CDKAL1 Protein

CDKAL1 Protein (CDK5 Regulatory Subunit Associated Protein 1-like 1)

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">CDKAL1</th></tr>
<tr><td><b>Protein Name</b></td><td>CDK5 Regulatory Subunit Associated Protein 1-like 1</td></tr>
<tr><td><b>Gene</b></td><td>[CDKAL1](/genes/cdkal1)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9Y5J9](https://www.uniprot.org/uniprot/Q9Y5J9)</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~62 kDa</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Cytoplasm</td></tr>
<tr><td><b>Protein Family</b></td><td>CDKAL1 family</td></tr>
<tr><td><b>Function</b></td><td>tRNA modification, translational control</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

CDKAL1 ([CDK5](/proteins/cdk5) Regulatory Subunit Associated Protein 1-like 1) is a highly conserved protein encoded by the [CDKAL1](/genes/cdkal1) gene. Originally identified as a CDK5 regulatory subunit-associated protein, CDKAL1 has been extensively studied for its role in type 2 diabetes mellitus (T2DM) risk. More recent research has revealed functions in the nervous system, with implications for [Parkinson's disease](/diseases/parkinsons-disease), [Alzheimer's disease](/diseases/alzheimers-disease), and other neurological conditions [1].

Structure and Function

Protein Architecture

CDKAL1 Protein (CDK5 Regulatory Subunit Associated Protein 1-like 1)

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#f0f0f0;">CDKAL1</th></tr>
<tr><td><b>Protein Name</b></td><td>CDK5 Regulatory Subunit Associated Protein 1-like 1</td></tr>
<tr><td><b>Gene</b></td><td>[CDKAL1](/genes/cdkal1)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9Y5J9](https://www.uniprot.org/uniprot/Q9Y5J9)</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~62 kDa</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Cytoplasm</td></tr>
<tr><td><b>Protein Family</b></td><td>CDKAL1 family</td></tr>
<tr><td><b>Function</b></td><td>tRNA modification, translational control</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

CDKAL1 ([CDK5](/proteins/cdk5) Regulatory Subunit Associated Protein 1-like 1) is a highly conserved protein encoded by the [CDKAL1](/genes/cdkal1) gene. Originally identified as a CDK5 regulatory subunit-associated protein, CDKAL1 has been extensively studied for its role in type 2 diabetes mellitus (T2DM) risk. More recent research has revealed functions in the nervous system, with implications for [Parkinson's disease](/diseases/parkinsons-disease), [Alzheimer's disease](/diseases/alzheimers-disease), and other neurological conditions [1].

Structure and Function

Protein Architecture

CDKAL1 is a 583-amino acid protein with several functional domains:

• N-terminal region: Contains methyltransferase-like domains
• C-terminal region: Associates with CDK5/p35 complex
• S-adenosylmethionine binding site: For methyltransferase activity

Biological Functions

tRNA Modification

CDKAL1 is a member of the methyltransferase family:

• Catalyzes 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) modification
• Modifies tRNA Lys(UUU) at position 37
• Essential for accurate and efficient translation

CDK5 Regulation

CDKAL1 interacts with the CDK5/p35 complex:

• Modulates CDK5 kinase activity
• Influences neuronal development
• Affects synaptic plasticity

CDKAL1 in Parkinson's Disease

Genetic Association

GWAS have identified CDKAL1 variants associated with [Parkinson's disease](/diseases/parkinsons-disease) risk:

• Single nucleotide polymorphisms (SNPs) in CDKAL1 locus correlate with PD susceptibility
• The same variants associated with T2DM risk also influence PD
• Meta-analyses confirm the association across populations

Mechanistic Links

How CDKAL1 dysfunction may contribute to PD:

Diabetes-Parkinson's Connection

The dual association with T2DM and PD suggests shared pathways:

• Insulin signaling crosstalk
• Mitochondrial dysfunction
• Endoplasmic reticulum stress
• [Neuroinflammation](/mechanisms/neuroinflammation)

CDKAL1 in Alzheimer's Disease

In [Alzheimer's disease](/diseases/alzheimers-disease), CDKAL1 may play roles through:

CDKAL1 in Other Neurological Conditions

Schizophrenia

CDKAL1 variants have been associated with:

• Increased risk for schizophrenia
• Cognitive deficits
• Altered brain structure

Autism Spectrum Disorders

Evidence suggests links to:

• Social cognitive impairments
• Altered brain development

Therapeutic Implications

Diabetes-Parkinson's Link

Understanding CDKAL1's role reveals potential therapeutic strategies:

Biomarker Potential

CDKAL1 genetic variants may serve as:

• Risk biomarkers for PD in diabetic patients
• Predictors of disease progression
• Targets for personalized medicine

Summary

CDKAL1 is a methyltransferase protein involved in tRNA modification and translational control. Originally studied in the context of type 2 diabetes, CDKAL1 has emerged as a risk factor for Parkinson's disease and other neurological disorders. The dual association with metabolic disease and neurodegeneration highlights the importance of cellular metabolism in neuronal health. Further research into CDKAL1 function may reveal novel therapeutic approaches for PD and AD.

See Also

• [CDKAL1 Gene](/genes/cdkal1)
• [Parkinson's disease](/diseases/parkinsons-disease)
• [Alzheimer's disease](/diseases/alzheimers-disease)

External Links

• [GeneCards: CDKAL1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDKAL1)

References