Alternative titles; symbols
HGNC Approved Gene Symbol: HSPBP1
Cytogenetic location: 19q13.42 Genomic coordinates (GRCh38) : 19:55,262,223-55,280,383 (from NCBI)
Using the ATPase domain of human HSP70 (see HSPA1A; 140550) as bait in a yeast 2-hybrid screen of a human heart cDNA library, Raynes and Guerriero (1998) cloned HSPBP1. The deduced 459-amino acid protein has a calculated molecular mass of 39.3 kD and contains 6 consecutive glycines near its N terminus. Northern blot analysis detected a 1.7-kb HSPBP1 transcript in all tissues examined, with highest expression in heart and skeletal muscle. Raynes and Guerriero (1998) also identified an HSPBP1 variant that they called HSPBP2, which has 2 polyadenylation signals rather than the single polyadenylation signal of HSPBP1. The deduced HSPBP2 protein is identical to HSPBP1 except that it has 9 consecutive glycines near the N terminus.
Using Northern blot analysis, Raynes and Guerriero (2000) found that the expression pattern of Hspbp1 in rat tissues was distinct from that in human. In rat, highest expression was in testis and lowest expression was in heart and skeletal muscle.
Raynes and Guerriero (1998) showed that human HSPBP1 coprecipitated with Hsp70 and Hsc70 (HSPA8; 600816) from bovine heart lysate. Recombinant HSPBP1 inhibited HSP40 (DNAJB1; 604572)-mediated stimulation of HSP70 ATPase activity in a dose-dependent manner, resulting in reduced ability of HSP70 to renature heat-denatured firefly luciferase. HSPBP1 specifically bound the ATPase domain of HSP70 and inhibited ATP binding.
Kabani et al. (2002) showed that human HSPBP1 functioned as a nucleotide exchange factor for HSP70, bovine Hsc70, and the yeast HSP70 ortholog Ssa1. HSPBP1 inhibited ATP binding and induced nucleotide dissociation. It inhibited refolding of luciferase by rabbit reticulocyte lysates, which contain factors required for protein refolding.
Raynes and Guerriero (2000) showed that the HSPBP1 and HSPBP2 isoforms had comparable inhibitory activities in luciferase refolding by rabbit reticulocyte lysates.
Alberti et al. (2004) found that epitope-tagged HSPBP1 immunoprecipitated HSC70 and the HSC70 cochaperone CHIP (STUB1; 607207) from HeLa cell lysates. In the absence of HSC70, HSPBP1 and CHIP bound each other with low affinity. In the presence of ubiquitin-activating and -conjugating enzymes, CHIP mediated ubiquitination of test proteins when bound to HSC70. Addition of HSPBP1 inhibited CHIP-mediated ubiquitination of test proteins as well as CHIP-mediated ubiquitination of HSC70. Complex formation between HSPBP1, HSC70, and CHIP was necessary for HSPBP1 to inhibit CHIP. Alberti et al. (2004) concluded that HSPBP1 regulates CHIP ubiquitin ligase activity.
Hartz (2009) mapped the HSPBP1 gene to chromosome 19q13.42 based on an alignment of the HSPBP1 sequence (GenBank AF093420) with the genomic sequence (build 36.1).
Alberti, S., Bohse, K., Arndt, V., Schmitz, A., Hohfeld, J. The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Molec. Biol. Cell 15: 4003-4010, 2004. [PubMed: 15215316] [Full Text: https://doi.org/10.1091/mbc.e04-04-0293]
Hartz, P. A. Personal Communication. Baltimore, Md. 7/17/2009.
Kabani, M., McLellan, C., Raynes, D. A., Guerriero, V., Brodsky, J. L. HspBP1, a homologue of the yeast Fes1 and Sls1 proteins, is an Hsc70 nucleotide exchange factor. FEBS Lett. 531: 339-342, 2002. [PubMed: 12417338] [Full Text: https://doi.org/10.1016/s0014-5793(02)03570-6]
Raynes, D. A., Guerriero, V. Isolation and characterization of isoforms of HspBP1, inhibitors of Hsp70. Biochim. Biophys. Acta 1490: 203-207, 2000. [PubMed: 10786638] [Full Text: https://doi.org/10.1016/s0167-4781(99)00238-9]
Raynes, D. A., Guerriero, V., Jr. Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein. J. Biol. Chem. 273: 32883-32888, 1998. [PubMed: 9830037] [Full Text: https://doi.org/10.1074/jbc.273.49.32883]