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. Hop (HSP organizing protein) mediates the interaction between different HSPs, forming HSP70–HSP90 complexes. TOM70 (translocase of the outer mitochondrial membrane of ~70 kDa) mediates translocation of client proteins through the import pore into the mitochondrial matrix. Isoforms Human HPS90AB1 shares 60% overall homology to its closest relative HSP90AA1. Murine HSP90AB1 was cloned in 1987 based on homology of the corresponding Drosophila melanogaster gene. Protein structure HSP90AB1 is active as homodimer, forming a V-shaped structure. It consists of three major domains: N-terminal domain (NTD) containing the ATP binding site middle domain, primarily responsible for substrate binding C-terminal domain (CTD) which is the dimerization domain (base of the V). Between these domains, there are short charged domains. Co-chaperones primarily bind to the NTD and CTD. The latter Co-chaperones usually contain a tetratricopeptide repeat (TPR) domain which binds to a MEEVD motif at the C-terminus