Tchem HSP90AB1 Heat shock protein HSP 90-beta

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. 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:16478993, PubMed:19696785). 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. 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. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues. 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. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery (PubMed:18239673). Main chaperone that is involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription (PubMed:20353823). This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Dec 2012]

Uniprot Accession IDs

• P08238
• B2R5P0
• Q5T9W7
• Q9NQW0
• Q9NTK6
• HSP 90

Gene Name

• HSP90AB1

Ensembl ID

• ENST00000353801
• ENSP00000325875
• ENSG00000096384
• ENST00000371554
• ENSP00000360609
• ENST00000371646
• ENSP00000360709
• ENST00000620073
• ENSP00000481908

Symbol

• HSP90B
• HSPC2
• HSPCB
• HSP84
• HSPC2
• HSPCB
• D6S182
• HSP90B

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
interacting protein	1
molecular function	1
protein complex	1
biological process	0.99

Protein Classes

PANTHER Classes

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

DTO Classes

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

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: 116.15   (req: < 5)

Gene RIFs: 90   (req: <= 3)

Antibodies: 1559   (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: 116.15   (req: >= 5)

Gene RIFs: 90   (req: > 3)

Antibodies: 1559   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 76

Tchem

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

Active Ligands: 352

Tclin

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

Active Drug: 0