Summary

Name HSP90AA1
Full Name Heat shock protein HSP 90-alpha
Synonyms Heat shock 86 kDa, HSP 86, HSP86, Lipopolysaccharide-associated protein 2, LAP-2, LPS-associated protein 2, Renal carcinoma antigen NY-REN-38 | HSP90A, HSPC1, HSPCA
Primary ID P07900
Links - -
Type protein
Relations 27
Pathways Glucocorticoid receptor Signaling
Inhibitors luminespib
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:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). 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). 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 mitochodria outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812).

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Modifications Tables

Relations

Regulator Mechanism target score
+ img/unknown.png phosphorylation HSP90AA1 0.545
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation HSP90AA1 0.26
Publications: 3 Organism: Homo Sapiens
+ img/unknown.png phosphorylation HSP90AA1 0.437
Publications: 2 Organism: Homo Sapiens
+ img/unknown.png phosphorylation HSP90AA1 0.461
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding FLCN 0.309
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding HSP90AA1 0.2
Publications: 1 Organism: Chlorocebus Aethiops
+ down-regulates img/direct_inhibition.png binding NR3C1 0.724
Publications: 1 Organism: Homo Sapiens
Pathways:Glucocorticoid receptor Signaling
+ up-regulates activity img/direct-activation.png binding AR 0.753
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding HSP90AA1 0.931
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding NOS3 0.748
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding LGMN 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding NOD2 0.354
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding PPP5C 0.762
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination HSP90AA1 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding HSP90AA1 0.418
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition HSP90AA1 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding HSP90AA1 0.764
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity img/direct-activation.png binding CBLL1 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding TGFBR2 0.394
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding PAFAH1B1 0.505
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding HSP90AA1 0.912
Publications: 1 Organism: In Vitro
+ up-regulates img/direct-activation.png binding TGFBR1 0.425
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding HSP90AA1 0.56
Publications: 1 Organism: Homo Sapiens