A2, mouse), captured
      by IntAct/curators as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:25416956
      supporting_text: A proteome-scale map of the human interactome network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and UHRF2 (NIRF), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:25852190
      supporting_text: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source
        of potential targets for combination therapy.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and HPV E7 (xeno), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:26496610
      supporting_text: A human interactome in three quantitative dimensions organized by stoichiometries
        and abundances.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2, xeno), captured
      by IntAct/curators as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: kinases) are enriched more than by chance, suggesting that such proteins are highly
        interactive (Extended Data Fig.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29997244
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and FBXW7, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:29997244
      supporting_text: 'LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative
        mapping of protein-protein interactions in mammalian cells.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30833792
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and STOML1, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:30833792
      supporting_text: A protein-interaction network of interferon-stimulated genes extends the innate
        immune system landscape.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31467278
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:31467278
      supporting_text: CMV cytomegalovirus, HSV-TK herpes simplex virus-thymidine kinase, UAS upstream
        activating sequence, IRES internal ribosome entry site.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and
        Uncovers Widespread Protein Aggregation in Affected Brains.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591612
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCND1 (cyclin D1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:34591612
      supporting_text: The BPIFA1-PIK3CA interaction we identified and the inhibition of WT PIK3CA kinase
        activity by BPIFA1 in vitro suggests that BPIFA1 may also directly modulate PI3K/AKT via PPI,
        which warrants a structural study of the complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:34591642
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:34591642
      supporting_text: Additionally, we observe mutation-enriched interactions between the human epidermal
        growth factor receptor 3 (HER3) receptor tyrosine kinase and PIK3CA (the alpha catalytic subunit
        of phosphatidylinositol 3-kinase) that can inform the response to HER3 inhibition in vivo.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37398436
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:37398436
      supporting_text: Notably, such a classification strategy has been successfully used to predict kinase
        substrates from phosphoproteomics data (Yang et al, 2019; Kim et al, 2021), or to classify cell
        types from single cell RNA-sequencing (Abdelaal et al, 2019).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDK7, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: Multimodal cell maps as a foundation for structural and functional genomics.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:7630397
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CKS1B, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8242750
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and EP300, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8242750
      supporting_text: Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8521818
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and MAPK15 (ERK8), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8521818
      supporting_text: In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a
        novel 36 kDa RING finger protein.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8684460
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8684460
      supporting_text: Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the
        cyclin A-Cdk2 complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8756328
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8756328
      supporting_text: Structural basis of cyclin-dependent kinase activation by phosphorylation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8756624
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8756624
      supporting_text: Cyclin-binding motifs are essential for the function of p21CIP1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9840943
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:9840943
      supporting_text: Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is
        induced by viral oncoproteins.
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Magnesium ion binding; CDK2 binds two Mg2+ ions required for catalysis.
    action: ACCEPT
    reason: Mg2+ is an essential catalytic cofactor; a second transiently bound Mg2+ activates catalysis.
    supported_by:
    - reference_id: PMID:21565702
      supporting_text: 'Briefly bound to activate: transient binding of a second catalytic magnesium activates
        the structure and dynamics of CDK2 kinase for catalysis.'
- term:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex.
    action: ACCEPT
    reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically
      conserved.
    supported_by:
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0000781
    label: chromosome, telomeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: chromosome, telomeric region localization, transferred by orthology (IEA) from the mouse
      ortholog.
    action: KEEP_AS_NON_CORE
    reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at
      telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional
      information; kept as non-core.
    supported_by:
    - reference_id: PMID:28216226
      supporting_text: Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2,
        promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
- term:
    id: GO:0000793
    label: condensed chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: condensed chromosome localization, transferred by orthology (IEA) from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at
      telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional
      information; kept as non-core.
    supported_by:
    - reference_id: PMID:28216226
      supporting_text: Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2,
        promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
- term:
    id: GO:0000805
    label: X chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: X chromosome localization, transferred by orthology (IEA) from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at
      telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional
      information; kept as non-core.
    supported_by:
    - reference_id: PMID:28216226
      supporting_text: Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2,
        promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
- term:
    id: GO:0000806
    label: Y chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Y chromosome localization, transferred by orthology (IEA) from the mouse ortholog.
    action: KEEP_AS_NON_CORE
    reason: Over-broad orthology-transferred chromosomal CC terms of low specificity. CDK2 does act at
      telomeres (NBN phosphorylation) and meiotic chromosomes, but these CC terms add little functional
      information; kept as non-core.
    supported_by:
    - reference_id: PMID:28216226
      supporting_text: Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2,
        promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent
      kinase activity).
    action: ACCEPT
    reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase
      activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific
      cyclin-dependent term is also annotated.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Nuclear localization of CDK2.
    action: ACCEPT
    reason: CDK2 acts on nuclear substrates; nuclear localization directly observed (IDA) and inferred
      by orthology.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005635
    label: nuclear envelope
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Nuclear envelope localization (IEA by orthology).
    action: KEEP_AS_NON_CORE
    reason: Low-specificity orthology-transferred localization; not a primary functional site.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005667
    label: transcription regulator complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Transcription regulator complex membership (IEA by orthology).
    action: KEEP_AS_NON_CORE
    reason: CDK2 regulates transcriptional programs (E2F via RB1; histone genes via NPAT) but is not itself
      a core transcription-complex subunit; broad orthology transfer.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Positive regulation of cell proliferation, consistent with CDK2's proliferative role.
    action: KEEP_AS_NON_CORE
    reason: Real but high-level/indirect consequence of CDK2 cell-cycle activity; non-core.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: Kinase activity (broad parent term, IEA by orthology).
    action: ACCEPT
    reason: Correct but very general; specific kinase MF terms are separately annotated.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: 'Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory
      activating subunits of the holoenzyme.'
    action: ACCEPT
    reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A
      binding drives the activating conformational change.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop.
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0097123
    label: cyclin A1-CDK2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Part of the cyclin A1-CDK2 complex, the germ-cell (cyclin A1) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
- term:
    id: GO:0097134
    label: cyclin E1-CDK2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Part of the cyclin E1-CDK2 complex, the G1/S (cyclin E1) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
- term:
    id: GO:0097135
    label: cyclin E2-CDK2 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: Part of the cyclin E2-CDK2 complex, the G1/S (cyclin E2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
- term:
    id: GO:0097472
    label: cyclin-dependent protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0007346
    label: regulation of mitotic cell cycle
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68911
  qualifier: involved_in
  review:
    summary: Regulation of the mitotic cell cycle (Reactome TAS).
    action: ACCEPT
    reason: Accurate higher-level process; CDK2 is a central cell-cycle regulator at G1/S and S/G2.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0045740
    label: positive regulation of DNA replication
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69656
  qualifier: involved_in
  review:
    summary: Positive regulation of DNA replication by cyclin-CDK2 (Reactome TAS).
    action: ACCEPT
    reason: Consistent with CDK2's core S-phase-promoting activity.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0090398
    label: cellular senescence
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2559583
  qualifier: involved_in
  review:
    summary: 'Cellular senescence: cyclin E/CDK2-mediated MYC phosphorylation suppresses Ras-induced senescence
      (Reactome TAS).'
    action: KEEP_AS_NON_CORE
    reason: Specific, context-dependent role; peripheral to the core cell-cycle kinase function.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: Oncogenic ras provokes premature cell senescence associated with accumulation of
        p53 and p16INK4a.
- term:
    id: GO:1905784
    label: regulation of anaphase-promoting complex-dependent catabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-176408
  qualifier: involved_in
  review:
    summary: 'Regulation of APC/C-dependent catabolism: CDK2 activates USP37 to antagonize APC/C-CDH1
      and promote S-phase entry.'
    action: KEEP_AS_NON_CORE
    reason: Specific mechanistic role at the G1/S boundary; peripheral to core MF.
    supported_by:
    - reference_id: PMID:21596315
      supporting_text: Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S
        phase entry.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174079
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187520
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187959
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188390
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3788705
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication.
    action: KEEP_AS_NON_CORE
    reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication.
      Directly observed (IDA/HPA) and by orthology.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0036064
    label: ciliary basal body
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Ciliary basal body localization (HPA immunofluorescence).
    action: KEEP_AS_NON_CORE
    reason: Basal body is closely related to the centriole/centrosome where CDK2 localizes; peripheral
      to core function.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0000082
    label: G1/S transition of mitotic cell cycle
  evidence_type: NAS
  original_reference_id: PMID:15838514
  qualifier: involved_in
  review:
    summary: G1/S transition of mitotic cell cycle, the canonical CDK2 function (cyclin E/CDK2).
    action: ACCEPT
    reason: 'Core biological role: cyclin E/CDK2 drives G1/S by phosphorylating RB1, NPAT and other substrates
      to launch the E2F program and DNA synthesis.'
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0000082
    label: G1/S transition of mitotic cell cycle
  evidence_type: NAS
  original_reference_id: PMID:9840943
  qualifier: involved_in
  review:
    summary: G1/S transition of mitotic cell cycle, the canonical CDK2 function (cyclin E/CDK2).
    action: ACCEPT
    reason: 'Core biological role: cyclin E/CDK2 drives G1/S by phosphorylating RB1, NPAT and other substrates
      to launch the E2F program and DNA synthesis.'
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0097123
    label: cyclin A1-CDK2 complex
  evidence_type: NAS
  original_reference_id: PMID:12244298
  qualifier: part_of
  review:
    summary: Part of the cyclin A1-CDK2 complex, the germ-cell (cyclin A1) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:12244298
      supporting_text: Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IPI
  original_reference_id: PMID:12244298
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:12244298
      supporting_text: Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor.
- term:
    id: GO:0097134
    label: cyclin E1-CDK2 complex
  evidence_type: IPI
  original_reference_id: PMID:8756624
  qualifier: part_of
  review:
    summary: Part of the cyclin E1-CDK2 complex, the G1/S (cyclin E1) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:8756624
      supporting_text: Cyclin-binding motifs are essential for the function of p21CIP1.
- term:
    id: GO:0097135
    label: cyclin E2-CDK2 complex
  evidence_type: IPI
  original_reference_id: PMID:15232106
  qualifier: part_of
  review:
    summary: Part of the cyclin E2-CDK2 complex, the G1/S (cyclin E2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:15232106
      supporting_text: Self-assembling protein microarrays.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:1396589
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:24670654
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:24728993
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:28216226
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:28666995
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:9030781
  qualifier: enables
  review:
    summary: Protein serine kinase activity, reflecting the RHEA serine-phosphorylation reaction CDK2
      catalyzes.
    action: ACCEPT
    reason: Correct; CDK2 phosphorylates serine (and threonine) residues. Directly demonstrated in multiple
      EXP/IDA studies of CDK2 substrate phosphorylation.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:24728993
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0120186
    label: negative regulation of protein localization to chromatin
  evidence_type: IDA
  original_reference_id: PMID:24728993
  qualifier: involved_in
  review:
    summary: 'Negative regulation of protein localization to chromatin: CDK2 phosphorylation of SUV39H1
      promotes its dissociation from chromatin.'
    action: KEEP_AS_NON_CORE
    reason: Specific mechanistic outcome of SUV39H1 phosphorylation; non-core.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
- term:
    id: GO:0120261
    label: regulation of heterochromatin organization
  evidence_type: IDA
  original_reference_id: PMID:24728993
  qualifier: involved_in
  review:
    summary: Regulation of heterochromatin organization via CDK2 phosphorylation of SUV39H1 at Ser391.
    action: KEEP_AS_NON_CORE
    reason: Specific, directly demonstrated function controlling heterochromatin replication; non-core.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
- term:
    id: GO:0097472
    label: cyclin-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:24670654
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:28216226
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0043247
    label: telomere maintenance in response to DNA damage
  evidence_type: IDA
  original_reference_id: PMID:28216226
  qualifier: involved_in
  review:
    summary: 'Telomere maintenance in response to DNA damage: cyclin A/CDK2 phosphorylates NBN/NBS1 to
      dictate dysfunctional-telomere repair choice.'
    action: KEEP_AS_NON_CORE
    reason: Specific, directly demonstrated (IDA) DNA-damage-response role; non-core.
    supported_by:
    - reference_id: PMID:28216226
      supporting_text: Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2,
        promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11953320
  qualifier: enables
  review:
    summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent
      kinase activity).
    action: ACCEPT
    reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase
      activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific
      cyclin-dependent term is also annotated.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0043687
    label: post-translational protein modification
  evidence_type: IDA
  original_reference_id: PMID:11746698
  qualifier: involved_in
  review:
    summary: Post-translational protein modification (broad), from CDK2 substrate phosphorylation.
    action: KEEP_AS_NON_CORE
    reason: Correct but very general parent of protein phosphorylation; non-core given more specific terms
      exist.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
- term:
    id: GO:0031453
    label: positive regulation of heterochromatin formation
  evidence_type: IDA
  original_reference_id: PMID:20935635
  qualifier: involved_in
  review:
    summary: 'Positive regulation of heterochromatin formation: CDK2 phosphorylates EZH2 to maintain H3K27me3
      and epigenetic silencing.'
    action: KEEP_AS_NON_CORE
    reason: Specific chromatin/epigenetic function via EZH2; peripheral to core cell-cycle role.
    supported_by:
    - reference_id: PMID:20935635
      supporting_text: Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation
        of EZH2.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IMP
  original_reference_id: PMID:29203878
  qualifier: involved_in
  review:
    summary: 'Protein phosphorylation: CDK2 phosphorylates numerous Ser/Thr substrates. In situ nuclear
      phosphoproteomics with analog-sensitive CDK2 defined a broad nuclear substrate landscape extending
      beyond canonical cell-cycle targets to chromatin modifiers, DNA-repair and transcription regulators.'
    action: ACCEPT
    reason: Direct readout of CDK2's catalytic function on protein substrates; well supported. An analog-sensitive
      in situ nuclear phosphorylation screen identified ~117 candidate nuclear CDK2 substrates (~43% of
      them previously known CDK substrates), validating the breadth of CDK2's phosphorylation activity.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
    - reference_id: file:human/CDK2/CDK2-deep-research-falcon.md
      supporting_text: identified 117 candidate nuclear CDK2 substrates, of which approximately 43% were
        previously known CDK substrates
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IDA
  original_reference_id: PMID:8684460
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:8684460
      supporting_text: Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the
        cyclin A-Cdk2 complex.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IGI
  original_reference_id: PMID:26996940
  qualifier: enables
  review:
    summary: Protein serine/threonine kinase activity of CDK2 (the parent class of its cyclin-dependent
      kinase activity).
    action: ACCEPT
    reason: Accurate but less specific than GO:0004693 (cyclin-dependent protein serine/threonine kinase
      activity), which is the appropriate term for CDK2. Accepted as a correct broader MF; the specific
      cyclin-dependent term is also annotated.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28666995
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:28666995
      supporting_text: Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO
        proteins.
- term:
    id: GO:0097472
    label: cyclin-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:28666995
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23781148
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CKS1B, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:23781148
      supporting_text: Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2
        expression and activation.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:12944431
  qualifier: involved_in
  review:
    summary: 'Protein phosphorylation: CDK2 phosphorylates numerous Ser/Thr substrates.'
    action: ACCEPT
    reason: Direct readout of CDK2's catalytic function on protein substrates; well supported.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IDA
  original_reference_id: PMID:23781148
  qualifier: enables
  review:
    summary: 'Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory
      activating subunits of the holoenzyme.'
    action: ACCEPT
    reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A
      binding drives the activating conformational change.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop.
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  evidence_type: IDA
  original_reference_id: PMID:1312467
  qualifier: part_of
  review:
    summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex.
    action: ACCEPT
    reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically
      conserved.
    supported_by:
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IDA
  original_reference_id: PMID:1312467
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0097472
    label: cyclin-dependent protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:1312467
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IPI
  original_reference_id: PMID:1312467
  qualifier: enables
  review:
    summary: 'Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory
      activating subunits of the holoenzyme.'
    action: ACCEPT
    reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A
      binding drives the activating conformational change.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop.
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: PMID:8245034
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:8876165
  qualifier: enables
  review:
    summary: Protein domain-specific binding, from CDK2 interactions with the CDK-inhibitor domains of
      p21/CDKN1A and p27/CDKN1B.
    action: KEEP_AS_NON_CORE
    reason: Reflects docking of CIP/KIP inhibitor domains onto the cyclin-CDK2 surface; valid but peripheral
      to CDK2's core catalytic function.
    supported_by:
    - reference_id: PMID:8876165
      supporting_text: 'Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational
        disorder mediates binding diversity.'
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IDA
  original_reference_id: PMID:8876165
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:8876165
      supporting_text: 'Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational
        disorder mediates binding diversity.'
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IPI
  original_reference_id: PMID:15024385
  qualifier: enables
  review:
    summary: Protein domain-specific binding, from CDK2 interactions with the CDK-inhibitor domains of
      p21/CDKN1A and p27/CDKN1B.
    action: KEEP_AS_NON_CORE
    reason: Reflects docking of CIP/KIP inhibitor domains onto the cyclin-CDK2 surface; valid but peripheral
      to CDK2's core catalytic function.
    supported_by:
    - reference_id: PMID:15024385
      supporting_text: p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced
        protein folding.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IPI
  original_reference_id: PMID:15024385
  qualifier: enables
  review:
    summary: 'Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory
      activating subunits of the holoenzyme.'
    action: ACCEPT
    reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A
      binding drives the activating conformational change.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop.
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IDA
  original_reference_id: PMID:15024385
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:15024385
      supporting_text: p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced
        protein folding.
- term:
    id: GO:0097124
    label: cyclin A2-CDK2 complex
  evidence_type: IDA
  original_reference_id: PMID:11746698
  qualifier: part_of
  review:
    summary: Part of the cyclin A2-CDK2 complex, the S/G2 (cyclin A2) active CDK2 holoenzyme.
    action: ACCEPT
    reason: Direct/curated complex membership consistent with CDK2's cyclin partners. Core structural
      context for CDK2 function.
    supported_by:
    - reference_id: PMID:11746698
      supporting_text: The cell cycle inhibitor p57Kip2 induces cell cycle arrest by inhibiting the activity
        of cyclin-dependent kinases.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:2227411
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:2227411
      supporting_text: Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of
        Saccharomyces cerevisiae and Schizosaccharomyces pombe.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8601310
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:8601310
      supporting_text: Crystal structure and mutational analysis of the human CDK2 kinase complex with
        cell cycle-regulatory protein CksHs1.
- term:
    id: GO:0007099
    label: centriole replication
  evidence_type: IMP
  original_reference_id: PMID:26297806
  qualifier: involved_in
  review:
    summary: 'Centriole replication: CDK2 is recruited by centriolar-satellite microcephaly proteins to
      promote centriole duplication.'
    action: KEEP_AS_NON_CORE
    reason: Specific, well-supported (IMP) function but peripheral to the core G1/S kinase role.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15107404
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN3 (KAP/Cdi1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15107404
      supporting_text: Mutation of Ser 193 to Ala also abolishes the ability of C/EBPalpha to cause growth
        arrest because of a lack of interactions with cdk2 and E2F-Rb complexes.
- term:
    id: GO:0018105
    label: peptidyl-serine phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:23184662
  qualifier: involved_in
  review:
    summary: Peptidyl-serine phosphorylation of CDK2 substrates.
    action: ACCEPT
    reason: Specific catalytic-outcome term consistent with CDK2 serine-kinase activity.
    supported_by:
    - reference_id: PMID:24728993
      supporting_text: CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin
        replication during cell cycle progression.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19150984
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNB2 (cyclin B2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:19150984
      supporting_text: Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-157906
  qualifier: located_in
  review:
    summary: Cytosolic localization (Reactome pathway annotation).
    action: KEEP_AS_NON_CORE
    reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative
      sites for CDK2 function.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174054
  qualifier: located_in
  review:
    summary: Cytosolic localization (Reactome pathway annotation).
    action: KEEP_AS_NON_CORE
    reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative
      sites for CDK2 function.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174273
  qualifier: located_in
  review:
    summary: Cytosolic localization (Reactome pathway annotation).
    action: KEEP_AS_NON_CORE
    reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative
      sites for CDK2 function.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69191
  qualifier: located_in
  review:
    summary: Cytosolic localization (Reactome pathway annotation).
    action: KEEP_AS_NON_CORE
    reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative
      sites for CDK2 function.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9858566
  qualifier: located_in
  review:
    summary: Cytosolic localization (Reactome pathway annotation).
    action: KEEP_AS_NON_CORE
    reason: Acceptable broad localization from Reactome TAS; nucleoplasm and centrosome are the more informative
      sites for CDK2 function.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1363303
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1363306
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1363311
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1363314
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-157906
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174079
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174110
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174164
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-174273
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-176298
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-176318
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187520
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187552
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187574
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187575
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187916
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187934
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187937
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187948
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187949
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-187959
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188350
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188371
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188386
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-188390
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3788705
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3788708
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4088024
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5684081
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5684096
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6793661
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6805109
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68916
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68917
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68918
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-68944
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69005
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69195
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69199
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-69562
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9624120
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9686521
  qualifier: located_in
  review:
    summary: Localizes to the nucleoplasm, where cyclin-CDK2 acts on nuclear cell-cycle substrates (RB1,
      NPAT, etc.).
    action: ACCEPT
    reason: Consistent with CDK2 nuclear localization and its nuclear substrates. Reactome TAS annotations
      to nucleoplasm are appropriate; duplicates across pathways are acceptable.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0000086
    label: G2/M transition of mitotic cell cycle
  evidence_type: NAS
  original_reference_id: PMID:1653904
  qualifier: involved_in
  review:
    summary: 'G2/M transition of mitotic cell cycle: cyclin A/CDK2 modulates entry into mitosis.'
    action: KEEP_AS_NON_CORE
    reason: CDK2 contributes to G2 progression and the timing of cyclin B/CDK1 activation, but the G2/M
      transition is principally CDK1-driven and CDK2 is dispensable for mitosis; non-core.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10767298
  qualifier: located_in
  review:
    summary: Nuclear localization of CDK2.
    action: ACCEPT
    reason: CDK2 acts on nuclear substrates; nuclear localization directly observed (IDA) and inferred
      by orthology.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:10767298
  qualifier: located_in
  review:
    summary: Cytoplasmic localization of CDK2.
    action: ACCEPT
    reason: CDK2 shuttles between nucleus and cytoplasm and has cytoplasmic/compartmentalized pools; directly
      observed.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0008284
    label: positive regulation of cell population proliferation
  evidence_type: IDA
  original_reference_id: PMID:10767298
  qualifier: involved_in
  review:
    summary: Positive regulation of cell proliferation, consistent with CDK2's proliferative role.
    action: KEEP_AS_NON_CORE
    reason: Real but high-level/indirect consequence of CDK2 cell-cycle activity; non-core.
    supported_by:
    - reference_id: PMID:10767298
      supporting_text: Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates
        cell cycle progression.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IDA
  original_reference_id: PMID:1653904
  qualifier: enables
  review:
    summary: 'Cyclin binding: CDK2 binds cyclin E (G1/S) and cyclin A (S/G2) partners, the obligatory
      activating subunits of the holoenzyme.'
    action: ACCEPT
    reason: Defining molecular feature of CDK2. Demonstrated biochemically and structurally; cyclin A
      binding drives the activating conformational change.
    supported_by:
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop.
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15611625
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE2 (cyclin E2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:15611625
      supporting_text: In addition to their activation via binding to cyclins, cyclin-dependent kinases
        (CDKs) can be activated via binding to a novel cell cycle regulator termed Speedy/Ringo, which
        shows no apparent similarity to cyclins.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19829063
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNA2 (cyclin A2), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:19829063
      supporting_text: Identification and characterization of CAC1 as a novel CDK2-associated cullin.
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:21262353
  qualifier: located_in
  review:
    summary: Endosomal localization of a compartmentalized CDK2 pool linked to insulin internalization.
    action: KEEP_AS_NON_CORE
    reason: Specific minor pool; peripheral to canonical cell-cycle function.
    supported_by:
    - reference_id: PMID:21262353
      supporting_text: Compartmentalized CDK2 is connected with SHP-1 and β-catenin and regulates insulin
        internalization.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: TAS
  original_reference_id: PMID:19238148
  qualifier: located_in
  review:
    summary: Centrosomal localization, where cyclin A/CDK2 coordinates centrosome/centriole duplication.
    action: KEEP_AS_NON_CORE
    reason: Well-supported localization linked to a specific (non-core) CDK2 function in centrosome duplication.
      Directly observed (IDA/HPA) and by orthology.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0006260
    label: DNA replication
  evidence_type: TAS
  original_reference_id: PMID:19238148
  qualifier: involved_in
  review:
    summary: 'DNA replication: cyclin E/A-CDK2 promotes origin firing and S-phase progression.'
    action: ACCEPT
    reason: Core role; CDK2 activity initiates and sustains DNA synthesis during S phase.
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0015030
    label: Cajal body
  evidence_type: IDA
  original_reference_id: PMID:10995387
  qualifier: located_in
  review:
    summary: Cajal body localization, where cyclin E/CDK2 phosphorylates NPAT to activate histone gene
      transcription.
    action: KEEP_AS_NON_CORE
    reason: Directly observed localization tied to a specific S-phase function (NPAT phosphorylation).
    supported_by:
    - reference_id: PMID:10995387
      supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
        promotes histone gene transcription.
- term:
    id: GO:0031571
    label: mitotic G1 DNA damage checkpoint signaling
  evidence_type: TAS
  original_reference_id: PMID:21319273
  qualifier: involved_in
  review:
    summary: Mitotic G1 DNA-damage checkpoint signaling; p21/CDKN1A inactivation of cyclin E/CDK2 enforces
      G1/S arrest.
    action: KEEP_AS_NON_CORE
    reason: Specific checkpoint role downstream of DNA damage; peripheral to core kinase function.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0051298
    label: centrosome duplication
  evidence_type: TAS
  original_reference_id: PMID:19238148
  qualifier: involved_in
  review:
    summary: 'Centrosome duplication: cyclin E/CDK2 phosphorylates NPM1 to license centrosome duplication.'
    action: KEEP_AS_NON_CORE
    reason: Well-established but specific non-core CDK2 function coordinated with S phase.
    supported_by:
    - reference_id: PMID:26297806
      supporting_text: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2
        and promote centriole duplication.
- term:
    id: GO:0051321
    label: meiotic cell cycle
  evidence_type: TAS
  original_reference_id: PMID:19238148
  qualifier: involved_in
  review:
    summary: 'Meiotic cell cycle: CDK2 is essential for meiosis (telomere attachment / meiotic progression).'
    action: KEEP_AS_NON_CORE
    reason: Genetically CDK2 is essential for meiosis though dispensable for mitosis; a real but tissue/context-restricted
      function, hence non-core for the general gene summary.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0071732
    label: cellular response to nitric oxide
  evidence_type: TAS
  original_reference_id: PMID:20079829
  qualifier: involved_in
  review:
    summary: 'Cellular response to nitric oxide: CDK2 is S-nitrosylated, contributing to NO-dependent
      cell-cycle effects.'
    action: KEEP_AS_NON_CORE
    reason: Context-specific signaling response; peripheral to core function.
    supported_by:
    - reference_id: PMID:19238148
      supporting_text: Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent
        kinase (CDK) activity.
- term:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:21596315
  qualifier: enables
  review:
    summary: CDK2 is a cyclin-dependent serine/threonine protein kinase (EC 2.7.11.22); this is its defining,
      well-established molecular function, active only when bound to a cyclin partner.
    action: ACCEPT
    reason: Core molecular function. CDK2 kinase activity is directly demonstrated biochemically and structurally
      and is conserved phylogenetically (IBA). Cyclin A binding induces the conformational changes that
      activate the kinase, and Thr160 activation-loop phosphorylation is required for activity.
    supported_by:
    - reference_id: PMID:1396589
      supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
        that phosphorylation at this site (as in CDC2) is required for kinase activity.
    - reference_id: PMID:7630397
      supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
        changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
        site residues and relieving the steric blockade at the entrance of the catalytic cleft.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21596315
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CCNE1 (cyclin E1), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:21596315
      supporting_text: Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S
        phase entry.
- term:
    id: GO:0007265
    label: Ras protein signal transduction
  evidence_type: IEP
  original_reference_id: PMID:9054499
  qualifier: involved_in
  review:
    summary: Ras protein signal transduction (IEP), associated with Ras-induced senescence where CDK2/cyclin
      E activity counteracts senescence via MYC.
    action: KEEP_AS_NON_CORE
    reason: IEP/correlative association observed in the context of oncogenic Ras-induced senescence; CDK2
      is not a canonical Ras-pathway transducer, so this is a peripheral, context-dependent link.
    supported_by:
    - reference_id: PMID:9054499
      supporting_text: Oncogenic ras provokes premature cell senescence associated with accumulation of
        p53 and p16INK4a.
- term:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  evidence_type: IDA
  original_reference_id: PMID:8692841
  qualifier: part_of
  review:
    summary: Part of the cyclin-dependent protein kinase holoenzyme (cyclin-CDK2) complex.
    action: ACCEPT
    reason: CDK2 is catalytically active only as part of a cyclin-CDK holoenzyme; well supported and phylogenetically
      conserved.
    supported_by:
    - reference_id: PMID:1312467
      supporting_text: Cyclin A is required at two points in the human cell cycle.
- term:
    id: GO:0035173
    label: histone kinase activity
  evidence_type: IDA
  original_reference_id: PMID:8692841
  qualifier: contributes_to
  review:
    summary: contributes_to histone kinase activity, assigned from a CAK/TFIIH-context study (PMID:8692841)
      in which CDK2-cyclin/CAK preparations phosphorylate histone H1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Histone H1 is a classic generic in vitro CDK substrate, but bona fide histone kinase activity
      is not a defining or physiologically primary CDK2 function. The contributes_to qualifier reflects
      activity within a complex preparation. Marked as over-annotation rather than removed.
    supported_by:
    - reference_id: PMID:8692841
      supporting_text: Recent studies have shown that TFIIH copurifies with the cyclin-dependent kinase
        (cdk)-activating kinase complex (CAK) that includes cdk7, cyclin H, and p36/MAT1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11980914
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1A (p21), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:11980914
      supporting_text: 'Human Speedy: a novel cell cycle regulator that enhances proliferation through
        activation of Cdk2.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12839962
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and CDKN1B (p27), captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:12839962
      supporting_text: Speedy (Spy1) is a novel cell cycle regulator that binds and activates cdk2, and
        was originally identified as a suppressor of Rad1 deficiency in Schizosaccharomyces pombe.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12361598
  qualifier: enables
  review:
    summary: Experimental physical interaction (IPI) between CDK2 and SCML2, captured by IntAct/curators
      as the generic term 'protein binding'.
    action: KEEP_AS_NON_CORE
    reason: Valid experimentally-supported binary interaction, but the bare 'protein binding' term is
      uninformative about CDK2's molecular function and curation guidance is to avoid endorsing it as
      a core function. Where the partner is a cyclin (CCNA/CCNE/CCNB/CCND/CCNH) or a CDK inhibitor (CDKN1A/p21,
      CDKN1B/p27), the functionally meaningful relationship is better captured by cyclin binding (GO:0030332)
      and the specific cyclin-CDK2 complex terms, which are separately annotated. Kept as non-core rather
      than removed because the underlying interaction data are sound.
    supported_by:
    - reference_id: PMID:12361598
      supporting_text: Centrosome duplication and separation are linked inextricably to certain cell cycle
        events, in particular activation of cyclin-dependent kinases (CDKs).
references:
- id: file:human/CDK2/CDK2-deep-research-falcon.md
  title: Falcon deep research report for CDK2
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: 'LLM-generated synthesis (Edison/Falcon) of recent CDK2 reviews and
      primary literature. Accurately summarizes the canonical CDK2 biology already captured
      in this review (cyclin E/A binding, Thr160/CAK activation, nuclear G1/S and S-phase
      roles, RB1/E2F pathway, NPAT/histone and centrosome substrates). Useful additions
      that strengthen specific annotations: (1) the proline-directed S/T-P substrate
      motif with quantitative support from an analog-sensitive in situ nuclear phosphorylation
      screen (Chi et al. 2020, Sci Adv) and a kinome-wide specificity atlas (Johnson
      et al. 2023, Nature); (2) a broad nuclear CDK2 substrate landscape (~117 candidates).
      Several cited PMIDs (Chi 2020, Johnson 2023, Fagundes & Teixeira 2021) are NOT in
      the local publications cache and were not independently verified here, so correctness
      is left UNVERIFIED; the report also occasionally over-states (e.g., framing CDK2
      as the "canonical" Rb kinase, whereas CDK4/6 initiate and CDK2 completes Rb hyperphosphorylation,
      and CDK2 is dispensable for the mitotic cell cycle).'
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: GO annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: GO annotation based on curation of immunofluorescence data (HPA)
  findings: []
- id: GO_REF:0000107
  title: Automatic annotation by orthology (Ensembl Compara)
  findings: []
- id: GO_REF:0000108
  title: GO annotations based on automatic mapping of inter-ontology links (GOC)
  findings: []
- id: GO_REF:0000116
  title: GO annotation based on RHEA mapping of catalytic activity
  findings: []
- id: GO_REF:0000120
  title: Automatic annotation of UniProtKB entries (UniRule/ARBA)
  findings: []
- id: PMID:10330164
  title: "Specificity of cyclin E-Cdk2, TFIIB, and E1A interactions with a common domain of the p300 coactivator."
  full_text_unavailable: true
  findings: []
- id: PMID:10767298
  title: 'Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression.'
  findings: []
- id: PMID:10995387
  title: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes
    histone gene transcription.
  findings: []
- id: PMID:11463386
  title: "Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with phosphoCDK2."
  full_text_unavailable: true
  findings: []
- id: PMID:11746698
  title: "Intrinsic structural disorder and sequence features of the cell cycle inhibitor p57Kip2."
  full_text_unavailable: true
  findings: []
- id: PMID:11953320
  title: "Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation."
  full_text_unavailable: true
  findings: []
- id: PMID:11980914
  title: "Human Speedy: a novel cell cycle regulator that enhances proliferation through activation of Cdk2."
  full_text_unavailable: true
  findings: []
- id: PMID:12244298
  title: "Structure-based design of a potent purine-based cyclin-dependent kinase inhibitor."
  full_text_unavailable: true
  findings: []
- id: PMID:12361598
  title: "CP110, a cell cycle-dependent CDK substrate, regulates centrosome duplication in human cells."
  full_text_unavailable: true
  findings: []
- id: PMID:12839962
  title: "Human Spy1 promotes survival of mammalian cells following DNA damage."
  full_text_unavailable: true
  findings: []
- id: PMID:12941338
  title: "Structure-based design of 2-arylamino-4-cyclohexylmethyl-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinases 1 and 2."
  full_text_unavailable: true
  findings: []
- id: PMID:12944431
  title: "DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes."
  full_text_unavailable: true
  findings: []
- id: PMID:1312467
  title: Cyclin A is required at two points in the human cell cycle.
  findings: []
- id: PMID:1396589
  title: Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
  findings: []
- id: PMID:15024385
  title: "p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding."
  full_text_unavailable: true
  findings: []
- id: PMID:15107404
  title: "Liver tumors escape negative control of proliferation via PI3K/Akt-mediated block of C/EBP alpha growth inhibitory activity."
  full_text_unavailable: true
  findings: []
- id: PMID:15178429
  title: "NIRF induces G1 arrest and associates with Cdk2."
  full_text_unavailable: true
  findings: []
- id: PMID:15189033
  title: "3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding."
  full_text_unavailable: true
  findings: []
- id: PMID:15232106
  title: "Self-assembling protein microarrays."
  full_text_unavailable: true
  findings: []
- id: PMID:15239650
  title: "N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2."
  full_text_unavailable: true
  findings: []
- id: PMID:15530371
  title: "The crystal structure of human CDK7 and its protein recognition properties."
  full_text_unavailable: true
  findings: []
- id: PMID:15611625
  title: "Identification and comparative analysis of multiple mammalian Speedy/Ringo proteins."
  full_text_unavailable: true
  findings: []
- id: PMID:15838514
  title: "Cyclin E in normal and neoplastic cell cycles."
  full_text_unavailable: true
  findings: []
- id: PMID:15890360
  title: "Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division."
  full_text_unavailable: true
  findings: []
- id: PMID:16061792
  title: "Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600."
  full_text_unavailable: true
  findings: []
- id: PMID:16209941
  title: "Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase."
  full_text_unavailable: true
  findings: []
- id: PMID:16326706
  title: "Shp-1 mediates the antiproliferative activity of tissue inhibitor of metalloproteinase-2 in human microvascular endothelial cells."
  full_text_unavailable: true
  findings: []
- id: PMID:16327805
  title: "Dichotomous but stringent substrate selection by the dual-function Cdk7 complex revealed by chemical genetics."
  full_text_unavailable: true
  findings: []
- id: PMID:16431923
  title: "The nucleocapsid protein of severe acute respiratory syndrome-coronavirus inhibits the activity of cyclin-cyclin-dependent kinase complex and blocks S phase progression in mammalian cells."
  full_text_unavailable: true
  findings: []
- id: PMID:1653904
  title: "Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase."
  full_text_unavailable: true
  findings: []
- id: PMID:16765349
  title: "Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced pre-B lymphoma cell apoptosis."
  full_text_unavailable: true
  findings: []
- id: PMID:16962592
  title: "Honokiol causes the p21WAF1-mediated G(1)-phase arrest of the cell cycle through inducing p38 mitogen activated protein kinase in vascular smooth muscle cells."
  full_text_unavailable: true
  findings: []
- id: PMID:17053782
  title: "C-terminal phosphorylation controls the stability and function of p27kip1."
  full_text_unavailable: true
  findings: []
- id: PMID:17254966
  title: "Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases."
  full_text_unavailable: true
  findings: []
- id: PMID:17254967
  title: "p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2."
  full_text_unavailable: true
  findings: []
- id: PMID:17418410
  title: "HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity."
  full_text_unavailable: true
  findings: []
- id: PMID:17698606
  title: "SCAPER, a novel cyclin A-interacting protein that regulates cell cycle progression."
  full_text_unavailable: true
  findings: []
- id: PMID:18177895
  title: "Role of intrinsic flexibility in signal transduction mediated by the cell cycle regulator, p27 Kip1."
  full_text_unavailable: true
  findings: []
- id: PMID:19150984
  title: "Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17."
  full_text_unavailable: true
  findings: []
- id: PMID:19238148
  title: 'Cell cycle, CDKs and cancer: a changing paradigm.'
  findings: []
- id: PMID:19470470
  title: "RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility."
  full_text_unavailable: true
  findings: []
- id: PMID:19829063
  title: "Identification and characterization of CAC1 as a novel CDK2-associated cullin."
  full_text_unavailable: true
  findings: []
- id: PMID:20079829
  title: "Cdk2 nitrosylation and loss of mitochondrial potential mediate NO-dependent biphasic effect on HL-60 cell cycle."
  full_text_unavailable: true
  findings: []
- id: PMID:20098747
  title: "Expanding the substantial interactome of NEMO using protein microarrays."
  full_text_unavailable: true
  findings: []
- id: PMID:20871633
  title: "p38 phosphorylates Rb on Ser567 by a novel, cell cycle-independent mechanism that triggers Rb-Hdm2 interaction and apoptosis."
  full_text_unavailable: true
  findings: []
- id: PMID:20935635
  title: Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2.
  findings: []
- id: PMID:21092281
  title: "HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression."
  full_text_unavailable: true
  findings: []
- id: PMID:21262353
  title: Compartmentalized CDK2 is connected with SHP-1 and beta-catenin and regulates insulin internalization.
  findings: []
- id: PMID:21319273
  title: "An important role for CDK2 in G1 to S checkpoint activation and DNA damage response in human embryonic stem cells."
  full_text_unavailable: true
  findings: []
- id: PMID:21423803
  title: "Role of T198 modification in the regulation of p27(Kip1) protein stability and function."
  full_text_unavailable: true
  findings: []
- id: PMID:21565702
  title: "Briefly bound to activate: transient binding of a second catalytic magnesium activates the structure and dynamics of CDK2 kinase for catalysis."
  findings: []
- id: PMID:21596315
  title: Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.
  findings: []
- id: PMID:21952639
  title: "NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor."
  full_text_unavailable: true
  findings: []
- id: PMID:2227411
  title: "Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe."
  full_text_unavailable: true
  findings: []
- id: PMID:22810586
  title: "Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins."
  full_text_unavailable: true
  findings: []
- id: PMID:22940584
  title: "The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme."
  full_text_unavailable: true
  findings: []
- id: PMID:23082202
  title: "The stomatin-like protein SLP-1 and Cdk2 interact with the F-Box protein Fbw7-γ."
  full_text_unavailable: true
  findings: []
- id: PMID:23184662
  title: "Phosphorylation of eukaryotic elongation factor 2 (eEF2) by cyclin A-cyclin-dependent kinase 2 regulates its inhibition by eEF2 kinase."
  full_text_unavailable: true
  findings: []
- id: PMID:23455922
  title: "Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS."
  full_text_unavailable: true
  findings: []
- id: PMID:23602568
  title: "The protein interaction landscape of the human CMGC kinase group."
  full_text_unavailable: true
  findings: []
- id: PMID:23781148
  title: "Overexpression of DOC-1R inhibits cell cycle G1/S transition by repressing CDK2 expression and activation."
  full_text_unavailable: true
  findings: []
- id: PMID:23853094
  title: "Foxp3 protein stability is regulated by cyclin-dependent kinase 2."
  full_text_unavailable: true
  findings: []
- id: PMID:24218572
  title: "CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome."
  full_text_unavailable: true
  findings: []
- id: PMID:24358021
  title: "Polycomb protein SCML2 regulates the cell cycle by binding and modulating CDK/CYCLIN/p21 complexes."
  full_text_unavailable: true
  findings: []
- id: PMID:24670654
  title: "Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus."
  full_text_unavailable: true
  findings: []
- id: PMID:24728993
  title: "CDK2-dependent phosphorylation of Suv39H1 is involved in control of heterochromatin replication during cell cycle progression."
  findings: []
- id: PMID:25218637
  title: "RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2."
  full_text_unavailable: true
  findings: []
- id: PMID:25241761
  title: "Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network."
  full_text_unavailable: true
  findings: []
- id: PMID:25416956
  title: "A proteome-scale map of the human interactome network."
  full_text_unavailable: true
  findings: []
- id: PMID:25852190
  title: "Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy."
  full_text_unavailable: true
  findings: []
- id: PMID:26297806
  title: Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote
    centriole duplication.
  findings: []
- id: PMID:26496610
  title: "A human interactome in three quantitative dimensions organized by stoichiometries and abundances."
  full_text_unavailable: true
  findings: []
- id: PMID:26996940
  title: "Regulation of Microtubule Assembly by Tau and not by Pin1."
  full_text_unavailable: true
  findings: []
- id: PMID:28216226
  title: NBS1 phosphorylation status dictates repair choice of dysfunctional telomeres.
  findings: []
- id: PMID:28514442
  title: "Architecture of the human interactome defines protein communities and disease networks."
  full_text_unavailable: true
  findings: []
- id: PMID:28666995
  title: Structural basis of divergent cyclin-dependent kinase activation by Spy1/RINGO proteins.
  findings: []
- id: PMID:29203878
  title: ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair pathway choice.
  findings: []
- id: PMID:29997244
  title: "LuTHy: a double-readout bioluminescence-based two-hybrid technology for quantitative mapping of protein-protein interactions in mammalian cells."
  full_text_unavailable: true
  findings: []
- id: PMID:30833792
  title: "A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape."
  full_text_unavailable: true
  findings: []
- id: PMID:31467278
  title: "Maximizing binary interactome mapping with a minimal number of assays."
  full_text_unavailable: true
  findings: []
- id: PMID:32814053
  title: "Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains."
  full_text_unavailable: true
  findings: []
- id: PMID:33961781
  title: "Dual proteome-scale networks reveal cell-specific remodeling of the human interactome."
  full_text_unavailable: true
  findings: []
- id: PMID:34591612
  title: "A protein interaction landscape of breast cancer."
  full_text_unavailable: true
  findings: []
- id: PMID:34591642
  title: "A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity."
  full_text_unavailable: true
  findings: []
- id: PMID:35271311
  title: "OpenCell: Endogenous tagging for the cartography of human cellular organization."
  full_text_unavailable: true
  findings: []
- id: PMID:37398436
  title: "AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor."
  full_text_unavailable: true
  findings: []
- id: PMID:40205054
  title: "Multimodal cell maps as a foundation for structural and functional genomics."
  full_text_unavailable: true
  findings: []
- id: PMID:7630397
  title: Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex.
  findings: []
- id: PMID:8242750
  title: "Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2."
  full_text_unavailable: true
  findings: []
- id: PMID:8245034
  title: "Structural and functional characterization of the HPV16 E7 protein expressed in bacteria."
  full_text_unavailable: true
  findings: []
- id: PMID:8521818
  title: "In vitro assembly of a functional human CDK7-cyclin H complex requires MAT1, a novel 36 kDa RING finger protein."
  full_text_unavailable: true
  findings: []
- id: PMID:8601310
  title: "Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1."
  full_text_unavailable: true
  findings: []
- id: PMID:8684460
  title: "Crystal structure of the p27Kip1 cyclin-dependent-kinase inhibitor bound to the cyclin A-Cdk2 complex."
  full_text_unavailable: true
  findings: []
- id: PMID:8692841
  title: 'Isolation and characterization of two human transcription factor IIH (TFIIH)-related complexes: ERCC2/CAK and TFIIH.'
  findings: []
- id: PMID:8756328
  title: "Structural basis of cyclin-dependent kinase activation by phosphorylation."
  full_text_unavailable: true
  findings: []
- id: PMID:8756624
  title: "Cyclin-binding motifs are essential for the function of p21CIP1."
  full_text_unavailable: true
  findings: []
- id: PMID:8876165
  title: "Structural studies of p21Waf1/Cip1/Sdi1 in the free and Cdk2-bound state: conformational disorder mediates binding diversity."
  full_text_unavailable: true
  findings: []
- id: PMID:9030781
  title: "Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5."
  full_text_unavailable: true
  findings: []
- id: PMID:9054499
  title: "Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a."
  findings: []
- id: PMID:9840943
  title: "Cyclin E2, a novel human G1 cyclin and activating partner of CDK2 and CDK3, is induced by viral oncoproteins."
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-1363303
  title: Reactome:R-HSA-1363303
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-1363306
  title: Reactome:R-HSA-1363306
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  findings: []
- id: Reactome:R-HSA-1363311
  title: Reactome:R-HSA-1363311
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  findings: []
- id: Reactome:R-HSA-1363314
  title: Reactome:R-HSA-1363314
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-157906
  title: Reactome:R-HSA-157906
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-174054
  title: Reactome:R-HSA-174054
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-174079
  title: Reactome:R-HSA-174079
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-174110
  title: Reactome:R-HSA-174110
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-174164
  title: Reactome:R-HSA-174164
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-174273
  title: Reactome:R-HSA-174273
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-176298
  title: Reactome:R-HSA-176298
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-176318
  title: Reactome:R-HSA-176318
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-176408
  title: Reactome:R-HSA-176408
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187520
  title: Reactome:R-HSA-187520
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187552
  title: Reactome:R-HSA-187552
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187574
  title: Reactome:R-HSA-187574
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187575
  title: Reactome:R-HSA-187575
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187916
  title: Reactome:R-HSA-187916
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187934
  title: Reactome:R-HSA-187934
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187937
  title: Reactome:R-HSA-187937
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187948
  title: Reactome:R-HSA-187948
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187949
  title: Reactome:R-HSA-187949
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-187959
  title: Reactome:R-HSA-187959
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-188350
  title: Reactome:R-HSA-188350
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-188371
  title: Reactome:R-HSA-188371
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-188386
  title: Reactome:R-HSA-188386
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-188390
  title: Reactome:R-HSA-188390
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-2559583
  title: Reactome:R-HSA-2559583
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-3788705
  title: Reactome:R-HSA-3788705
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-3788708
  title: Reactome:R-HSA-3788708
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-4088024
  title: Reactome:R-HSA-4088024
  full_text_unavailable: true
  findings: []
- id: Reactome:R-HSA-5684081
  title: Reactome:R-HSA-5684081
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- id: Reactome:R-HSA-5684096
  title: Reactome:R-HSA-5684096
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- id: Reactome:R-HSA-6793661
  title: Reactome:R-HSA-6793661
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- id: Reactome:R-HSA-6805109
  title: Reactome:R-HSA-6805109
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- id: Reactome:R-HSA-68911
  title: Reactome:R-HSA-68911
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- id: Reactome:R-HSA-68916
  title: Reactome:R-HSA-68916
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- id: Reactome:R-HSA-68917
  title: Reactome:R-HSA-68917
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- id: Reactome:R-HSA-68918
  title: Reactome:R-HSA-68918
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- id: Reactome:R-HSA-68944
  title: Reactome:R-HSA-68944
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- id: Reactome:R-HSA-69005
  title: Reactome:R-HSA-69005
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- id: Reactome:R-HSA-69191
  title: Reactome:R-HSA-69191
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- id: Reactome:R-HSA-69195
  title: Reactome:R-HSA-69195
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- id: Reactome:R-HSA-69199
  title: Reactome:R-HSA-69199
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- id: Reactome:R-HSA-69562
  title: Reactome:R-HSA-69562
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  title: Reactome:R-HSA-69656
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  title: Reactome:R-HSA-9624120
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  title: Reactome:R-HSA-9686521
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core_functions:
- description: CDK2 is a cyclin-dependent serine/threonine protein kinase that, in complex with cyclin
    E (G1/S) or cyclin A (S/G2), phosphorylates substrates to drive the G1/S transition and DNA replication.
  molecular_function:
    id: GO:0004693
    label: cyclin-dependent protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0000082
    label: G1/S transition of mitotic cell cycle
  - id: GO:0006260
    label: DNA replication
  locations:
  - id: GO:0005654
    label: nucleoplasm
  in_complex:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  supported_by:
  - reference_id: PMID:1396589
    supporting_text: Replacement of T160 with alanine abolishes the kinase activity of CDK2, indicating
      that phosphorylation at this site (as in CDC2) is required for kinase activity.
  - reference_id: PMID:10995387
    supporting_text: Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies
      promotes histone gene transcription.
- description: CDK2 binds cyclin partners; cyclin binding is obligatory for kinase activation, inducing
    the conformational change that aligns the active site.
  molecular_function:
    id: GO:0030332
    label: cyclin binding
  in_complex:
    id: GO:0000307
    label: cyclin-dependent protein kinase holoenzyme complex
  supported_by:
  - reference_id: PMID:7630397
    supporting_text: CyclinA binds to one side of CDK2's catalytic cleft, inducing large conformational
      changes in its PSTAIRE helix and T-loop. These changes activate the kinase by realigning active
      site residues and relieving the steric blockade at the entrance of the catalytic cleft.
proposed_new_terms: []
suggested_questions:
- question: Given that Cdk2-null mice are viable and CDK2 is dispensable for the mitotic cell cycle (CDK1
    compensates) but essential for meiosis, should the meiotic role be elevated relative to the canonical
    mitotic G1/S role in the gene's core annotation?
  experts:
  - Kaldis P
  - Sicinski P
- question: Many CDK2 substrate-specific processes (EZH2/heterochromatin, NBN/telomere repair, USP37/APC
    regulation) are supported by single studies; which represent physiologically core CDK2 functions versus
    context-specific or redundant CDK1/CDK2 activities?
  experts:
  - Malumbres M
  - Morgan DO
suggested_experiments:
- hypothesis: Cyclin E/CDK2 versus cyclin A/CDK2 phosphorylate distinct, partner-specified substrate sets
    at G1/S versus S/G2.
  description: Perform analog-sensitive (as-CDK2) chemical-genetic phosphoproteomics with cyclin E- versus
    cyclin A-synchronized cells to map partner-specific substrate repertoires in vivo.
  experiment_type: phosphoproteomics
- hypothesis: CDK2's essential meiotic function (e.g., telomere attachment) is mechanistically separable
    from its mitotic G1/S role.
  description: Use separation-of-function CDK2 alleles and germ-cell-specific conditional knockouts to
    dissect meiosis-specific substrates and phenotypes.
  experiment_type: genetic separation-of-function analysis

Property	Summary	Key details / examples	Evidence / citations
Identity verified	Human CDK2 encodes cyclin-dependent kinase 2, a CMGC-family serine/threonine protein kinase that functions in cell-cycle control	Matches UniProt P24941 description: cyclin-dependent kinase 2; activity centered on G1/S and S-phase progression; functions with cyclin partners rather than as a constitutively active kinase (pluta2024cyclin‐dependentkinasesmasters pages 3-5, pellarin2025cyclindependentproteinkinases pages 2-4)	(pluta2024cyclin‐dependentkinasesmasters pages 3-5, pellarin2025cyclindependentproteinkinases pages 2-4)
Protein structure and domains	CDK2 has the canonical bilobed protein kinase fold, including the ATP-binding site, PSTAIRE helix, and activation/T-loop that must adopt an active conformation	Cyclin binding reorganizes the kinase conformation; the catalytic site becomes fully competent after activating phosphorylation of Thr160 in the T-loop by CAK; recent structural analyses emphasize conformational tuning of catalytic efficiency in CDK2 versus CDK4 (zhang2024cdk2andcdk4 pages 1-2, fagundes2021cyclinecdk2dna pages 2-3)	(zhang2024cdk2andcdk4 pages 1-2, fagundes2021cyclinecdk2dna pages 2-3)
Enzymatic function	CDK2 catalyzes ATP-dependent phosphorylation of serine/threonine residues on protein substrates	Primary biochemical role is phosphotransfer to substrate S/T residues, especially in cell-cycle regulators and chromatin-associated proteins; phosphorylation controls substrate activity, stability, or protein-protein interactions during G1/S and S phase (chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 1-2)	(chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 1-2)
Catalytic mechanism	CDK2 is activated in a multistep manner requiring cyclin binding and T-loop phosphorylation	Cyclin E or cyclin A binds CDK2 through the cyclin box/PSTAIRE interface, inducing conformational changes that expose the catalytic site; CAK then phosphorylates Thr160, stabilizing the active kinase state (fagundes2021cyclinecdk2dna pages 2-3, pluta2024cyclin‐dependentkinasesmasters pages 3-5)	(fagundes2021cyclinecdk2dna pages 2-3, pluta2024cyclin‐dependentkinasesmasters pages 3-5)
Cyclin partners	Principal activating partners are cyclin E1/E2 and cyclin A	Cyclin E–CDK2 predominates in late G1/G1-S transition; cyclin A–CDK2 acts later in S phase and into G2-associated functions; cyclin E is the main G1 activator and cyclin A sustains later interphase CDK2 activity (chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 1-2, rubin2020integratingoldand pages 1-3)	(chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 1-2, rubin2020integratingoldand pages 1-3)
Cell-cycle phases of activity	CDK2 activity peaks across late G1, G1/S transition, and S phase, with cyclin-specific phase usage	Cyclin E/CDK2 promotes S-phase entry; cyclin A/CDK2 coordinates S-phase progression and later interphase events; newer work also indicates CDK2 activity in interphase depends on continued upstream mitogen/CDK4/6 support more than older irreversible models predicted (kim2022cdk46initiatesrb pages 1-2, cornwell2023lossofcdk46 pages 1-2)	(kim2022cdk46initiatesrb pages 1-2, cornwell2023lossofcdk46 pages 1-2)
Core pathway role	Central effector in the CDK4/6–Rb–E2F–cyclin E/A–CDK2 pathway controlling commitment to DNA replication	CDK4/6 initiates Rb inactivation and E2F activation; rising CDK2 activity then drives stronger Rb phosphorylation, promotes E2F-dependent transcription, and helps coordinate commitment with G1/S transition (kim2022cdk46initiatesrb pages 1-2, rubin2020integratingoldand pages 1-3, hume2020aunifiedmodel pages 1-2)	(kim2022cdk46initiatesrb pages 1-2, rubin2020integratingoldand pages 1-3, hume2020aunifiedmodel pages 1-2)
Substrate specificity motif	CDK2 is a proline-directed kinase with preference for S/T-P phosphoacceptor motifs	In the in situ nuclear substrate screen, 156/166 AS-CDK2-specific thiophosphopeptides (93%) contained at least one S/T-P site; kinome-wide profiling further shows specificity is shaped by both positive residue preference and negative selectivity around the phosphosite (chi2020anovellandscape pages 2-3, johnson2023anatlasof pages 1-2)	(chi2020anovellandscape pages 2-3, johnson2023anatlasof pages 1-2)
Cyclin-mediated substrate recognition	Substrate docking is influenced by cyclin features in addition to the catalytic pocket	Cyclin E contains substrate-interaction surfaces including MRAIL and VDCLE regions that help engage RLX-containing proteins and pocket proteins such as RB family members, contributing to substrate selection beyond the kinase active site alone (fagundes2021cyclinecdk2dna pages 2-3)	(fagundes2021cyclinecdk2dna pages 2-3)
Major validated substrate: RB1/Rb	Retinoblastoma protein (Rb) is a canonical CDK2 substrate and a key mediator of CDK2-driven cell-cycle progression	Cyclin E/CDK2 contributes to late G1 hyperphosphorylation of Rb, disrupting Rb–E2F repression and promoting transcription of S-phase genes; reported sites include T373, S795, S807/S811 among others (janostiak2022understandingretinoblastomaposttranslational pages 2-4, kim2022cdk46initiatesrb pages 1-2, hume2020aunifiedmodel pages 1-2)	(janostiak2022understandingretinoblastomaposttranslational pages 2-4, kim2022cdk46initiatesrb pages 1-2, hume2020aunifiedmodel pages 1-2)
Other validated substrates: CKI/transcription regulators	CDK2 phosphorylates regulators that reinforce proliferation and transcriptional output	Examples summarized in recent reviews include p27KIP1, E2F5, and CBP/p300, linking CDK2 to CKI regulation and transcriptional control (fagundes2021cyclinecdk2dna pages 2-3)	(fagundes2021cyclinecdk2dna pages 2-3)
Other validated substrates: replication / histone control	CDK2 directly regulates DNA replication and histone gene expression machinery	Reported substrates include CDC6, NPAT, and HIRA; these support replication origin function and histone biosynthesis needed for S phase (fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2)	(fagundes2021cyclinecdk2dna pages 2-3, fagundes2021cyclinecdk2dna pages 1-2)
Other validated substrates: centrosome cycle	CDK2 phosphorylates centrosome-associated proteins important for duplication and cell-cycle coordination	Validated examples include NPM, CP110, and MPS1, supporting centrosome duplication and broader cell-cycle execution (fagundes2021cyclinecdk2dna pages 2-3)	(fagundes2021cyclinecdk2dna pages 2-3)
Nuclear substrate landscape	Proteomics identified a broad nuclear CDK2 substrate network beyond classic cell-cycle proteins	An in situ phosphorylation study identified 117 candidate nuclear substrates, with ~43% already known CDK substrates; validated novel targets included LSD1, DOT1L, and Rad54, extending CDK2 function into chromatin, DNA repair, and transcription-linked regulation (chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3)	(chi2020anovellandscape pages 1-2, chi2020anovellandscape pages 2-3)
Subcellular localization	CDK2 functions primarily in the nucleus, where it phosphorylates Rb and many chromatin-associated substrates	Nuclear context was important for recovering physiological substrates in isolated nuclei; cyclin E is also described as mainly nuclear; nuclear localization aligns with roles in Rb/E2F control, replication, and histone transcription (chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 2-3)	(chi2020anovellandscape pages 1-2, fagundes2021cyclinecdk2dna pages 2-3)
Cytoplasmic/extranuclear function	A subset of CDK2 activity also occurs outside the nucleus in later interphase	At the S/G2 transition, cyclin A2–CDK2 appears in the cytoplasm and can activate PLK1 through Bora phosphorylation, indicating regulated compartment switching for specific downstream outputs (fagundes2021cyclinecdk2dna pages 2-3)	(fagundes2021cyclinecdk2dna pages 2-3)
Positive regulation	CDK2 is positively regulated by cyclin accumulation, CAK, mitogen-driven upstream signaling, and Rb/E2F feedback	Mitogenic signaling induces cyclin D then E2F, leading to cyclin E accumulation and CDK2 activation; CAK phosphorylation of Thr160 is required for full activity; increasing CDK2 activity helps establish the Rb/E2F positive-feedback module before DNA replication (kim2022cdk46initiatesrb pages 1-2, fagundes2021cyclinecdk2dna pages 2-3, rubin2020integratingoldand pages 1-3)	(kim2022cdk46initiatesrb pages 1-2, fagundes2021cyclinecdk2dna pages 2-3, rubin2020integratingoldand pages 1-3)
Negative regulation	CDK2 is restrained by p21CIP1, p27KIP1, inhibitory phosphorylation pathways, and loss of mitogenic support	Cip/Kip proteins inhibit cyclin-CDK2 complexes and limit CAK access/substrate engagement; broader CDK control also involves inhibitory phosphorylation and phosphatase circuits; recent work shows CDK2 activity can collapse when mitogen/CDK4/6 support is lost, even outside G1 (pluta2024cyclin‐dependentkinasesmasters pages 3-5, fagundes2021cyclinecdk2dna pages 2-3, cornwell2023lossofcdk46 pages 1-2)	(pluta2024cyclin‐dependentkinasesmasters pages 3-5, fagundes2021cyclinecdk2dna pages 2-3, cornwell2023lossofcdk46 pages 1-2)
Current expert view	Modern models treat CDK2 as a phase-specific amplifier and executor of G1/S commitment rather than a simple redundant kinase	Reviews and recent single-cell studies support a model in which CDK2 integrates upstream mitogenic state, Rb/E2F feedback, and replication-entry machinery; it is especially important for the timing and threshold of commitment to DNA replication (rubin2020integratingoldand pages 1-3, kim2022cdk46initiatesrb pages 1-2, cornwell2023lossofcdk46 pages 1-2, matthews2022cellcyclecontrol pages 1-4)	(rubin2020integratingoldand pages 1-3, kim2022cdk46initiatesrb pages 1-2, cornwell2023lossofcdk46 pages 1-2, matthews2022cellcyclecontrol pages 1-4)

CDK2

Gene Description

Existing Annotations Review

Core Functions

CDK2 is a cyclin-dependent serine/threonine protein kinase that, in complex with cyclin E (G1/S) or cyclin A (S/G2), phosphorylates substrates to drive the G1/S transition and DNA replication.

CDK2 binds cyclin partners; cyclin binding is obligatory for kinase activation, inducing the conformational change that aligns the active site.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Comprehensive Research Report: CDK2 Gene Functional Annotation

Gene/Protein Identity Verification

Primary Enzymatic Function and Catalytic Mechanism

Biochemical Reaction Catalyzed

Activation Mechanism

Substrate Specificity

Subcellular Localization

Signaling and Biochemical Pathways

The CDK-Rb-E2F Pathway and G1/S Transition

Recent Paradigm Updates

Coordination with DNA Replication and S Phase Progression

Substrate Specificity and Key Protein Substrates

Retinoblastoma Protein (Rb)

Cyclin-Dependent Kinase Inhibitors

Transcription Factors and Coactivators

DNA Replication and Histone Regulation

Centrosome Cycle Regulation

Expanded Nuclear Substrate Landscape

Regulatory Mechanisms

Positive Regulation

Negative Regulation

Current Expert Perspectives and Recent Developments (2023-2025)

Summary Table

Conclusions

Artifacts

Citations

📚 Additional Documentation

Notes

CDK2 (P24941) — Research Notes

Core molecular function (kinase + cyclin partners)

Inhibitors

Cell-cycle substrates / biological roles

Localization

Knockout / redundancy notes

Annotation strategy

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