Alternative titles; symbols
HGNC Approved Gene Symbol: HSP90AB1
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:44,246,194-44,253,883 (from NCBI)
HSP90 proteins are highly conserved molecular chaperones that have key roles in signal transduction, protein folding, protein degradation, and morphologic evolution. HSP90 proteins normally associate with other cochaperones and play important roles in folding newly synthesized proteins or stabilizing and refolding denatured proteins after stress. There are 2 major cytosolic HSP90 proteins, HSP90AA1 (140571), an inducible form, and HSP90AB1, a constitutive form. Other HSP90 proteins are found in endoplasmic reticulum (HSP90B1; 191175) and mitochondria (TRAP1; 606219) (Chen et al., 2005).
By database analysis, Chen et al. (2005) identified several HSP90AB1 variants encoding proteins of 571, 632, 724, and 737 amino acids. Like other HSP90 proteins, the 724-amino acid HSP90AB1 protein has a highly conserved N-terminal domain, a charged domain, a middle domain involved in ATPase activity, a second charged domain, and a C-terminal domain. It also has a 4-helical cytokine motif, a gln-rich region, and a C-terminal MEEVD motif characteristic of cytosolic HSP90 proteins. The 737-amino acid HSP90AB1 isoform is identical to the 724-amino acid isoform except for a short C-terminal extension.
Rebbe et al. (1989) determined the complete genomic sequence of the HSP90B gene, including 1,102 bp upstream of the transcription initiation site. The gene consists of 12 exons and 11 introns. The exons range in size from 99 to 396 bp and the introns from 91 to 1,433 bp. Chen et al. (2005) also determined that the HSP90AB1 gene contains 12 exons.
By PCR amplification from a panel of hybrid cell lines, Durkin et al. (1993) mapped the HSPCB gene to chromosome 6 near the TCTE1 gene (186975) at 6p21. They were able to differentiate the structural gene from pseudogenes by designing primers from intronic sequences. By designing primers that bracket an intron, they were able to map 2 HSPCB pseudogenes, one to chromosome 4 and the other to chromosome 15. Saito et al. (1992) isolated 68 new RFLP markers on human chromosome 6, of which 64 were localized on chromosomal bands by fluorescence in situ hybridization. Takahashi et al. (1994) found that one of these markers, cloned into a cosmid vector and located at the D6S182 locus, contained the sequence corresponding to the 5-prime upstream region of the HSP90B gene. This strongly suggested that the gene is located at 6p12 inasmuch as the cosmid clone had been mapped to that band by Saito et al. (1992).
By genomic sequence analysis, Chen et al. (2005) mapped the HSP90AB1 gene to chromosome 6p21.1. They identified HSP90AB pseudogenes on chromosomes 4p15.33 (HSP90AB2P), 4q22.1 (HSP90AB3P), 15q21.3 (HSP90AB4P), 3p12.3 (HSP90AB5P), and 13q32.1 (HSP90AB6P).
Chen et al. (2005) provided a revised nomenclature system for the HSP90 gene family. Under this system, the root HSP90A indicates cytosolic HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA representing conventional HSP90-alpha, and HSP90AB representing HSP90-beta. The number following the root/class represents the gene in that class, and a 'P' at the end indicates a putative pseudogene.
Chen, B., Piel, W. H., Gui, L., Bruford, E., Monteiro, A. The HSP90 family of genes in the human genome: insights into their divergence and evolution. Genomics 86: 627-637, 2005. [PubMed: 16269234] [Full Text: https://doi.org/10.1016/j.ygeno.2005.08.012]
Durkin, A. S., Maglott, D. R., Vamvakopoulos, N. C., Zoghbi, H. Y., Nierman, W. C. Assignment of an intron-containing human heat-shock protein gene (hsp90-beta, HSPCB) to chromosome 6 near TCTE1 (6p21) and two intronless pseudogenes to chromosomes 4 and 15 by polymerase chain reaction amplification from a panel of hybrid cell lines. Genomics 18: 452-454, 1993. [PubMed: 8288256] [Full Text: https://doi.org/10.1006/geno.1993.1498]
Rebbe, N. F., Hickman, W. S., Ley, T. J., Stafford, D. W., Hickman, S. Nucleotide sequence and regulation of a human 90-kDa heat shock protein gene. J. Biol. Chem. 264: 15006-15011, 1989. [PubMed: 2768249]
Saito, S., Okui, K., Tokino, T., Oshimura, M., Nakamura, Y. Isolation and mapping of 68 RFLP markers on human chromosome 6. Am. J. Hum. Genet. 50: 65-70, 1992. [PubMed: 1346080]
Takahashi, I., Tanuma, R., Hirata, M., Hashimoto, K. A cosmid clone at the D6S182 locus on human chromosome 6p12 contains the 90-kDa heat shock protein beta-gene (HSP90-beta). Mammalian Genome 5: 121-122, 1994. [PubMed: 8180474] [Full Text: https://doi.org/10.1007/BF00292342]