Tchem HSP90AA1 Heat shock protein HSP 90-alpha

Protein Summary

Description

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: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:27295069, PubMed:26991466). 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). The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Uniprot Accession IDs

• P07900
• A8K500
• B3KPJ9
• Q2PP14
• Q5CAQ6
• Q5CAQ7
• Q9BVQ5

Gene Name

• HSP90AA1

Ensembl ID

• ENST00000216281
• ENSP00000216281
• ENSG00000080824
• ENST00000334701
• ENSP00000335153

Symbol

• HSP90A
• HSPC1
• HSPCA
• EL52
• HSPN
• LAP2
• HSP86
• HSPC1
• HSPCA
• Hsp89
• Hsp90
• LAP-2
• HSP89A
• HSP90A
• HSP90N
• Hsp103
• HSPCAL1
• HSPCAL4
• HEL-S-65p

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug	1
hub protein	1
interacting protein	1
molecular function	1
disease perturbation	0.99

Protein Classes

PANTHER Classes

Protein / Chaperone / Hsp90 Family Chaperone / Heat Shock Protein Hsp 90-alpha

DTO Classes

Protein / Chaperone / Hsp90 Family Chaperone / Heat Shock Protein Hsp 90-alpha

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7152.23   (req: < 5)

Gene RIFs: 484   (req: <= 3)

Antibodies: 1647   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 7152.23   (req: >= 5)

Gene RIFs: 484   (req: > 3)

Antibodies: 1647   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 61

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1134

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4