DNAJA3: A Key Regulator of Mitochondrial Apoptosis and Cellular Stress
Comprehensive genomic and proteomic overview of the DnaJ heat shock protein family member A3 gene
Gene Information Card
| Symbol | DNAJA3 |
|---|---|
| Full Name | DnaJ heat shock protein family (Hsp40) member A3 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 9093 ncbi.nlm.nih.gov/gene/9093 |
| Ensembl ID | ENSG00000103423 |
| UniProt ID | Q96EY1 |
| OMIM ID | 608382 |
| HGNC ID | 11873 |
| Aliases | Tid1, hTid-1, HCA3 |
Description
DNAJA3 encodes a member of the DnaJ/Hsp40 family of co-chaperones, localized primarily to mitochondria. The protein interacts with Hsp70 chaperones to regulate protein folding, mitochondrial import, and apoptosis. It acts as a tumor suppressor by modulating p53 and NF-κB signaling, and its loss is implicated in cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of DNAJA3 reduces p53-mediated apoptosis, promoting cell survival | PMID: 19029910; COSMIC |
| Lung cancer | Downregulation of DNAJA3 correlates with poor prognosis and increased metastasis | PMID: 21804532; NCBI Gene |
| Huntington disease | DNAJA3 interacts with mutant huntingtin, modulating mitochondrial dysfunction | PMID: 20080796; UniProt |
| Colorectal cancer | Reduced DNAJA3 expression linked to chemoresistance via NF-κB activation | PMID: 23361061; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Brain | 8.9 | Medium |
| Skeletal muscle | 7.6 | Low |
| Kidney | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.3 | Cervical cancer cell line |
| HepG2 | 11.8 | Hepatocellular carcinoma |
| A549 | 9.5 | Lung adenocarcinoma |
| MCF7 | 8.1 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | 0.01% (gnomAD) | Reduced chaperone activity; associated with altered apoptosis |
| c.112G>A (p.Gly38Ser) | Missense | 0.005% | Impaired mitochondrial localization |
| c.742_743insA | Frameshift | <0.001% | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the J-domain or C-terminal region, impairing Hsp70 interaction and mitochondrial import.
Gain of Function (GOF)
Not reported in literature or curated databases.
Dominant Negative (DN)
Missense mutations in the J-domain (e.g., p.Arg163Trp) may interfere with wild-type DNAJA3 function by competing for Hsp70 binding.
View complete mutation data：
Gene Ontology (GO)
| • Mitochondrion | • Protein folding |
| • Chaperone cofactor-dependent protein refolding | • Apoptotic process |
| • ATP binding | • Heat shock protein binding |
| • Negative regulation of NF-κB transcription factor activity | • Positive regulation of p53 class mediator |
Pathways
• p53 signaling pathway (KEGG: hsa04115)
• Apoptosis (KEGG: hsa04210)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Hsp70 chaperone cycle (Reactome: R-HSA-3371568)
Protein Summary
DNAJA3 (Tid1) is a 480-amino-acid mitochondrial co-chaperone containing a conserved J-domain that stimulates Hsp70 ATPase activity. It exists in two splice isoforms (long and short) and regulates apoptosis by modulating p53 stability and NF-κB signaling. The protein is ubiquitously expressed with highest levels in heart and liver. Loss of DNAJA3 promotes tumorigenesis and chemoresistance, while mutations in its J-domain impair its pro-apoptotic function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID |
|---|
