id: Q00535 gene_symbol: CDK5 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- CDK5 encodes a proline-directed serine/threonine kinase activated by CDK5R1/p35, CDK5R1/p25, and CDK5R2/p39 family regulators, with major functions in neuronal development, neurite and axon growth, cytoskeletal and dendritic-spine dynamics, synaptic vesicle cycling, synaptic plasticity, and p25-linked neurodegenerative apoptosis as a stress/disease context. Human CDK5 also regulates induced neuronal autophagy through phosphorylation of SH3GLB1/endophilin B1. Beyond the nervous system, CDK5 partners with cyclin B1 in proliferating cells and is active during mitosis, where it acts as a canonical CDK-cyclin kinase required for mitotic fidelity. alternative_products: - name: '1' id: Q00535-1 - name: 2 (CDK5-SV {ECO:0000303|PubMed:19693690}) id: Q00535-2 sequence_note: VSP_041948 existing_annotations: - term: id: GO:0000307 label: cyclin-dependent protein kinase holoenzyme complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: cyclin-dependent protein kinase holoenzyme complex is a supported CDK5 kinase-complex annotation. action: ACCEPT reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: cytoplasm is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: cyclin-dependent protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:1901987 label: regulation of cell cycle phase transition evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: regulation of cell cycle phase transition is a core CDK5 process. CDK5 was long classified as an atypical CDK with no direct cell-cycle role, but Zheng et al. 2024 (Nature) demonstrated that CDK5 is active during mitosis, partners with cyclin B1, and is required for mitotic fidelity - a direct, enzymatically-mediated function rather than over-propagation. action: ACCEPT reason: Experimentally established direct function- CDK5-cyclin B1 acts as a canonical CDK-cyclin complex that phosphorylates mitotic substrates to ensure mitotic fidelity (Zheng et al. 2024, PMID:39232161). This is a bona fide core CDK5 kinase function operating in proliferating cells via cyclin B1, complementary to (not subordinate to) its p35/p39-activated neuronal kinase role. supported_by: - reference_id: PMID:39232161 supporting_text: CDK5 is active throughout mitosis - reference_id: PMID:39232161 supporting_text: cyclin B1 is a mitotic co-factor of CDK5 - reference_id: file:human/CDK5/CDK5-deep-research-falcon.md supporting_text: CDK5 can form a complex with cyclin B1 and regulate mitotic fidelity, challenging the traditional view that CDK5 has no cell cycle function - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - term: id: GO:0007409 label: axonogenesis evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: axonogenesis is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0048489 label: synaptic vesicle transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: synaptic vesicle transport is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0051402 label: neuron apoptotic process evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Keep neuron apoptotic process as a non-core p25-linked neurotoxicity/stress annotation rather than canonical core CDK5 neuronal kinase biology. action: KEEP_AS_NON_CORE reason: The strongest apoptosis evidence is pathological calpain cleavage of CDK5R1/p35 to p25, causing constitutive and mislocalized CDK5 activity in neurodegenerative stress models; this is not the core developmental/synaptic CDK5 function. supported_by: - reference_id: PMID:10604467 supporting_text: p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease - reference_id: PMID:10604467 supporting_text: p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis - reference_id: PMID:10604467 supporting_text: cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases - term: id: GO:0004672 label: protein kinase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: protein kinase activity is correct but too broad for CDK5. action: MODIFY reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. proposed_replacement_terms: - id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0005524 label: ATP binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: ATP binding is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: nucleus is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: cytoplasm is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: plasma membrane is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0007409 label: axonogenesis evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: axonogenesis is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0014069 label: postsynaptic density evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept postsynaptic density as a supported synaptic CDK5 localization. action: ACCEPT reason: UniProt gives a specific postsynaptic density localization by similarity, consistent with CDK5 synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Postsynaptic density - term: id: GO:0030027 label: lamellipodium evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Accept lamellipodium as a specific CDK5 cell-projection localization supported by UniProt. action: ACCEPT reason: The UniProt subcellular-location line explicitly includes lamellipodium in the cell-projection context. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Perikaryon. Cell projection, lamellipodium - term: id: GO:0030426 label: growth cone evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: growth cone is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0043204 label: perikaryon evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept perikaryon as a specific CDK5 neuronal-cell-body localization supported by UniProt. action: ACCEPT reason: The UniProt subcellular-location line explicitly includes perikaryon. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Perikaryon. Cell projection, lamellipodium - term: id: GO:0045202 label: synapse evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: synapse is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0051649 label: establishment of localization in cell evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: establishment of localization in cell is a secondary or broad CDK5 process annotation. action: KEEP_AS_NON_CORE reason: The term reflects a true downstream or disease/stress context, but it is broader or less central than CDK5 kinase activity and neuronal/synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0051726 label: regulation of cell cycle evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: regulation of cell cycle is a core CDK5 process. Historically CDK5 was thought to lack a direct cell-cycle role; Zheng et al. 2024 (Nature) showed CDK5 is active during mitosis and, with cyclin B1, is required for mitotic fidelity, establishing this as a genuine direct function. action: ACCEPT reason: Experimentally established by the demonstration that CDK5 forms a functional CDK-cyclin complex with cyclin B1 and ensures mitotic fidelity (Zheng et al. 2024, PMID:39232161). Treated as a core CDK5 kinase function in proliferating cells, complementary to its p35/p39-activated neuronal/synaptic signaling. supported_by: - reference_id: PMID:39232161 supporting_text: CDK5 is active throughout mitosis - reference_id: PMID:39232161 supporting_text: cyclin B1 is a mitotic co-factor of CDK5 - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - term: id: GO:0098793 label: presynapse evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Keep presynapse as non-core synaptic localization context. action: KEEP_AS_NON_CORE reason: The accessible UniProt text supports synapse broadly, but not presynapse specifically; the core localization should remain broader synapse/postsynaptic density/growth cone/neuron projection contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Synapse - term: id: GO:0106310 label: protein serine kinase activity evidence_type: IEA original_reference_id: GO_REF:0000116 qualifier: enables review: summary: Protein serine kinase activity is too narrow/incomplete for CDK5. action: MODIFY reason: CDK5 phosphorylates both serine and threonine residues, so protein serine/threonine kinase activity is the better molecular-function term. proposed_replacement_terms: - id: GO:0004674 label: protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14521924 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15689152 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15890360 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17078951 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20133653 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20559324 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21220307 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22078880 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23455922 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23543736 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23602568 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25852190 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26871637 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27107012 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30833792 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32707033 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32812023 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34591612 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35016035 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35063084 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0002039 label: p53 binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: p53 binding is a specific substrate/regulator binding context, not the core molecular function. action: KEEP_AS_NON_CORE reason: This binding annotation is more specific than generic protein binding, but CDK5 should primarily be represented by kinase activity and substrate phosphorylation/regulation terms. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Interacts with P53/TP53 in neurons - term: id: GO:0005176 label: ErbB-2 class receptor binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: ErbB-2 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0016533 label: protein kinase 5 complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. action: ACCEPT reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0030175 label: filopodium evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Keep filopodium as non-core fine cell-projection localization context. action: KEEP_AS_NON_CORE reason: The accessible evidence supports CDK5 at cell projections and lamellipodia/growth cones, but not a specific filopodium localization as a core CDK5 compartment. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Perikaryon. Cell projection, lamellipodium - term: id: GO:0030424 label: axon evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: axon is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0030547 label: signaling receptor inhibitor activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: signaling receptor inhibitor activity overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0030549 label: acetylcholine receptor activator activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: acetylcholine receptor activator activity overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0043125 label: ErbB-3 class receptor binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: ErbB-3 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0051879 label: Hsp90 protein binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: Hsp90 protein binding overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0051966 label: regulation of synaptic transmission, glutamatergic evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: regulation of synaptic transmission, glutamatergic is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0061001 label: regulation of dendritic spine morphogenesis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: regulation of dendritic spine morphogenesis is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:1903076 label: regulation of protein localization to plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: regulation of protein localization to plasma membrane is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0000307 label: cyclin-dependent protein kinase holoenzyme complex evidence_type: IPI original_reference_id: PMID:16039528 qualifier: part_of review: summary: cyclin-dependent protein kinase holoenzyme complex is a supported CDK5 kinase-complex annotation. action: ACCEPT reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0016533 label: protein kinase 5 complex evidence_type: IPI original_reference_id: PMID:15689152 qualifier: part_of review: summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. action: ACCEPT reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0016533 label: protein kinase 5 complex evidence_type: IPI original_reference_id: PMID:16039528 qualifier: part_of review: summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. action: ACCEPT reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: nucleoplasm is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: plasma membrane is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-399944 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-8863007 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-8863011 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-8863014 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-180047 qualifier: enables review: summary: cyclin-dependent protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: IDA original_reference_id: PMID:24607229 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0030547 label: signaling receptor inhibitor activity evidence_type: IMP original_reference_id: PMID:24607229 qualifier: enables review: summary: signaling receptor inhibitor activity overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0035255 label: ionotropic glutamate receptor binding evidence_type: IPI original_reference_id: PMID:24607229 qualifier: enables review: summary: ionotropic glutamate receptor binding is a specific substrate/regulator binding context, not the core molecular function. action: KEEP_AS_NON_CORE reason: This binding annotation is more specific than generic protein binding, but CDK5 should primarily be represented by kinase activity and substrate phosphorylation/regulation terms. supported_by: - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:12691662 qualifier: located_in review: summary: nucleus is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:12691662 qualifier: located_in review: summary: cytoplasm is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005886 label: plasma membrane evidence_type: EXP original_reference_id: PMID:17009320 qualifier: located_in review: summary: plasma membrane is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0014069 label: postsynaptic density evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept postsynaptic density as a supported synaptic CDK5 localization. action: ACCEPT reason: UniProt gives a specific postsynaptic density localization by similarity, consistent with CDK5 synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Postsynaptic density - term: id: GO:0045202 label: synapse evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: synapse is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0099533 label: positive regulation of presynaptic cytosolic calcium concentration evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: positive regulation of presynaptic cytosolic calcium concentration is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:1903234 label: negative regulation of calcium ion-dependent exocytosis of neurotransmitter evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: acts_upstream_of_or_within review: summary: negative regulation of calcium ion-dependent exocytosis of neurotransmitter is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: PMID:17491008 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0030036 label: actin cytoskeleton organization evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: actin cytoskeleton organization is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:8090221 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0048156 label: tau protein binding evidence_type: NAS original_reference_id: PMID:28386764 qualifier: enables review: summary: tau protein binding is a specific substrate/regulator binding context, not the core molecular function. action: KEEP_AS_NON_CORE reason: This binding annotation is more specific than generic protein binding, but CDK5 should primarily be represented by kinase activity and substrate phosphorylation/regulation terms. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: MAPT/TAU, MAP2, MAP1B - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) - term: id: GO:0050321 label: tau-protein kinase activity evidence_type: NAS original_reference_id: PMID:28386764 qualifier: enables review: summary: tau-protein kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: MAPT/TAU, MAP2, MAP1B - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0016020 label: membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: membrane is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0030426 label: growth cone evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: growth cone is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0043005 label: neuron projection evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: neuron projection is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: NAS original_reference_id: PMID:28386764 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0051966 label: regulation of synaptic transmission, glutamatergic evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of synaptic transmission, glutamatergic is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005737 label: cytoplasm evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: cytoplasm is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0005874 label: microtubule evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: colocalizes_with review: summary: microtubule is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: Microtubule polymers but not the alpha/beta-tubulin heterodimer block p35 interaction with Cdk5 - term: id: GO:0008017 label: microtubule binding evidence_type: TAS original_reference_id: PMID:17491008 qualifier: enables negated: true review: summary: Microtubule binding is over-attributed to CDK5 itself. action: MARK_AS_OVER_ANNOTATED reason: The cited evidence supports microtubule binding by the p35/CDK5R1 activator and regulation of CDK5-p35 activity by microtubules, not direct CDK5 microtubule-binding as its molecular function. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: Microtubule polymers but not the alpha/beta-tubulin heterodimer block p35 interaction with Cdk5 - term: id: GO:0000226 label: microtubule cytoskeleton organization evidence_type: TAS original_reference_id: PMID:17491008 qualifier: involved_in review: summary: microtubule cytoskeleton organization is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0031175 label: neuron projection development evidence_type: TAS original_reference_id: PMID:17491008 qualifier: involved_in review: summary: neuron projection development is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0048167 label: regulation of synaptic plasticity evidence_type: TAS original_reference_id: PMID:24607229 qualifier: involved_in review: summary: regulation of synaptic plasticity is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:1903076 label: regulation of protein localization to plasma membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of protein localization to plasma membrane is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:1904646 label: cellular response to amyloid-beta evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: cellular response to amyloid-beta is a secondary or broad CDK5 process annotation. action: KEEP_AS_NON_CORE reason: The term reflects a true downstream or disease/stress context, but it is broader or less central than CDK5 kinase activity and neuronal/synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8863014 qualifier: located_in review: summary: nucleoplasm is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8863587 qualifier: located_in review: summary: nucleoplasm is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6805276 qualifier: located_in review: summary: nucleoplasm is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: TAS original_reference_id: PMID:21499257 qualifier: involved_in review: summary: Regulation of macroautophagy is a supported PN-relevant CDK5 substrate-specific process. action: ACCEPT reason: Human/neuron evidence shows CDK5 phosphorylates SH3GLB1/endophilin B1 and is required for induced autophagy in starved neurons and Parkinson disease models. supported_by: - reference_id: PMID:21499257 supporting_text: unexpected role for Cdk5 in the regulation of induced autophagy in neurons - reference_id: PMID:21499257 supporting_text: autophagy induction in starved neurons - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons - term: id: GO:1903421 label: regulation of synaptic vesicle recycling evidence_type: NAS original_reference_id: PMID:22745285 qualifier: involved_in review: summary: regulation of synaptic vesicle recycling is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0045861 label: negative regulation of proteolysis evidence_type: IMP original_reference_id: PMID:24548080 qualifier: involved_in review: summary: negative regulation of proteolysis is a secondary or broad CDK5 process annotation. action: KEEP_AS_NON_CORE reason: The term reflects a true downstream or disease/stress context, but it is broader or less central than CDK5 kinase activity and neuronal/synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-399944 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-399951 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-NUL-9032945 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-180047 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863007 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863011 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863013 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863587 qualifier: located_in review: summary: cytosol is a broad or complex-context CDK5 localization. action: KEEP_AS_NON_CORE reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - term: id: GO:0048167 label: regulation of synaptic plasticity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of synaptic plasticity is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0001764 label: neuron migration evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: neuron migration is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0007268 label: chemical synaptic transmission evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: chemical synaptic transmission is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0007416 label: synapse assembly evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: synapse assembly is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0016079 label: synaptic vesicle exocytosis evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: synaptic vesicle exocytosis is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0030182 label: neuron differentiation evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: neuron differentiation is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0042981 label: regulation of apoptotic process evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: regulation of apoptotic process is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0048167 label: regulation of synaptic plasticity evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: regulation of synaptic plasticity is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0048488 label: synaptic vesicle endocytosis evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: synaptic vesicle endocytosis is a core CDK5 synaptic process. action: ACCEPT reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:24607229 supporting_text: serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) - reference_id: PMID:24607229 supporting_text: increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0048675 label: axon extension evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: axon extension is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0048709 label: oligodendrocyte differentiation evidence_type: IDA original_reference_id: PMID:18042622 qualifier: involved_in review: summary: oligodendrocyte differentiation is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0051402 label: neuron apoptotic process evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: Keep neuron apoptotic process as a non-core p25-linked neurotoxicity/stress annotation rather than canonical core CDK5 neuronal kinase biology. action: KEEP_AS_NON_CORE reason: The strongest apoptosis evidence is pathological calpain cleavage of CDK5R1/p35 to p25, causing constitutive and mislocalized CDK5 activity in neurodegenerative stress models; this is not the core developmental/synaptic CDK5 function. supported_by: - reference_id: PMID:10604467 supporting_text: p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease - reference_id: PMID:10604467 supporting_text: p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis - reference_id: PMID:10604467 supporting_text: cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases - term: id: GO:0051726 label: regulation of cell cycle evidence_type: TAS original_reference_id: PMID:21473899 qualifier: involved_in review: summary: regulation of cell cycle is a core CDK5 process. Historically CDK5 was thought to lack a direct cell-cycle role; Zheng et al. 2024 (Nature) showed CDK5 is active during mitosis and, with cyclin B1, is required for mitotic fidelity, establishing this as a genuine direct function. action: ACCEPT reason: Experimentally established by the demonstration that CDK5 forms a functional CDK-cyclin complex with cyclin B1 and ensures mitotic fidelity (Zheng et al. 2024, PMID:39232161). Treated as a core CDK5 kinase function in proliferating cells, complementary to its p35/p39-activated neuronal/synaptic signaling. supported_by: - reference_id: PMID:39232161 supporting_text: CDK5 is active throughout mitosis - reference_id: PMID:39232161 supporting_text: cyclin B1 is a mitotic co-factor of CDK5 - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - term: id: GO:0061001 label: regulation of dendritic spine morphogenesis evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: regulation of dendritic spine morphogenesis is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: IDA original_reference_id: PMID:20357208 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0045892 label: negative regulation of DNA-templated transcription evidence_type: IMP original_reference_id: PMID:20357208 qualifier: involved_in review: summary: negative regulation of DNA-templated transcription is a secondary or broad CDK5 process annotation. action: KEEP_AS_NON_CORE reason: The term reflects a true downstream or disease/stress context, but it is broader or less central than CDK5 kinase activity and neuronal/synaptic substrate regulation. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: IDA original_reference_id: PMID:21145489 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0005176 label: ErbB-2 class receptor binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: ErbB-2 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12223541 qualifier: enables review: summary: Generic protein binding does not describe CDK5 function. action: MARK_AS_OVER_ANNOTATED reason: The specific function is CDK5-regulated phosphorylation in CDK5R/p35-p25-p39 complexes and substrate-specific neuronal/autophagy signaling. Generic protein binding rows should not be treated as informative GO molecular-function annotations. - term: id: GO:0005634 label: nucleus evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: nucleus is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0016301 label: kinase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: kinase activity is correct but too broad for CDK5. action: MODIFY reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. proposed_replacement_terms: - id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0030182 label: neuron differentiation evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: neuron differentiation is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0030424 label: axon evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: axon is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0030425 label: dendrite evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: dendrite is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0030549 label: acetylcholine receptor activator activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: acetylcholine receptor activator activity overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0031175 label: neuron projection development evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: neuron projection development is part of core CDK5 neuronal kinase biology. action: ACCEPT reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0031594 label: neuromuscular junction evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: neuromuscular junction is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0043025 label: neuronal cell body evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: neuronal cell body is a supported CDK5 localization/context. action: ACCEPT reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm' - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:12691662} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Cell membrane {ECO:0000269|PubMed:17009320} - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - term: id: GO:0043125 label: ErbB-3 class receptor binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: ErbB-3 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. action: MARK_AS_OVER_ANNOTATED reason: These transferred receptor/regulator-binding terms do not capture CDK5's catalytic function and are less defensible than kinase activity plus substrate-specific process annotations. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0043525 label: positive regulation of neuron apoptotic process evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep positive regulation of neuron apoptotic process as a non-core p25-linked neurotoxicity/stress annotation rather than canonical core CDK5 neuronal kinase biology. action: KEEP_AS_NON_CORE reason: The strongest apoptosis evidence is pathological calpain cleavage of CDK5R1/p35 to p25, causing constitutive and mislocalized CDK5 activity in neurodegenerative stress models; this is not the core developmental/synaptic CDK5 function. supported_by: - reference_id: PMID:10604467 supporting_text: p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease - reference_id: PMID:10604467 supporting_text: p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis - reference_id: PMID:10604467 supporting_text: cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases - term: id: GO:0050321 label: tau-protein kinase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: tau-protein kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: MAPT/TAU, MAP2, MAP1B - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - term: id: GO:0004672 label: protein kinase activity evidence_type: TAS original_reference_id: PMID:1639063 qualifier: enables review: summary: protein kinase activity is correct but too broad for CDK5. action: MODIFY reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. proposed_replacement_terms: - id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004672 label: protein kinase activity evidence_type: TAS original_reference_id: PMID:7834371 qualifier: enables review: summary: protein kinase activity is correct but too broad for CDK5. action: MODIFY reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. proposed_replacement_terms: - id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - term: id: GO:0004674 label: protein serine/threonine kinase activity evidence_type: TAS original_reference_id: PMID:1639063 qualifier: enables review: summary: protein serine/threonine kinase activity is a core CDK5 molecular function. action: ACCEPT reason: CDK5 is a CDK-family proline-directed serine/threonine protein kinase that uses ATP and is activated in CDK5R-containing kinase complexes; tau/MAPT and other neuronal proteins are established substrates. supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000116 title: Automatic Gene Ontology annotation based on Rhea mapping findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:39232161 title: CDK5-cyclin B1 regulates mitotic fidelity. findings: - statement: CDK5, long classified as an atypical CDK without a direct cell-cycle role, is active during mitosis and partners with cyclin B1 (not only its neuronal p35/p39 activators) to maintain mitotic fidelity, validating CDK5 cell-cycle-regulation annotations as a genuine extra-neuronal function. supporting_text: CDK5 is active throughout mitosis reference_review: relevance: HIGH correctness: VERIFIED review_notes: PubMed/PMC-verified (PMID:39232161, Nature 2024). Establishes a bona fide, direct mitotic role for CDK5 via cyclin B1 (a canonical CDK-cyclin complex ensuring mitotic fidelity); basis for treating regulation of cell cycle / cell cycle phase transition as a core CDK5 function alongside its neuronal kinase biology. - id: file:human/CDK5/CDK5-deep-research-falcon.md title: Falcon deep research report for CDK5 findings: - statement: Falcon deep research corroborates the existing CDK5 review (p35/p39 activation, p25 hyperactivation, tau/synaptic/cytoskeletal substrates, neurodegeneration) and surfaces the 2024 Nature CDK5-cyclin B1 mitotic-fidelity finding plus additional substrate-specific roles (Drp1 mitochondrial fission, CLOCK/PER2 circadian, PRMT1-mTORC1). supporting_text: CDK5 can form a complex with cyclin B1 and regulate mitotic fidelity, challenging the traditional view that CDK5 has no cell cycle function - id: PMID:12223541 title: The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner. findings: [] - id: PMID:12691662 title: Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. findings: [] - id: PMID:14521924 title: Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein. findings: [] - id: PMID:15689152 title: Mechanism of CDK5/p25 binding by CDK inhibitors. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached abstract supports the CDK5/p25 kinase-complex structure used for CDK5 complex and inhibitor-binding context, but it is not the primary physiological-function evidence. - id: PMID:15890360 title: Molecular basis for the specificity of p27 toward cyclin-dependent kinases that regulate cell division. findings: [] - id: PMID:16039528 title: Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. findings: [] - id: PMID:1639063 title: A family of human cdc2-related protein kinases. findings: [] - id: PMID:17009320 title: cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells. findings: [] - id: PMID:17078951 title: PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners. findings: [] - id: PMID:17491008 title: Microtubule association of the neuronal p35 activator of Cdk5. findings: - statement: p35/CDK5R1, not necessarily CDK5 itself, binds microtubules and regulates CDK5-p35 activity. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached abstract supports microtubule association of the p35 activator and regulation of CDK5-p35 activity; this cautions against treating CDK5 itself as the direct microtubule-binding protein. - id: PMID:18042622 title: Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin. findings: [] - id: PMID:20133653 title: No difference in kinetics of tau or histone phosphorylation by CDK5/p25 versus CDK5/p35 in vitro. findings: [] - id: PMID:20357208 title: Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor. findings: [] - id: PMID:20559324 title: Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress. findings: [] - id: PMID:21145489 title: The proapoptotic function of Noxa in human leukemia cells is regulated by the kinase Cdk5 and by glucose. findings: [] - id: PMID:21220307 title: Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control. findings: [] - id: PMID:21473899 title: 'Cdk5: multitasking between physiological and pathological conditions.' findings: - statement: Review summarizing CDK5 as a proline-directed serine/threonine kinase linked to neuronal migration, cortical layering, synaptic plasticity, and neurodegenerative dysregulation. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Review article supporting high-level CDK5 neuronal and neurodegeneration framing; useful synthesis but not primary experimental evidence. - id: PMID:21499257 title: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. findings: - statement: CDK5 phosphorylates SH3GLB1/endophilin B1 and is required for induced neuronal autophagy in starvation and Parkinson disease models. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract directly supports CDK5-mediated phosphorylation of endophilin B1/SH3GLB1 and CDK5 requirement for induced neuronal autophagy. - id: PMID:22078880 title: "Adipocyte NCoR knockout decreases PPAR\u03B3 phosphorylation and enhances PPAR\u03B3 activity and insulin sensitivity." findings: [] - id: PMID:22745285 title: Synaptic vesicle pools and dynamics. findings: [] - id: PMID:23455922 title: Interlaboratory reproducibility of large-scale human protein-complex analysis by standardized AP-MS. findings: [] - id: PMID:23543736 title: Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation independently of its hydrolase activity. findings: [] - id: PMID:23602568 title: The protein interaction landscape of the human CMGC kinase group. findings: [] - id: PMID:24548080 title: CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration. findings: [] - id: PMID:24607229 title: Memory enhancement by targeting Cdk5 regulation of NR2B. findings: - statement: CDK5 phosphorylates NR2B/GluN2B Ser1116, regulating NMDAR surface expression, synaptic transmission, and memory. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached full-text record supports CDK5 phosphorylation of NR2B/GluN2B and regulation of NMDA receptor surface expression, synaptic transmission, and memory. - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:25852190 title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. findings: [] - id: PMID:26871637 title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. findings: [] - id: PMID:27107012 title: Pooled-matrix protein interaction screens using Barcode Fusion Genetics. findings: [] - id: PMID:28386764 title: Roles of tau protein in health and disease. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:30833792 title: A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32707033 title: Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. findings: [] - id: PMID:32812023 title: Phosphorylated tau interactome in the human Alzheimer's disease brain. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:34591612 title: A protein interaction landscape of breast cancer. findings: [] - id: PMID:35016035 title: Identification and functional characterization of transcriptional activators in human cells. findings: [] - id: PMID:35063084 title: Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:7834371 title: Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase, in the mature and developing mouse central and peripheral nervous systems. findings: [] - id: PMID:8090221 title: p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract supports CDK5 activation by the neuronal p35 regulatory subunit and the CDK5-p35 kinase-complex model. - id: Reactome:R-HSA-180047 title: CDK5 phosphorylates DARPP-32 on Thr75 findings: [] - id: Reactome:R-HSA-399944 title: Phosphorylation of CRMPs by Cdk5 findings: [] - id: Reactome:R-HSA-399951 title: Phosphorylation of CRMPs by GSK3beta findings: [] - id: Reactome:R-HSA-6805276 title: CDK5 phosphorylates TP53 findings: [] - id: Reactome:R-HSA-8863007 title: p25-bound CDK5 phosphorylates CDC25B findings: [] - id: Reactome:R-HSA-8863011 title: p25-bound CDK5 phosphorylates CDC25C findings: [] - id: Reactome:R-HSA-8863013 title: CDK5 binds p25 findings: [] - id: Reactome:R-HSA-8863014 title: p25-bound CDK5 phosphorylates CDC25A findings: [] - id: Reactome:R-HSA-8863587 title: CDK5:p25 translocates to the nucleus findings: [] - id: Reactome:R-NUL-9032945 title: Ntrk2 phosohorylates CDK5 findings: [] - id: file:human/CDK5/CDK5-uniprot.txt title: UniProtKB record for human CDK5 findings: - statement: UniProt summarizes CDK5 as a proline-directed serine/threonine kinase activated by CDK5R1/CDK5R2, with neuronal, synaptic, cytoskeletal, apoptosis, and substrate-specific autophagy functions. - id: file:human/CDK5/CDK5-notes.md title: CDK5 review notes findings: - statement: Manual PN-focused CDK5 notes; Drosophila Cdk5-Acinus autophagy evidence was treated as context only, while human SH3GLB1/endophilin B1 evidence supported regulation of macroautophagy. core_functions: - molecular_function: id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity description: CDK5 is a CDK5R-activated proline-directed serine/threonine kinase that phosphorylates neuronal, synaptic, cytoskeletal, stress-response, and autophagy-associated substrates. directly_involved_in: - id: GO:0007409 label: axonogenesis - id: GO:0001764 label: neuron migration - id: GO:0030182 label: neuron differentiation - id: GO:0031175 label: neuron projection development - id: GO:0048675 label: axon extension - id: GO:0007416 label: synapse assembly - id: GO:0016079 label: synaptic vesicle exocytosis - id: GO:0048488 label: synaptic vesicle endocytosis - id: GO:0048167 label: regulation of synaptic plasticity - id: GO:0051966 label: regulation of synaptic transmission, glutamatergic - id: GO:0061001 label: regulation of dendritic spine morphogenesis - id: GO:0016241 label: regulation of macroautophagy locations: - id: GO:0014069 label: postsynaptic density - id: GO:0030426 label: growth cone - id: GO:0045202 label: synapse - id: GO:0030424 label: axon - id: GO:0005737 label: cytoplasm - id: GO:0005634 label: nucleus in_complex: id: GO:0016533 label: protein kinase 5 complex supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity - reference_id: PMID:24607229 supporting_text: controls the receptor's cell surface expression - reference_id: PMID:21499257 supporting_text: unexpected role for Cdk5 in the regulation of induced autophagy in neurons - reference_id: PMID:21499257 supporting_text: autophagy induction in starved neurons - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons - molecular_function: id: GO:0004693 label: cyclin-dependent protein serine/threonine kinase activity description: In proliferating (non-neuronal) cells CDK5 partners with cyclin B1, rather than its neuronal p35/p39 activators, and is active during mitosis; this CDK5-cyclin B1 complex behaves as a canonical CDK-cyclin kinase that phosphorylates mitotic substrates to safeguard mitotic fidelity and genome stability. directly_involved_in: - id: GO:0051726 label: regulation of cell cycle - id: GO:1901987 label: regulation of cell cycle phase transition supported_by: - reference_id: PMID:39232161 supporting_text: CDK5 is active throughout mitosis - reference_id: PMID:39232161 supporting_text: cyclin B1 is a mitotic co-factor of CDK5 - reference_id: file:human/CDK5/CDK5-deep-research-falcon.md supporting_text: CDK5 can form a complex with cyclin B1 and regulate mitotic fidelity, challenging the traditional view that CDK5 has no cell cycle function - molecular_function: id: GO:0050321 label: tau-protein kinase activity description: CDK5 phosphorylates MAPT/tau and other microtubule-associated neuronal substrates, contributing to cytoskeletal regulation and neurodegeneration-relevant tau biology. directly_involved_in: - id: GO:0000226 label: microtubule cytoskeleton organization locations: - id: GO:0043005 label: neuron projection - id: GO:0043025 label: neuronal cell body supported_by: - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: MAPT/TAU, MAP2, MAP1B - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Proline-directed serine/threonine-protein kinase - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] - reference_id: file:human/CDK5/CDK5-uniprot.txt supporting_text: Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission - reference_id: PMID:21473899 supporting_text: normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity proposed_new_terms: [] suggested_questions: - question: Should human CDK5 be curated directly to basal autophagy/autophagosome maturation based on conserved Acinus regulation, or only to SH3GLB1-dependent regulation of induced macroautophagy? experts: - GO autophagy editors - CDK5 neuronal signaling experts - Drosophila autophagy experts - question: Which CDK5 substrate-binding annotations should be retained as specific MF annotations versus represented as phosphorylation/regulatory process annotations? experts: - GO molecular-function editors - neurobiology curators suggested_experiments: - description: Test whether human CDK5 phosphorylates ACIN1 at sites corresponding to Drosophila Acinus S437 and whether this affects basal autophagy flux or autophagosome maturation in neuronal cells. hypothesis: The Drosophila Cdk5-Acinus basal-autophagy module is conserved only if human CDK5 directly phosphorylates ACIN1 and changes basal autophagic flux. experiment_type: kinase assay/autophagy flux assay - description: Dissect CDK5-dependent SH3GLB1/endophilin B1 phosphorylation from other CDK5 neuronal substrates using phosphosite-specific rescue mutants in starved neurons. hypothesis: CDK5 regulation of macroautophagy is mediated through SH3GLB1 phosphorylation rather than a general CDK5 role in all autophagy steps. experiment_type: phosphosite rescue/autophagy imaging - description: Using the analog-sensitive CDK5 chemical-genetic system from Zheng et al. 2024, map the mitotic CDK5-cyclin B1 phosphoproteome in non-neuronal proliferating cells and compare it to the CDK1-cyclin B1 substrate set, to determine whether CDK5 cell-cycle annotations should be refined to specific mitotic substrates/processes. hypothesis: CDK5-cyclin B1 phosphorylates a distinct subset of mitotic substrates that ensures chromosome segregation fidelity, separable from CDK1-cyclin B1 activity. experiment_type: analog-sensitive kinase phosphoproteomics