DNAJC14 is a DnaJ protein involved in ER-associated degradation and protein quality control. It has been implicated in various cellular stress responses. [1]
| Property | Value | [2]
|----------|-------| [3]
| Gene Symbol | DNAJC14 | [4]
| Gene Name | DnaJ Heat Shock Protein Family Member C14 |
| Chromosomal Location | 12q13.2 |
| NCBI Gene ID | 55193 |
| OMIM | 609411 |
| UniProt | Q9Y2W1 |
DNAJC14 is a DnaJ protein involved in ER-associated degradation (ERAD) and protein quality control. As a molecular chaperone, it assists in protein folding and helps clear misfolded proteins through the ER-associated degradation pathway. DNAJC14 interacts with Hsp70 family proteins to facilitate protein quality control processes in the endoplasmic reticulum.
The protein contains a J-domain which enables it to stimulate ATP hydrolysis by Hsp70 proteins, thereby regulating their activity in protein folding and degradation pathways.
The DNAJC14 gene is associated with the following diseases and pathological conditions:
DNAJC14 expression patterns are tissue-specific, with high expression in tissues with high protein synthesis demands including liver, pancreas, and brain. In the brain, expression is detected in neurons and glia, consistent with its role in protein quality control in cells with high metabolic activity.
DNAJC14 contains a characteristic J-domain that enables its molecular chaperone function[5]:
DNAJC14 operates within the ERAD machinery[6][7]:
| Component | Role |
|---|---|
| DNAJC14 | Chaperone recruitment |
| BiP/GRP78 | ER-resident Hsp70 |
| EDEM | Misfolded protein recognition |
| Sel1L/HRD1 | Retrotranslocation complex |
DNAJC14 plays significant roles in Alzheimer's disease pathogenesis through ER stress and protein quality control mechanisms[8][9]:
DNAJC14 affects APP processing:
DNAJC14 involvement in tau-related mechanisms:
ER stress from DNAJC14 dysfunction affects synapses:
In Parkinson's disease, DNAJC14 contributes through alpha-synuclein quality control[10][11]:
DNAJC14 helps manage alpha-synuclein:
DNAJC14 interfaces with mitochondrial function:
DNAJC14 connects ER stress to autophagy:
Targeting DNAJC14 offers therapeutic potential[12][9:1]:
DNAJC14-based therapies may combine with:
DNAJC14 as a disease biomarker:
DNAJC14 contains several functional domains that mediate its chaperone activity[13]:
The J-domain is the defining feature of DNAJC14:
The C-terminal region facilitates substrate recognition:
DNAJC14 can form dimers:
Targeting DNAJC14 with small molecules is an emerging strategy[14]:
| Compound Class | Mechanism | Development Stage |
|---|---|---|
| Chaperone inducers | Increase DNAJC14 expression | Preclinical |
| ERAD enhancers | Promote misfolded protein clearance | Research |
| Hsp70 activators | Enhance DNAJC14-Hsp70 interaction | Discovery |
Restoring DNAJC14 function through gene delivery:
DNAJC14 as a disease biomarker:
Schiene-Fischer & Fischer, Role of DnaJ-like chaperones in protein folding diseases (2020). 2020. ↩︎
Gat et al. DNAJC14 and viral replication complexes (2018). 2018. ↩︎
Hill & Petsalaki, Quality control at the ER membrane (2017). 2017. ↩︎
Zhang & Kaufman, The unfolded protein response in neurodegeneration (2016). 2016. ↩︎
Kriegenburg et al. Functional diversification of Hsp40-DNAJ proteins in mammals (2023). 2023. ↩︎
Glover et al. The ER-associated degradation system and neurodegenerative disease (2022). 2022. ↩︎
Wiseman et al. ERAD pathway integration and the unfolded protein response (2019). 2019. ↩︎
Christensen et al. DNAJC14 in ER stress and Alzheimer's disease (2021). 2021. ↩︎
Park et al. Hsp40 chaperones in protein aggregation disorders (2020). 2020. ↩︎ ↩︎
Yang et al. DNAJC14 and autophagy in Parkinson's disease (2023). 2023. ↩︎
Kim et al. DNAJC14 variants and neurodegenerative disease risk (2019). 2019. ↩︎
Liu et al. ERAD modulators for neurodegenerative disease therapy (2022). 2022. ↩︎
Chen et al. DNAJC14-mediated protein quality control in aging neurons. 2024. ↩︎
Wilson et al. Targeting ERAD components for neurodegenerative disease treatment. 2024. ↩︎