CDK5R1 encodes the neuronal CDK5 activator p35 and its calpain-cleaved p25 fragment. Its core function is to bind and activate CDK5 as a regulatory subunit of the protein kinase 5 complex, thereby supporting neuronal development, neurite and axon growth, cortical lamination, dendritic-spine and cytoskeletal regulation, and p25-linked neurodegenerative stress signaling. p35 is myristoylated and membrane/neuronal process-associated, while p25 is more stable and relocalizes CDK5 activity to cytoplasmic, nuclear, and perinuclear compartments. CDK5R1 may contribute to induced autophagy indirectly through CDK5 activation, although direct human autophagy evidence is centered on CDK5 phosphorylation of SH3GLB1/endophilin B1 rather than CDK5R1-specific assays.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0007420 brain development | IBA GO_REF:0000033 | ACCEPT | Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0007411 axon guidance | IBA GO_REF:0000033 | ACCEPT | Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0019901 protein kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0030426 growth cone | IBA GO_REF:0000033 | ACCEPT | Summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0016533 protein kinase 5 complex | IEA GO_REF:0000120 | ACCEPT | Summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0043005 neuron projection | IEA GO_REF:0000044 | ACCEPT | Summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0043204 perikaryon | IEA GO_REF:0000044 | ACCEPT | Summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IEA GO_REF:0000120 | ACCEPT | Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0005515 protein binding | IPI PMID:14521924 Apoptosis-associated tyrosine kinase is a Cdk5 activator p35... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:20133653 No difference in kinetics of tau or histone phosphorylation ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:21220307 Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| 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 is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| 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 is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0001764 neuron migration | IEA GO_REF:0000107 | ACCEPT | Summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0002020 protease binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: protease binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0003779 actin binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: actin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | ACCEPT | Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0007158 neuron cell-cell adhesion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007411 axon guidance | IEA GO_REF:0000107 | ACCEPT | Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007413 axonal fasciculation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007420 brain development | IEA GO_REF:0000107 | ACCEPT | Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | ACCEPT | Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0021799 cerebral cortex radially oriented cell migration | IEA GO_REF:0000107 | ACCEPT | Summary: Accept cerebral cortex radially oriented cell migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0032956 regulation of actin cytoskeleton organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Keep regulation of actin cytoskeleton organization as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0035255 ionotropic glutamate receptor binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: ionotropic glutamate receptor binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0048013 ephrin receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0051015 actin filament binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: actin filament binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0061001 regulation of dendritic spine morphogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0070507 regulation of microtubule cytoskeleton organization | IEA GO_REF:0000107 | ACCEPT | Summary: Accept regulation of microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:16039528 Defining Cdk5 ligand chemical space with small molecule inhi... | ACCEPT | Summary: Accept cyclin-dependent protein kinase holoenzyme complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0016533 protein kinase 5 complex | IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors. | ACCEPT | Summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005634 nucleus | EXP PMID:18507738 Myristoylation of p39 and p35 is a determinant of cytoplasmi... | ACCEPT | Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0043204 perikaryon | EXP PMID:10604467 Conversion of p35 to p25 deregulates Cdk5 activity and promo... | ACCEPT | Summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IGI PMID:17517623 Roles of heat-shock protein 90 in maintaining and facilitati... | ACCEPT | Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| 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 is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0030295 protein kinase activator activity | TAS PMID:8090221 p35 is a neural-specific regulatory subunit of cyclin-depend... | MODIFY | Summary: protein kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0030426 growth cone | ISS GO_REF:0000024 | ACCEPT | Summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0031116 positive regulation of microtubule polymerization | ISS GO_REF:0000024 | ACCEPT | Summary: Accept positive regulation of microtubule polymerization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules |
| GO:0043005 neuron projection | ISS GO_REF:0000024 | ACCEPT | Summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0043014 alpha-tubulin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Accept alpha-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. Reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules |
| GO:0048487 beta-tubulin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Accept beta-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. Reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules |
| GO:0000226 microtubule cytoskeleton organization | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: Accept microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules |
| GO:0031175 neuron projection development | TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk... | ACCEPT | Summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863007 | KEEP AS NON CORE | Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863011 | KEEP AS NON CORE | Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863013 | KEEP AS NON CORE | Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8863587 | KEEP AS NON CORE | Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805276 | ACCEPT | Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8863014 | ACCEPT | Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8863587 | ACCEPT | Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-399944 | ACCEPT | Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-399951 | ACCEPT | Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9616110 | ACCEPT | Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0016241 regulation of macroautophagy | NAS PMID:21499257 Cdk5-mediated phosphorylation of endophilin B1 is required f... | KEEP AS NON CORE | Summary: Keep regulation of macroautophagy as PN-relevant complex-level context, but not as the primary CDK5R1 core function. Reason: The direct human autophagy evidence is for CDK5-mediated SH3GLB1/endophilin B1 phosphorylation; CDK5R1 is inferred as the CDK5 activator rather than directly tested in that paper. 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/CDK5R1/CDK5R1-notes.md It does not specifically establish a CDK5R1 perturbation requirement, so the CDK5R1 macroautophagy row should be retained as complex-level/proteostasis context rather than treated as the primary core function. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina... | MODIFY | Summary: peptidyl-serine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. Reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. Proposed replacements: regulation of cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0018107 peptidyl-threonine phosphorylation | IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina... | MODIFY | Summary: peptidyl-threonine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. Reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. Proposed replacements: regulation of cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0043539 protein serine/threonine kinase activator activity | IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina... | MODIFY | Summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0014069 postsynaptic density | ISS GO_REF:0000024 | ACCEPT | Summary: Accept postsynaptic density; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0048013 ephrin receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0061001 regulation of dendritic spine morphogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:20357208 Cyclin-dependent kinase 5 modulates the transcriptional acti... | KEEP AS NON CORE | Summary: Keep negative regulation of DNA-templated transcription as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0019901 protein kinase binding | IPI PMID:12832520 Identification of a novel, membrane-associated neuronal kina... | ACCEPT | Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity |
| GO:0048471 perinuclear region of cytoplasm | IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina... | ACCEPT | Summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0007213 G protein-coupled acetylcholine receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep G protein-coupled acetylcholine receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0001764 neuron migration | ISS GO_REF:0000024 | ACCEPT | Summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0005509 calcium ion binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: calcium ion binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| 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 is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0007158 neuron cell-cell adhesion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007411 axon guidance | ISS GO_REF:0000024 | ACCEPT | Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007413 axonal fasciculation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0007420 brain development | ISS GO_REF:0000024 | ACCEPT | Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0016020 membrane | ISS GO_REF:0000024 | MODIFY | Summary: Membrane is too broad for CDK5R1; plasma membrane is the better supported specific cellular component for myristoylated p35. Reason: The p35 form is myristoylated and membrane-associated, while p25 relocalizes away from this membrane anchor. Proposed replacements: plasma membrane Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0016301 kinase activity | ISS GO_REF:0000024 | MODIFY | Summary: kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. Reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0030182 neuron differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Accept neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0030424 axon | ISS GO_REF:0000024 | ACCEPT | Summary: Accept axon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0030425 dendrite | ISS GO_REF:0000024 | ACCEPT | Summary: Accept dendrite; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | ACCEPT | Summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0031594 neuromuscular junction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep neuromuscular junction as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0035235 ionotropic glutamate receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep ionotropic glutamate receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | ACCEPT | Summary: Accept neuronal cell body; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | ACCEPT | Summary: Accept dendritic spine; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| GO:0043292 contractile muscle fiber | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Keep contractile muscle fiber as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35 |
| 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 secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0043539 protein serine/threonine kinase activator activity | ISS GO_REF:0000024 | MODIFY | Summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0045296 cadherin binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: cadherin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0005515 protein binding | IPI PMID:10721722 Cloning of three novel neuronal Cdk5 activator binding prote... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity | TAS PMID:7592934 An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) ... | ACCEPT | Summary: Accept regulation of cyclin-dependent protein serine/threonine kinase activity as a core process-level statement for p35/p25 activation of CDK5. Reason: CDK5R1 binds CDK5 and activates the kinase complex in neurons. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity |
| GO:0004672 protein kinase activity | TAS PMID:7592934 An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) ... | MODIFY | Summary: protein kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. Reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate. |
| GO:0007420 brain development | NAS PMID:10915792 Identification of a common protein association region in the... | ACCEPT | Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
| GO:0045664 regulation of neuron differentiation | NAS PMID:10721722 Cloning of three novel neuronal Cdk5 activator binding prote... | ACCEPT | Summary: Accept regulation of neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth |
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Download this section (compressed HTML)Q: Is the CDK5R1 macroautophagy annotation supported by direct perturbation of p35/p25, or should it remain an inferred CDK5-complex context annotation?
Suggested experts: GO autophagy editors, CDK5 neuronal signaling experts
Q: Should p35 and p25 be represented with isoform/product-specific annotation extensions for membrane-associated p35 versus nuclear/perinuclear p25 localization and function?
Suggested experts: GO annotation-extension editors, UniProt CDK5R curators
Q: Are the broad synaptic receptor-signaling and adhesion annotations sufficiently direct for human CDK5R1, or should they be limited to CDK5 complex/substrate annotations?
Suggested experts: neurobiology curators, GO molecular-function editors
Experiment: Test CDK5R1-specific depletion or p35/p25 rescue in neuronal induced-autophagy assays measuring SH3GLB1 phosphorylation, LC3 lipidation, and autophagic flux.
Hypothesis: CDK5R1 is required for the CDK5-dependent induced-autophagy phenotype only when p35/p25 activates CDK5 in the relevant neuronal compartment.
Type: CDK5R1 rescue/autophagy flux assay
Experiment: Compare p35 and p25 mutants for CDK5 activation, subcellular localization, and substrate phosphorylation in human neuronal cells.
Hypothesis: p35 and p25 drive distinct CDK5 substrate/localization outputs because p25 lacks the p35 membrane/tubulin-associated N-terminal region.
Type: phosphoproteomics/localization assay
Experiment: Use tubulin-binding-defective p35 mutants to determine whether the direct p35-tubulin interaction is required for neuronal microtubule organization and neurite outgrowth.
Hypothesis: p35 tubulin binding contributes to neurite and microtubule organization independently of generic CDK5 kinase activation.
Type: mutational rescue/microtubule imaging
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