HSP90AB1
Description
The HSP90AB1 (heat shock protein 90 alpha family class B member 1) is a protein-coding gene located on chromosome 6.
Heat shock protein HSP 90-beta, also called HSP90beta, is a protein that in humans is encoded by the HSP90AB1 gene.
== Function == HSP90AB1 is a molecular chaperone. Chaperones are proteins that bind to other proteins, thereby stabilizing them in an ATP-dependent manner. Chaperones stabilize new proteins during translation, mature proteins which are partially unstable but also proteins that have become partially denatured due to various kinds of cellular stress. In case proper folding or refolding is impossible, HSPs mediate protein degradation. They also have specialized functions, such as intracellular transport into organelles.
== Classification ==
Human HSPs are classified into 5 major groups according to the HGNC:
HSP70 DnaJ (HSP40) HSPB (small heat shock proteins) HSPC (HSP90) chaperonins Chaperonins are characterized by their barrel-shaped structure with binding sites for client proteins inside the barrels. The human HSP90 group consists of 5 members according to the HGNC:
HSP90AA1 (heat shock protein 90 kDa alpha, class A, member 1) HSP90AA3P (heat shock protein 90 alpha family class A member 3, pseudogene) HSP90AB1 (heat shock protein 90 kDa alpha, class B, member 1) (this protein) HSP90B1 (heat shock protein 90 kDA beta, member 1) TRAP1 (TNF receptor associated protein 1) Whereas HSP90AA1 and HSP90AB1 are located primarily in the cytoplasm of the cells, HSP90B1 can be found in the endoplasmic reticulum and Trap1 in mitochondria.
== Co-chaperones == Co-chaperones bind to HSPs and influence their activity, substrate (client) specificity and interaction with other HSPs. For example, the co-chaperone CDC37 (cell division cycle 37) stabilizes the cell cycle regulatory proteins CDK4 (cyclin dependent kinase 4) and Cdk6.
HSP90AB1, also known as HSP90-beta or Heat shock 84 kDa, is a molecular chaperone that plays a crucial role in the proper folding, stability, and regulation of various client proteins involved in critical cellular processes like cell cycle control and signal transduction. This protein undergoes a functional cycle driven by its ATPase activity, where conformational changes in the client proteins are likely induced, leading to their activation. HSP90AB1 interacts dynamically with various co-chaperones, which modulate its substrate recognition, ATPase cycle, and chaperone function. Through these co-chaperones, HSP90AB1 engages with a diverse range of client proteins, acting as an adaptor that bridges the specific client protein with the central chaperone itself. The functional chaperone complex is assembled by the sequential recruitment of ATP, a co-chaperone, and a client protein. Once the chaperoning process is complete, the properly folded client protein and co-chaperone dissociate from HSP90, leaving it in an ADP-bound partially open conformation. Finally, ADP is released from HSP90, restoring its open conformation for the next chaperone cycle. Beyond its chaperone activity, HSP90AB1 also contributes to the regulation of the transcriptional machinery. It, along with its co-chaperones, modulates transcription at multiple levels: Firstly, they adjust the steady-state levels of specific transcription factors in response to various physiological cues. Secondly, they influence the activity of certain epigenetic modifiers, like histone deacetylases or DNA methyltransferases, adapting to environmental changes. Lastly, they participate in the removal of histones from the promoter region of specific genes, ultimately activating gene expression. In addition to its regulatory roles in transcription and protein folding, HSP90AB1 also plays a role in signal transduction pathways. It acts as an antagonist to STUB1, preventing the inhibition of TGF-beta signaling by inhibiting STUB1-mediated SMAD3 ubiquitination and degradation. It contributes to cell differentiation by chaperoning BIRC2, safeguarding it from auto-ubiquitination and degradation by the proteasomal machinery. Additionally, HSP90AB1 acts as the primary chaperone involved in the phosphorylation and activation of STAT1 under heat shock conditions. This process involves chaperoning both JAK2 and PRKCE, ultimately leading to the activation of its own transcription. Furthermore, HSP90AB1 is involved in the translocation of leaderless cargos, which lack the secretion signal sequence, into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment). This translocation process is facilitated by the cargo receptor TMED10. {ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:18239673, ECO:0000269|PubMed:19696785, ECO:0000269|PubMed:20353823, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:32272059, ECO:0000303|PubMed:25973397, ECO:0000303|PubMed:26991466, ECO:0000303|PubMed:27295069}
HSP90AB1 is also known as D6S182, HSP84, HSP90B, HSPC2, HSPCB.
