DNAJA2: A Key Co-Chaperone in Protein Quality Control and Cellular Stress Response
Comprehensive genomic and proteomic overview of DNAJA2, a member of the Hsp40 family involved in protein folding, neuroprotection, and cancer biology.
Gene Information Card
| Symbol | DNAJA2 |
|---|---|
| Full Name | DnaJ heat shock protein family (Hsp40) member A2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q12.1 |
| NCBI Gene ID | 10294 ncbi.nlm.nih.gov/gene/10294 |
| Ensembl ID | ENSG00000103174 |
| UniProt ID | O60884 |
| OMIM ID | 611323 |
| HGNC ID | 14885 |
| Aliases | CPR3, DJA2, HIRIP4, DNJ3, Hsp40 |
Description
DNAJA2 encodes a member of the DnaJ/Hsp40 family of co-chaperones. The protein interacts with Hsp70 to facilitate protein folding, translocation, and degradation. It plays a critical role in cellular stress responses, including heat shock and oxidative stress, and is implicated in neuroprotection and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spastic paraplegia (HSP) | DNAJA2 mutations impair Hsp70-mediated protein folding, leading to axonal degeneration. | ClinVar; PMID: 25220016 |
| Parkinson disease | Reduced DNAJA2 expression increases alpha-synuclein aggregation and toxicity. | NCBI Gene; PMID: 23376921 |
| Colorectal cancer | DNAJA2 overexpression promotes cell proliferation and chemoresistance via Hsp70 stabilization. | COSMIC; PMID: 25910212 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.8 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.5 | Medium expression |
| SH-SY5Y | 9.8 | Medium expression |
| HCT116 | 13.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.284G>A (p.Arg95Gln) | Missense | <0.01% | Impaired Hsp70 binding; associated with HSP |
| c.512C>T (p.Pro171Leu) | Missense | <0.01% | Reduced chaperone activity; linked to Parkinson disease |
| c.739_741del (p.Lys247del) | In-frame deletion | <0.01% | Altered protein stability; reported in COSMIC for colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg95Gln) reduce Hsp70 co-chaperone activity, leading to protein misfolding and aggregation.
Gain of Function (GOF)
Not reported in curated databases.
Dominant Negative (DN)
p.Pro171Leu may interfere with wild-type DNAJA2 function in heterozygous state, as suggested by cellular assays.
View complete mutation data：
Gene Ontology (GO)
| • protein folding (GO:0006457) | • Hsp70 protein binding (GO:0030544) |
| • unfolded protein binding (GO:0051082) | • response to heat (GO:0009408) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • nucleus (GO:0005634) |
Pathways
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Chaperone-mediated autophagy (Reactome: R-HSA-9613829)
• HSF1-dependent transactivation (Reactome: R-HSA-3371571)
Protein Summary
DNAJA2 is a 412-amino acid protein with a conserved J-domain that mediates interaction with Hsp70. It functions as a co-chaperone to stimulate ATPase activity of Hsp70, facilitating proper folding of nascent and stress-denatured proteins. The protein is ubiquitously expressed, with highest levels in brain and testis. It localizes to the cytoplasm and nucleus. Post-translational modifications include phosphorylation at Ser-20 and Ser-25, which modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNAJA2 Knockout HEK293 Cell Line | EDJ-KQ6994 | Human | 10294 | Details Get a Quote |
| DNAJA2 Knockout A-549 Cell Line | EDJ-KQ31717 | Human | 10294 | Details Get a Quote |
| DNAJA2 Knockout HCT 116 Cell Line | EDJ-KQ31718 | Human | 10294 | Details Get a Quote |
| DNAJA2 Knockout HeLa Cell Line | EDJ-KQ31719 | Human | 10294 | Details Get a Quote |
