HSPA1A is a human gene whose product hSPBP1** (Hsp70 Binding Protein 1), also known as FISP1 (Hsp70-interacting protein), is a co-chaperone that modulates Hsp70 family protein function. It contains a J domain and interacts with Hsp70 proteins to regulate their activity in protein quality control. 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
[^3]
HSPBP1
[^4]
Full Name
Hsp70 Binding Protein 1
Chromosomal Location
19q13.32
NCBI Gene ID
[23640](https://www.ncbi.nlm.nih.gov/gene/23640)
OMIM
[609377](https://www.omim.org/entry/609377)
Ensembl ID
ENSG00000066501
UniProt ID
[Q9Y4X5](https://www.uniprot.org/uniprot/Q9Y4X5)
Protein
[HSPBP1-protein](/proteins/hspbp1-protein)
Associated Diseases
[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis), Cancer
HSPBP1 (Hsp70 Binding Protein 1), also known as FISP1 (Hsp70-interacting protein), is a co-chaperone that modulates Hsp70 family protein function. It contains a J domain and interacts with Hsp70 proteins to regulate their activity in protein quality control.
HSPBP1 functions as an Hsp70 co-chaperone:
- J-domain containing protein: Activates Hsp70 ATPase activity
- Protein folding assistance: Facilitates Hsp70-mediated protein folding
- Protein quality control: Targets misfolded proteins for degradation
- Stress response: Modulates cellular stress responses
- Anti-apoptotic function: Protects cells from stress-induced death
HSPBP1 interacts with:
HSPBP1 is implicated in AD pathogenesis:
- Modulates Aβ clearance through Hsp70 system
- Regulates tau protein homeostasis
- Altered expression in AD brain
- Potential therapeutic target [1]
In PD, HSPBP1 contributes to neuroprotection:
In ALS:
- Helps clear TDP-43 aggregates (TARDBP)
- Protects against SOD1 (SOD1) mutant toxicity
- Supports protein homeostasis
- May compensate for defective clearance [3]
HSPBP1 has complex roles:
- Overexpressed in various cancers
- Promotes cell survival
- May confer stress resistance
HSPBP1 is expressed in various brain regions:
- Cerebral cortex: Moderate to high expression in neurons
- Hippocampus: Strong expression in CA1-CA3 and dentate gyrus
- Substantia nigra: Present in dopaminergic neurons
- Cerebellum: Detected in Purkinje cells
- Glial cells: Expressed in astrocytes
HSPBP1 expression is regulated by:
- Stress-responsive transcription factors
- Cellular stress conditions
- Developmental stage
- Disease states
| Variant |
Type |
Effect |
Significance |
| rs2038863 |
Promoter |
Expression modifier |
Cancer association |
| rs7255274 |
3'UTR |
miRNA binding |
mRNA stability |
| rs10519 |
Coding |
Synonymous |
Functional impact |
- Co-chaperone modulators: Enhance HSPBP1 function
- HSF1 activators: Boost heat shock response
- Hsp70/Hsp40 complex enhancers
- Gene therapy for neurodegeneration
- Small molecule modulators
- Combination therapies