HSPA1A is a human gene whose product dNAJA2** (DnaJ Heat Shock Protein Family (Hsp40) Member A2) is a co-chaperone that stimulates the ATPase activity of Hsp70 proteins. It contains a J-domain that delivers client proteins to Hsp70 and facilitates protein folding, refolding, and degradation. Variants in HSPA1A have been implicated in Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
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Gene Symbol
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DNAJA2
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Full Name
DnaJ Heat Shock Protein Family (Hsp40) Member A2
Chromosomal Location
16p13.3
NCBI Gene ID
[10284](https://www.ncbi.nlm.nih.gov/gene/10284)
OMIM
[604455](https://www.omim.org/entry/604455)
Ensembl ID
ENSG00000067715
UniProt ID
[O60830](https://www.uniprot.org/uniprot/O60830)
Protein
[DNAJA2-protein](/proteins/dnaja2-protein)
Associated Diseases
[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), Cancer
DNAJA2 (DnaJ Heat Shock Protein Family (Hsp40) Member A2) is a co-chaperone that stimulates the ATPase activity of Hsp70 proteins. It contains a J-domain that delivers client proteins to Hsp70 and facilitates protein folding, refolding, and degradation.
DNAJA2 has essential co-chaperone functions:
- J-domain protein (JDP): Contains characteristic J-domain that activates Hsp70 ATPase
- Substrate delivery: Binds misfolded proteins and delivers them to Hsp70
- Protein folding: Assists Hsp70 in de novo protein folding
- Protein refolding: Helps refold stress-denatured proteins
- Protein degradation: Targets misfolded proteins for proteasomal or autophagic clearance
- Transcription regulation: Associates with transcription factors
DNAJA2 interacts with:
DNAJA2 is implicated in AD through protein homeostasis:
- Facilitates clearance of Aβ aggregates
- Helps refold tau protein
- DNAJA2 levels are altered in AD brain
- Therapeutic potential for enhancing protein clearance [1]
In PD, DNAJA2 contributes to neuroprotection:
In ALS:
- Helps clear TDP-43 aggregates (TARDBP)
- Protects against SOD1 (SOD1) mutant toxicity
- Supports C9orf72 (C9orf72) repeat clearance
- Protein homeostasis maintenance is critical [3]
DNAJA2 has complex roles:
- Overexpressed in various cancers
- Promotes cell survival under stress
- May confer chemoresistance
DNAJA2 is expressed throughout the brain:
- Cerebral cortex: High expression in pyramidal neurons
- Hippocampus: Strong expression in all regions
- Substantia nigra: Present in dopaminergic neurons
- Cerebellum: Expressed in Purkinje cells
- Glial cells: Detected in astrocytes and microglia
DNAJA2 expression is regulated by:
- Heat shock factor 1 (HSF1) via heat shock elements
- Stress conditions (heat, oxidative stress, proteotoxic stress)
- Developmental and tissue-specific factors
- Disease states (altered in neurodegeneration)
| Variant |
Type |
Effect |
Significance |
| rs2071724 |
Promoter |
Expression modifier |
Associated with cancer |
| rs2071725 |
3'UTR |
miRNA binding |
mRNA stability |
| rs3741983 |
Coding |
Missense |
Functional impact |
- J-domain activators: Enhance Hsp70 co-chaperone function
- HSF1 activators: Boost heat shock response
- JDP-specific modulators: Target specific JDP functions
- Gene therapy to overexpress DNAJA2
- Small molecule J-domain mimetics
- Combination with proteostasis enhancers
Gene Expression: Human brain expression data from Allen Brain Atlas shows DNAJA2 is expressed across multiple brain regions with highest expression in cerebral cortex and basal ganglia. Expression patterns are consistent with its role in protein quality control and ER stress.
Single-Cell Expression: Single-cell RNA-seq data from the Allen Brain Cell Atlas shows DNAJA2 expression across major brain cell types, with enrichment in neurons and oligodendrocytes.
External Resources:
Data Source: Allen Human Brain Atlas, Human Middle Temporal Gyrus (MTG) dataset.