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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: cyclin-dependent protein kinase holoenzyme complex is a supported CDK5 kinase-complex annotation. Reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: cytoplasm is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: cyclin-dependent protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:1901987 regulation of cell cycle phase transition | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:39232161 CDK5 is active throughout mitosis PMID:39232161 cyclin B1 is a mitotic co-factor of CDK5 file:human/CDK5/CDK5-deep-research-falcon.md CDK5 can form a complex with cyclin B1 and regulate mitotic fidelity, challenging the traditional view that CDK5 has no cell cycle function file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase |
| GO:0007409 axonogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: axonogenesis is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0048489 synaptic vesicle transport | IBA GO_REF:0000033 | ACCEPT | Summary: synaptic vesicle transport is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0051402 neuron apoptotic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Keep neuron apoptotic process as a non-core p25-linked neurotoxicity/stress annotation rather than canonical core CDK5 neuronal kinase biology. 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. Supporting Evidence: PMID:10604467 p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease PMID:10604467 p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis PMID:10604467 cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases |
| GO:0004672 protein kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: protein kinase activity is correct but too broad for CDK5. Reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: plasma membrane is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0007409 axonogenesis | IEA GO_REF:0000117 | ACCEPT | Summary: axonogenesis is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | ACCEPT | Summary: Accept postsynaptic density as a supported synaptic CDK5 localization. Reason: UniProt gives a specific postsynaptic density localization by similarity, consistent with CDK5 synaptic substrate regulation. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Postsynaptic density |
| GO:0030027 lamellipodium | IEA GO_REF:0000120 | ACCEPT | Summary: Accept lamellipodium as a specific CDK5 cell-projection localization supported by UniProt. Reason: The UniProt subcellular-location line explicitly includes lamellipodium in the cell-projection context. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Perikaryon. Cell projection, lamellipodium |
| GO:0030426 growth cone | IEA GO_REF:0000044 | ACCEPT | Summary: growth cone is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: Accept perikaryon as a specific CDK5 neuronal-cell-body localization supported by UniProt. Reason: The UniProt subcellular-location line explicitly includes perikaryon. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Perikaryon. Cell projection, lamellipodium |
| GO:0045202 synapse | IEA GO_REF:0000044 | ACCEPT | Summary: synapse is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0051649 establishment of localization in cell | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: establishment of localization in cell is a secondary or broad CDK5 process annotation. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000117 | ACCEPT | 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. 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. Supporting Evidence: PMID:39232161 CDK5 is active throughout mitosis PMID:39232161 cyclin B1 is a mitotic co-factor of CDK5 file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase |
| GO:0098793 presynapse | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Keep presynapse as non-core synaptic localization context. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Synapse |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | MODIFY | Summary: Protein serine kinase activity is too narrow/incomplete for CDK5. Reason: CDK5 phosphorylates both serine and threonine residues, so protein serine/threonine kinase activity is the better molecular-function term. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005515 protein binding | IPI PMID:14521924 Apoptosis-associated tyrosine kinase is a Cdk5 activator p35... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors. | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:15890360 Molecular basis for the specificity of p27 toward cyclin-dep... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:17078951 PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:20133653 No difference in kinetics of tau or histone phosphorylation ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:20559324 Cables1 protects p63 from proteasomal degradation to ensure ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:21220307 Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:22078880 Adipocyte NCoR knockout decreases PPARΞ³ phosphorylation and ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:23455922 Interlaboratory reproducibility of large-scale human protein... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:26871637 Widespread Expansion of Protein Interaction Capabilities by ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:32812023 Phosphorylated tau interactome in the human Alzheimer's dise... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:35016035 Identification and functional characterization of transcript... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:35063084 Tau interactome maps synaptic and mitochondrial processes as... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0002039 p53 binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: p53 binding is a specific substrate/regulator binding context, not the core molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Interacts with P53/TP53 in neurons |
| GO:0005176 ErbB-2 class receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: ErbB-2 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0016533 protein kinase 5 complex | IEA GO_REF:0000120 | ACCEPT | Summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. Reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0030175 filopodium | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Keep filopodium as non-core fine cell-projection localization context. Reason: The accessible evidence supports CDK5 at cell projections and lamellipodia/growth cones, but not a specific filopodium localization as a core CDK5 compartment. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Perikaryon. Cell projection, lamellipodium |
| GO:0030424 axon | IEA GO_REF:0000107 | ACCEPT | Summary: axon is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0030547 signaling receptor inhibitor activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: signaling receptor inhibitor activity overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0030549 acetylcholine receptor activator activity | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: acetylcholine receptor activator activity overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0043125 ErbB-3 class receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: ErbB-3 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0051879 Hsp90 protein binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Hsp90 protein binding overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0051966 regulation of synaptic transmission, glutamatergic | IEA GO_REF:0000107 | ACCEPT | Summary: regulation of synaptic transmission, glutamatergic is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0061001 regulation of dendritic spine morphogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: regulation of dendritic spine morphogenesis is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:1903076 regulation of protein localization to plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: regulation of protein localization to plasma membrane is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:16039528 Defining Cdk5 ligand chemical space with small molecule inhi... | ACCEPT | Summary: cyclin-dependent protein kinase holoenzyme complex is a supported CDK5 kinase-complex annotation. Reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0016533 protein kinase 5 complex | IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors. | ACCEPT | Summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. Reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0016533 protein kinase 5 complex | IPI PMID:16039528 Defining Cdk5 ligand chemical space with small molecule inhi... | ACCEPT | Summary: protein kinase 5 complex is a supported CDK5 kinase-complex annotation. Reason: CDK5 functions as a catalytic subunit in heterodimeric CDK5R-containing kinase complexes. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: nucleoplasm is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: plasma membrane is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-399944 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-8863007 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-8863011 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-8863014 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004693 cyclin-dependent protein serine/threonine kinase activity | TAS Reactome:R-HSA-180047 | ACCEPT | Summary: cyclin-dependent protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:24607229 Memory enhancement by targeting Cdk5 regulation of NR2B. | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0030547 signaling receptor inhibitor activity | IMP PMID:24607229 Memory enhancement by targeting Cdk5 regulation of NR2B. | MARK AS OVER ANNOTATED | Summary: signaling receptor inhibitor activity overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0035255 ionotropic glutamate receptor binding | IPI PMID:24607229 Memory enhancement by targeting Cdk5 regulation of NR2B. | KEEP AS NON CORE | Summary: ionotropic glutamate receptor binding is a specific substrate/regulator binding context, not the core molecular function. 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. Supporting Evidence: PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation |
| GO:0005634 nucleus | EXP PMID:12691662 Cdk5-mediated inhibition of the protective effects of transc... | ACCEPT | Summary: nucleus is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005737 cytoplasm | EXP PMID:12691662 Cdk5-mediated inhibition of the protective effects of transc... | ACCEPT | Summary: cytoplasm is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005886 plasma membrane | EXP PMID:17009320 cdk5 modulates beta- and delta-catenin/Pin1 interactions in ... | ACCEPT | Summary: plasma membrane is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0014069 postsynaptic density | ISS GO_REF:0000024 | ACCEPT | Summary: Accept postsynaptic density as a supported synaptic CDK5 localization. Reason: UniProt gives a specific postsynaptic density localization by similarity, consistent with CDK5 synaptic substrate regulation. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Postsynaptic density |
| GO:0045202 synapse | ISS GO_REF:0000024 | ACCEPT | Summary: synapse is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0099533 positive regulation of presynaptic cytosolic calcium concentration | ISS GO_REF:0000024 | ACCEPT | Summary: positive regulation of presynaptic cytosolic calcium concentration is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:1903234 negative regulation of calcium ion-dependent exocytosis of neurotransmitter | ISS GO_REF:0000024 | ACCEPT | Summary: negative regulation of calcium ion-dependent exocytosis of neurotransmitter is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0030036 actin cytoskeleton organization | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: actin cytoskeleton organization is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005515 protein binding | IPI PMID:8090221 p35 is a neural-specific regulatory subunit of cyclin-depend... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | KEEP AS NON CORE | Summary: tau protein binding is a specific substrate/regulator binding context, not the core molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt MAPT/TAU, MAP2, MAP1B file:human/CDK5/CDK5-uniprot.txt microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) |
| GO:0050321 tau-protein kinase activity | NAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: tau-protein kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt MAPT/TAU, MAP2, MAP1B file:human/CDK5/CDK5-uniprot.txt microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0016020 membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: membrane is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0030426 growth cone | ISS GO_REF:0000024 | ACCEPT | Summary: growth cone is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | ACCEPT | Summary: neuron projection is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0004674 protein serine/threonine kinase activity | NAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0051966 regulation of synaptic transmission, glutamatergic | ISS GO_REF:0000024 | ACCEPT | Summary: regulation of synaptic transmission, glutamatergic is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: cytoplasm is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0005874 microtubule | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: microtubule is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 Microtubule polymers but not the alpha/beta-tubulin heterodimer block p35 interaction with Cdk5 |
| GO:0008017 microtubule binding | TAS NOT PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | MARK AS OVER ANNOTATED | Summary: Microtubule binding is over-attributed to CDK5 itself. 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. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 Microtubule polymers but not the alpha/beta-tubulin heterodimer block p35 interaction with Cdk5 |
| GO:0000226 microtubule cytoskeleton organization | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: microtubule cytoskeleton organization is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0031175 neuron projection development | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: neuron projection development is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0048167 regulation of synaptic plasticity | TAS PMID:24607229 Memory enhancement by targeting Cdk5 regulation of NR2B. | ACCEPT | Summary: regulation of synaptic plasticity is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:1903076 regulation of protein localization to plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: regulation of protein localization to plasma membrane is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:1904646 cellular response to amyloid-beta | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: cellular response to amyloid-beta is a secondary or broad CDK5 process annotation. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8863014 | KEEP AS NON CORE | Summary: nucleoplasm is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8863587 | KEEP AS NON CORE | Summary: nucleoplasm is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805276 | KEEP AS NON CORE | Summary: nucleoplasm is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0016241 regulation of macroautophagy | TAS PMID:21499257 Cdk5-mediated phosphorylation of endophilin B1 is required f... | ACCEPT | Summary: Regulation of macroautophagy is a supported PN-relevant CDK5 substrate-specific process. Reason: Human/neuron evidence shows CDK5 phosphorylates SH3GLB1/endophilin B1 and is required for induced autophagy in starved neurons and Parkinson disease models. Supporting Evidence: PMID:21499257 unexpected role for Cdk5 in the regulation of induced autophagy in neurons PMID:21499257 autophagy induction in starved neurons file:human/CDK5/CDK5-uniprot.txt Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons |
| GO:1903421 regulation of synaptic vesicle recycling | NAS PMID:22745285 Synaptic vesicle pools and dynamics. | ACCEPT | Summary: regulation of synaptic vesicle recycling is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0045861 negative regulation of proteolysis | IMP PMID:24548080 CDK5 protects from caspase-induced Ataxin-3 cleavage and neu... | KEEP AS NON CORE | Summary: negative regulation of proteolysis is a secondary or broad CDK5 process annotation. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005829 cytosol | TAS Reactome:R-HSA-399944 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-399951 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-NUL-9032945 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-180047 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863007 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863011 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863013 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863587 | KEEP AS NON CORE | Summary: cytosol is a broad or complex-context CDK5 localization. Reason: This location is compatible with CDK5 biology but is less informative than CDK5 kinase-complex, synaptic, neuronal projection, and growth-cone contexts. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} |
| GO:0048167 regulation of synaptic plasticity | ISS GO_REF:0000024 | ACCEPT | Summary: regulation of synaptic plasticity is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0001764 neuron migration | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: neuron migration is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0007268 chemical synaptic transmission | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: chemical synaptic transmission is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0007416 synapse assembly | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: synapse assembly is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0016079 synaptic vesicle exocytosis | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: synaptic vesicle exocytosis is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0030182 neuron differentiation | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: neuron differentiation is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0042981 regulation of apoptotic process | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: regulation of apoptotic process is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0048167 regulation of synaptic plasticity | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: regulation of synaptic plasticity is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0048488 synaptic vesicle endocytosis | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: synaptic vesicle endocytosis is a core CDK5 synaptic process. Reason: CDK5 phosphorylates synaptic release, endocytosis, and NMDAR-associated substrates and regulates synaptic plasticity/neurotransmission. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity PMID:24607229 controls the receptor's cell surface expression PMID:24607229 serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5) PMID:24607229 increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0048675 axon extension | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | Summary: axon extension is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0048709 oligodendrocyte differentiation | IDA PMID:18042622 Cdk5 regulates differentiation of oligodendrocyte precursor ... | ACCEPT | Summary: oligodendrocyte differentiation is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0051402 neuron apoptotic process | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | KEEP AS NON CORE | Summary: Keep neuron apoptotic process as a non-core p25-linked neurotoxicity/stress annotation rather than canonical core CDK5 neuronal kinase biology. 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. Supporting Evidence: PMID:10604467 p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease PMID:10604467 p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis PMID:10604467 cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases |
| GO:0051726 regulation of cell cycle | TAS PMID:21473899 Cdk5: multitasking between physiological and pathological co... | ACCEPT | 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. 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. Supporting Evidence: PMID:39232161 CDK5 is active throughout mitosis PMID:39232161 cyclin B1 is a mitotic co-factor of CDK5 file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase |
| GO:0061001 regulation of dendritic spine morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: regulation of dendritic spine morphogenesis is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:20357208 Cyclin-dependent kinase 5 modulates the transcriptional acti... | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20357208 Cyclin-dependent kinase 5 modulates the transcriptional acti... | KEEP AS NON CORE | Summary: negative regulation of DNA-templated transcription is a secondary or broad CDK5 process annotation. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:21145489 The proapoptotic function of Noxa in human leukemia cells is... | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0005176 ErbB-2 class receptor binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ErbB-2 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0005515 protein binding | IPI PMID:12223541 The cyclin-dependent kinase 5 activators p35 and p39 interac... | MARK AS OVER ANNOTATED | Summary: Generic protein binding does not describe CDK5 function. 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. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: nucleus is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0016301 kinase activity | ISS GO_REF:0000024 | MODIFY | Summary: kinase activity is correct but too broad for CDK5. Reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0030182 neuron differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: neuron differentiation is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0030424 axon | ISS GO_REF:0000024 | ACCEPT | Summary: axon is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0030425 dendrite | ISS GO_REF:0000024 | ACCEPT | Summary: dendrite is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0030549 acetylcholine receptor activator activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: acetylcholine receptor activator activity overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | ACCEPT | Summary: neuron projection development is part of core CDK5 neuronal kinase biology. Reason: CDK5 regulates neuronal development, neurite/axon growth, cytoskeletal dynamics, synaptogenesis, oligodendrocyte differentiation, and neuronal survival/death. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0031594 neuromuscular junction | ISS GO_REF:0000024 | ACCEPT | Summary: neuromuscular junction is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | ACCEPT | Summary: neuronal cell body is a supported CDK5 localization/context. Reason: The localization is consistent with CDK5 neuronal kinase function across cytoplasm, nucleus, membranes, synapses, growth cones, and neuronal projections. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm file:human/CDK5/CDK5-uniprot.txt Nucleus {ECO:0000269|PubMed:12691662} file:human/CDK5/CDK5-uniprot.txt Cell membrane {ECO:0000269|PubMed:17009320} file:human/CDK5/CDK5-uniprot.txt Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission PMID:21473899 normally associated with neuronal processes such as migration, cortical layering and synaptic plasticity |
| GO:0043125 ErbB-3 class receptor binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ErbB-3 class receptor binding overstates a downstream/regulatory interaction as a CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0043525 positive regulation of neuron apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:10604467 p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease PMID:10604467 p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis PMID:10604467 cleavage of p35, followed by accumulation of p25, may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases |
| GO:0050321 tau-protein kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: tau-protein kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt MAPT/TAU, MAP2, MAP1B file:human/CDK5/CDK5-uniprot.txt microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B) file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] |
| GO:0004672 protein kinase activity | TAS PMID:1639063 A family of human cdc2-related protein kinases. | MODIFY | Summary: protein kinase activity is correct but too broad for CDK5. Reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004672 protein kinase activity | TAS PMID:7834371 Expression of CDK5 (PSSALRE kinase), a neural cdc2-related p... | MODIFY | Summary: protein kinase activity is correct but too broad for CDK5. Reason: Replace the broad kinase parent with the more informative cyclin-dependent protein serine/threonine kinase activity term. Proposed replacements: cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
| GO:0004674 protein serine/threonine kinase activity | TAS PMID:1639063 A family of human cdc2-related protein kinases. | ACCEPT | Summary: protein serine/threonine kinase activity is a core CDK5 molecular function. 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. Supporting Evidence: file:human/CDK5/CDK5-uniprot.txt Proline-directed serine/threonine-protein kinase file:human/CDK5/CDK5-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP file:human/CDK5/CDK5-uniprot.txt Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] file:human/CDK5/CDK5-uniprot.txt Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39) file:human/CDK5/CDK5-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 |
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Download this section (compressed HTML)Q: 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?
Suggested experts: GO autophagy editors, CDK5 neuronal signaling experts, Drosophila autophagy experts
Q: Which CDK5 substrate-binding annotations should be retained as specific MF annotations versus represented as phosphorylation/regulatory process annotations?
Suggested experts: GO molecular-function editors, neurobiology curators
Experiment: 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.
Type: kinase assay/autophagy flux assay
Experiment: 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.
Type: phosphosite rescue/autophagy imaging
Experiment: 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.
Type: analog-sensitive kinase phosphoproteomics
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