HSPA4: Heat Shock Protein Family A (Hsp70) Member 4
A molecular chaperone involved in protein folding, stress response, and cellular homeostasis; implicated in cancer and neurodegenerative disorders.
Gene Information Card
| Symbol | HSPA4 |
|---|---|
| Full Name | Heat Shock Protein Family A (Hsp70) Member 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.1 |
| NCBI Gene ID | 3308 ncbi.nlm.nih.gov/gene/3308 |
| Ensembl ID | ENSG00000176974 |
| UniProt ID | P34932 |
| OMIM ID | 601113 |
| HGNC ID | 5237 |
| Aliases | APG-2, HSP70RY, HSP70-4, RY, hsp70 |
Description
HSPA4 encodes a member of the heat shock protein 70 (Hsp70) family of molecular chaperones. The protein is constitutively expressed and functions in protein folding, transport, and protection against cellular stress. It interacts with co-chaperones such as HSPH1 and BAG3 to regulate protein homeostasis and apoptosis. HSPA4 is upregulated in various cancers and has been linked to neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of HSPA4 promotes tumor cell survival by inhibiting apoptosis and enhancing protein folding under hypoxic stress. | COSMIC; PMID: 25691885 |
| Alzheimer's disease | HSPA4 co-localizes with tau aggregates and may modulate tau pathology. | UniProt; PMID: 21147778 |
| Huntington's disease | HSPA4 interacts with mutant huntingtin and influences aggregate formation. | PMID: 16987963 |
| Hereditary spastic paraplegia | Mutations in HSPA4 have been reported in patients with autosomal dominant HSP. | ClinVar; PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 38.2 | High |
| Brain (cerebellum) | 25.1 | Medium |
| Heart | 22.8 | Medium |
| Liver | 18.5 | Medium |
| Lung | 15.3 | Medium |
| Kidney | 14.9 | Medium |
| Pancreas | 12.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 32.4 | Cervical cancer cell line; high expression |
| HEK293 | 28.7 | Embryonic kidney; moderate expression |
| MCF7 | 26.3 | Breast cancer; moderate expression |
| A549 | 24.1 | Lung cancer; moderate expression |
| K562 | 20.5 | Leukemia; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124G>A (p.Arg375Gln) | Missense | <0.01% | Reported in hereditary spastic paraplegia; may impair chaperone function (ClinVar). |
| c.1670C>T (p.Thr557Met) | Missense | <0.01% | Found in cancer samples; functional impact unknown (COSMIC). |
| c.214G>A (p.Gly72Ser) | Missense | <0.01% | Rare variant; associated with altered protein stability (ClinVar). |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg375Gln) reduce ATPase activity and chaperone function, leading to impaired protein folding and stress response.
Gain of Function (GOF)
Not well characterized; overexpression in tumors may confer a gain-of-function by enhancing cell survival.
Dominant Negative (DN)
p.Arg375Gln may act in a dominant-negative manner by disrupting co-chaperone interactions.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • unfolded protein binding (GO:0051082) |
| • protein folding (GO:0006457) | • response to heat (GO:0009408) |
| • ubiquitin protein ligase binding (GO:0031625) | • negative regulation of apoptotic process (GO:0043066) |
| • cytosol (GO:0005829) | • nucleus (GO:0005634) |
Pathways
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
• HSP70 chaperone cycle (Reactome R-HSA-3371568)
• Cellular response to heat stress (Reactome R-HSA-3371556)
• Apoptosis modulation by HSP70 (WikiPathways WP254)
Protein Summary
HSPA4 (UniProt P34932) is a 840-amino-acid protein with an N-terminal ATPase domain and a C-terminal peptide-binding domain. It functions as a molecular chaperone that assists in protein folding, prevents aggregation, and regulates apoptosis. The protein is constitutively expressed in most tissues, with highest levels in testis and brain. It interacts with co-chaperones such as HSPH1, BAG3, and STIP1. Post-translational modifications include phosphorylation and acetylation, which modulate its activity. HSPA4 is implicated in cancer progression and neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HSPA4 Knockout HEK293 Cell Line | EDJ-KQ963 | Human | 3308 | Details Get a Quote |
| HSPA4L Knockout HEK293 Cell Line | EDJ-KQ12195 | Human | 22824 | Details Get a Quote |
| HSPA4 Knockout A-549 Cell Line | EDJ-KQ19961 | Human | 3308 | Details Get a Quote |
| HSPA4 Knockout HeLa Cell Line | EDJ-KQ19963 | Human | 3308 | Details Get a Quote |
| HSPA4L Knockout A-549 Cell Line | EDJ-KQ40919 | Human | 22824 | Details Get a Quote |
| HSPA4L Knockout HCT 116 Cell Line | EDJ-KQ40920 | Human | 22824 | Details Get a Quote |
| HSPA4 Knockout HCT 116 Cell Line | EDJ-KQ18639 | Human | 3308 | Details Get a Quote |
| HSPA4L Knockout HeLa Cell Line | EDJ-KQ39681 | Human | 22824 | Details Get a Quote |
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