DNAJC17 Gene

title: DNAJC17 Gene
category: gene

DNAJC17 Gene

<div class="infobox infobox-gene"> [@soto2011]
<table> [@jha2018]
<tr><th colspan="2" style="background:#f3e5f5; text-align:center; font-size:1.1em;">DNAJC17</th></tr> [@sweeney2017]
<tr><td><strong>Gene Symbol</strong></td><td>DNAJC17</td></tr> [@jiang2019]
<tr><td><strong>Full Name</strong></td><td>DnaJ Heat Shock Protein Family Member C17</td></tr> [@cox2020]
<tr><td><strong>Chromosomal Location</strong></td><td>15q21.1</td></tr> [@mitra2021]
<tr><td><strong>NCBI Gene ID</strong></td><td>[56126](https://www.ncbi.nlm.nih.gov/gene/56126)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000149691</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>[613358](https://www.omim.org/entry/613358)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NWV8](https://www.uniprot.org/uniprot/Q9NWV8)</td></tr>
<tr><td><strong>Protein Length</strong></td><td>304 amino acids</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>34.5 kDa</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

title: DNAJC17 Gene
category: gene

DNAJC17 Gene

<div class="infobox infobox-gene"> [@soto2011]
<table> [@jha2018]
<tr><th colspan="2" style="background:#f3e5f5; text-align:center; font-size:1.1em;">DNAJC17</th></tr> [@sweeney2017]
<tr><td><strong>Gene Symbol</strong></td><td>DNAJC17</td></tr> [@jiang2019]
<tr><td><strong>Full Name</strong></td><td>DnaJ Heat Shock Protein Family Member C17</td></tr> [@cox2020]
<tr><td><strong>Chromosomal Location</strong></td><td>15q21.1</td></tr> [@mitra2021]
<tr><td><strong>NCBI Gene ID</strong></td><td>[56126](https://www.ncbi.nlm.nih.gov/gene/56126)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000149691</td></tr>
<tr><td><strong>OMIM ID</strong></td><td>[613358](https://www.omim.org/entry/613358)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q9NWV8](https://www.uniprot.org/uniprot/Q9NWV8)</td></tr>
<tr><td><strong>Protein Length</strong></td><td>304 amino acids</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>34.5 kDa</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

DNAJC17 (DnaJ Heat Shock Protein Family Member C17) is a member of the DNAJ family of co-chaperones, which are characterized by the presence of a conserved J domain that enables them to interact with [Hsp70](/proteins/hsp70-protein) [heat shock proteins](/entities/heat-shock-proteins) and regulate their ATPase activity. DNAJC17 is a Type II DNAJ protein, containing a J domain at the N-terminus followed by a glycine/phenylalanine-rich region and a C-terminal client-binding domain. While DNAJC17 was initially predicted to function as a molecular chaperone, its exact biological roles and disease associations remain an active area of investigation.

The DNAJ protein family (also known as Hsp40 family) consists of over 40 members in humans, categorized into three main classes based on their domain architecture: Type I (DNAJA), Type II (DNAJB), and Type III (DNAJC). DNAJC17 represents a relatively uncharacterized member of this family, with emerging evidence suggesting roles in [protein quality control](/mechanisms/protein-quality-control-network)mechanisms/protein-quality-control-network), [RNA processing](/mechanisms/rna-processing), and potentially in [neurodegenerative disease](/diseases/alzheimers-disease) contexts.

Gene Structure and Expression

Genomic Organization

The DNAJC17 gene is located on chromosome 15q21.1, spanning approximately 8.5 kilobases of genomic DNA. The gene consists of 9 exons encoding a 304-amino acid protein. The gene structure is relatively simple compared to other DNAJ family members, with a compact architecture reflecting its specialized function.

Tissue Expression

DNAJC17 exhibits broad but specific expression patterns across human tissues:

• High expression: Heart, skeletal muscle, kidney, and brain
• Moderate expression: Liver, pancreas, lung, and placenta
• Low expression: Peripheral blood leukocytes

Cellular Localization

DNAJC17 localizes primarily to the [cytoplasm](/cellular-structures/cytoplasm), where it can interact with its Hsp70 partners. Some studies suggest additional localization to the [nucleus](/cellular-structures/nucleus), particularly in association with RNA processing compartments. The protein may also associate with [mitochondria](/mechanisms/mitochondrial-dysfunction-neurodegeneration) in certain cell types.

Protein Structure and Function

Domain Architecture

DNAJC17 contains several functional domains:

Molecular Functions

While DNAJC17 remains incompletely characterized, several molecular functions have been proposed:

Chaperone Activity: As a DNAJ co-chaperone, DNAJC17 likely assists Hsp70 in protein folding, refolding, and clearance of misfolded proteins. The J domain couples substrate delivery to Hsp70 ATP hydrolysis.

Protein Quality Control: DNAJC17 may participate in the cellular protein quality control network, helping to target damaged or aggregation-prone proteins for refolding or degradation via the [proteasome](/proteins/proteasome-20s) or [autophagy](/mechanisms/autophagy) pathways.

RNA Processing: Some evidence suggests DNAJ proteins can associate with RNA-protein complexes, potentially linking protein quality control to RNA metabolism.

Role in Neurodegenerative Diseases

Alzheimer's Disease

While direct evidence linking DNAJC17 to [Alzheimer's disease (AD)](/diseases/alzheimers-disease) is limited, several indirect connections suggest potential involvement:

• Protein homeostasis disruption: AD is characterized by accumulation of misfolded proteins ([amyloid-beta](/proteins/amyloid-beta-protein), [tau](/proteins/tau)). DNAJC17 may help manage proteotoxic stress, and alterations in its expression could affect disease progression.
• Hsp70 involvement: Hsp70 and its co-chaperones are major players in protein aggregation management. Modulating DNAJC17 levels could influence Hsp70 activity in AD brain.
• Transcriptional regulation: Some DNAJ proteins regulate gene expression, potentially affecting pathways relevant to neurodegeneration.

Parkinson's Disease

Similar considerations apply to [Parkinson's disease (PD)](/diseases/parkinsons-disease):

• [Alpha-synuclein](/proteins/alpha-synuclein) handling: The aggregation of [alpha-synuclein](/proteins/alpha-synuclein) is central to PD pathogenesis. DNAJC17 may contribute to managing synuclein proteostasis.
• Mitochondrial quality control: PD involves mitochondrial dysfunction. DNAJ proteins participate in mitochondrial protein import and quality control.

Amyotrophic Lateral Sclerosis

[ALS](/diseases/amyotrophic-lateral-sclerosis) involves aggregation of [TDP-43](/mechanisms/tdp-43-proteinopathy), FUS, and SOD1 proteins. DNAJ proteins may influence the handling of these disease proteins.

Interaction Network

Hsp70 Partners

DNAJC17 primarily interacts with cytosolic Hsp70 proteins:

• [HSPA1A/Hsp70-1](/genes/hspa1a): The major inducible Hsp70
• [HSPA8/Hsc70](/genes/hspa8): Constitutively expressed Hsc70
• [HSPA4/Hsp70-4](/genes/hspa4): Hsp70 family member

Potential Client Proteins

While specific client proteins for DNAJC17 are not well established, the protein may handle:

• Newly synthesized polypeptides
• Stress-denatured proteins
• Aggregation-prone disease proteins

Pathway Involvement

DNAJC17 participates in several cellular pathways:

• [Protein folding and quality control](/mechanisms/protein-quality-control-network))
• [Ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system)
• [Autophagy-lysosome pathway](/mechanisms/autophagy)
• [Stress response signaling](/mechanisms/stress-response-neurodegeneration))

Research Methods

Experimental Approaches

• Recombinant protein expression: Purification of DNAJC17 for biochemical studies
• Co-immunoprecipitation: Identifying protein interaction partners
• RNAi/CRISPR knockdown: Functional studies in cell models
• Mass spectrometry: Proteomic analysis of DNAJC17 complexes
• Cell fractionation: Subcellular localization studies

Model Systems

• Yeast models: Functional complementation studies
• Cell culture: Neuronal and non-neuronal cell lines
• Transgenic mice: In vivo functional studies
• Patient samples: Expression analysis in disease tissue

Therapeutic Potential

While DNAJC17 is not currently a therapeutic target, understanding its function may provide insights into:

Summary

DNAJC17 is a member of the DNAJ/Hsp40 co-chaperone family with predicted roles in protein quality control and potentially in RNA processing. While its exact functions remain under investigation, DNAJC17 participates in Hsp70-mediated protein folding and clearance pathways relevant to neurodegenerative diseases. Further research is needed to fully characterize DNAJC17's biological roles and therapeutic potential in conditions like [Alzheimer's](/diseases/alzheimers-disease), [Parkinson's](/diseases/parkinsons-disease-disease), and ALS.

External Links

• [Wikipedia](https://en.wikipedia.org/)
• [NCBI Resources](https://www.ncbi.nlm.nih.gov/)

See Also

• DNAJ Gene Family
• [Hsp70 Proteins](/content/proteins)
• [Protein Quality Control](/mechanisms/protein-quality-control)