Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the HSP90AA1 gene. Function The gene, HSP90AA1, encodes the human stress-inducible 90-kDa heat shock protein alpha (Hsp90A). Complemented by the constitutively expressed paralog Hsp90B which shares over 85% amino acid sequence identity, Hsp90A expression is initiated when a cell experiences proteotoxic stress. Once expressed Hsp90A dimers operate as molecular chaperones that bind and fold other proteins into their functional 3-dimensional structures. This molecular chaperoning ability of Hsp90A is driven by a cycle of structural rearrangements fueled by ATP hydrolysis. Current research on Hsp90A focuses in its role as a drug target due to its interaction with a large number of tumor promoting proteins and its role in cellular stress adaptation. Gene structure Human HSP90AA1 is encoded on the complement strand of Chromosome 14q32.33 and spans over 59 kbp. Several pseudogenes of HSP90AA1 exist throughout the human genome located on Chromosomes 3, 4, 11 and 14. The HSP90AA1 gene encodes for two distinct mRNA transcripts initiated from separate transcription start sites (TSS). No mRNA splice variants of HSP90AA1 have presently been verified. Transcript variant 1 (TV1, NM_001017963.2) encodes the infrequently observed 854 amino acid isoform 1 of Hsp90A (NP_001017963) from a 3,887 bp mRNA transcript containing 12 exons spanning 59, 012 bp. Transcript variant 1 is located directly next to the WDR20 gene, which is encoded on the opposite coding strand. Transcript variant 2 (TV2, NM_005348.3) encodes the well-studied 732 amino acid isoform 2 (NP_005339) from a 3,366 bp mRNA transcript containing 11 exons spanning 6,438 bp. DYNC1H1 encodes the gene product on the other side of HSP90AA1, which coincidentally has been found to interact with Hsp90A. Hsp90A TV1 and TV2 are identical except for an additional 112 amino acids on the N-terminus of isoform 1 encoded by its first 2 exons. The function of the extended N-terminal domain on isoform 1 is currently not understood. This information was gathered from both NCBI Gene and the UCSC Genome Browser. Expression Despite sharing similar amino acid sequence, Hsp90A expression is regulated in a different manner than Hsp90B. Hsp90A is the stress inducible isoform while Hsp90B is expressed constitutively. Several heat shock elements (HSE) are located upstream of Hsp90A allowing for its inducible expression. RNA levels measured in cell lines collected from cancer patients as well as normal tissue can be found at The Human Protein Atlas. Promoter Transcription