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.
| 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 Ξ²-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-Ξ³. |
| 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 Ξ²-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). |
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Download this section (compressed HTML)Q: 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?
Suggested experts: Kaldis P, Sicinski P
Q: 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?
Suggested experts: Malumbres M, Morgan DO
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
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