Summary

Name HSP90AB1
Full Name Heat shock protein HSP 90-beta
Synonyms HSP 90, Heat shock 84 kDa, HSP 84, HSP84 | HSP90B, HSPC2, HSPCB
Primary ID P08238
Links - -
Type protein
Relations 16
Inhibitors NVP-BEP800; 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 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. They first 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 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). Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059).

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▶Modifications Tables

Relations

Regulator Mechanism target score ℹ
+ CSNK2A1down-regulates img/direct_inhibition.png phosphorylation HSP90AB1 0.339
Publications: 2 Organism: Homo Sapiens
+ SRCup-regulates img/direct-activation.png phosphorylation HSP90AB1 0.57
Publications: 1 Organism: Homo Sapiens
+ HSP90AB1up-regulates quantity img/direct-activation.png binding CBLL1 0.2
Publications: 1 Organism: Homo Sapiens
+ STIP1down-regulates activity img/direct_inhibition.png binding HSP90AB1 0.848
Publications: 1 Organism: Homo Sapiens
+ HSP90AB1up-regulates activity img/direct-activation.png binding NOS3 0.528
Publications: 1 Organism: Homo Sapiens
+ NVP-BEP800down-regulates img/direct_inhibition.png chemical inhibition HSP90AB1 0.8
Publications: 1 Organism: Homo Sapiens
+ FNIP2down-regulates activity img/direct_inhibition.png binding HSP90AB1 0.267
Publications: 1 Organism: Homo Sapiens
+ AHSA1up-regulates activity img/direct-activation.png binding HSP90AB1 0.681
Publications: 1 Organism: Homo Sapiens
+ HSP90AB1down-regulates img/direct_inhibition.png binding APAF1 0.398
Publications: 1 Organism: Homo Sapiens
+ HSP90AB1up-regulates activity img/direct-activation.png binding AR 0.692
Publications: 1 Organism: Homo Sapiens
+ luminespibdown-regulates img/direct_inhibition.png chemical inhibition HSP90AB1 0.8
Publications: 1 Organism: Homo Sapiens
+ FNIP1down-regulates activity img/direct_inhibition.png binding HSP90AB1 0.2
Publications: 1 Organism: Homo Sapiens
+ HSP90AB1up-regulates quantity by stabilization img/direct-activation.png binding FLCN 0.2
Publications: 2 Organism: Homo Sapiens
+ HSP90AB1up-regulates quantity by stabilization img/direct-activation.png binding NOD2 0.326
Publications: 1 Organism: Homo Sapiens