The HSP90 family of genes in the human genome: Insights into their divergence and evolution

Abstract

HSP90 proteins are important molecular chaperones. Transcriptome and genome analyses revealed that the human HSP90 family includes 17 genes that fall into four classes. A standardized nomenclature for each of these genes is presented here. Classes HSP90AA, HSP90AB, HSP90B, and TRAP contain 7, 6, 3, and 1 genes, respectively. HSP90AA genes mapped onto chromosomes 1, 3, 4, and 11; HSP90AB genes mapped onto 3, 4, 6, 13 and 15; HSP90B genes mapped onto 1, 12, and 15; and the TRAP1 gene mapped onto 16. Six genes, HSP90AA1, HSP90AA2, HSP90N, HSP90AB1, HSP90B1 and TRAP1, were recognized as functional, and the remaining 11 genes were considered putative pseudogenes. Amino acid polymorphic variants were detected for genes HSP90AA1, HSP90AA2, HSP90AB1, HSP90B1, and TRAP1. The structures of these genes and the functional motifs and polymorphic variants of their proteins were documented and the features and functions of their proteins were discussed. Phylogenetic analyses based on both nucleotide and protein data demonstrated that HSP90(AA+AB+B) formed a monophyletic clade, whereas TRAP is a relatively distant paralogue of this clade.

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

“…One of the genes deleted in this region is a subtype of heat-shock protein 90, HSP90AB6. HSP 90 is a molecular chaperone whose association is required for stability and function of multiple signalling proteins that promote cancer cell growth and/or survival (Chen et al, 2005). Further studies with a larger sample size focusing on this particular region are warranted.…”

TRAP1 regulation of mitochondrial life or death decision in cancer cells and mitochondria-targeted TRAP1 inhibitors

“…TRAP1 and Hsp90 share conserved domain architectures with high amino acid sequence similarity, molecular chaperone functions, and homo-dimeric quaternary structures (11)(12)(13)15). Apart from the structural similarity between them, TRAP1 has the additional mitochondrial targeting sequence at its N-terminus, which is cleaved off after mitochondrial translocation, and lacks the highly charged flexible region between the N and M domains of Hsp90 (11)(12)(13). The N domain contains an ATP binding site and is the most conserved region between Hsp90 and TRAP1 (12,13).…”

“…Various classes of Hsp90 inhibitors have been developed, and some of them are already in clinical trials (10). The Hsp90 family in mammalian cells is composed of 4 major homologs: Hsp90α (inducible form) and Hsp90β (constitutive form) are cytosolic isoforms; the 94kDa glucose-regulated protein (GRP94) is localized to the endoplasmic reticulum, and TRAP1 resides in the mitochondrial matrix (6,11). In this review, recent progress concerning mitochondrial Hsp90 studies associated with cytoprotective functions in cancer cells, and the development of mitochondria-targeted inhibitors will be discussed.…”

Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway

“…H eat shock protein (HSP) grp94 (1), also known as gp96 (2), encoded by HSP90b1 (3), is the endoplasmic reticulum (ER) paralog of cytosolic HSP90. Like other HSPs, grp94 is induced by the accumulation of misfolded proteins (4) and binds and hydrolizes ATP (5-7).…”