CDK4 (cyclin-dependent kinase 4) is a 303-residue serine/threonine protein kinase of the CMGC group, CDC2/CDKX subfamily (EC 2.7.11.22), and the catalytic subunit of the cyclin D-CDK4 holoenzyme. It is catalytically inactive as a monomer and is activated by binding a D-type cyclin (CCND1, CCND2 or CCND3) together with phosphorylation of the activation-loop residue Thr172; activity is opposed by the INK4 inhibitors (p16/CDKN2A, p15/CDKN2B, p18/CDKN2C, p19/CDKN2D) and modulated by the CIP/KIP proteins (p21/CDKN1A, p27/CDKN1B, p57/CDKN1C), which both promote complex assembly and, at higher stoichiometry, inhibit. Before assembly CDK4 is chaperoned by Hsp90-Cdc37. In early-to-mid G1 the cyclin D-CDK4 complex phosphorylates the retinoblastoma-family pocket proteins RB1/pRb, RBL1/p107 and RBL2/p130, relieving their repression of E2F transcription factors and thereby licensing E2F-dependent gene expression and the G1/S transition; cyclin E-CDK2 subsequently completes RB hyperphosphorylation. Additional substrates include SMAD3, FOXM1 and RUNX2. CDK4 is cytoplasmic when uncomplexed; the cyclin D-CDK4 complex assembles in the cytoplasm, accumulates at the nuclear membrane and translocates into the nucleus at the G1/S transition, where it colocalizes with RB1, and is also detected in nucleoli and heterochromatin. Together with its paralog CDK6, CDK4 is the dedicated metazoan G1 cyclin-dependent kinase. It is a major oncology drug target: CDK4 amplification and activating mutations occur in cancer, the germline R24C variant causes familial melanoma, loss-of-function variants cause autosomal-recessive primary microcephaly, and CDK4/6 inhibitors are established therapies in HR-positive breast cancer.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IDA PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | ACCEPT | Summary: CDK4 drives the G1/S transition of the mitotic cell cycle as the catalytic subunit of cyclin D-CDK4. Reason: Core biological process for CDK4: cyclin D-CDK4 phosphorylates RB-family proteins in G1 to license E2F-dependent S-phase gene expression. Supported by IDA/IMP and phylogeny; consistent across all evidence types. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. |
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: CDK4 drives the G1/S transition of the mitotic cell cycle as the catalytic subunit of cyclin D-CDK4. Reason: Core biological process for CDK4: cyclin D-CDK4 phosphorylates RB-family proteins in G1 to license E2F-dependent S-phase gene expression. Supported by IDA/IMP and phylogeny; consistent across all evidence types. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. |
| GO:0000082 G1/S transition of mitotic cell cycle | IMP PMID:7603984 Growth suppression by p16ink4 requires functional retinoblas... | ACCEPT | Summary: CDK4 drives the G1/S transition of the mitotic cell cycle as the catalytic subunit of cyclin D-CDK4. Reason: Core biological process for CDK4: cyclin D-CDK4 phosphorylates RB-family proteins in G1 to license E2F-dependent S-phase gene expression. Supported by IDA/IMP and phylogeny; consistent across all evidence types. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. |
| GO:0000082 G1/S transition of mitotic cell cycle | NAS PMID:7603984 Growth suppression by p16ink4 requires functional retinoblas... | ACCEPT | Summary: CDK4 drives the G1/S transition of the mitotic cell cycle as the catalytic subunit of cyclin D-CDK4. Reason: Core biological process for CDK4: cyclin D-CDK4 phosphorylates RB-family proteins in G1 to license E2F-dependent S-phase gene expression. Supported by IDA/IMP and phylogeny; consistent across all evidence types. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the 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, inherited via the pan-CDK PAINT node. Reason: This IBA descends from the ancestral cyclin-dependent kinase node (PANTHER:PTN000623979), whose deepest members include the single essential yeast/animal mitotic CDK. CDK4 itself is a dedicated G1 kinase and is not the driver of the G2/M transition (that is CDK1); retain as a phylogenetically-inherited non-core process rather than a CDK4-specific function. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:17420273 CDK4 and CDK6 delay senescence by kinase-dependent and p16IN... | ACCEPT | Summary: CDK4 is the catalytic subunit of a cyclin-dependent protein kinase holoenzyme (cyclin D-CDK4). Reason: CDK4 is catalytically active only as part of a cyclin D-CDK4 holoenzyme; directly demonstrated (IDA) and conserved. Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: CDK4 is the catalytic subunit of a cyclin-dependent protein kinase holoenzyme (cyclin D-CDK4). Reason: CDK4 is catalytically active only as part of a cyclin D-CDK4 holoenzyme; directly demonstrated (IDA) and conserved. Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IEA GO_REF:0000107 | ACCEPT | Summary: CDK4 is the catalytic subunit of a cyclin-dependent protein kinase holoenzyme (cyclin D-CDK4). Reason: CDK4 is catalytically active only as part of a cyclin D-CDK4 holoenzyme; directly demonstrated (IDA) and conserved. Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0000785 chromatin | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Chromatin localization of a CDK4 pool (heterochromatin lumps). Reason: A minor chromatin/heterochromatin-associated pool is observed by immunolocalization; peripheral to the core nuclear RB-kinase function. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein kinase activity (broad parent), IEA. Reason: Correct but general; the specific cyclin-dependent protein serine/threonine kinase activity (GO:0004693) is the appropriate leaf term and is separately annotated. Acceptable as a broader mapping. Supporting Evidence: PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IDA PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB file:human/CDK4/CDK4-deep-research-falcon.md Its best-established catalytic substrates are the nuclear retinoblastoma-family pocket proteins RB1/pRb, RBL1/p107, and RBL2/p130. |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IDA PMID:8114739 Identification of G1 kinase activity for cdk6, a novel cycli... | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | TAS Reactome:R-HSA-9008412 | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | TAS Reactome:R-HSA-9929482 | ACCEPT | Summary: Cyclin-dependent protein serine/threonine kinase activity (EC 2.7.11.22) - CDK4's defining molecular function, active as the cyclin D-CDK4 holoenzyme. Reason: Core molecular function, directly demonstrated biochemically and by phylogeny (IBA). Requires D-cyclin binding and Thr172 activation-loop phosphorylation. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. PMID:8114739 endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB |
| GO:0005515 protein binding | IPI PMID:11896535 Cell cycle progression of chronic lymphocytic leukemia cells... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:11896535 Cell cycle progression of chronic lymphocytic leukemia cells... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:11900540 Novel insights into the INK4-CDK4/6-Rb pathway: counter acti... | REMOVE | Summary: Experimental physical interaction between CDK4 and PSMD10 (gankyrin/p28GANK), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-PSMD10 (gankyrin/p28GANK) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:14641107 A novel partner for D-type cyclins: protein kinase A-anchori... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:15107404 Liver tumors escape negative control of proliferation via PI... | REMOVE | Summary: Experimental physical interaction between CDK4 and CEBPA, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CEBPA interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:15232106 Self-assembling protein microarrays. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:15558030 Characterization of VIK-1: a new Vav-interacting Kruppel-lik... | REMOVE | Summary: Experimental physical interaction between CDK4 and ZNF655, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-ZNF655 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:15681588 Structural and biochemical studies of human proliferating ce... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:16326706 Shp-1 mediates the antiproliferative activity of tissue inhi... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:16327805 Dichotomous but stringent substrate selection by the dual-fu... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDK7, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDK7 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:16431923 The nucleocapsid protein of severe acute respiratory syndrom... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:16962592 Honokiol causes the p21WAF1-mediated G(1)-phase arrest of th... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:17053782 C-terminal phosphorylation controls the stability and functi... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:17517622 Functional characterization of human PFTK1 as a cyclin-depen... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:17909018 A CDKN2A mutation in familial melanoma that abrogates bindin... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:17955473 Proteomic analysis of p16ink4a-binding proteins. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:19237555 The structure of CDK4/cyclin D3 has implications for models ... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:19470470 RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA ... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:20399237 TM4SF5 accelerates G1/S phase progression via cytosolic p27K... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:21242975 Cyclin D1 interacts and collaborates with Ral GTPases enhanc... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:21871133 Apigenin inhibits proliferation and induces apoptosis in hum... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Experimental physical interaction between CDK4 and MYC, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-MYC interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:22094256 A systematic screen for CDK4/6 substrates links FOXM1 phosph... | REMOVE | Summary: Experimental physical interaction between CDK4 and MYC, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-MYC interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:22094256 A systematic screen for CDK4/6 substrates links FOXM1 phosph... | REMOVE | Summary: Experimental physical interaction between CDK4 and RBL1 (p107), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-RBL1 (p107) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:22094256 A systematic screen for CDK4/6 substrates links FOXM1 phosph... | REMOVE | Summary: Experimental physical interaction between CDK4 and RBL2 (p130), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-RBL2 (p130) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:22939624 Quantitative analysis of HSP90-client interactions reveals p... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | REMOVE | Summary: Experimental physical interaction between CDK4 and UCHL1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-UCHL1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24218572 CDK10/cyclin M is a protein kinase that controls ETS2 degrad... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:24855949 A code for RanGDP binding in ankyrin repeats defines a nucle... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:24855949 A code for RanGDP binding in ankyrin repeats defines a nucle... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25036637 A quantitative chaperone interaction network reveals the arc... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Experimental physical interaction between CDK4 and HOOK1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HOOK1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Experimental physical interaction between CDK4 and HOOK1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HOOK1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:27339980 Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 trap... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:27353360 The FNIP co-chaperones decelerate the Hsp90 chaperone cycle ... | REMOVE | Summary: Experimental physical interaction between CDK4 and FNIP1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-FNIP1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:27353360 The FNIP co-chaperones decelerate the Hsp90 chaperone cycle ... | REMOVE | Summary: Experimental physical interaction between CDK4 and FNIP2, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-FNIP2 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:31217276 The DNA deaminase APOBEC3B interacts with the cell-cycle pro... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:31217276 The DNA deaminase APOBEC3B interacts with the cell-cycle pro... | REMOVE | Summary: Experimental physical interaction between CDK4 and APOBEC3B, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-APOBEC3B interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Experimental physical interaction between CDK4 and HOOK1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HOOK1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and INCA1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-INCA1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and ZNF655, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-ZNF655 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and HOOK1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HOOK1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and IKZF3 (Aiolos), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-IKZF3 (Aiolos) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Experimental physical interaction between CDK4 and OGDHL, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-OGDHL interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1C (p57), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1C (p57) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and RBL2 (p130), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-RBL2 (p130) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2C (p18INK4C), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2C (p18INK4C) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Experimental physical interaction between CDK4 and FBXW7, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-FBXW7 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:38890443 CDK4/6 inhibitors dephosphorylate RNF26 to stabilize TSC1 an... | REMOVE | Summary: Experimental physical interaction between CDK4 and RNF26, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-RNF26 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND2, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | REMOVE | Summary: Experimental physical interaction between CDK4 and Legionella effector lpg1972, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-Legionella effector lpg1972 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Experimental physical interaction between CDK4 and HSP90AB1, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-HSP90AB1 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:7568034 Identification of human cyclin-dependent kinase 8, a putativ... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:8078588 p15INK4B is a potential effector of TGF-beta-induced cell cy... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2B (p15INK4B), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2B (p15INK4B) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:8259215 A new regulatory motif in cell-cycle control causing specifi... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:8741839 Isolation and characterization of p19INK4d, a p16-related in... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2D (p19INK4D), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2D (p19INK4D) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:8756624 Cyclin-binding motifs are essential for the function of p21C... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND1, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | MODIFY | Summary: Experimental physical interaction between CDK4 and its activating D-type cyclin CCND3, captured as the generic term 'protein binding'. Reason: The functionally meaningful relationship is cyclin binding: CDK4's obligate D-type cyclin partner assembles the active holoenzyme. Replace the uninformative bare 'protein binding' with cyclin binding (GO:0030332), which is evidence-backed and separately annotated. Proposed replacements: cyclin binding Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1A (p21), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1A (p21) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1B (p27), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1B (p27) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:9106657 New functional activities for the p21 family of CDK inhibito... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN1C (p57), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN1C (p57) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:9150368 Interaction between Cdc37 and Cdk4 in human cells. | REMOVE | Summary: Experimental physical interaction between CDK4 and CDC37, captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDC37 interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005515 protein binding | IPI PMID:9529249 ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a ... | REMOVE | Summary: Experimental physical interaction between CDK4 and CDKN2A (p16INK4A), captured as the generic term 'protein binding'. Reason: Per repository curation policy, bare 'protein binding' (GO:0005515) is uninformative about CDK4's molecular function. The CDK4-CDKN2A (p16INK4A) interaction is genuine and documented in UniProt, but no specific molecular function should be invented from interaction evidence alone; removal does not assert the interaction is false. Where a partner defines a functional relationship (D-type cyclins, INK4/CIP-KIP regulators, Hsp90-Cdc37 chaperone, cyclin D-CDK4 complexes) that relationship is captured by the dedicated cyclin-binding, complex and holoenzyme terms already annotated. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding, the phosphate donor for CDK4 catalysis. Reason: Required for kinase catalysis; UniProt resolves the glycine-rich ATP-binding loop (residues 12-20) and an ATP-binding residue at 35. |
| GO:0005634 nucleus | EXP PMID:9106657 New functional activities for the p21 family of CDK inhibito... | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005634 nucleus | IDA PMID:16109376 The bromodomain protein Brd4 is a positive regulatory compon... | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005634 nucleus | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005634 nucleus | IDA PMID:20399237 TM4SF5 accelerates G1/S phase progression via cytosolic p27K... | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization - the compartment where cyclin D-CDK4 phosphorylates RB-family proteins. Reason: The activated cyclin D-CDK4 complex enters the nucleus at the G1/S transition and colocalizes with RB1; the nucleus is the core functional location. Supported by direct assays (EXP/IDA) and phylogeny. Supporting Evidence: PMID:18827403 the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226094 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1226095 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3215385 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3215426 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5205799 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5205861 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5216234 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5661117 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69227 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-75822 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8942836 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9008412 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9624112 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9754130 | ACCEPT | Summary: Nucleoplasmic localization where cyclin D-CDK4 acts on nuclear substrates. Reason: Consistent with the core nuclear RB-kinase function (HPA IDA and Reactome pathway annotations); nucleoplasm is the operative subnuclear compartment. |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Transcription regulator complex, from automatic ortholog transfer (Ensembl Compara). Reason: Over-propagated ortholog IEA. CDK4 phosphorylates transcription factors (e.g. SMAD3, RUNX2, FOXM1) but is not itself a structural subunit of a transcription regulator complex; the informative relationship is its kinase activity, separately annotated. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleolar localization of a CDK4 pool. Reason: A nucleolar pool is observed (HPA and immunolocalization); a minor/non-core localization relative to nucleoplasmic RB phosphorylation. |
| GO:0005730 nucleolus | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Nucleolar localization of a CDK4 pool. Reason: A nucleolar pool is observed (HPA and immunolocalization); a minor/non-core localization relative to nucleoplasmic RB phosphorylation. |
| GO:0005737 cytoplasm | EXP PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Cytoplasmic localization - uncomplexed CDK4 and the site of initial cyclin D-CDK4 assembly. Reason: CDK4 is cytoplasmic when non-complexed; cyclin D-CDK4 assembles in the cytoplasm before nuclear import. Directly observed (EXP) and conserved (IBA). Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization - uncomplexed CDK4 and the site of initial cyclin D-CDK4 assembly. Reason: CDK4 is cytoplasmic when non-complexed; cyclin D-CDK4 assembles in the cytoplasm before nuclear import. Directly observed (EXP) and conserved (IBA). Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization - uncomplexed CDK4 and the site of initial cyclin D-CDK4 assembly. Reason: CDK4 is cytoplasmic when non-complexed; cyclin D-CDK4 assembles in the cytoplasm before nuclear import. Directly observed (EXP) and conserved (IBA). Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182594 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-75822 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848414 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8848436 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8941895 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8941915 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942607 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8942803 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9630792 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9630795 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9929482 | ACCEPT | Summary: Cytosolic localization of the resting/assembling CDK4 pool. Reason: Consistent with the cytoplasmic pool of uncomplexed CDK4 and pre-import cyclin D-CDK4 (HPA IDA and Reactome). Overlaps the cytoplasm annotation. |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Bicellular tight junction, from automatic ortholog transfer (Ensembl Compara). Reason: Spurious over-propagation via orthology; there is no evidence that CDK4 functions at tight junctions, and it is inconsistent with the established nuclear/cytoplasmic cell-cycle biology. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Signal transduction (broad), inherited via the CDK PAINT node. Reason: Cyclin D-CDK4 integrates mitogenic signals to control G1 progression, so a signalling role is defensible, but 'signal transduction' is a high-level term; the specific, informative function is the G1/S RB-kinase activity. Retain as non-core. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:7603984 Growth suppression by p16ink4 requires functional retinoblas... | KEEP AS NON CORE | Summary: Positive regulation of cell population proliferation. Reason: A genuine downstream consequence of CDK4-driven G1/S progression, demonstrated by p16-mediated growth suppression requiring functional RB; retained as a non-core outcome rather than the direct molecular function. Supporting Evidence: PMID:7603984 the pRB is the critical target acted upon by cyclin D-dependent kinases in the G1 phase of the cell cycle. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18291362 Sulindac suppresses beta-catenin expression in human cancer ... | MARK AS OVER ANNOTATED | Summary: Response to xenobiotic stimulus (IEP), from a study where cdk4 mRNA falls after sulindac treatment. Reason: The cited work shows cdk4 expression is suppressed downstream of sulindac-induced beta-catenin repression; CDK4 is a downstream target of the drug response, not an executor of a xenobiotic-response process. Over-annotation of an expression change. |
| GO:0010468 regulation of gene expression | IMP PMID:17420273 CDK4 and CDK6 delay senescence by kinase-dependent and p16IN... | KEEP AS NON CORE | Summary: Regulation of gene expression (broad), via RB phosphorylation and E2F derepression. Reason: CDK4 regulates gene expression indirectly by inactivating RB-family repressors, releasing E2F-dependent transcription. Real but high-level and downstream; the informative annotations are the kinase activity and G1/S process. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IDA PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | MARK AS OVER ANNOTATED | Summary: Positive regulation of G2/M transition (IDA), from an INSM1 cell-cycle-arrest study. Reason: In this study overexpressed cyclin D1-CDK4 reversed an INSM1-imposed G1/S block, so cells progressed and were scored in G2/M by flow cytometry. CDK4's direct action is at G1/S; appearance of cells in G2/M is a downstream readout of resumed cycling, not a CDK4-specific G2/M function. Supporting Evidence: PMID:19124461 INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein. |
| GO:0016301 kinase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Kinase activity (broad parent), IEA. Reason: Correct but general; subsumed by the specific cyclin-dependent protein serine/threonine kinase activity (GO:0004693). |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | TAS Reactome:R-HSA-3215385 | MODIFY | Summary: Cyclin-dependent protein serine/threonine kinase regulator activity (TAS, Reactome). Reason: This molecular function describes the regulatory (cyclin) subunit that modulates a CDK, not the catalytic kinase. CDK4 is the catalytic subunit that phosphorylates substrates (e.g. WDR77 in the CCND1:CDK4:PRMT5:WDR77 context); its correct MF is cyclin-dependent protein serine/threonine kinase activity. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity |
| GO:0030332 cyclin binding | IEA GO_REF:0000120 | ACCEPT | Summary: Cyclin binding - CDK4 binds D-type cyclins (CCND1/2/3); binding is obligatory for kinase activation. Reason: Core molecular function: D-cyclin binding assembles the active holoenzyme and is required for activity. Directly demonstrated (IPI with CCND1) and conserved. Supporting Evidence: PMID:19124461 INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein. |
| GO:0030332 cyclin binding | IPI PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | ACCEPT | Summary: Cyclin binding - CDK4 binds D-type cyclins (CCND1/2/3); binding is obligatory for kinase activation. Reason: Core molecular function: D-cyclin binding assembles the active holoenzyme and is required for activity. Directly demonstrated (IPI with CCND1) and conserved. Supporting Evidence: PMID:19124461 INSM1 binding to cyclin D1 interrupts its association with CDK4 and induces hypophosphorylation of the retinoblastoma protein. |
| GO:0031965 nuclear membrane | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear membrane localization - transient accumulation of cyclin D-CDK4 during nuclear import at G1/S. Reason: A real but transient localization: the cyclin D-CDK4 complex accumulates on the nuclear membrane before entering the nucleus at the G1/S transition. Non-core relative to the nucleoplasmic site of RB phosphorylation. Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0031965 nuclear membrane | IDA PMID:18827403 Migratory localization of cyclin D2-Cdk4 complex suggests a ... | KEEP AS NON CORE | Summary: Nuclear membrane localization - transient accumulation of cyclin D-CDK4 during nuclear import at G1/S. Reason: A real but transient localization: the cyclin D-CDK4 complex accumulates on the nuclear membrane before entering the nucleus at the G1/S transition. Non-core relative to the nucleoplasmic site of RB phosphorylation. Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0031965 nuclear membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear membrane localization - transient accumulation of cyclin D-CDK4 during nuclear import at G1/S. Reason: A real but transient localization: the cyclin D-CDK4 complex accumulates on the nuclear membrane before entering the nucleus at the G1/S transition. Non-core relative to the nucleoplasmic site of RB phosphorylation. Supporting Evidence: PMID:18827403 They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. |
| GO:0048146 positive regulation of fibroblast proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Positive regulation of fibroblast proliferation. Reason: CDK4/6 kinase activity extends the replicative lifespan of human diploid fibroblasts and delays senescence; a genuine cell-type-specific downstream consequence of the core G1/S function, retained as non-core. Supporting Evidence: PMID:17420273 CDK4 and CDK6 and their INK4-insensitive variants can extend the life span of HDFs |
| GO:0048146 positive regulation of fibroblast proliferation | IMP PMID:17420273 CDK4 and CDK6 delay senescence by kinase-dependent and p16IN... | KEEP AS NON CORE | Summary: Positive regulation of fibroblast proliferation. Reason: CDK4/6 kinase activity extends the replicative lifespan of human diploid fibroblasts and delays senescence; a genuine cell-type-specific downstream consequence of the core G1/S function, retained as non-core. Supporting Evidence: PMID:17420273 CDK4 and CDK6 and their INK4-insensitive variants can extend the life span of HDFs |
| GO:0051726 regulation of cell cycle | IDA PMID:19124461 Zinc finger transcription factor INSM1 interrupts cyclin D1 ... | KEEP AS NON CORE | Summary: Regulation of cell cycle (broad parent). Reason: A correct but high-level BP; CDK4's specific contribution (G1/S transition, GO:0000082) is separately and more informatively annotated. |
| GO:0060260 regulation of transcription initiation by RNA polymerase II | TAS Reactome:R-HSA-212436 | MARK AS OVER ANNOTATED | Summary: Regulation of transcription initiation by RNA polymerase II (TAS, Reactome generic transcription pathway). Reason: Indirect/high-level: CDK4 influences transcription only via RB phosphorylation and E2F derepression, not by direct action on the Pol II initiation machinery. Over-annotation relative to the informative G1/S and kinase annotations. |
| GO:0097128 cyclin D1-CDK4 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Component of the cyclin D1-CDK4 complex. Reason: Directly demonstrated (crystal structure of CDK4 with cyclin D1; IPI) and phylogenetically supported; a core active form of CDK4. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the |
| GO:0097128 cyclin D1-CDK4 complex | IEA GO_REF:0000107 | ACCEPT | Summary: Component of the cyclin D1-CDK4 complex. Reason: Directly demonstrated (crystal structure of CDK4 with cyclin D1; IPI) and phylogenetically supported; a core active form of CDK4. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the |
| GO:0097128 cyclin D1-CDK4 complex | IPI PMID:19237565 Crystal structure of human CDK4 in complex with a D-type cyc... | ACCEPT | Summary: Component of the cyclin D1-CDK4 complex. Reason: Directly demonstrated (crystal structure of CDK4 with cyclin D1; IPI) and phylogenetically supported; a core active form of CDK4. Supporting Evidence: PMID:19237565 The cyclin D1-cyclin-dependent kinase 4 (CDK4) complex is a key regulator of the |
| GO:0097129 cyclin D2-CDK4 complex | IEA GO_REF:0000107 | ACCEPT | Summary: Component of the cyclin D2-CDK4 complex. Reason: Directly demonstrated: cyclin D2-CDK4 immune complexes are functional RB kinases (IPI). Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0097129 cyclin D2-CDK4 complex | IPI PMID:11896535 Cell cycle progression of chronic lymphocytic leukemia cells... | ACCEPT | Summary: Component of the cyclin D2-CDK4 complex. Reason: Directly demonstrated: cyclin D2-CDK4 immune complexes are functional RB kinases (IPI). Supporting Evidence: PMID:11896535 immune complexes consisting of cyclin D2 and cdk4 or cyclin D3 and cdk4 were both functional and phosphorylated the RB protein in vitro. |
| GO:0097130 cyclin D3-CDK4 complex | IPI PMID:19237555 The structure of CDK4/cyclin D3 has implications for models ... | ACCEPT | Summary: Component of the cyclin D3-CDK4 complex. Reason: Directly demonstrated by the CDK4/cyclin D3 crystal structure and activity assays (IPI). Supporting Evidence: PMID:19237555 Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27(Kip1). |
| GO:0106310 protein serine kinase activity | EXP PMID:9106657 New functional activities for the p21 family of CDK inhibito... | ACCEPT | Summary: Protein serine kinase activity (RHEA:17989), the seryl half-reaction of CDK4's EC 2.7.11.22 activity. Reason: Correct and specific; CDK4 phosphorylates Ser (and Thr) residues of protein substrates. Consistent with the CDK/kinase activity annotations. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity (RHEA:17989), the seryl half-reaction of CDK4's EC 2.7.11.22 activity. Reason: Correct and specific; CDK4 phosphorylates Ser (and Thr) residues of protein substrates. Consistent with the CDK/kinase activity annotations. Supporting Evidence: PMID:19237555 Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. |
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Download this section (compressed HTML)Q: Given that CDK4 and CDK6 are largely redundant metazoan G1 kinases, which CDK4-specific substrates or contexts (e.g. tissue-restricted D-cyclin partners) justify CDK4-specific rather than CDK4/6-shared annotation?
Suggested experts: Sicinski P, Malumbres M
Q: Should the many CDK4 'protein binding' (IPI) interactions with substrates, regulators and interactome-screen partners be systematically re-curated to has_input / substrate or regulatory relationships on the appropriate activity, rather than left as uninformative GO:0005515?
Suggested experts: Thomas PD
Experiment: Analog-sensitive (as-CDK4) chemical-genetic phosphoproteomics in synchronized cells to map direct cyclin D-CDK4 substrates in G1 and distinguish them from CDK6- and CDK2-specific targets.
Hypothesis: Cyclin D-CDK4 phosphorylates a specific, partner-directed set of nuclear substrates beyond the RB family in G1.
Type: phosphoproteomics
Experiment: Quantify Thr172 phosphorylation stoichiometry and CDK4 activity across the G1/S transition using phospho-specific and separation-of-function alleles.
Hypothesis: Thr172 activation-loop phosphorylation is rate-limiting for cyclin D-CDK4 activation in vivo.
Type: biochemical/genetic separation-of-function analysis
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