CDK5R1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	IBA GO_REF:0000033	ACCEPT	Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0007420 brain development	IBA GO_REF:0000033	ACCEPT	Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0007411 axon guidance	IBA GO_REF:0000033	ACCEPT	Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0019901 protein kinase binding	IBA GO_REF:0000033	ACCEPT	Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0030426 growth cone	IBA GO_REF:0000033	ACCEPT	Summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0016533 protein kinase 5 complex	IEA GO_REF:0000120	ACCEPT	Summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0043005 neuron projection	IEA GO_REF:0000044	ACCEPT	Summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043204 perikaryon	IEA GO_REF:0000044	ACCEPT	Summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	IEA GO_REF:0000120	ACCEPT	Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0005515 protein binding	IPI PMID:14521924 Apoptosis-associated tyrosine kinase is a Cdk5 activator p35...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors.	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:20133653 No difference in kinetics of tau or histone phosphorylation ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:21220307 Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:23543736 Ubiquitin C-terminal hydrolase L1 (UCH-L1) acts as a novel p...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:23602568 The protein interaction landscape of the human CMGC kinase g...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0001764 neuron migration	IEA GO_REF:0000107	ACCEPT	Summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0002020 protease binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: protease binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0003779 actin binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: actin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005737 cytoplasm	IEA GO_REF:0000107	ACCEPT	Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0007158 neuron cell-cell adhesion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007411 axon guidance	IEA GO_REF:0000107	ACCEPT	Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007413 axonal fasciculation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007420 brain development	IEA GO_REF:0000107	ACCEPT	Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0019901 protein kinase binding	IEA GO_REF:0000107	ACCEPT	Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0021799 cerebral cortex radially oriented cell migration	IEA GO_REF:0000107	ACCEPT	Summary: Accept cerebral cortex radially oriented cell migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0032956 regulation of actin cytoskeleton organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Keep regulation of actin cytoskeleton organization as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0035255 ionotropic glutamate receptor binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: ionotropic glutamate receptor binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0048013 ephrin receptor signaling pathway	IEA GO_REF:0000107	ACCEPT	Summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0051015 actin filament binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: actin filament binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0061001 regulation of dendritic spine morphogenesis	IEA GO_REF:0000107	ACCEPT	Summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0070507 regulation of microtubule cytoskeleton organization	IEA GO_REF:0000107	ACCEPT	Summary: Accept regulation of microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules
GO:0000307 cyclin-dependent protein kinase holoenzyme complex	IPI PMID:16039528 Defining Cdk5 ligand chemical space with small molecule inhi...	ACCEPT	Summary: Accept cyclin-dependent protein kinase holoenzyme complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0016533 protein kinase 5 complex	IPI PMID:15689152 Mechanism of CDK5/p25 binding by CDK inhibitors.	ACCEPT	Summary: Accept protein kinase 5 complex; CDK5R1/p35 or p25 is a regulatory subunit of the active CDK5 kinase complex. Reason: The CDK5 holoenzyme requires CDK5 plus the CDK5R1 regulatory subunit for kinase activity. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) file:human/CDK5R1/CDK5R1-uniprot.txt macromolecular complex composed of at least CDK5, CDK5R1 (p35) file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005634 nucleus	EXP PMID:18507738 Myristoylation of p39 and p35 is a determinant of cytoplasmi...	ACCEPT	Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043204 perikaryon	EXP PMID:10604467 Conversion of p35 to p25 deregulates Cdk5 activity and promo...	ACCEPT	Summary: Accept perikaryon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	IGI PMID:17517623 Roles of heat-shock protein 90 in maintaining and facilitati...	ACCEPT	Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity	TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk...	ACCEPT	Summary: Accept cyclin-dependent protein serine/threonine kinase activator activity; this is the most specific seeded term for CDK5R1/p35-p25 as the CDK5 regulatory activator. Reason: CDK5R1 is the p35/p25 regulatory subunit that binds CDK5 and activates the CDK5 kinase complex. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0005515 protein binding	IPI PMID:8090221 p35 is a neural-specific regulatory subunit of cyclin-depend...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0030295 protein kinase activator activity	TAS PMID:8090221 p35 is a neural-specific regulatory subunit of cyclin-depend...	MODIFY	Summary: protein kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0030426 growth cone	ISS GO_REF:0000024	ACCEPT	Summary: Accept growth cone; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0031116 positive regulation of microtubule polymerization	ISS GO_REF:0000024	ACCEPT	Summary: Accept positive regulation of microtubule polymerization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules
GO:0043005 neuron projection	ISS GO_REF:0000024	ACCEPT	Summary: Accept neuron projection; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043014 alpha-tubulin binding	ISS GO_REF:0000024	ACCEPT	Summary: Accept alpha-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. Reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules
GO:0048487 beta-tubulin binding	ISS GO_REF:0000024	ACCEPT	Summary: Accept beta-tubulin binding; p35 directly binds alpha/beta tubulin and microtubules. Reason: This binding is experimentally supported for p35 and underlies its microtubule-associated neuronal cytoskeletal role. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules
GO:0000226 microtubule cytoskeleton organization	TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk...	ACCEPT	Summary: Accept microtubule cytoskeleton organization as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: PMID:17491008 p35 binds directly to alpha/beta-tubulin and microtubules PMID:17491008 p25, a neurotoxin-induced and truncated form of p35, does not have tubulin and microtubule binding activities PMID:17491008 promoting microtubule assembly and inducing formation of microtubule bundles PMID:17491008 p35 localizes to microtubules
GO:0031175 neuron projection development	TAS PMID:17491008 Microtubule association of the neuronal p35 activator of Cdk...	ACCEPT	Summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0005829 cytosol	TAS Reactome:R-HSA-8863007	KEEP AS NON CORE	Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005829 cytosol	TAS Reactome:R-HSA-8863011	KEEP AS NON CORE	Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005829 cytosol	TAS Reactome:R-HSA-8863013	KEEP AS NON CORE	Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005829 cytosol	TAS Reactome:R-HSA-8863587	KEEP AS NON CORE	Summary: Keep cytosol as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6805276	ACCEPT	Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8863014	ACCEPT	Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8863587	ACCEPT	Summary: Accept nucleoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005886 plasma membrane	TAS Reactome:R-HSA-399944	ACCEPT	Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005886 plasma membrane	TAS Reactome:R-HSA-399951	ACCEPT	Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005886 plasma membrane	TAS Reactome:R-HSA-9616110	ACCEPT	Summary: Accept plasma membrane; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0016241 regulation of macroautophagy	NAS PMID:21499257 Cdk5-mediated phosphorylation of endophilin B1 is required f...	KEEP AS NON CORE	Summary: Keep regulation of macroautophagy as PN-relevant complex-level context, but not as the primary CDK5R1 core function. Reason: The direct human autophagy evidence is for CDK5-mediated SH3GLB1/endophilin B1 phosphorylation; CDK5R1 is inferred as the CDK5 activator rather than directly tested in that paper. Supporting Evidence: PMID:21499257 unexpected role for Cdk5 in the regulation of induced autophagy in neurons PMID:21499257 autophagy induction in starved neurons file:human/CDK5R1/CDK5R1-notes.md It does not specifically establish a CDK5R1 perturbation requirement, so the CDK5R1 macroautophagy row should be retained as complex-level/proteostasis context rather than treated as the primary core function.
GO:0018105 peptidyl-serine phosphorylation	IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina...	MODIFY	Summary: peptidyl-serine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. Reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. Proposed replacements: regulation of cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0018107 peptidyl-threonine phosphorylation	IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina...	MODIFY	Summary: peptidyl-threonine phosphorylation reflects phosphorylation by the CDK5-p35 complex, but CDK5R1 should be represented as regulating/activating CDK activity. Reason: The catalytic phosphorylation activity belongs to CDK5; CDK5R1 is the regulatory subunit required for the active CDK5 complex. Proposed replacements: regulation of cyclin-dependent protein serine/threonine kinase activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0043539 protein serine/threonine kinase activator activity	IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina...	MODIFY	Summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0014069 postsynaptic density	ISS GO_REF:0000024	ACCEPT	Summary: Accept postsynaptic density; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0048013 ephrin receptor signaling pathway	ISS GO_REF:0000024	ACCEPT	Summary: Accept ephrin receptor signaling pathway as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0061001 regulation of dendritic spine morphogenesis	ISS GO_REF:0000024	ACCEPT	Summary: Accept regulation of dendritic spine morphogenesis as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0045892 negative regulation of DNA-templated transcription	IMP PMID:20357208 Cyclin-dependent kinase 5 modulates the transcriptional acti...	KEEP AS NON CORE	Summary: Keep negative regulation of DNA-templated transcription as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0019901 protein kinase binding	IPI PMID:12832520 Identification of a novel, membrane-associated neuronal kina...	ACCEPT	Summary: Accept protein kinase binding as a valid CDK5R1 regulatory-subunit interaction term, while recognizing that CDK5 activator activity is the more informative core molecular-function term. Reason: CDK5R1 binds CDK5 and other kinase partners in regulatory p35/p25 kinase-complex contexts. Supporting Evidence: PMID:12832520 Cprk interacts with p35 in the yeast-two hybrid system PMID:12832520 Cdk5/p35 inhibits cprk activity
GO:0048471 perinuclear region of cytoplasm	IDA PMID:12832520 Identification of a novel, membrane-associated neuronal kina...	ACCEPT	Summary: Accept perinuclear region of cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0007213 G protein-coupled acetylcholine receptor signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep G protein-coupled acetylcholine receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0001764 neuron migration	ISS GO_REF:0000024	ACCEPT	Summary: Accept neuron migration as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0005509 calcium ion binding	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: calcium ion binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:12223541 The cyclin-dependent kinase 5 activators p35 and p39 interac...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005634 nucleus	ISS GO_REF:0000024	ACCEPT	Summary: Accept nucleus; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: Accept cytoplasm; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0007158 neuron cell-cell adhesion	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep neuron cell-cell adhesion as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007411 axon guidance	ISS GO_REF:0000024	ACCEPT	Summary: Accept axon guidance as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007413 axonal fasciculation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep axonal fasciculation as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0007420 brain development	ISS GO_REF:0000024	ACCEPT	Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0016020 membrane	ISS GO_REF:0000024	MODIFY	Summary: Membrane is too broad for CDK5R1; plasma membrane is the better supported specific cellular component for myristoylated p35. Reason: The p35 form is myristoylated and membrane-associated, while p25 relocalizes away from this membrane anchor. Proposed replacements: plasma membrane Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0016301 kinase activity	ISS GO_REF:0000024	MODIFY	Summary: kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. Reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0030182 neuron differentiation	ISS GO_REF:0000024	ACCEPT	Summary: Accept neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0030424 axon	ISS GO_REF:0000024	ACCEPT	Summary: Accept axon; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0030425 dendrite	ISS GO_REF:0000024	ACCEPT	Summary: Accept dendrite; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0031175 neuron projection development	ISS GO_REF:0000024	ACCEPT	Summary: Accept neuron projection development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0031594 neuromuscular junction	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep neuromuscular junction as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0035235 ionotropic glutamate receptor signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep ionotropic glutamate receptor signaling pathway as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0043025 neuronal cell body	ISS GO_REF:0000024	ACCEPT	Summary: Accept neuronal cell body; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043197 dendritic spine	ISS GO_REF:0000024	ACCEPT	Summary: Accept dendritic spine; CDK5R1/p35-p25 localizes to neuronal projections, membrane/cytoplasmic regions, and p25-associated nuclear/perinuclear compartments. Reason: The location pattern is consistent with myristoylated p35 at neuronal membranes/projections and p25 relocalization to cytoplasmic, nuclear, and perinuclear regions. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043292 contractile muscle fiber	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep contractile muscle fiber as secondary localization context for p35/p25 or transferred CDK5R-family biology. Reason: These compartments are compatible with specific p35/p25 contexts but are not the defining localization/function of CDK5R1. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt Cell membrane file:human/CDK5R1/CDK5R1-uniprot.txt Cell projection, neuron projection file:human/CDK5R1/CDK5R1-uniprot.txt p35 is present in the peripheries and nerve terminals. file:human/CDK5R1/CDK5R1-uniprot.txt The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions PMID:18507738 myristoylation regulates the membrane association of p39 as well as p35
GO:0043525 positive regulation of neuron apoptotic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Keep positive regulation of neuron apoptotic process as secondary neuronal/CDK5-complex context rather than the core CDK5R1 function. Reason: These terms reflect downstream or pathway-specific consequences of CDK5-p35/p25 signaling; the core GO statement for CDK5R1 is CDK5 activation and complex membership. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0043539 protein serine/threonine kinase activator activity	ISS GO_REF:0000024	MODIFY	Summary: protein serine/threonine kinase activator activity is directionally correct but should be replaced by the CDK5-specific activator term. Reason: The generic kinase-activator parent is less informative than cyclin-dependent protein serine/threonine kinase activator activity for CDK5R1. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0045296 cadherin binding	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: cadherin binding is weakly informative or indirectly transferred for CDK5R1 and should not be treated as a core molecular function. Reason: The core molecular function is CDK5 regulatory-subunit/activator activity; these binding terms are not the best supported informative statements. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md The core molecular function is regulatory-subunit/activator activity toward CDK5, not catalytic kinase activity by CDK5R1 itself. file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0005515 protein binding	IPI PMID:10721722 Cloning of three novel neuronal Cdk5 activator binding prote...	MARK AS OVER ANNOTATED	Summary: Generic protein binding is over-annotated for CDK5R1 and does not capture the informative regulatory-subunit function. Reason: CDK5R1 has many interaction rows, but GO curation should prefer CDK5 activator activity, protein kinase binding, and protein kinase 5 complex membership over generic protein binding. Supporting Evidence: file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0000079 regulation of cyclin-dependent protein serine/threonine kinase activity	TAS PMID:7592934 An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) ...	ACCEPT	Summary: Accept regulation of cyclin-dependent protein serine/threonine kinase activity as a core process-level statement for p35/p25 activation of CDK5. Reason: CDK5R1 binds CDK5 and activates the kinase complex in neurons. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity
GO:0004672 protein kinase activity	TAS PMID:7592934 An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) ...	MODIFY	Summary: protein kinase activity is not appropriate as a catalytic activity for CDK5R1 alone; replace with CDK5 activator activity. Reason: CDK5R1 regulates and activates CDK5 but is not the catalytic kinase subunit that transfers phosphate. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt p35 is a neuron specific activator of CDK5 file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. PMID:8090221 associates physically with Cdk5 in vivo and activates the Cdk5 kinase PMID:10604467 To be activated, Cdk5 has to associate with its regulatory subunit, p35. file:human/CDK5R1/CDK5R1-uniprot.txt Only the heterodimer shows kinase activity file:human/CDK5R1/CDK5R1-notes.md Generic protein binding rows, broad kinase activity rows, and broad peptidyl-serine/threonine phosphorylation rows should be treated cautiously. file:human/CDK5R1/CDK5R1-notes.md CDK5R1 itself is not the catalytic kinase that transfers phosphate.
GO:0007420 brain development	NAS PMID:10915792 Identification of a common protein association region in the...	ACCEPT	Summary: Accept brain development as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth
GO:0045664 regulation of neuron differentiation	NAS PMID:10721722 Cloning of three novel neuronal Cdk5 activator binding prote...	ACCEPT	Summary: Accept regulation of neuron differentiation as part of the neuronal CDK5R1-p35/CDK5 developmental and cytoskeletal function. Reason: CDK5R1 activation of CDK5 is a core neuronal regulatory activity with neurite, cortical-lamination, dendritic-spine, and microtubule-associated consequences. Supporting Evidence: file:human/CDK5R1/CDK5R1-uniprot.txt The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. file:human/CDK5R1/CDK5R1-uniprot.txt Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Reactome:R-HSA-9616110 The complex of CDK5:CDK5R1 is required for neurite outgrowth

📄 View Raw YAML

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

Gene Description

Existing Annotations Review

Core Functions

CDK5R1/p35 and p25 bind CDK5 as regulatory subunits and activate the CDK5 kinase complex in neuronal and stress-associated contexts.

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.

References

Suggested Questions for Experts

Suggested Experiments

📚 Additional Documentation

Notes

CDK5R1 review notes

Description cleanup note

2026-06-20 second-pass audit

Pn Notes

CDK5R1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Specific function in autophagosome maturation and lysosome fusion unknown

Note

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