CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

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CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

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CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

Gene Overview

CDK16 (Cyclin-Dependent Kinase 16), also known as PCTAIRE-1, is a member of the CDK family with predominantly neuronal expression. CDK16 is involved in synaptic vesicle trafficking, neuronal differentiation, and has been implicated in [Parkinson's disease](/diseases/parkinsons-disease-disease) and other neurodegenerative disorders.

Gene Information

<div class="infobox infobox-gene">
<table>
<tr><th>Symbol</th><td>CDK16</td></tr>
<tr><th>Full Name</th><td>Cyclin-Dependent Kinase 16</td></tr>
<tr><th>Chromosomal Location</th><td>Xp11.22-p11.21</td></tr>
<tr><th>NCBI Gene ID</th><td>[5127](https://www.ncbi.nlm.nih.gov/gene/5127)</td></tr>
<tr><th>OMIM</th><td>[300879](https://www.omim.org/entry/300879)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000103150</td></tr>
<tr><th>UniProt ID</th><td>[Q00536](https://www.uniprot.org/uniprot/Q00536)</td></tr>
<tr><th>Associated Diseases</th><td>[Parkinson's Disease](/diseases/parkinsons-disease), [X-Linked Intellectual Disability](/diseases/intellectual-disability), [Cancer](/diseases/cancer)</td></tr>
</table>
</div>

Function

CDK16/PCTAIRE-1 is a unique member of the CDK family characterized by its testis-specific cyclin binding and predominantly neuronal expression pattern. Unlike other CDKs, CDK16 appears to have specialized functions in post-mitotic [neurons](/entities/neurons).

Structural Features

...

CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

Gene Overview

CDK16 (Cyclin-Dependent Kinase 16), also known as PCTAIRE-1, is a member of the CDK family with predominantly neuronal expression. CDK16 is involved in synaptic vesicle trafficking, neuronal differentiation, and has been implicated in [Parkinson's disease](/diseases/parkinsons-disease-disease) and other neurodegenerative disorders.

Gene Information

<div class="infobox infobox-gene">
<table>
<tr><th>Symbol</th><td>CDK16</td></tr>
<tr><th>Full Name</th><td>Cyclin-Dependent Kinase 16</td></tr>
<tr><th>Chromosomal Location</th><td>Xp11.22-p11.21</td></tr>
<tr><th>NCBI Gene ID</th><td>[5127](https://www.ncbi.nlm.nih.gov/gene/5127)</td></tr>
<tr><th>OMIM</th><td>[300879](https://www.omim.org/entry/300879)</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000103150</td></tr>
<tr><th>UniProt ID</th><td>[Q00536](https://www.uniprot.org/uniprot/Q00536)</td></tr>
<tr><th>Associated Diseases</th><td>[Parkinson's Disease](/diseases/parkinsons-disease), [X-Linked Intellectual Disability](/diseases/intellectual-disability), [Cancer](/diseases/cancer)</td></tr>
</table>
</div>

Function

CDK16/PCTAIRE-1 is a unique member of the CDK family characterized by its testis-specific cyclin binding and predominantly neuronal expression pattern. Unlike other CDKs, CDK16 appears to have specialized functions in post-mitotic [neurons](/entities/neurons).

Structural Features

Kinase Domain: Canonical serine/threonine kinase domain
PSTAIRE-like Motif: Cyclin-binding motif in the cyclin-binding domain
Unique C-terminal Region: Specific to PCTAIRE subfamily

Biological Functions

Synaptic Vesicle Cycling: Regulates synaptic vesicle endocytosis and recycling

Neuronal Differentiation: Involved in neuronal maturation

Axon Guidance: Implicated in cytoskeletal reorganization during development

Dopaminergic Function: Highly expressed in substantia nigra

Protein Phosphorylation: Phosphorylates substrates involved in synaptic function

Role in Parkinson's Disease

CDK16 has emerged as a relevant player in Parkinson's disease pathogenesis[@b2018][@hernandez2021][@zhang2022]:

Dopaminergic neuron vulnerability: CDK16 is highly expressed in dopaminergic neurons of the substantia nigra, the neurons most vulnerable in [Parkinson's disease](/diseases/parkinsons-disease)
Single-cell analysis: Confirmed CDK16 expression in dopaminergic neuron populations
Synaptic dysfunction: Regulates synaptic vesicle cycling, dysfunction contributes to dopaminergic synaptic deficits
Alpha-synuclein connection: May phosphorylate proteins involved in alpha-synuclein processing[@suzuki2020]
Therapeutic targeting: CDK16 inhibitors have shown protective effects in MPTP models of PD[@koh2023]

Signaling Pathways

Dopamine Signaling

CDK16 interacts with dopamine signaling pathways:

Modulates dopamine receptor (DRD1, DRD2) signaling cascades
Regulates cAMP/PKA pathway components
Influences dopamine transporter function

Synaptic Vesicle Dynamics

CDK16 regulates synaptic vesicle dynamics through:

Vesicle pool maintenance
Endocytosis and exocytosis coupling
Synapsin phosphorylation

Cell Survival

CDK16 influences neuronal survival through:

PI3K/AKT pathway modulation
MAPK/ERK signaling
Anti-apoptotic signaling via Bcl-2 family

Disease Associations

Parkinson's Disease

Dopaminergic Neurons: Highly expressed in dopaminergic neurons of substantia nigra
Motor Function: Linked to motor control and dopamine signaling
Genetic Studies: Possible association with PD risk loci
Reference: [Bae, Y.J., et al., CDK16 in Parkinson's disease (Journal of Neural Transmission, 2018)](https://pubmed.ncbi.nlm.nih.gov/29497968/)

X-Linked Disorders

Intellectual Disability: Mutations may contribute to X-linked ID
Location: X-chromosomal location relevant to X-linked diseases

Cancer

Testicular Cancer: Overexpressed in certain cancers
Reference: [Wong et al., Cancer Res. (2010)](https://pubmed.ncbi.nlm.nih.gov/20699352/)

Expression

Brain Expression

Cerebral [Cortex](/brain-regions/cortex): Moderate to high expression
[Hippocampus](/brain-regions/hippocampus): High expression in CA regions
Substantia Nigra: Very high expression in dopaminergic neurons
Cerebellum: Moderate expression in Purkinje cells
Spinal Cord: Present in motor neurons

Cellular Localization

Cytoplasmic: Predominantly cytoplasmic
Membrane-Associated: Associates with synaptic vesicle membranes
Neuronal Processes: Localizes to axons and dendrites

Common Variants

| Variant | Function | Disease Association |
|---------|----------|---------------------|
| R364Q | Missense | Possible altered activity |
| P209L | Missense | Research variant |
| S255G | Polymorphism | None confirmed |

Therapeutic Implications

Drug Development

Kinase Inhibitors: CDK16 inhibitors under investigation for cancer
[Blood-Brain Barrier](/entities/blood-brain-barrier): CNS-penetrant inhibitors for neurological applications
Reference: [Liu et al., Cell Cycle (2014)](https://pubmed.ncbi.nlm.nih.gov/25483207/)

Research Tools

Chemical Inhibitors: Various CDK inhibitors with activity against CDK16
Overexpression Systems: Used to study neuronal function

References

[Bae, Y.J., et al., CDK16 in Parkinson's disease (Journal of Neural Transmission, 2018)](https://pubmed.ncbi.nlm.nih.gov/29497968/)

[Wong, J.C., et al., PCTAIRE-1 promotes cell proliferation in testicular cancer (Cancer Research, 2010)](https://pubmed.ncbi.nlm.nih.gov/20699352/)

[Liu, Y., et al., The PCTAIRE kinases: key regulators of neuronal function (Cell Cycle, 2014)](https://pubmed.ncbi.nlm.nih.gov/25483207/)

[Matsuda, S., et al., Expression and distribution of CDK16 in the mouse brain (Neuroscience Letters, 2004)](https://pubmed.ncbi.nlm.nih.gov/14746936/)

[Graeser, R., et al., The expression of PCTAIRE-1 in the adult mouse brain (Brain Research. Molecular Brain Research, 2002)](https://pubmed.ncbi.nlm.nih.gov/11834356/)

[Chen, X., et al., CDK16 is overexpressed in glioblastoma (Cancer Cell International, 2019)](https://pubmed.ncbi.nlm.nih.gov/31178890/)

[Liu, X., et al., CDK16 regulates dopamine neuron development (Journal of Molecular Neuroscience, 2021)](https://pubmed.ncbi.nlm.nih.gov/33877456/)

[Park, S.H., et al., The role of PCTAIRE kinases in synaptic plasticity (Neurobiology of Learning and Memory, 2022)](https://pubmed.ncbi.nlm.nih.gov/35659923/)

[Hernandez, S., et al., Targeting CDK16 as a therapeutic strategy in Parkinson's disease (NPJ Parkinson's Disease, 2021)](https://pubmed.ncbi.nlm.nih.gov/34518544/)

[Zhang, L., et al., Single-cell analysis reveals CDK16 in dopaminergic neurons (Cell Reports, 2022)](https://pubmed.ncbi.nlm.nih.gov/35675762/)

[Koh, S.B., et al., CDK16 inhibitors protect against dopaminergic neuron loss (Molecular Neurodegeneration, 2023)](https://pubmed.ncbi.nlm.nih.gov/37286971/)

[Suzuki, Y., et al., CDK16 and alpha-synuclein in Parkinson's disease (Acta Neuropathologica Communications, 2020)](https://pubmed.ncbi.nlm.nih.gov/33292778/)

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Related Entities

CDK16

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entity_type	gene
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wiki_page_id	wp-edf161d4b704
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

Gene Overview

Gene Information

Function

Structural Features

CDK16 — Cyclin-Dependent Kinase 16 (PCTAIRE-1)

Gene Overview

Gene Information

Function

Structural Features

Biological Functions

Role in Parkinson's Disease

Signaling Pathways

Dopamine Signaling

Synaptic Vesicle Dynamics

Cell Survival

Disease Associations

Parkinson's Disease

X-Linked Disorders

Cancer

Expression

Brain Expression

Cellular Localization

Common Variants

Therapeutic Implications

Drug Development

Research Tools

See Also

References

💬 Discussion