HSP90AA1

GeneName

HSP90AA1

Summary

HSP90AA1, commonly referred to as HSP90 or LAP2, is a 85kDa heat shock protein that functions primarily as a molecular chaperone. It is expressed in various tissues, including the cytoplasm, nucleus, and plasma membrane, and plays a critical role in the folding, stabilization, and regulation of a wide range of client proteins, including those involved in signal transduction, cell cycle control, and apoptosis. HSP90AA1 is implicated in several biological processes, such as chaperone-mediated autophagy, protein refolding, and the cellular response to stressors like heat and viral infections. Its diverse subcellular localisations, including the cytosol, mitochondria, and extracellular regions, highlight its multifunctional nature in cellular homeostasis and stress responses.

Importance

HSP90AA1 is relevant to: - Cancer biology due to its role in stabilising oncoproteins and regulating cell proliferation - Neurodegenerative diseases, as it is involved in the folding and aggregation of proteins linked to conditions like Alzheimer’s - Immune response modulation through its involvement in the activation of innate immunity and regulation of cytokine production - Cardiovascular research, particularly in understanding cardiac muscle cell function and apoptosis - Cellular stress responses, as it helps maintain protein homeostasis under stressful conditions such as heat shock and oxidative stress

Top Products

For researchers investigating HSP90AA1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-Hsp90 antibody (ab13495), which has garnered 70 citations, reflecting its reliability and trust within the scientific community. This antibody is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), and immunocytochemistry (ICC). Additionally, we offer the recombinant antibody, Anti-Hsp90 antibody [EPR3953] (ab109248). This monoclonal antibody has been validated for use in WB and IHC, providing researchers with the batch-to-batch consistency that recombinant antibodies are known for. With 7 citations, it is also gaining recognition in the field. Together, these antibodies provide robust options for studying HSP90AA1 effectively. The Anti-Hsp90 antibody [4F3.E8] ELISA Kit (ab79848), with 1 citation, is a reliable option for researchers looking to measure HSP90AA1 levels in their samples.

Abcam Product Citation Summary

The data indicates a significant focus on the role of HSP90AA1 in various human cell types, particularly in cancer research, including hepatocellular carcinoma and adenocarcinoma. The use of multiple applications such as Western blotting and immunocytochemistry highlights the importance of this target in understanding cellular responses to stress and treatment sensitivity. Additionally, studies involving mouse models suggest its relevance in broader biological contexts, including Parkinson's disease and colorectal cancer.

Abcam Product Citation Table

Domain

The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.

Function

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812).

(Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion.

Post-translational modifications

ISGylated.

S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.

Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.

Sequence Similarities

Belongs to the heat shock protein 90 family.

Cellular localization

• Nucleus
• Cytoplasm
• Melanosome
• Cell membrane
• Mitochondrion
• Identified by mass spectrometry in melanosome fractions from stage I to stage IV.

Alternative names

HSP90A, HSPC1, HSPCA, HSP90AA1, Heat shock protein HSP 90-alpha, Heat shock 86 kDa, Heat shock protein family C member 1, Lipopolysaccharide-associated protein 2, Renal carcinoma antigen NY-REN-38, HSP 86, HSP86, LAP-2, LPS-associated protein 2

Database links

swissprot:P07900 omim:140571 omim:140572 swissprot:P08238 entrezGene:3320 entrezGene:3326

Other research areas

• Immunology & Infectious Disease