AHSA1: Activator of HSP90 ATPase Activity 1
A key co-chaperone regulating HSP90 function in protein folding and cellular stress response
Gene Information Card
| Symbol | AHSA1 |
|---|---|
| Full Name | Activator of HSP90 ATPase Activity 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 10598 ncbi.nlm.nih.gov/gene/10598 |
| Ensembl ID | ENSG00000100591 |
| UniProt ID | O95433 |
| OMIM ID | 608466 |
| HGNC ID | 360 |
| Aliases | AHA1, HSP90-ATPase activator 1, p38 |
Description
AHSA1 (also known as AHA1) encodes a co-chaperone that stimulates the ATPase activity of HSP90, a molecular chaperone essential for the maturation and stabilization of client proteins involved in cell cycle control, signal transduction, and stress response. By binding to the middle domain of HSP90, AHSA1 accelerates ATP hydrolysis, facilitating client protein activation. AHSA1 is implicated in cancer progression and other diseases where HSP90 function is dysregulated.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | AHSA1 overexpression enhances HSP90 activity, promoting stabilization of oncogenic client proteins such as HER2 and Akt. | PMID: 23543788; COSMIC |
| Prostate cancer | AHSA1 upregulation correlates with increased androgen receptor signaling and resistance to therapy. | PMID: 26080835; COSMIC |
| Lung cancer | AHSA1 amplification and overexpression contribute to HSP90-dependent survival of tumor cells. | PMID: 27498916; COSMIC |
| Colorectal cancer | AHSA1 expression is elevated and associated with poor prognosis, likely via HSP90-mediated stabilization of β-catenin. | PMID: 29057922; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Brain | 6.1 | Low |
| Lung | 9.7 | Medium |
| Kidney | 10.2 | Medium |
| Testis | 15.8 | High |
| Spleen | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression in embryonic kidney cells |
| HeLa | 11.8 | Moderate expression in cervical cancer cells |
| MCF7 | 13.5 | High expression in breast cancer cells |
| A549 | 10.1 | Moderate expression in lung cancer cells |
| HepG2 | 9.3 | Moderate expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.287A>G (p.Asn96Ser) | Missense | <0.01% | Unknown; rare variant reported in ClinVar |
| c.502C>T (p.Arg168Trp) | Missense | <0.01% | Unknown; rare variant reported in ClinVar |
| c.724G>A (p.Glu242Lys) | Missense | <0.01% | Unknown; rare variant reported in ClinVar |
| c.1030C>T (p.Arg344Cys) | Missense | <0.01% | Unknown; rare variant reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in human disease; experimental knockdown reduces HSP90 ATPase activity.
Gain of Function (GOF)
Overexpression in cancers is considered a gain-of-function, enhancing HSP90 activity and client protein maturation.
Dominant Negative (DN)
No dominant-negative mutations described for AHSA1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005524 - ATP binding | • GO:0016887 - ATP hydrolysis activity |
| • GO:0030544 - Hsp70 protein binding | • GO:0051082 - unfolded protein binding |
| • GO:0006457 - protein folding | • GO:0031625 - ubiquitin protein ligase binding |
| • GO:0042802 - identical protein binding | • GO:0005829 - cytosol |
| • GO:0005634 - nucleus |
Pathways
• HSP90 chaperone cycle (Reactome: R-HSA-3371497)
• Protein folding (KEGG: hsa04141)
• Chaperone-mediated protein folding (WikiPathways: WP254)
Protein Summary
AHSA1 (AHA1) is a 38 kDa protein that functions as a positive regulator of HSP90 ATPase activity. It binds to the middle domain of HSP90, inducing a conformational change that accelerates ATP hydrolysis and client protein maturation. AHSA1 is expressed in multiple tissues, with highest levels in testis and heart. Its overexpression is observed in several cancers, where it contributes to oncogenic signaling by stabilizing HSP90 clients such as HER2, Akt, and androgen receptor. AHSA1 is a potential therapeutic target for modulating HSP90 activity in disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AHSA1 Knockout HEK293 Cell Line | EDJ-KQ2260 | Human | 10598 | Details Get a Quote |
| AHSA1 Knockout A-549 Cell Line | EDJ-KQ22582 | Human | 10598 | Details Get a Quote |
| AHSA1 Knockout HCT 116 Cell Line | EDJ-KQ22583 | Human | 10598 | Details Get a Quote |
| AHSA1 Knockout HeLa Cell Line | EDJ-KQ22584 | Human | 10598 | Details Get a Quote |
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