id: Q15078 gene_symbol: CDK5R1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. existing_annotations: - term: id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0007420 label: brain development evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0005737 label: cytoplasm evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0007411 label: axon guidance evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0019901 label: protein kinase binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0030426 label: growth cone evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0016533 label: protein kinase 5 complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. action: ACCEPT reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: macromolecular complex composed of at least CDK5, CDK5R1 (p35) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0043005 label: neuron projection evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043204 label: perikaryon evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0048471 label: perinuclear region of cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14521924 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15689152 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20133653 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21220307 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23543736 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23602568 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0001764 label: neuron migration evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0002020 label: protease binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: protease binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0003779 label: actin binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: actin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0007158 label: neuron cell-cell adhesion evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007411 label: axon guidance evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007413 label: axonal fasciculation evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007420 label: brain development evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0019901 label: protein kinase binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0021799 label: cerebral cortex radially oriented cell migration evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept cerebral cortex radially oriented cell migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0032956 label: regulation of actin cytoskeleton organization evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Keep regulation of actin cytoskeleton organization as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0035255 label: ionotropic glutamate receptor binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: ionotropic glutamate receptor binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0048013 label: ephrin receptor signaling pathway evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0051015 label: actin filament binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: actin filament binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0061001 label: regulation of dendritic spine morphogenesis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0070507 label: regulation of microtubule cytoskeleton organization evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Accept regulation of microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules - term: id: GO:0000307 label: cyclin-dependent protein kinase holoenzyme complex evidence_type: IPI original_reference_id: PMID:16039528 qualifier: part_of review: summary: Accept cyclin-dependent protein kinase holoenzyme complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. action: ACCEPT reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: macromolecular complex composed of at least CDK5, CDK5R1 (p35) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0016533 label: protein kinase 5 complex evidence_type: IPI original_reference_id: PMID:15689152 qualifier: part_of review: summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. action: ACCEPT reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: macromolecular complex composed of at least CDK5, CDK5R1 (p35) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0005654 label: nucleoplasm evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:18507738 qualifier: located_in review: summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043204 label: perikaryon evidence_type: EXP original_reference_id: PMID:10604467 qualifier: located_in review: summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity evidence_type: IGI original_reference_id: PMID:17517623 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity evidence_type: TAS original_reference_id: PMID:17491008 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:8090221 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0030295 label: protein kinase activator activity evidence_type: TAS original_reference_id: PMID:8090221 qualifier: enables review: summary: protein kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. action: MODIFY reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. proposed_replacement_terms: - id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0030426 label: growth cone evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0031116 label: positive regulation of microtubule polymerization evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept positive regulation of microtubule polymerization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules - term: id: GO:0043005 label: neuron projection evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043014 label: alpha-tubulin binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: Accept alpha-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. action: ACCEPT reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules - term: id: GO:0048487 label: beta-tubulin binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: Accept beta-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. action: ACCEPT reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules - term: id: GO:0000226 label: microtubule cytoskeleton organization evidence_type: TAS original_reference_id: PMID:17491008 qualifier: involved_in review: summary: Accept microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules - term: id: GO:0031175 label: neuron projection development evidence_type: TAS original_reference_id: PMID:17491008 qualifier: involved_in review: summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863007 qualifier: located_in review: summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863011 qualifier: located_in review: summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863013 qualifier: located_in review: summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-8863587 qualifier: located_in review: summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-6805276 qualifier: located_in review: summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8863014 qualifier: located_in review: summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-8863587 qualifier: located_in review: summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005886 label: plasma membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-399944 qualifier: located_in review: summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005886 label: plasma membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-399951 qualifier: located_in review: summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005886 label: plasma membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9616110 qualifier: located_in review: summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: NAS original_reference_id: PMID:21499257 qualifier: involved_in review: summary: Keep regulation of macroautophagy as PN-relevant complex-level context, but not as the primary CDK5R1 core function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:21499257 supporting_text: unexpected role for Cdk5 in the regulation of induced autophagy in neurons - reference_id: PMID:21499257 supporting_text: autophagy induction in starved neurons - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: 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. - term: id: GO:0018105 label: peptidyl-serine phosphorylation evidence_type: IDA original_reference_id: PMID:12832520 qualifier: involved_in review: summary: peptidyl-serine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. action: MODIFY reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. proposed_replacement_terms: - id: GO:0000079 label: regulation of cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: PMID:12832520 supporting_text: Cprk interacts with p35 in the yeast-two hybrid system - reference_id: PMID:12832520 supporting_text: Cdk5/p35 inhibits cprk activity - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0018107 label: peptidyl-threonine phosphorylation evidence_type: IDA original_reference_id: PMID:12832520 qualifier: involved_in review: summary: peptidyl-threonine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. action: MODIFY reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. proposed_replacement_terms: - id: GO:0000079 label: regulation of cyclin-dependent protein serine/threonine kinase activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: PMID:12832520 supporting_text: Cprk interacts with p35 in the yeast-two hybrid system - reference_id: PMID:12832520 supporting_text: Cdk5/p35 inhibits cprk activity - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0043539 label: protein serine/threonine kinase activator activity evidence_type: IDA original_reference_id: PMID:12832520 qualifier: enables review: summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. action: MODIFY reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. proposed_replacement_terms: - id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0014069 label: postsynaptic density evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept postsynaptic density; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0048013 label: ephrin receptor signaling pathway evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0061001 label: regulation of dendritic spine morphogenesis evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0045892 label: negative regulation of DNA-templated transcription evidence_type: IMP original_reference_id: PMID:20357208 qualifier: involved_in review: summary: Keep negative regulation of DNA-templated transcription as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0019901 label: protein kinase binding evidence_type: IPI original_reference_id: PMID:12832520 qualifier: enables review: 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. action: ACCEPT reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. supported_by: - reference_id: PMID:12832520 supporting_text: Cprk interacts with p35 in the yeast-two hybrid system - reference_id: PMID:12832520 supporting_text: Cdk5/p35 inhibits cprk activity - term: id: GO:0048471 label: perinuclear region of cytoplasm evidence_type: IDA original_reference_id: PMID:12832520 qualifier: located_in review: summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0007213 label: G protein-coupled acetylcholine receptor signaling pathway evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep G protein-coupled acetylcholine receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0001764 label: neuron migration evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0005509 label: calcium ion binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: calcium ion binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12223541 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005634 label: nucleus evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0005737 label: cytoplasm evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0007158 label: neuron cell-cell adhesion evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007411 label: axon guidance evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007413 label: axonal fasciculation evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0007420 label: brain development evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0016020 label: membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Membrane is too broad for CDK5R1; plasma membrane is the better supported specific cellular component for myristoylated p35. action: MODIFY reason: The p35 form is myristoylated and membrane-associated, while p25 relocalizes away from this membrane anchor. proposed_replacement_terms: - id: GO:0005886 label: plasma membrane supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0016301 label: kinase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. action: MODIFY reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. proposed_replacement_terms: - id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0030182 label: neuron differentiation evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0030424 label: axon evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept axon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0030425 label: dendrite evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept dendrite; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0031175 label: neuron projection development evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0031594 label: neuromuscular junction evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Keep neuromuscular junction as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0035235 label: ionotropic glutamate receptor signaling pathway evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep ionotropic glutamate receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0043025 label: neuronal cell body evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept neuronal cell body; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043197 label: dendritic spine evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Accept dendritic spine; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. action: ACCEPT reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043292 label: contractile muscle fiber evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Keep contractile muscle fiber as secondary localization context for p35/p25 or transferred CDK5R-family biology. action: KEEP_AS_NON_CORE reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - term: id: GO:0043525 label: positive regulation of neuron apoptotic process evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: Keep positive regulation of neuron apoptotic process as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0043539 label: protein serine/threonine kinase activator activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. action: MODIFY reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. proposed_replacement_terms: - id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0045296 label: cadherin binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: cadherin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. action: MARK_AS_OVER_ANNOTATED reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:10721722 qualifier: enables review: summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0000079 label: regulation of cyclin-dependent protein serine/threonine kinase activity evidence_type: TAS original_reference_id: PMID:7592934 qualifier: involved_in review: summary: Accept regulation of cyclin-dependent protein serine/threonine kinase activity as a core process-level statement for p35/p25 activation of CDK5. action: ACCEPT reason: CDK5R1 binds CDK5 and activates the kinase complex in neurons. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - term: id: GO:0004672 label: protein kinase activity evidence_type: TAS original_reference_id: PMID:7592934 qualifier: enables review: summary: protein kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. action: MODIFY reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. proposed_replacement_terms: - id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: CDK5R1 itself is not the catalytic kinase that transfers phosphate. - term: id: GO:0007420 label: brain development evidence_type: NAS original_reference_id: PMID:10915792 qualifier: involved_in review: summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth - term: id: GO:0045664 label: regulation of neuron differentiation evidence_type: NAS original_reference_id: PMID:10721722 qualifier: involved_in review: summary: Accept regulation of neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. action: ACCEPT reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. - reference_id: Reactome:R-HSA-9616110 supporting_text: The complex of CDK5:CDK5R1 is required for neurite outgrowth references: - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:10604467 title: Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract supports calpain-derived p25 as a CDK5-activating, mislocalized, more stable form of p35 that changes CDK5 activity and substrate context. - id: PMID:10721722 title: Cloning of three novel neuronal Cdk5 activator binding proteins. findings: [] - id: PMID:10915792 title: Identification of a common protein association region in the neuronal Cdk5 activator. findings: [] - id: PMID:12223541 title: The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner. findings: [] - id: PMID:12832520 title: Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached full-text record supports p35 interaction with a membrane-associated neuronal kinase and CDK5/p35-dependent regulation, useful for non-core binding/regulatory context. - id: PMID:14521924 title: Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein. findings: [] - id: PMID:15689152 title: Mechanism of CDK5/p25 binding by CDK inhibitors. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached abstract supports the CDK5/p25 structural complex and inhibitor-binding context; relevant to p25-containing CDK5R1 complexes. - id: PMID:16039528 title: Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. findings: [] - id: PMID:17491008 title: Microtubule association of the neuronal p35 activator of Cdk5. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract directly supports p35/CDK5R1 binding to tubulin and microtubules, microtubule assembly effects, and regulation of CDK5-p35 activity. - id: PMID:17517623 title: Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. findings: [] - id: PMID:18507738 title: Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cyclin-dependent kinase 5 complexes. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract supports p35 myristoylation and N-terminal sequence control of active CDK5 complex membrane versus nuclear localization. - id: PMID:20133653 title: No difference in kinetics of tau or histone phosphorylation by CDK5/p25 versus CDK5/p35 in vitro. findings: [] - id: PMID:20357208 title: Cyclin-dependent kinase 5 modulates the transcriptional activity of the mineralocorticoid receptor and regulates expression of brain-derived neurotrophic factor. findings: [] - id: PMID:21220307 title: Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control. findings: [] - id: PMID:21499257 title: Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Cached abstract supports CDK5-mediated endophilin B1 phosphorylation in induced neuronal autophagy; CDK5R1 relevance is complex-level rather than direct p35-specific evidence. - id: PMID:23543736 title: Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel potentiator of cyclin-dependent kinases to enhance cell proliferation independently of its hydrolase activity. findings: [] - id: PMID:23602568 title: The protein interaction landscape of the human CMGC kinase group. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:7592934 title: An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. findings: [] - id: PMID:8090221 title: p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Cached abstract directly establishes p35/CDK5R1 as a neuronal regulatory subunit that physically associates with and activates CDK5. - id: Reactome:R-HSA-399944 title: Phosphorylation of CRMPs by Cdk5 findings: [] - id: Reactome:R-HSA-399951 title: Phosphorylation of CRMPs by GSK3beta findings: [] - id: Reactome:R-HSA-6805276 title: CDK5 phosphorylates TP53 findings: [] - id: Reactome:R-HSA-8863007 title: p25-bound CDK5 phosphorylates CDC25B findings: [] - id: Reactome:R-HSA-8863011 title: p25-bound CDK5 phosphorylates CDC25C findings: [] - id: Reactome:R-HSA-8863013 title: CDK5 binds p25 findings: [] - id: Reactome:R-HSA-8863014 title: p25-bound CDK5 phosphorylates CDC25A findings: [] - id: Reactome:R-HSA-8863587 title: CDK5:p25 translocates to the nucleus findings: [] - id: Reactome:R-HSA-9616110 title: EGR1-dependent CDK5R1 gene expression findings: [] - id: file:human/CDK5R1/CDK5R1-uniprot.txt title: UniProtKB record for human CDK5R1 findings: - statement: UniProt summarizes CDK5R1 as p35/p25, a neuron-specific CDK5 activator whose processed forms differ in localization and stability. - id: file:human/CDK5R1/CDK5R1-notes.md title: CDK5R1 review notes findings: - statement: Manual PN-focused CDK5R1 notes; autophagy was treated as CDK5-complex context unless CDK5R1-specific evidence is available. core_functions: - molecular_function: id: GO:0061575 label: cyclin-dependent protein serine/threonine kinase activator activity description: CDK5R1/p35 and p25 bind CDK5 as regulatory subunits and activate the CDK5 kinase complex in neuronal and stress-associated contexts. directly_involved_in: - id: GO:0000079 label: regulation of cyclin-dependent protein serine/threonine kinase activity - id: GO:0001764 label: neuron migration - id: GO:0007411 label: axon guidance - id: GO:0007420 label: brain development - id: GO:0030182 label: neuron differentiation - id: GO:0031175 label: neuron projection development - id: GO:0061001 label: regulation of dendritic spine morphogenesis locations: - id: GO:0005886 label: plasma membrane - id: GO:0043005 label: neuron projection - id: GO:0030426 label: growth cone - id: GO:0043204 label: perikaryon - id: GO:0048471 label: perinuclear region of cytoplasm - id: GO:0005634 label: nucleus in_complex: id: GO:0016533 label: protein kinase 5 complex supported_by: - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is a neuron specific activator of CDK5 - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. - reference_id: PMID:8090221 supporting_text: associates physically with Cdk5 in vivo and activates the Cdk5 kinase - reference_id: PMID:10604467 supporting_text: To be activated, Cdk5 has to associate with its regulatory subunit, p35. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: macromolecular complex composed of at least CDK5, CDK5R1 (p35) - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Only the heterodimer shows kinase activity - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: Cell projection, neuron projection - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: p35 is present in the peripheries and nerve terminals. - reference_id: file:human/CDK5R1/CDK5R1-uniprot.txt supporting_text: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions - reference_id: PMID:18507738 supporting_text: myristoylation regulates the membrane association of p39 as well as p35 - reference_id: PMID:21499257 supporting_text: unexpected role for Cdk5 in the regulation of induced autophagy in neurons - reference_id: PMID:21499257 supporting_text: autophagy induction in starved neurons - reference_id: file:human/CDK5R1/CDK5R1-notes.md supporting_text: 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. - molecular_function: id: GO:0043014 label: alpha-tubulin binding description: The p35 form of CDK5R1 directly binds alpha/beta-tubulin and microtubules, promotes microtubule assembly/bundling, and helps organize neuronal microtubule-associated CDK5 signaling; p25 lacks this tubulin/microtubule-binding activity. directly_involved_in: - id: GO:0000226 label: microtubule cytoskeleton organization - id: GO:0031116 label: positive regulation of microtubule polymerization - id: GO:0031175 label: neuron projection development locations: - id: GO:0030426 label: growth cone - id: GO:0043005 label: neuron projection - id: GO:0030424 label: axon supported_by: - reference_id: PMID:17491008 supporting_text: p35 binds directly to alpha/beta-tubulin and microtubules - reference_id: PMID:17491008 supporting_text: p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities - reference_id: PMID:17491008 supporting_text: promoting microtubule assembly and inducing formation of microtubule bundles - reference_id: PMID:17491008 supporting_text: p35 localizes to microtubules proposed_new_terms: [] suggested_questions: - question: Is the CDK5R1 macroautophagy annotation supported by direct perturbation of p35/p25, or should it remain an inferred CDK5-complex context annotation? experts: - GO autophagy editors - CDK5 neuronal signaling experts - question: Should p35 and p25 be represented with isoform/product-specific annotation extensions for membrane-associated p35 versus nuclear/perinuclear p25 localization and function? experts: - GO annotation-extension editors - UniProt CDK5R curators - question: Are the broad synaptic receptor-signaling and adhesion annotations sufficiently direct for human CDK5R1, or should they be limited to CDK5 complex/substrate annotations? experts: - neurobiology curators - GO molecular-function editors suggested_experiments: - description: 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. experiment_type: CDK5R1 rescue/autophagy flux assay - description: 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. experiment_type: phosphoproteomics/localization assay - description: 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. experiment_type: mutational rescue/microtubule imaging