Cdk5r1 encodes p35, a neuron-enriched regulatory activator of CDK5, and its calpain-generated p25 cleavage product. p35/p25 are not kinases themselves; they bind CDK5 in the protein kinase 5 complex and activate CDK5-dependent phosphorylation programs that control neuronal migration, cortical lamination, axon guidance, cytoskeletal organization, synaptic development, and neuronal survival. Myristoylated p35 is membrane/cytoplasmic, while p25 is more cytosolic and nuclear, explaining the mixed cellular localization annotations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
Cdk5r1/p35 is not an enzyme; its primary molecular function is to activate and spatially target the serine/threonine kinase CDK5 by direct binding.
|
|
GO:0007420
brain development
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005737
cytoplasm
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0007411
axon guidance
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0019901
protein kinase binding
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030426
growth cone
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005634
nucleus
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0016533
protein kinase 5 complex
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0021722
superior olivary nucleus maturation
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0021819
layer formation in cerebral cortex
|
IEA
GO_REF:0000117 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043005
neuron projection
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043204
perikaryon
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0048471
perinuclear region of cytoplasm
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0048511
rhythmic process
|
IEA
GO_REF:0000043 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005515
protein binding
|
IPI
PMID:17341134 Cdk5 is involved in BDNF-stimulated dendritic growth in hipp... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:17341134
Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons.
|
|
GO:0005515
protein binding
|
IPI
PMID:18325333 CDK5 activator p35 downregulates E-cadherin precursor indepe... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:18325333
CDK5 activator p35 downregulates E-cadherin precursor independently of CDK5.
|
|
GO:0005515
protein binding
|
IPI
PMID:24561619 Role of the SIK2-p35-PJA2 complex in pancreatic β-cell funct... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:24561619
Role of the SIK2-p35-PJA2 complex in pancreatic β-cell functional compensation.
|
|
GO:0016533
protein kinase 5 complex
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005654
nucleoplasm
|
IEA
GO_REF:0000107 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0019901
protein kinase binding
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043539
protein serine/threonine kinase activator activity
|
IEA
GO_REF:0000107 |
MODIFY |
Summary: Supported but less specific than the CDK-specific activator term.
Reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this broader serine/threonine kinase activator term with the more specific cyclin-dependent protein serine/threonine kinase activator activity.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
Supporting Evidence:
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
p35 is the obligate regulatory activator of CDK5 and determines where CDK5 acts via myristoylation-dependent membrane targeting.
|
|
GO:0045892
negative regulation of DNA-templated transcription
|
IEA
GO_REF:0000107 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0018105
peptidyl-serine phosphorylation
|
ISO
GO_REF:0000119 |
MODIFY |
Summary: The annotation attributes kinase/phosphorylation activity to the CDK5 activator subunit.
Reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the replacement term better represents the molecular role.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
|
|
GO:0018107
peptidyl-threonine phosphorylation
|
ISO
GO_REF:0000119 |
MODIFY |
Summary: The annotation attributes kinase/phosphorylation activity to the CDK5 activator subunit.
Reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the replacement term better represents the molecular role.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
|
|
GO:0000307
cyclin-dependent protein kinase holoenzyme complex
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005509
calcium ion binding
|
ISO
GO_REF:0000096 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0005634
nucleus
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005654
nucleoplasm
|
ISO
GO_REF:0000119 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005737
cytoplasm
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0007213
G protein-coupled acetylcholine receptor signaling pathway
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0009792
embryo development ending in birth or egg hatching
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0014069
postsynaptic density
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0016020
membrane
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0016301
kinase activity
|
ISO
GO_REF:0000096 |
MODIFY |
Summary: The annotation attributes kinase/phosphorylation activity to the CDK5 activator subunit.
Reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the replacement term better represents the molecular role.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
|
|
GO:0016533
protein kinase 5 complex
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0019901
protein kinase binding
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0019901
protein kinase binding
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030182
neuron differentiation
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0030424
axon
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030425
dendrite
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030426
growth cone
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0031175
neuron projection development
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0031594
neuromuscular junction
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0035235
ionotropic glutamate receptor signaling pathway
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043025
neuronal cell body
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043197
dendritic spine
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043292
contractile muscle fiber
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043525
positive regulation of neuron apoptotic process
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043539
protein serine/threonine kinase activator activity
|
ISO
GO_REF:0000096 |
MODIFY |
Summary: Supported but less specific than the CDK-specific activator term.
Reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this broader serine/threonine kinase activator term with the more specific cyclin-dependent protein serine/threonine kinase activator activity.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
Supporting Evidence:
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
p35 is the obligate regulatory activator of CDK5 and determines where CDK5 acts via myristoylation-dependent membrane targeting.
|
|
GO:0043539
protein serine/threonine kinase activator activity
|
ISO
GO_REF:0000119 |
MODIFY |
Summary: Supported but less specific than the CDK-specific activator term.
Reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this broader serine/threonine kinase activator term with the more specific cyclin-dependent protein serine/threonine kinase activator activity.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
Supporting Evidence:
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
p35 is the obligate regulatory activator of CDK5 and determines where CDK5 acts via myristoylation-dependent membrane targeting.
|
|
GO:0045296
cadherin binding
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0045348
positive regulation of MHC class II biosynthetic process
|
ISO
GO_REF:0000119 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0045892
negative regulation of DNA-templated transcription
|
ISO
GO_REF:0000119 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0046875
ephrin receptor binding
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0048471
perinuclear region of cytoplasm
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
ISO
GO_REF:0000119 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0098693
regulation of synaptic vesicle cycle
|
ISO
GO_REF:0000096 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0098793
presynapse
|
ISO
GO_REF:0000096 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:1903265
positive regulation of tumor necrosis factor-mediated signaling pathway
|
ISO
GO_REF:0000119 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-MMU-9634937 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0070315
G1 to G0 transition involved in cell differentiation
|
IMP
PMID:21566658 A novel RING finger protein, Znf179, modulates cell cycle ex... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:21566658
A novel RING finger protein, Znf179, modulates cell cycle exit and neuronal differentiation of P19 embryonal carcinoma cells.
|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
IMP
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0061575
cyclin-dependent protein serine/threonine kinase activator activity
|
TAS
PMID:12516540 The TGF-beta response to Leishmania chagasi in the absence o... |
REMOVE |
Summary: The cited PMID does not support a Cdk5r1/CDK5 activator annotation.
Reason: PMID:12516540 is a Leishmania/IL-12/TGF-beta study and does not provide evidence for Cdk5r1 acting as a CDK5 activator. The molecular function is supported elsewhere in this review, but this evidence assertion should not be retained.
Supporting Evidence:
PMID:12516540
The TGF-beta response to Leishmania chagasi in the absence of IL-12.
|
|
GO:0009792
embryo development ending in birth or egg hatching
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0003779
actin binding
|
IPI
PMID:19118186 Spatial learning impairment, enhanced CDK5/p35 activity, and... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:19118186
Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
|
|
GO:0002020
protease binding
|
IPI
PMID:19118186 Spatial learning impairment, enhanced CDK5/p35 activity, and... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:19118186
Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
|
|
GO:0019901
protein kinase binding
|
IPI
PMID:19118186 Spatial learning impairment, enhanced CDK5/p35 activity, and... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:19118186
Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
|
|
GO:0035255
ionotropic glutamate receptor binding
|
IPI
PMID:19118186 Spatial learning impairment, enhanced CDK5/p35 activity, and... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:19118186
Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
|
|
GO:0051015
actin filament binding
|
IPI
PMID:19118186 Spatial learning impairment, enhanced CDK5/p35 activity, and... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:19118186
Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
|
|
GO:0042501
serine phosphorylation of STAT protein
|
IDA
PMID:15096606 Cyclin-dependent kinase 5 phosphorylates signal transducer a... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:15096606
Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity.
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-MMU-8868356 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005654
nucleoplasm
|
TAS
Reactome:R-MMU-8868383 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-8863416 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-8868331 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-8868583 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-8868589 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-MMU-8868677 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-NUL-8870566 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-MMU-8863416 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0005515
protein binding
|
IPI
PMID:18054859 Cdk5 promotes synaptogenesis by regulating the subcellular d... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:18054859
Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.
|
|
GO:0090314
positive regulation of protein targeting to membrane
|
IDA
PMID:18054859 Cdk5 promotes synaptogenesis by regulating the subcellular d... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:18054859
Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the MAGUK family member CASK.
|
|
GO:0001764
neuron migration
|
IGI
PMID:11226314 Synergistic contributions of cyclin-dependant kinase 5/p35 a... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:11226314
Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain.
|
|
GO:0001764
neuron migration
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0005515
protein binding
|
IPI
PMID:15096606 Cyclin-dependent kinase 5 phosphorylates signal transducer a... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:15096606
Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity.
|
|
GO:0005515
protein binding
|
IPI
PMID:15489224 Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated r... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:15489224
Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription.
|
|
GO:0005515
protein binding
|
IPI
PMID:17529984 Cyclin-dependent kinase 5 governs learning and synaptic plas... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:17529984
Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation.
|
|
GO:0005515
protein binding
|
IPI
PMID:17591690 Stabilization and activation of p53 induced by Cdk5 contribu... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:17591690
Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death.
|
|
GO:0005634
nucleus
|
IDA
PMID:15096606 Cyclin-dependent kinase 5 phosphorylates signal transducer a... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:15096606
Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of transcription 3 and regulates its transcriptional activity.
|
|
GO:0005634
nucleus
|
IDA
PMID:17591690 Stabilization and activation of p53 induced by Cdk5 contribu... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:17591690
Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death.
|
|
GO:0005737
cytoplasm
|
IDA
PMID:15123626 Cyclin-dependent kinase 5 associated with p39 promotes Munc1... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:15123626
Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis.
|
|
GO:0021549
cerebellum development
|
IMP
PMID:11226314 Synergistic contributions of cyclin-dependant kinase 5/p35 a... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:11226314
Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain.
|
|
GO:0021549
cerebellum development
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0021722
superior olivary nucleus maturation
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0021766
hippocampus development
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0021819
layer formation in cerebral cortex
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
|
|
GO:0045860
positive regulation of protein kinase activity
|
IGI
PMID:11517264 p35 and p39 are essential for cyclin-dependent kinase 5 func... |
MODIFY |
Summary: Supported, but too broad for the specific Cdk5r1 molecular function.
Reason: PMID:11517264 supports p35/p39 requirement for CDK5 function, so the more specific cyclin-dependent protein serine/threonine kinase activator activity term should replace this broad positive regulation of protein kinase activity annotation.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
Supporting Evidence:
PMID:11517264
p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment.
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
p35 is the obligate regulatory activator of CDK5 and determines where CDK5 acts via myristoylation-dependent membrane targeting.
|
|
GO:0005515
protein binding
|
IPI
PMID:17143272 Cdk5 regulates EphA4-mediated dendritic spine retraction thr... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:17143272
Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism.
|
|
GO:0014069
postsynaptic density
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0048013
ephrin receptor signaling pathway
|
IMP
PMID:17143272 Cdk5 regulates EphA4-mediated dendritic spine retraction thr... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:17143272
Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism.
|
|
GO:0061001
regulation of dendritic spine morphogenesis
|
IMP
PMID:17143272 Cdk5 regulates EphA4-mediated dendritic spine retraction thr... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:17143272
Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism.
|
|
GO:0021799
cerebral cortex radially oriented cell migration
|
IMP
PMID:20624590 Dixdc1 is a critical regulator of DISC1 and embryonic cortic... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:20624590
Dixdc1 is a critical regulator of DISC1 and embryonic cortical development.
|
|
GO:0032956
regulation of actin cytoskeleton organization
|
IMP
PMID:20624590 Dixdc1 is a critical regulator of DISC1 and embryonic cortic... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:20624590
Dixdc1 is a critical regulator of DISC1 and embryonic cortical development.
|
|
GO:0070507
regulation of microtubule cytoskeleton organization
|
IMP
PMID:20624590 Dixdc1 is a critical regulator of DISC1 and embryonic cortic... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:20624590
Dixdc1 is a critical regulator of DISC1 and embryonic cortical development.
|
|
GO:0005515
protein binding
|
IPI
PMID:11276227 Cdk5 is involved in neuregulin-induced AChR expression at th... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:11276227
Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular junction.
|
|
GO:0007213
G protein-coupled acetylcholine receptor signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0001764
neuron migration
|
IDA
PMID:9010203 Mice lacking p35, a neuronal specific activator of Cdk5, dis... |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:9010203
Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality.
|
|
GO:0005509
calcium ion binding
|
ISS
GO_REF:0000024 |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
|
|
GO:0005634
nucleus
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005737
cytoplasm
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0007158
neuron cell-cell adhesion
|
IMP
PMID:10753743 Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 k... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:10753743
Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase.
|
|
GO:0007411
axon guidance
|
IMP
PMID:10545161 Callosal axon guidance defects in p35(-/-) mice. |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
Supporting Evidence:
PMID:10545161
Callosal axon guidance defects in p35(-/-) mice.
|
|
GO:0007413
axonal fasciculation
|
IMP
PMID:10545161 Callosal axon guidance defects in p35(-/-) mice. |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:10545161
Callosal axon guidance defects in p35(-/-) mice.
|
|
GO:0007420
brain development
|
IMP
PMID:10545161 Callosal axon guidance defects in p35(-/-) mice. |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:10545161
Callosal axon guidance defects in p35(-/-) mice.
|
|
GO:0016020
membrane
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0016301
kinase activity
|
ISS
GO_REF:0000024 |
MODIFY |
Summary: The annotation attributes kinase/phosphorylation activity to the CDK5 activator subunit.
Reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the replacement term better represents the molecular role.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
|
|
GO:0030182
neuron differentiation
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0030424
axon
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030425
dendrite
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0030426
growth cone
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0031175
neuron projection development
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0031594
neuromuscular junction
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0035235
ionotropic glutamate receptor signaling pathway
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043025
neuronal cell body
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043197
dendritic spine
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Supported core p35/p25-CDK5 regulatory function or neuronal localization/process.
Reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal migration, axon guidance, cytoskeletal organization, or synaptic development.
|
|
GO:0043292
contractile muscle fiber
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043525
positive regulation of neuron apoptotic process
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0043539
protein serine/threonine kinase activator activity
|
ISS
GO_REF:0000024 |
MODIFY |
Summary: Supported but less specific than the CDK-specific activator term.
Reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this broader serine/threonine kinase activator term with the more specific cyclin-dependent protein serine/threonine kinase activator activity.
Proposed replacements:
cyclin-dependent protein serine/threonine kinase activator activity
Supporting Evidence:
file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
p35 is the obligate regulatory activator of CDK5 and determines where CDK5 acts via myristoylation-dependent membrane targeting.
|
|
GO:0045296
cadherin binding
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
|
|
GO:0005515
protein binding
|
IPI
PMID:12496365 CDK5 regulates cell adhesion and migration in corneal epithe... |
MARK AS OVER ANNOTATED |
Summary: The annotation is too broad, indirect, or poorly supported as a direct Cdk5r1 function.
Reason: This term should not be used as a primary functional annotation for p35/p25 because it either describes vague binding or an indirect pathway consequence.
Supporting Evidence:
PMID:12496365
CDK5 regulates cell adhesion and migration in corneal epithelial cells.
|
|
GO:0008092
cytoskeletal protein binding
|
TAS
PMID:12496365 CDK5 regulates cell adhesion and migration in corneal epithe... |
KEEP AS NON CORE |
Summary: Supported but downstream or context-specific Cdk5r1 biology.
Reason: The annotation is compatible with p35/p25-CDK5 biology but describes a developmental, synaptic, binding, or localization consequence rather than the primary CDK5 activation role.
Supporting Evidence:
PMID:12496365
CDK5 regulates cell adhesion and migration in corneal epithelial cells.
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template_file: templates/gene_research_go_focused.md
template_variables:
organism: mouse
gene_id: Cdk5r1
gene_symbol: Cdk5r1
uniprot_accession: P61809
protein_description: 'RecName: Full=Cyclin-dependent kinase 5 activator 1; Short=CDK5
activator 1; AltName: Full=Cyclin-dependent kinase 5 regulatory subunit 1; AltName:
Full=TPKII regulatory subunit; Contains: RecName: Full=Cyclin-dependent kinase
5 activator 1, p35; Short=p35; Contains: RecName: Full=Cyclin-dependent kinase
5 activator 1, p25; Short=p25; AltName: Full=Tau protein kinase II 23 kDa subunit;
Short=p23; Flags: Precursor;'
gene_info: Name=Cdk5r1; Synonyms=Cdk5r, Nck5a;
organism_full: Mus musculus (Mouse).
protein_family: Belongs to the cyclin-dependent kinase 5 activator family.
protein_domains: CDK5_activator. (IPR004944); Cyclin-like_sf. (IPR036915); CDK5_activator
(PF03261)
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citation_count: 34
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Cdk5r1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Cdk5r1 (gene ID: Cdk5r1, UniProt: P61809) in mouse.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Question: You are an expert researcher providing comprehensive, well-cited information.
Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies
Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.
BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.
DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'Cdk5r1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information
Please provide a comprehensive research report on the gene Cdk5r1 (gene ID: Cdk5r1, UniProt: P61809) in mouse.
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Mouse Cdk5r1 encodes p35, the neuron-enriched, non-cyclin regulatory subunit that is obligatory for activation and spatial targeting of cyclin-dependent kinase 5 (CDK5) in the nervous system. p35 is N-terminally myristoylated, concentrating active CDK5 at membranes, growth cones, and synapses to support neuronal development and synaptic function. Under cellular stress, calpain cleaves p35 to p25, removing the N-terminal membrane-targeting element and producing a longer-lived activator that can mislocalize CDK5 activity to cytoplasmic/nuclear compartments, a mechanism widely implicated in neurodegeneration (pao2021threedecadesof pages 3-4, pao2021threedecadesof pages 1-3, nikhil2023cdk5anoncogene pages 1-2).
The gene symbol Cdk5r1 in mouse is consistently used in the literature to denote CDK5 regulatory subunit 1 (p35), including its proteolytic products p25/p10, matching the UniProt P61809 entry description and processing (p35/p25) context (pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4). p35 is repeatedly described as the principal neuronal activator of CDK5 and as a membrane-associated targeting subunit through N-terminal myristoylation (pao2021threedecadesof pages 1-3, pao2021threedecadesof pages 3-4).
CDK5 is a proline-directed serine/threonine kinase that—unlike classical cell-cycle CDKs—achieves functional activity in neurons primarily via binding to non-cyclin activators p35 (Cdk5r1) or p39 (Cdk5r2). p35 is described as an obligate regulatory subunit: CDK5 is functionally activated by direct binding to p35 in brain/neuronal contexts (pao2021threedecadesof pages 1-3, pao2021threedecadesof pages 3-4). CDK5 activity is highest in the nervous system largely because p35/p39 expression is enriched in post-mitotic neurons (pao2021threedecadesof pages 1-3, wong2023improvingnkand pages 28-33).
A central concept for functional annotation is that p35 can be cleaved by calpain into p25 (C-terminal CDK5-activating fragment) and p10 (N-terminal fragment). This cleavage removes the N-terminal membrane targeting module (p10), generating p25 that retains CDK5 activation capacity but is more stable, often causing dysregulated signaling (lunghi2015theroleof pages 38-43, nikhil2023cdk5anoncogene pages 1-2). Quantitatively, p25/p29 are reported to have ~5–10-fold longer half-lives than p35/p39 in summarized mechanistic literature (lunghi2015theroleof pages 38-43).
p35 contains an N-terminal myristoylation signal (notably a conserved Gly2) that targets p35 and bound CDK5 to membrane-associated compartments. Subcellular fractionation and mechanistic summaries support enrichment of p35 in membrane fractions and dependence on myristoylation for membrane targeting (pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4). Cleavage to p25 removes this N-terminus and is described to favor cytoplasmic and nuclear mislocalization of CDK5 activity in pathological contexts (nikhil2023cdk5anoncogene pages 1-2).
p35 is described as labile and under tight negative-feedback control: autophosphorylation and ubiquitin–proteasome turnover contribute to rapid degradation (wong2023improvingnkand pages 28-33, lunghi2015theroleof pages 38-43). Reported p35 half-life values include 20–30 minutes (one source) and 30–60 minutes (a 2023 review), emphasizing rapid turnover relative to p25 (wong2023improvingnkand pages 28-33, nikhil2023cdk5anoncogene pages 2-3). CDK5-dependent phosphorylation of p35 at S8 is reported to promote release from the membrane to the cytoplasm, changing spatial substrate access (nikhil2023cdk5anoncogene pages 1-2). Additionally, CDK5 activity can suppress calpain-dependent cleavage of p35 (regulatory feedback on p25 generation) (takada2015effectsofp35 pages 4-7).
Cdk5r1/p35 is not an enzyme; its primary molecular function is to activate and spatially target the serine/threonine kinase CDK5 by direct binding, thereby determining CDK5’s neuronal activity and substrate access (pao2021threedecadesof pages 3-4, pao2021threedecadesof pages 1-3).
Cdk5/p35 is repeatedly implicated in:
- Neurite outgrowth and axon formation, with p35/Cdk5 present in soma, neuronal processes, and growth cones, including lamella/filopodia regions consistent with cytoskeletal remodeling roles (kwon2000theroleof pages 1-4, pao2021threedecadesof pages 3-4).
- Neuronal migration and cortical lamination, with genetic disruptions causing lamination defects; mechanistic summaries list cytoskeletal substrates (FAK Ser732, DCX Ser297) and adhesion signaling (N-cadherin complex; RapGEF2) as downstream nodes (wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 1-3).
- Synaptic vesicle cycling/endocytosis and neurotransmission, with CDK5/p35 regulating presynaptic proteins (e.g., synapsin I, MUNC18, amphiphysin, synaptojanin 1, dynamin/dephosphins) (wang2007cellcycleregulation pages 40-45, lunghi2015theroleof pages 38-43).
- Synaptic plasticity, learning and memory, particularly via postsynaptic mechanisms impacting LTD and dendritic spine stability (mishiba2014cdk5p35functionsas pages 2-4, takahashi2022involvementofcdk5 pages 4-8).
A pathway/substrate-centered summary is provided in the artifact below.
| Process/pathway | Representative substrates or nodes regulated by Cdk5/p35 | Functional consequence | Main subcellular compartment | Supporting citation IDs |
|---|---|---|---|---|
| Neuronal migration and cortical lamination | FAK Ser732, DCX Ser297, RapGEF2 S1124, N-cadherin adhesion complex | Coordinates centrosome/microtubule dynamics, neuronal positioning, adhesion signaling, and proper cortical layering during development | Migrating neurons, leading process, membrane-associated cytoskeletal compartments | (wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 1-3, lunghi2015theroleof pages 38-43) |
| Neurite outgrowth and axon formation | Actin-associated growth cone machinery; Rac/Pak-related signaling; p35/Cdk5 complex itself targeted by myristoylated p35 | Promotes neurite extension, axon elongation, and growth-cone dynamics; loss/inactivation inhibits outgrowth | Growth cones, lamella/filopodia, soma and neurites, membrane/cytosol | (pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4, pao2021threedecadesof pages 13-14) |
| Dendrite morphogenesis and neuronal architecture | Cytoskeletal regulators including tau; broader dendritic-development signaling downstream of p35/Cdk5 | Shapes axonal/dendritic trajectories and dendritic structure needed for circuit assembly | Developing neurites and dendrites | (pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4) |
| Synaptic vesicle cycling and endocytosis | Dynamin, synapsin I, MUNC18, amphiphysin, synaptojanin 1, dephosphins | Regulates neurotransmitter release and synaptic vesicle endocytosis/recycling | Presynaptic terminal, synaptic membrane | (wang2007cellcycleregulation pages 40-45, lunghi2015theroleof pages 38-43) |
| Postsynaptic signaling and synaptic plasticity | NMDA receptor subunits (including NR2A), PSD-95, DARPP-32 Thr75 | Tunes synaptic strength and plasticity; supports hippocampal learning/memory and LTD regulation | Postsynaptic density, synaptic membrane, dendritic spine | (wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 3-4, mishiba2014cdk5p35functionsas pages 7-9, mishiba2014cdk5p35functionsas pages 2-4, takahashi2022involvementofcdk5 pages 4-8) |
| Hippocampal LTD and memory retention | NMDAR-dependent LTD pathway; GluR1 Ser831; CaMKII Thr286 / Thr305 states altered in p35 cKO hippocampus | p35 is required for normal NMDAR-dependent LTD and spatial/associative memory; adult p35 loss reduces postsynaptic responsiveness and spine density while sparing LTP in some paradigms | CA1 postsynaptic compartment, dendritic spines | (mishiba2014cdk5p35functionsas pages 7-9, mishiba2014cdk5p35functionsas pages 4-6, mishiba2014cdk5p35functionsas pages 2-4, takahashi2022involvementofcdk5 pages 1-2, takahashi2022involvementofcdk5 pages 4-8) |
| Cytoskeletal remodeling and microtubule regulation | Tau; nestin degradation pathway; FAK/DCX axis | Couples kinase activity to cytoskeletal organization, differentiation, and structural stability in neurons | Cytosol, neurites, growth cone | (wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 7-9) |
| Membrane-targeted physiological CDK5 signaling | Myristoylated p35/p39, membrane-localized Cdk5 complexes; p35 S8 phosphorylation controls membrane release | N-terminal myristoylation targets active Cdk5 to membranes for physiological signaling; release from membrane alters substrate access | Plasma membrane/peripheral membrane, then cytoplasm upon release | (nikhil2023cdk5anoncogene pages 1-2, kwon2000theroleof pages 1-4, pao2021threedecadesof pages 3-4) |
| Pathological p25-driven mislocalized signaling | p25 (calpain-cleaved p35 lacking myristoylated p10), tau phosphorylation sites including T181, S202, T205, T212, T217, S235, S396, S404 | Produces longer-lived, mislocalized CDK5 activity in cytoplasm/nucleus, driving aberrant substrate phosphorylation, tauopathy, synaptic dysfunction, and neurotoxicity | Cytoplasm and nucleus rather than membrane-restricted compartments | (nikhil2023cdk5anoncogene pages 1-2, pao2021threedecadesof pages 7-9) |
Table: This table summarizes the major neuronal biological processes regulated by CDK5 when activated by mouse Cdk5r1/p35, along with representative downstream substrates or signaling nodes, functional consequences, and subcellular context. It is useful for functional annotation because it links p35-dependent CDK5 activity to specific developmental and synaptic roles supported by the cited evidence.
Under physiological conditions, p35’s N-terminal myristoylation drives membrane association and supports localization of active CDK5 at membranes, growth cones, and synapses—consistent with roles in adhesion, cytoskeletal dynamics, and synaptic signaling (pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4). Under neurotoxic conditions, calpain cleavage to p25 removes the N-terminal targeting element; reviews describe consequent redistribution of CDK5 activity into cytoplasmic and nuclear compartments with neurotoxic substrate hyperphosphorylation (nikhil2023cdk5anoncogene pages 1-2).
The following schematic (Figure 2 in a highly cited review) visually summarizes this physiological vs pathological axis:
(pao2021threedecadesof media 8c184d3c)
A tamoxifen-inducible adult p35 conditional knockout (CreER-p35 cKO) study provides direct quantitative evidence that p35 is required for NMDAR-dependent synaptic depression and memory:
- CA1 LTD after low-frequency stimulation: 82.1 ± 2.3% (control) vs 98.2 ± 2.3% (p35 cKO), p = 0.0003, indicating loss of LTD expression (mishiba2014cdk5p35functionsas pages 2-4).
- Behavioral deficits in Morris water maze learning (mixed ANOVA p = 0.027) and probe performance (e.g., fewer platform crossings p = 0.034) with preserved swim speed/distance, supporting a cognitive-specific phenotype (mishiba2014cdk5p35functionsas pages 4-6, mishiba2014cdk5p35functionsas pages 2-4).
These data provide strong support for functional annotation of Cdk5r1 in adult synaptic plasticity and spatial learning.
Conditional deletion in excitatory (CamKII-Cre) CA1 neurons impairs NMDAR-dependent LTD and contextual fear memory retention, while inhibitory-neuron deletion (Dlx-Cre) shows minimal phenotypes in the tested paradigms, indicating a key postsynaptic requirement of p35 in excitatory CA1 neurons (takahashi2022involvementofcdk5 pages 4-8, takahashi2022involvementofcdk5 pages 1-2).
p35 is reported to be short-lived (20–30 minutes or 30–60 minutes depending on source), supporting a model where p35 provides tightly regulated activation in physiological conditions (wong2023improvingnkand pages 28-33, nikhil2023cdk5anoncogene pages 2-3). In contrast, p25 has a substantially extended lifetime (reported 5–10× increase) and is linked to sustained CDK5 activation (lunghi2015theroleof pages 38-43).
A compact quantitative/statistical summary is included here:
| Feature | Summary for mouse Cdk5r1 (UniProt P61809) | Key quantitative metrics | Year / URL | Supporting citations |
|---|---|---|---|---|
| Gene / protein identity | Cdk5r1 encodes p35, the neuron-enriched regulatory/activator subunit of CDK5; common synonyms include Cdk5r, Nck5a, CDK5R1, and the cleavage product p25. p35 is the obligate non-cyclin activator that gives CDK5 its major neuronal activity. | p35 is a 307 aa protein in the human ortholog literature often used to define conserved architecture; mouse studies consistently use p35 as the principal neuronal CDK5 activator. | 2021, https://doi.org/10.1186/s12929-021-00774-y ; 2000, https://doi.org/10.1007/978-3-540-48002-0_10 | (pao2021threedecadesof pages 3-4, pao2021threedecadesof pages 1-3, kwon2000theroleof pages 1-4) |
| Protein processing | Full-length p35 is proteolytically cleaved by calpain to generate p25 (C-terminal CDK5-activating fragment) and p10 (N-terminal fragment containing the membrane-targeting motif). p25 remains able to activate CDK5 but is more stable and pathogenic when accumulated. | p25/p29 reported to have 5–10-fold longer half-life than p35/p39; ionomycin assay in cells converted about 20% of p35 to p25 in one study. | 2015, https://doi.org/10.1371/journal.pone.0140821 ; 2023, https://doi.org/10.1186/s12943-023-01895-8 | (lunghi2015theroleof pages 38-43, nikhil2023cdk5anoncogene pages 2-3, takada2015effectsofp35 pages 4-7) |
| CDK5 activation mechanism | CDK5 is largely inactive as a monomer and is activated by direct binding to p35 (or p39). p35 binding forms the active serine/threonine kinase complex; p25 can also activate CDK5, often causing more constitutive and mislocalized activity. | p35 half-life reported as 20–30 min in one source and 30–60 min in another review; mutation of certain p35 phosphosites increased stability by about 3-fold. | 2021, https://doi.org/10.1186/s12929-021-00774-y ; 2023, https://doi.org/10.1186/s12943-023-01895-8 | (pao2021threedecadesof pages 3-4, wong2023improvingnkand pages 28-33, nikhil2023cdk5anoncogene pages 2-3) |
| Localization determinants | p35 contains an N-terminal myristoylation signal (notably at Gly2) that targets p35 and associated CDK5 to membranes/peripheral neuronal compartments. Cleavage to p25 removes this N-terminal targeting module, favoring redistribution to cytoplasm and nucleus. | Membrane association depends on the N-terminus; p35 is predominantly membrane-associated, whereas CDK5 is found in both membrane and cytosolic fractions. | 2021, https://doi.org/10.1186/s12929-021-00774-y ; 2000, https://doi.org/10.1007/978-3-540-48002-0_10 ; 2023, https://doi.org/10.1186/s12943-023-01895-8 | (nikhil2023cdk5anoncogene pages 1-2, kwon2000theroleof pages 1-4, wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 3-4) |
| Primary neuronal functions | The Cdk5/p35 complex regulates neuronal migration, cortical lamination, neurite outgrowth, axon/dendrite development, growth cone dynamics, synaptic vesicle cycling, and synaptic plasticity/learning and memory. | Cdk5-null mice die around birth with major layering defects; p35/p39 double knockout phenocopies severe CDK5 loss. | 2021, https://doi.org/10.1186/s12929-021-00774-y ; 2001, https://doi.org/10.1523/JNEUROSCI.21-17-06758.2001 ; 2000, https://doi.org/10.1007/978-3-540-48002-0_10 | (wang2007cellcycleregulation pages 40-45, pao2021threedecadesof pages 3-4, kwon2000theroleof pages 1-4) |
| Synaptic plasticity role in adult mouse | Adult or excitatory-neuron-selective p35 loss impairs hippocampal NMDAR-dependent LTD and memory retention, while LTP is often preserved. This supports a specific postsynaptic role for p35 in tuning synaptic depression and memory encoding. | In inducible adult p35 cKO, LTD after low-frequency stimulation was 82.1 ± 2.3% in controls vs 98.2 ± 2.3% in p35 cKO (p = 0.0003); Morris water maze learning curve deficit p = 0.027; target-quadrant probe preference in controls p = 0.0054; fewer platform crossings p = 0.034. | 2014, https://doi.org/10.1186/s13041-014-0082-x ; 2022, https://doi.org/10.1186/s13041-022-00922-x | (mishiba2014cdk5p35functionsas pages 4-6, mishiba2014cdk5p35functionsas pages 2-4, takahashi2022involvementofcdk5 pages 1-2, takahashi2022involvementofcdk5 pages 4-8) |
| Pathological p25/CDK5 axis | Under neurotoxic conditions (Aβ, excitotoxicity, oxidative stress, Ca2+ dysregulation), calpain cleavage to p25 causes hyperactive, mislocalized CDK5, linked to tau hyperphosphorylation, aberrant substrate phosphorylation, neuronal cell-cycle re-entry, synaptic dysfunction, and neurodegeneration. | Human AD-related literature summarized in reviews reports 20–40-fold higher p25 in AD brains in one source; ~3.7% of neurons in human AD brains showed S-phase activity in one cited review summary. | 2024, https://doi.org/10.3390/ijms25179626 ; 2024, https://doi.org/10.1186/s40035-024-00427-8 ; 2021, https://doi.org/10.1186/s12929-021-00774-y | (wu2024proteinkinasecdelta pages 1-2, pao2021threedecadesof pages 7-9, li2024neuronaldoublestrandeddna pages 7-9) |
| Recent 2023–2024 developments | Recent work links altered p35/p25-CDK5 signaling to Parkinson disease, AD/tauopathy, and DNA damage/inflammatory pathways. A 2024 study showed DNase II deficiency increased p25/p35 ratio, Calpain2, CDK5 activity, and tau phosphorylation; 2024 reviews emphasize therapeutic targeting of the calpain–p35/p25–CDK5 axis. | DNase II study used n=10/group for AAV-shDNase2a in vivo and n=8/group for AAV-DNase2a rescue; roscovitine at 2.5 μM suppressed tau phosphorylation in deficient neurons. | 2024, https://doi.org/10.1186/s40035-024-00427-8 ; 2024, https://doi.org/10.1111/jcmm.18412 ; 2024, https://doi.org/10.4103/1673-5374.389645 | (li2024neuronaldoublestrandeddna pages 7-9, li2024neuronaldoublestrandeddna pages 3-4, alrouji2024cyclin‐dependentkinase5 pages 1-2, viorel2024p38mapkandcdk5 pages 2-2) |
| Therapeutic / application relevance | Current implementations include genetic blockade of p25 generation (Δp35KI), CDK5 inhibitors such as roscovitine, calpain inhibition, and peptide approaches that preferentially block pathological CDK5/p25. Repurposed agents discussed in 2024 reviews include statins, metformin, fenofibrate, rosiglitazone/pioglitazone. | Mostly preclinical evidence; no established clinical CDK5R1-targeted therapy. | 2024, https://doi.org/10.1111/jcmm.18412 ; 2021, https://doi.org/10.1186/s12929-021-00774-y | (pao2021threedecadesof pages 7-9, alrouji2024cyclin‐dependentkinase5 pages 1-2, alrouji2024cyclin‐dependentkinase5 pages 5-6, pao2021threedecadesof pages 10-11) |
Table: This table summarizes the core functional annotation of mouse Cdk5r1/p35, including its identity, proteolytic processing to p25, mechanism of CDK5 activation, localization, neuronal roles, and quantitative findings from mouse studies. It is useful as a compact evidence map linking foundational and recent literature to specific annotation claims.
A 2023 Molecular Cancer review synthesizes evidence that CDK5 biological output is strongly determined by subcellular localization and by whether CDK5 is activated by p35 (physiological) versus p25 (often pathological). It emphasizes that calpain cleavage (loss of N-terminal myristoylated p10) yields stable p25 and mislocalized CDK5 activity to cytoplasm/nucleus, driving neurotoxicity through aberrant phosphorylation patterns (nikhil2023cdk5anoncogene pages 1-2). The review also reports p35 half-life 30–60 min, consistent with rapid turnover compared with p25 (nikhil2023cdk5anoncogene pages 2-3).
A 2024 primary study in differentiated cortical neurons reports a mechanistic cascade where Aβ induces STAT3-dependent PKCδ and triggers calpain2-dependent conversion of p35 to p25, causing CDK5 overactivation and downstream cell-cycle reentry and apoptosis markers (cyclin D1, PCNA, p-Histone H3; caspase-3 cleavage; PUMA induction) (wu2024proteinkinasecdelta pages 1-2). Although performed in rat neurons, the pathway directly concerns p35 processing and provides a recent, experimentally defined upstream regulatory mechanism.
A 2024 Translational Neurodegeneration study identifies neuronal DNase II deficiency (and cytoplasmic dsDNA accumulation) as a driver of tauopathy-like mechanisms via kinase/phosphatase imbalance, including increased CDK5 levels and CDK5 activity inferred by elevated p25/p35 ratio, alongside increased Calpain2 and tau phosphorylation (Ser202/Thr205, Thr231). The study used AAV-based neuronal knockdown/overexpression and reports that CDK5 inhibition with roscovitine (2.5 μM, 24 h) significantly inhibited tau phosphorylation in DNase II-deficient neurons (li2024neuronaldoublestrandeddna pages 7-9, li2024neuronaldoublestrandeddna pages 3-4).
A curated summary of these 2023–2024 sources is provided here:
| Study | Type | System/model | Key finding related to Cdk5r1/p35/p25 | Quantitative/statistical highlights | URL |
|---|---|---|---|---|---|
| Nikhil, 2023 | Review | Broad mechanistic review; neuronal and cancer contexts | Summarizes that p35/CDK5R1 is a membrane-associated CDK5 activator; calpain cleavage removes the N-terminal myristoylated p10 to generate more stable p25, which mislocalizes CDK5 activity to cytoplasm/nucleus and promotes constitutive hyperphosphorylation and neurotoxicity. Also notes p35 S8 phosphorylation can release p35 from membrane to cytoplasm. (nikhil2023cdk5anoncogene pages 1-2, nikhil2023cdk5anoncogene pages 2-3) | p35 half-life reported as 30–60 min; p25/p29 described as having much longer half-lives than p35/p39. No direct p-values reported in the cited excerpt. (nikhil2023cdk5anoncogene pages 2-3) | https://doi.org/10.1186/s12943-023-01895-8 |
| Wu, 2024 | Primary | Fully differentiated primary rat cortical neurons exposed to Aβ25-35 or Aβ1-42 | Defines a recent upstream mechanism for pathological p35 processing: STAT3 → PKCδ → calpain2 → p35 cleavage to p25 → CDK5 overactivation, leading to neuronal cell-cycle re-entry and apoptosis in post-mitotic neurons. (wu2024proteinkinasecdelta pages 1-2) | Cell-cycle re-entry monitored with cyclin D1, PCNA, p-Histone H3; no numerical effect sizes or p-values are given in the provided excerpt. (wu2024proteinkinasecdelta pages 1-2) | https://doi.org/10.3390/ijms25179626 |
| Li, 2024 | Primary | Mouse primary hippocampal neurons; WT and Tau-P301S mice; human AD/MCI plasma and transcriptomic datasets | Shows that neuronal DNase II deficiency increases Calpain2, elevates the p25/p35 ratio, increases CDK5 activity, and enhances tau phosphorylation, linking altered p35 processing to neurodegeneration and cognitive decline. Rescue experiments support pathway reversibility. (li2024neuronaldoublestrandeddna pages 7-9, li2024neuronaldoublestrandeddna pages 1-3) | In vivo design included n=10/group for AAV-shDnase2a and n=8/group for AAV-Dnase2a rescue; human plasma groups n=13–15; GEO analysis included 8 controls, 20 EOAD, 19 LOAD. Roscovitine 2.5 μM for 24 h significantly inhibited tau phosphorylation in DNase II-deficient neurons. Specific p-values not provided in the excerpt. (li2024neuronaldoublestrandeddna pages 7-9, li2024neuronaldoublestrandeddna pages 3-4) | https://doi.org/10.1186/s40035-024-00427-8 |
| Alrouji, 2024 | Review | Parkinson disease-focused review integrating neuronal and preclinical model evidence | Reviews therapeutic targeting of the calpain–p35/p25–CDK5 axis in neurodegeneration. Emphasizes that stress-induced cleavage of p35 to the more stable p25 drives hyperactive CDK5, tau/neurofilament hyperphosphorylation, and neuronal death; discusses repurposed inhibitors and pathway modulation. (alrouji2024cyclin‐dependentkinase5 pages 1-2, alrouji2024cyclin‐dependentkinase5 pages 5-6, alrouji2024cyclin‐dependentkinase5 pages 2-4) | Names candidate/repurposed agents including statins, metformin, fenofibrate, rosiglitazone/pioglitazone, but the cited excerpts provide no study-level p-values or effect sizes. (alrouji2024cyclin‐dependentkinase5 pages 1-2, alrouji2024cyclin‐dependentkinase5 pages 5-6) | https://doi.org/10.1111/jcmm.18412 |
| Viorel, 2024 | Review | Alzheimer disease/neuroinflammation perspective | Highlights the calpain–CDK5–p38α axis as a therapeutic target in AD, arguing that blocking upstream calpain activity or pathological p25 generation could reduce glial-driven neuroinflammation and downstream degeneration. Mentions peptide- and roscovitine-based CDK5-targeting strategies with preclinical support. (viorel2024p38mapkandcdk5 pages 2-2) | No direct numerical effect sizes or p-values reported in the provided excerpt. (viorel2024p38mapkandcdk5 pages 2-2) | https://doi.org/10.4103/1673-5374.389645 |
Table: This table summarizes recent 2023–2024 studies and reviews most relevant to mouse Cdk5r1/p35/p25 biology and the broader CDK5 axis. It highlights new mechanisms, disease links, and therapeutic implications, while preserving only quantitative details explicitly supported by the cited evidence.
A 2024 PD-focused review discusses repurposed agents with putative activity on CDK5/calpain signaling (e.g., statins, metformin, fenofibrate, rosiglitazone/pioglitazone) as preclinical strategies to attenuate neurodegenerative progression, while emphasizing the lack of proven clinical efficacy and the challenge of inhibitor specificity (alrouji2024cyclin‐dependentkinase5 pages 5-6, alrouji2024cyclin‐dependentkinase5 pages 1-2).
A recurrent expert-level theme is that the CDK5 system acts as a spatiotemporal rheostat, where p35 provides localized, tightly regulated activation, while p25 can convert the kinase into a longer-lived, mislocalized activity state with altered substrate access and toxicity. This “localization/activity-state” view is central in both the highly cited Cdk5 field review (Pao & Tsai, 2021) and a 2023 synthesis emphasizing location-dependent CDK5 phenotypes (pao2021threedecadesof pages 7-9, nikhil2023cdk5anoncogene pages 1-2). These sources further emphasize that therapeutic targeting should ideally be complex-selective (e.g., preferentially targeting CDK5/p25 rather than globally inhibiting CDKs) (pao2021threedecadesof pages 10-11).
Several 2023–2024 sources retrieved here (especially reviews) provide strong mechanistic synthesis but limited numeric effect sizes for p25 abundance, localization fractionation, or cytokine changes. The most precise quantitative mouse functional data obtained in this run are from inducible p35 deletion impacting LTD and behavior (mishiba2014cdk5p35functionsas pages 2-4) and from reported turnover statistics for p35 and relative stability of p25 (nikhil2023cdk5anoncogene pages 2-3, lunghi2015theroleof pages 38-43). For deeper quantitative biomarker statistics (e.g., absolute p25 concentrations, brain-region fold changes) additional targeted full-text extraction from the primary studies cited within these reviews would be required.
References
(pao2021threedecadesof pages 3-4): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(pao2021threedecadesof pages 1-3): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(nikhil2023cdk5anoncogene pages 1-2): Kumar Nikhil and Kavita Shah. Cdk5: an oncogene or an anti-oncogene: location location location. Molecular Cancer, Nov 2023. URL: https://doi.org/10.1186/s12943-023-01895-8, doi:10.1186/s12943-023-01895-8. This article has 18 citations and is from a highest quality peer-reviewed journal.
(kwon2000theroleof pages 1-4): Young T. Kwon and Li-Huei Tsai. The role of the p35/cdk5 kinase in cortical development. Results and problems in cell differentiation, 30:241-53, Jan 2000. URL: https://doi.org/10.1007/978-3-540-48002-0_10, doi:10.1007/978-3-540-48002-0_10. This article has 40 citations.
(wong2023improvingnkand pages 28-33): DP Wong. Improving nk and t cell immunotherapies for hematologic malignancies. Unknown journal, 2023.
(lunghi2015theroleof pages 38-43): M Lunghi. The role of mir-15/107 family in p35/cdk5 regulation in alzheimer's disease. Unknown journal, 2015.
(nikhil2023cdk5anoncogene pages 2-3): Kumar Nikhil and Kavita Shah. Cdk5: an oncogene or an anti-oncogene: location location location. Molecular Cancer, Nov 2023. URL: https://doi.org/10.1186/s12943-023-01895-8, doi:10.1186/s12943-023-01895-8. This article has 18 citations and is from a highest quality peer-reviewed journal.
(takada2015effectsofp35 pages 4-7): Shunsuke Takada, Keiko Mizuno, Taro Saito, Akiko Asada, Karl Peter Giese, and Shin-ichi Hisanaga. Effects of p35 mutations associated with mental retardation on the cellular function of p35-cdk5. PLoS ONE, 10:e0140821, Oct 2015. URL: https://doi.org/10.1371/journal.pone.0140821, doi:10.1371/journal.pone.0140821. This article has 3 citations and is from a peer-reviewed journal.
(wang2007cellcycleregulation pages 40-45): L Wang. Cell cycle regulation in the post-mitotic neuronal cells. Unknown journal, 2007.
(mishiba2014cdk5p35functionsas pages 2-4): Tomohide Mishiba, Mika Tanaka, Naoki Mita, Xiaojuan He, Kodai Sasamoto, Shigeyoshi Itohara, and Toshio Ohshima. Cdk5/p35 functions as a crucial regulator of spatial learning and memory. Molecular Brain, Nov 2014. URL: https://doi.org/10.1186/s13041-014-0082-x, doi:10.1186/s13041-014-0082-x. This article has 49 citations and is from a peer-reviewed journal.
(takahashi2022involvementofcdk5 pages 4-8): Miyuki Takahashi, Takeru Nakabayashi, Naoki Mita, Xiaohua Jin, Yuta Aikawa, Kodai Sasamoto, Goichi Miyoshi, Mariko Miyata, Takafumi Inoue, and Toshio Ohshima. Involvement of cdk5 activating subunit p35 in synaptic plasticity in excitatory and inhibitory neurons. Molecular Brain, Apr 2022. URL: https://doi.org/10.1186/s13041-022-00922-x, doi:10.1186/s13041-022-00922-x. This article has 14 citations and is from a peer-reviewed journal.
(pao2021threedecadesof pages 13-14): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(mishiba2014cdk5p35functionsas pages 7-9): Tomohide Mishiba, Mika Tanaka, Naoki Mita, Xiaojuan He, Kodai Sasamoto, Shigeyoshi Itohara, and Toshio Ohshima. Cdk5/p35 functions as a crucial regulator of spatial learning and memory. Molecular Brain, Nov 2014. URL: https://doi.org/10.1186/s13041-014-0082-x, doi:10.1186/s13041-014-0082-x. This article has 49 citations and is from a peer-reviewed journal.
(mishiba2014cdk5p35functionsas pages 4-6): Tomohide Mishiba, Mika Tanaka, Naoki Mita, Xiaojuan He, Kodai Sasamoto, Shigeyoshi Itohara, and Toshio Ohshima. Cdk5/p35 functions as a crucial regulator of spatial learning and memory. Molecular Brain, Nov 2014. URL: https://doi.org/10.1186/s13041-014-0082-x, doi:10.1186/s13041-014-0082-x. This article has 49 citations and is from a peer-reviewed journal.
(takahashi2022involvementofcdk5 pages 1-2): Miyuki Takahashi, Takeru Nakabayashi, Naoki Mita, Xiaohua Jin, Yuta Aikawa, Kodai Sasamoto, Goichi Miyoshi, Mariko Miyata, Takafumi Inoue, and Toshio Ohshima. Involvement of cdk5 activating subunit p35 in synaptic plasticity in excitatory and inhibitory neurons. Molecular Brain, Apr 2022. URL: https://doi.org/10.1186/s13041-022-00922-x, doi:10.1186/s13041-022-00922-x. This article has 14 citations and is from a peer-reviewed journal.
(pao2021threedecadesof pages 7-9): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(pao2021threedecadesof media 8c184d3c): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(wu2024proteinkinasecdelta pages 1-2): Ming-Hsuan Wu, A-Ching Chao, Yi-Heng Hsieh, You Lien, Yi-Chun Lin, and Ding-I Yang. Protein kinase c-delta mediates cell cycle reentry and apoptosis induced by amyloid-beta peptide in post-mitotic cortical neurons. International Journal of Molecular Sciences, 25:9626, Sep 2024. URL: https://doi.org/10.3390/ijms25179626, doi:10.3390/ijms25179626. This article has 2 citations.
(li2024neuronaldoublestrandeddna pages 7-9): Ling-jie Li, Xiao-ying Sun, Ya-ru Huang, Shuai Lu, Yu-Ming Xu, Jing Yang, Xi-xiu Xie, Jie Zhu, Xiao-yun Niu, Dan-yang Wang, Shi-yu Liang, Xiao-yu Du, Sheng-jie Hou, Xiao‐lin Yu, and Rui‐tian Liu. Neuronal double-stranded dna accumulation induced by dnase ii deficiency drives tau phosphorylation and neurodegeneration. Translational Neurodegeneration, Aug 2024. URL: https://doi.org/10.1186/s40035-024-00427-8, doi:10.1186/s40035-024-00427-8. This article has 12 citations and is from a domain leading peer-reviewed journal.
(li2024neuronaldoublestrandeddna pages 3-4): Ling-jie Li, Xiao-ying Sun, Ya-ru Huang, Shuai Lu, Yu-Ming Xu, Jing Yang, Xi-xiu Xie, Jie Zhu, Xiao-yun Niu, Dan-yang Wang, Shi-yu Liang, Xiao-yu Du, Sheng-jie Hou, Xiao‐lin Yu, and Rui‐tian Liu. Neuronal double-stranded dna accumulation induced by dnase ii deficiency drives tau phosphorylation and neurodegeneration. Translational Neurodegeneration, Aug 2024. URL: https://doi.org/10.1186/s40035-024-00427-8, doi:10.1186/s40035-024-00427-8. This article has 12 citations and is from a domain leading peer-reviewed journal.
(alrouji2024cyclin‐dependentkinase5 pages 1-2): Mohammed Alrouji, Haydar M. Al‐kuraishy, Ali I. Al‐Gareeb, Mohammed S. Alshammari, Athanasios Alexiou, Marios Papadakis, Mostafa M. Bahaa, and Gaber El‐Saber Batiha. Cyclin‐dependent kinase 5 (cdk5) inhibitors in parkinson disease. Journal of Cellular and Molecular Medicine, Jun 2024. URL: https://doi.org/10.1111/jcmm.18412, doi:10.1111/jcmm.18412. This article has 17 citations and is from a peer-reviewed journal.
(viorel2024p38mapkandcdk5 pages 2-2): Vlad Ionut Viorel, Ylenia Pastorello, Nosherwan Bajwa, and Mark Slevin. P38-mapk and cdk5, signaling pathways in neuroinflammation: a potential therapeutic intervention in alzheimer's disease? Neural Regeneration Research, 19:1649-1650, Dec 2024. URL: https://doi.org/10.4103/1673-5374.389645, doi:10.4103/1673-5374.389645. This article has 15 citations and is from a peer-reviewed journal.
(alrouji2024cyclin‐dependentkinase5 pages 5-6): Mohammed Alrouji, Haydar M. Al‐kuraishy, Ali I. Al‐Gareeb, Mohammed S. Alshammari, Athanasios Alexiou, Marios Papadakis, Mostafa M. Bahaa, and Gaber El‐Saber Batiha. Cyclin‐dependent kinase 5 (cdk5) inhibitors in parkinson disease. Journal of Cellular and Molecular Medicine, Jun 2024. URL: https://doi.org/10.1111/jcmm.18412, doi:10.1111/jcmm.18412. This article has 17 citations and is from a peer-reviewed journal.
(pao2021threedecadesof pages 10-11): Ping-Chieh Pao and Li-Huei Tsai. Three decades of cdk5. Journal of Biomedical Science, Nov 2021. URL: https://doi.org/10.1186/s12929-021-00774-y, doi:10.1186/s12929-021-00774-y. This article has 169 citations and is from a domain leading peer-reviewed journal.
(li2024neuronaldoublestrandeddna pages 1-3): Ling-jie Li, Xiao-ying Sun, Ya-ru Huang, Shuai Lu, Yu-Ming Xu, Jing Yang, Xi-xiu Xie, Jie Zhu, Xiao-yun Niu, Dan-yang Wang, Shi-yu Liang, Xiao-yu Du, Sheng-jie Hou, Xiao‐lin Yu, and Rui‐tian Liu. Neuronal double-stranded dna accumulation induced by dnase ii deficiency drives tau phosphorylation and neurodegeneration. Translational Neurodegeneration, Aug 2024. URL: https://doi.org/10.1186/s40035-024-00427-8, doi:10.1186/s40035-024-00427-8. This article has 12 citations and is from a domain leading peer-reviewed journal.
(alrouji2024cyclin‐dependentkinase5 pages 2-4): Mohammed Alrouji, Haydar M. Al‐kuraishy, Ali I. Al‐Gareeb, Mohammed S. Alshammari, Athanasios Alexiou, Marios Papadakis, Mostafa M. Bahaa, and Gaber El‐Saber Batiha. Cyclin‐dependent kinase 5 (cdk5) inhibitors in parkinson disease. Journal of Cellular and Molecular Medicine, Jun 2024. URL: https://doi.org/10.1111/jcmm.18412, doi:10.1111/jcmm.18412. This article has 17 citations and is from a peer-reviewed journal.
id: P61809
gene_symbol: Cdk5r1
product_type: PROTEIN
status: COMPLETE
description: 'Cdk5r1 encodes p35, a neuron-enriched regulatory activator of CDK5, and its
calpain-generated p25 cleavage product. p35/p25 are not kinases themselves; they bind CDK5
in the protein kinase 5 complex and activate CDK5-dependent phosphorylation programs that
control neuronal migration, cortical lamination, axon guidance, cytoskeletal organization,
synaptic development, and neuronal survival. Myristoylated p35 is membrane/cytoplasmic,
while p25 is more cytosolic and nuclear, explaining the mixed cellular localization annotations.'
taxon:
id: NCBITaxon:10090
label: Mus musculus
existing_annotations:
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: Cdk5r1/p35 is not an enzyme; its primary molecular function is
to activate and spatially target the serine/threonine kinase CDK5 by direct
binding.
- term:
id: GO:0007420
label: brain development
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0007411
label: axon guidance
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030426
label: growth cone
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005634
label: nucleus
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0016533
label: protein kinase 5 complex
evidence_type: IEA
original_reference_id: GO_REF:0000002
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0021722
label: superior olivary nucleus maturation
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0021819
label: layer formation in cerebral cortex
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043005
label: neuron projection
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043204
label: perikaryon
evidence_type: IEA
original_reference_id: GO_REF:0000044
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0048511
label: rhythmic process
evidence_type: IEA
original_reference_id: GO_REF:0000043
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17341134
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:17341134
supporting_text: Cdk5 is involved in BDNF-stimulated dendritic growth in
hippocampal neurons.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18325333
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:18325333
supporting_text: CDK5 activator p35 downregulates E-cadherin precursor
independently of CDK5.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24561619
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:24561619
supporting_text: Role of the SIK2-p35-PJA2 complex in pancreatic β-cell functional
compensation.
- term:
id: GO:0016533
label: protein kinase 5 complex
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043539
label: protein serine/threonine kinase activator activity
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: Supported but less specific than the CDK-specific activator term.
action: MODIFY
reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this
broader serine/threonine kinase activator term with the more specific
cyclin-dependent protein serine/threonine kinase activator activity.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
- term:
id: GO:0045892
label: negative regulation of DNA-templated transcription
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0018105
label: peptidyl-serine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: The annotation attributes kinase/phosphorylation activity to the CDK5
activator subunit.
action: MODIFY
reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the
replacement term better represents the molecular role.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
- term:
id: GO:0018107
label: peptidyl-threonine phosphorylation
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: The annotation attributes kinase/phosphorylation activity to the CDK5
activator subunit.
action: MODIFY
reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the
replacement term better represents the molecular role.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
- term:
id: GO:0000307
label: cyclin-dependent protein kinase holoenzyme complex
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0005634
label: nucleus
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0007213
label: G protein-coupled acetylcholine receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0009792
label: embryo development ending in birth or egg hatching
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0014069
label: postsynaptic density
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0016020
label: membrane
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0016301
label: kinase activity
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: The annotation attributes kinase/phosphorylation activity to the CDK5
activator subunit.
action: MODIFY
reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the
replacement term better represents the molecular role.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
- term:
id: GO:0016533
label: protein kinase 5 complex
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030182
label: neuron differentiation
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0030424
label: axon
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030425
label: dendrite
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030426
label: growth cone
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0031175
label: neuron projection development
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0031594
label: neuromuscular junction
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0035235
label: ionotropic glutamate receptor signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043025
label: neuronal cell body
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043197
label: dendritic spine
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043292
label: contractile muscle fiber
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043525
label: positive regulation of neuron apoptotic process
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043539
label: protein serine/threonine kinase activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but less specific than the CDK-specific activator term.
action: MODIFY
reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this
broader serine/threonine kinase activator term with the more specific
cyclin-dependent protein serine/threonine kinase activator activity.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
- term:
id: GO:0043539
label: protein serine/threonine kinase activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported but less specific than the CDK-specific activator term.
action: MODIFY
reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this
broader serine/threonine kinase activator term with the more specific
cyclin-dependent protein serine/threonine kinase activator activity.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
- term:
id: GO:0045296
label: cadherin binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0045348
label: positive regulation of MHC class II biosynthetic process
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0045892
label: negative regulation of DNA-templated transcription
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0046875
label: ephrin receptor binding
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0048471
label: perinuclear region of cytoplasm
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0098693
label: regulation of synaptic vesicle cycle
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0098793
label: presynapse
evidence_type: ISO
original_reference_id: GO_REF:0000096
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:1903265
label: positive regulation of tumor necrosis factor-mediated signaling pathway
evidence_type: ISO
original_reference_id: GO_REF:0000119
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-MMU-9634937
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0070315
label: G1 to G0 transition involved in cell differentiation
evidence_type: IMP
original_reference_id: PMID:21566658
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:21566658
supporting_text: A novel RING finger protein, Znf179, modulates cell cycle exit
and neuronal differentiation of P19 embryonal carcinoma cells.
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: IMP
original_reference_id: PMID:11517264
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
evidence_type: TAS
original_reference_id: PMID:12516540
review:
summary: The cited PMID does not support a Cdk5r1/CDK5 activator annotation.
action: REMOVE
reason: PMID:12516540 is a Leishmania/IL-12/TGF-beta study and does not provide
evidence for Cdk5r1 acting as a CDK5 activator. The molecular function is supported
elsewhere in this review, but this evidence assertion should not be retained.
supported_by:
- reference_id: PMID:12516540
supporting_text: The TGF-beta response to Leishmania chagasi in the absence of
IL-12.
- term:
id: GO:0009792
label: embryo development ending in birth or egg hatching
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0003779
label: actin binding
evidence_type: IPI
original_reference_id: PMID:19118186
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:19118186
supporting_text: Spatial learning impairment, enhanced CDK5/p35 activity, and
downregulation of NMDA receptor expression in transgenic mice expressing
tau-tubulin kinase 1.
- term:
id: GO:0002020
label: protease binding
evidence_type: IPI
original_reference_id: PMID:19118186
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:19118186
supporting_text: Spatial learning impairment, enhanced CDK5/p35 activity, and
downregulation of NMDA receptor expression in transgenic mice expressing
tau-tubulin kinase 1.
- term:
id: GO:0019901
label: protein kinase binding
evidence_type: IPI
original_reference_id: PMID:19118186
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:19118186
supporting_text: Spatial learning impairment, enhanced CDK5/p35 activity, and
downregulation of NMDA receptor expression in transgenic mice expressing
tau-tubulin kinase 1.
- term:
id: GO:0035255
label: ionotropic glutamate receptor binding
evidence_type: IPI
original_reference_id: PMID:19118186
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:19118186
supporting_text: Spatial learning impairment, enhanced CDK5/p35 activity, and
downregulation of NMDA receptor expression in transgenic mice expressing
tau-tubulin kinase 1.
- term:
id: GO:0051015
label: actin filament binding
evidence_type: IPI
original_reference_id: PMID:19118186
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:19118186
supporting_text: Spatial learning impairment, enhanced CDK5/p35 activity, and
downregulation of NMDA receptor expression in transgenic mice expressing
tau-tubulin kinase 1.
- term:
id: GO:0042501
label: serine phosphorylation of STAT protein
evidence_type: IDA
original_reference_id: PMID:15096606
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:15096606
supporting_text: Cyclin-dependent kinase 5 phosphorylates signal transducer and
activator of transcription 3 and regulates its transcriptional activity.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868356
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005654
label: nucleoplasm
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868383
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8863416
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868331
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868583
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868589
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8868677
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-NUL-8870566
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-MMU-8863416
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18054859
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:18054859
supporting_text: Cdk5 promotes synaptogenesis by regulating the subcellular
distribution of the MAGUK family member CASK.
- term:
id: GO:0090314
label: positive regulation of protein targeting to membrane
evidence_type: IDA
original_reference_id: PMID:18054859
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:18054859
supporting_text: Cdk5 promotes synaptogenesis by regulating the subcellular
distribution of the MAGUK family member CASK.
- term:
id: GO:0001764
label: neuron migration
evidence_type: IGI
original_reference_id: PMID:11226314
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:11226314
supporting_text: Synergistic contributions of cyclin-dependant kinase 5/p35 and
Reelin/Dab1 to the positioning of cortical neurons in the developing mouse
brain.
- term:
id: GO:0001764
label: neuron migration
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15096606
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:15096606
supporting_text: Cyclin-dependent kinase 5 phosphorylates signal transducer and
activator of transcription 3 and regulates its transcriptional activity.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:15489224
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:15489224
supporting_text: Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated
repression of transcription.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17529984
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:17529984
supporting_text: Cyclin-dependent kinase 5 governs learning and synaptic
plasticity via control of NMDAR degradation.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17591690
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:17591690
supporting_text: Stabilization and activation of p53 induced by Cdk5 contributes
to neuronal cell death.
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:15096606
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:15096606
supporting_text: Cyclin-dependent kinase 5 phosphorylates signal transducer and
activator of transcription 3 and regulates its transcriptional activity.
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:17591690
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:17591690
supporting_text: Stabilization and activation of p53 induced by Cdk5 contributes
to neuronal cell death.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:15123626
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:15123626
supporting_text: Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1
phosphorylation and Ca(2+)-dependent exocytosis.
- term:
id: GO:0021549
label: cerebellum development
evidence_type: IMP
original_reference_id: PMID:11226314
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:11226314
supporting_text: Synergistic contributions of cyclin-dependant kinase 5/p35 and
Reelin/Dab1 to the positioning of cortical neurons in the developing mouse
brain.
- term:
id: GO:0021549
label: cerebellum development
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0021722
label: superior olivary nucleus maturation
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0021766
label: hippocampus development
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0021819
label: layer formation in cerebral cortex
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- term:
id: GO:0045860
label: positive regulation of protein kinase activity
evidence_type: IGI
original_reference_id: PMID:11517264
review:
summary: Supported, but too broad for the specific Cdk5r1 molecular function.
action: MODIFY
reason: PMID:11517264 supports p35/p39 requirement for CDK5 function, so the more
specific cyclin-dependent protein serine/threonine kinase activator activity term
should replace this broad positive regulation of protein kinase activity annotation.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
supported_by:
- reference_id: PMID:11517264
supporting_text: p35 and p39 are essential for cyclin-dependent kinase 5 function
during neurodevelopment.
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17143272
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:17143272
supporting_text: Cdk5 regulates EphA4-mediated dendritic spine retraction through
an ephexin1-dependent mechanism.
- term:
id: GO:0014069
label: postsynaptic density
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0048013
label: ephrin receptor signaling pathway
evidence_type: IMP
original_reference_id: PMID:17143272
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:17143272
supporting_text: Cdk5 regulates EphA4-mediated dendritic spine retraction through
an ephexin1-dependent mechanism.
- term:
id: GO:0061001
label: regulation of dendritic spine morphogenesis
evidence_type: IMP
original_reference_id: PMID:17143272
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:17143272
supporting_text: Cdk5 regulates EphA4-mediated dendritic spine retraction through
an ephexin1-dependent mechanism.
- term:
id: GO:0021799
label: cerebral cortex radially oriented cell migration
evidence_type: IMP
original_reference_id: PMID:20624590
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:20624590
supporting_text: Dixdc1 is a critical regulator of DISC1 and embryonic cortical
development.
- term:
id: GO:0032956
label: regulation of actin cytoskeleton organization
evidence_type: IMP
original_reference_id: PMID:20624590
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:20624590
supporting_text: Dixdc1 is a critical regulator of DISC1 and embryonic cortical
development.
- term:
id: GO:0070507
label: regulation of microtubule cytoskeleton organization
evidence_type: IMP
original_reference_id: PMID:20624590
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:20624590
supporting_text: Dixdc1 is a critical regulator of DISC1 and embryonic cortical
development.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:11276227
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:11276227
supporting_text: Cdk5 is involved in neuregulin-induced AChR expression at the
neuromuscular junction.
- term:
id: GO:0007213
label: G protein-coupled acetylcholine receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0001764
label: neuron migration
evidence_type: IDA
original_reference_id: PMID:9010203
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:9010203
supporting_text: Mice lacking p35, a neuronal specific activator of Cdk5, display
cortical lamination defects, seizures, and adult lethality.
- term:
id: GO:0005509
label: calcium ion binding
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
- term:
id: GO:0005634
label: nucleus
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005737
label: cytoplasm
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0007158
label: neuron cell-cell adhesion
evidence_type: IMP
original_reference_id: PMID:10753743
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:10753743
supporting_text: Regulation of N-cadherin-mediated adhesion by the p35-Cdk5
kinase.
- term:
id: GO:0007411
label: axon guidance
evidence_type: IMP
original_reference_id: PMID:10545161
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
supported_by:
- reference_id: PMID:10545161
supporting_text: Callosal axon guidance defects in p35(-/-) mice.
- term:
id: GO:0007413
label: axonal fasciculation
evidence_type: IMP
original_reference_id: PMID:10545161
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:10545161
supporting_text: Callosal axon guidance defects in p35(-/-) mice.
- term:
id: GO:0007420
label: brain development
evidence_type: IMP
original_reference_id: PMID:10545161
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:10545161
supporting_text: Callosal axon guidance defects in p35(-/-) mice.
- term:
id: GO:0016020
label: membrane
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0016301
label: kinase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: The annotation attributes kinase/phosphorylation activity to the CDK5
activator subunit.
action: MODIFY
reason: Cdk5r1/p35 is not the catalytic kinase; it activates CDK5, so the
replacement term better represents the molecular role.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
- term:
id: GO:0030182
label: neuron differentiation
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0030424
label: axon
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030425
label: dendrite
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0030426
label: growth cone
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0031175
label: neuron projection development
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0031594
label: neuromuscular junction
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0035235
label: ionotropic glutamate receptor signaling pathway
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043025
label: neuronal cell body
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043197
label: dendritic spine
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported core p35/p25-CDK5 regulatory function or neuronal
localization/process.
action: ACCEPT
reason: The term reflects Cdk5r1 as the regulatory activator of CDK5 in neuronal
migration, axon guidance, cytoskeletal organization, or synaptic development.
- term:
id: GO:0043292
label: contractile muscle fiber
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043525
label: positive regulation of neuron apoptotic process
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0043539
label: protein serine/threonine kinase activator activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but less specific than the CDK-specific activator term.
action: MODIFY
reason: Cdk5r1/p35 activates the cyclin-dependent kinase CDK5; replace this
broader serine/threonine kinase activator term with the more specific
cyclin-dependent protein serine/threonine kinase activator activity.
proposed_replacement_terms:
- id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
- term:
id: GO:0045296
label: cadherin binding
evidence_type: ISS
original_reference_id: GO_REF:0000024
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:12496365
review:
summary: The annotation is too broad, indirect, or poorly supported as a direct
Cdk5r1 function.
action: MARK_AS_OVER_ANNOTATED
reason: This term should not be used as a primary functional annotation for p35/p25
because it either describes vague binding or an indirect pathway consequence.
supported_by:
- reference_id: PMID:12496365
supporting_text: CDK5 regulates cell adhesion and migration in corneal epithelial
cells.
- term:
id: GO:0008092
label: cytoskeletal protein binding
evidence_type: TAS
original_reference_id: PMID:12496365
review:
summary: Supported but downstream or context-specific Cdk5r1 biology.
action: KEEP_AS_NON_CORE
reason: The annotation is compatible with p35/p25-CDK5 biology but describes a
developmental, synaptic, binding, or localization consequence rather than the
primary CDK5 activation role.
supported_by:
- reference_id: PMID:12496365
supporting_text: CDK5 regulates cell adhesion and migration in corneal epithelial
cells.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to
orthologs by curator judgment of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000043
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
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:0000096
title: Automated transfer of experimentally-verified manual GO annotation data to
mouse-rat orthologs
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to
orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000119
title: Automated transfer of experimentally-verified manual GO annotation data to
mouse-human orthologs
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10545161
title: Callosal axon guidance defects in p35(-/-) mice.
findings: []
- id: PMID:10753743
title: Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase.
findings: []
- id: PMID:11226314
title: Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to
the positioning of cortical neurons in the developing mouse brain.
findings: []
- id: PMID:11276227
title: Cdk5 is involved in neuregulin-induced AChR expression at the neuromuscular
junction.
findings: []
- id: PMID:11517264
title: p35 and p39 are essential for cyclin-dependent kinase 5 function during
neurodevelopment.
findings: []
- id: PMID:12496365
title: CDK5 regulates cell adhesion and migration in corneal epithelial cells.
findings: []
- id: PMID:12516540
title: The TGF-beta response to Leishmania chagasi in the absence of IL-12.
findings: []
- id: PMID:15096606
title: Cyclin-dependent kinase 5 phosphorylates signal transducer and activator of
transcription 3 and regulates its transcriptional activity.
findings: []
- id: PMID:15123626
title: Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation
and Ca(2+)-dependent exocytosis.
findings: []
- id: PMID:15489224
title: Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of
transcription.
findings: []
- id: PMID:17143272
title: Cdk5 regulates EphA4-mediated dendritic spine retraction through an
ephexin1-dependent mechanism.
findings: []
- id: PMID:17341134
title: Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons.
findings: []
- id: PMID:17529984
title: Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control
of NMDAR degradation.
findings: []
- id: PMID:17591690
title: Stabilization and activation of p53 induced by Cdk5 contributes to neuronal
cell death.
findings: []
- id: PMID:18054859
title: Cdk5 promotes synaptogenesis by regulating the subcellular distribution of the
MAGUK family member CASK.
findings: []
- id: PMID:18325333
title: CDK5 activator p35 downregulates E-cadherin precursor independently of CDK5.
findings: []
- id: PMID:19118186
title: Spatial learning impairment, enhanced CDK5/p35 activity, and downregulation of
NMDA receptor expression in transgenic mice expressing tau-tubulin kinase 1.
findings: []
- id: PMID:20624590
title: Dixdc1 is a critical regulator of DISC1 and embryonic cortical development.
findings: []
- id: PMID:21566658
title: A novel RING finger protein, Znf179, modulates cell cycle exit and neuronal
differentiation of P19 embryonal carcinoma cells.
findings: []
- id: PMID:24561619
title: Role of the SIK2-p35-PJA2 complex in pancreatic β-cell functional compensation.
findings: []
- id: PMID:9010203
title: Mice lacking p35, a neuronal specific activator of Cdk5, display cortical
lamination defects, seizures, and adult lethality.
findings: []
- id: Reactome:R-MMU-8863416
title: Calpain 1 or Calpain 2 cleaves Cdk5r1 (p35)
findings: []
- id: Reactome:R-MMU-8868331
title: Cdk5:p25 phosphorylates Golga2
findings: []
- id: Reactome:R-MMU-8868356
title: Cdk5:p25 phosphorylates lamin A
findings: []
- id: Reactome:R-MMU-8868383
title: Cdk5:p25 phosphorylates lamin B1
findings: []
- id: Reactome:R-MMU-8868583
title: Cdk5:p25 phosphorylates Prdx1
findings: []
- id: Reactome:R-MMU-8868589
title: Cdk5:p25 phosphorylates Prdx2
findings: []
- id: Reactome:R-MMU-8868677
title: Cdk5:p25 phosphorylates Jun
findings: []
- id: Reactome:R-MMU-9634937
title: Cdk5r1 gene expression is stimulated by Npas4
findings: []
- id: Reactome:R-NUL-8870566
title: Cdk5:p25 phosphorylates FOXO3
findings: []
- id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
title: Falcon deep research synthesis for mouse Cdk5r1
findings:
- statement: Cdk5r1/p35 is the non-catalytic regulatory activator that binds and
spatially targets CDK5 in neurons.
supporting_text: Cdk5r1/p35 is not an enzyme; its primary molecular function is
to activate and spatially target the serine/threonine kinase CDK5 by direct
binding.
- statement: Myristoylated p35 localizes CDK5 activity to membrane-associated
neuronal compartments, while calpain-cleaved p25 can redistribute activity to
cytoplasmic and nuclear compartments.
supporting_text: p35 is the obligate regulatory activator of CDK5 and determines
where CDK5 acts via myristoylation-dependent membrane targeting.
core_functions:
- description: p35/p25 activates CDK5 in the protein kinase 5 complex to regulate
neuronal migration, axon guidance, and neuronal cytoskeletal organization.
molecular_function:
id: GO:0061575
label: cyclin-dependent protein serine/threonine kinase activator activity
directly_involved_in:
- id: GO:0001764
label: neuron migration
- id: GO:0007411
label: axon guidance
- id: GO:0032956
label: regulation of actin cytoskeleton organization
locations:
- id: GO:0005737
label: cytoplasm
- id: GO:0005886
label: plasma membrane
- id: GO:0030426
label: growth cone
in_complex:
id: GO:0016533
label: protein kinase 5 complex
supported_by:
- reference_id: file:mouse/Cdk5r1/Cdk5r1-uniprot.txt
supporting_text: p35 is a neuron specific activator of CDK5
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: Cdk5r1/p35 is not an enzyme; its primary molecular function is
to activate and spatially target the serine/threonine kinase CDK5 by direct
binding.
- reference_id: file:mouse/Cdk5r1/Cdk5r1-deep-research-falcon.md
supporting_text: Neuronal migration, neurite outgrowth, synaptic vesicle cycling,
and postsynaptic plasticity are repeatedly implicated in Cdk5/p35 biology.