Isoforms
Hsp90 is highly conserved and expressed in a variety of different organisms from bacteria to mammals – including the prokaryotic analogue HtpG (high-temperature protein G) with 40% sequence identity and 55% similarity to the human protein. Yeast Hsp90 is 60% identical to human Hsp90α.
In mammalian cells, there are two or more genes encoding cytosolic Hsp90 homologues, with the human Hsp90α showing 85% sequence identity to Hsp90β. The α- and the β-forms are thought to be the result of a gene duplication event that occurred millions of years ago.
The five functional human genes encoding Hsp90 protein isoforms are listed below:
| family | subcellular location |
subfamily | gene | protein |
|---|---|---|---|---|
| HSP90A | cytosolic | HSP90AA (inducible) |
HSP90AA1 | Hsp90-α1 |
| HSP90AA2 | Hsp90-α2 | |||
| HSP90AB (constitutively expressed) |
HSP90AB1 | Hsp90-β | ||
| HSP90B | endoplasmic reticulum |
HSP90B1 | Endoplasmin/ GRP-94 |
|
| TRAP | mitochondrial | TRAP1 | TNF Receptor- Associated Protein 1 |
There are 12 human pseudogenes (non-functional genes) that encode additional Hsp90 isoforms that are not expressed as proteins.
A membrane-associated variant of cytosolic Hsp90, lacking an ATP-binding site, has recently been identified and was named Hsp90N. This HSP90α-Δ-N transcript is a chimera, with the first 105 bp of the coding sequence derived from the CD47 gene on chromosome 3q13.2, and the remaining coding sequence derived from HSP90AA1. However, gene-encoding Hsp90N was later proven to be non-existent in human genome. It is possibly a cloning artifact or a product of chromosomal rearrangement occurring in a single cell line.
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