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Gene Review

HSPA8  -  heat shock 70kDa protein 8

Homo sapiens

Synonyms: HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, ...
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Disease relevance of HSPA8


Psychiatry related information on HSPA8


High impact information on HSPA8

  • We demonstrate that purified light chains and synthetic peptides derived from their sequences bind hsc70 to stimulate ATP hydrolysis [7].
  • Our results show that LCa is more important for interactions with hsc70 than is LCb and suggest a model in which the LCa conformation regulates coated vesicle uncoating [7].
  • These differences correlate with high sequence divergence in the proline- and glycine-rich region (residues 47-71) that forms the hsc70 binding site [7].
  • In lymphoblastoid cells homozygous for these same HLA-DRB1 alleles the constitutive 70-kD HSP, HSP73, that targets selected proteins to lysosomes coprecipitated with HLA-DR [8].
  • Thus the QKRAA and RRRAA amino acid motifs of HLA-DR mediate binding of HLA-DR to HSP73 [8].

Chemical compound and disease context of HSPA8


Biological context of HSPA8


Anatomical context of HSPA8


Associations of HSPA8 with chemical compounds


Physical interactions of HSPA8

  • The earliest stage at which Hdj-2/Hsc70 could bind CFTR translation intermediates coincided with the expression of NBD1 in the cytosol [15].
  • Although peptides corresponding to the C-terminal region of p53 also contain potential binding sites, p53 proteins with C-terminal deletions are capable of binding to Hsc70, indicating that this region is not required for complex formation [22].
  • HspBP1 attenuates the ubiquitin ligase activity of CHIP when complexed with Hsc70 [23].
  • Hsc70 is among the proteins coimmunoprecipitated with stathmin, and it is the main protein retained specifically on stathmin-Sepharose beads identified by one- and two-dimensional electrophoresis and immunoblots [24].
  • These experiments show a profound effect of heat shock on the structure and stability of HSF-1 complexes during nuclear localization and support the hypothesis that HSC70 binding may control HSF-1 function [25].

Enzymatic interactions of HSPA8

  • A putative step in the CFTR folding pathway catalyzed by Hdj-2/Hsc70 is the formation of an intramolecular NBD1-R-domain complex [15].

Regulatory relationships of HSPA8

  • Thus, BAG-1 regulates the Hsc70 ATPase in a manner contrary to the Hsc70-interacting protein Hip, which stabilizes the ADP-bound state [14].
  • Bovine serum albumin (BSA)-Sepharose did not bind Hsc70, and anti-stathmin antisera specifically inhibited the interaction of Hsc70 with stathmin-Sepharose [24].
  • An additional mechanism for unmasking the NES may regulate nucleocytoplasmic trafficking of Hsc70 [16].
  • 4PBA downregulates protein and mRNA expression of the heat shock cognate protein HSC70 (the constitutively expressed member of the 70-kDa heat shock protein family) by approximately 40-50% and decreases formation of a HSC70-DeltaF508 CFTR complex that may be important in the intracellular degradation of DeltaF508 CFTR [26].
  • Hsp70 was induced in fibroblasts upon heavy metal exposure concentrations as low as 0.01 microM whereas hsc70 expression was induced upon organochlorine exposure concentrations as low as 0.001 microM [27].
  • All combinations of DJA1 or DJA2 with the three NEFs stimulated the Hsc70 ATPase rate, although Hsp110 became less effective with increasing concentrations [28].

Other interactions of HSPA8

  • Here we show that BAG-1 is a regulator of the Hsc70 chaperone [14].
  • Unexpectedly, dj2, but not dj1, together with hsc70 refolded the protein efficiently [17].
  • An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators [29].
  • We have screened a library of overlapping biotinylated peptides, spanning the entire human p53 sequence, for binding to the HSP70 proteins, Hsc70 and DnaK [22].
  • We propose that GAK is a required cofactor for the uncoating of clathrin-coated vesicles by Hsc70 in non-neuronal cells [30].

Analytical, diagnostic and therapeutic context of HSPA8


  1. CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survival. Shimura, H., Schwartz, D., Gygi, S.P., Kosik, K.S. J. Biol. Chem. (2004) [Pubmed]
  2. BAG-i expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data. Townsend, P.A., Dublin, E., Hart, I.R., Kao, R.H., Hanby, A.M., Cutress, R.I., Poulsom, R., Ryder, K., Barnes, D.M., Packham, G. J. Pathol. (2002) [Pubmed]
  3. Heat shock protein 72 expression in osteosarcomas correlates with good response to neoadjuvant chemotherapy. Trieb, K., Lechleitner, T., Lang, S., Windhager, R., Kotz, R., Dirnhofer, S. Hum. Pathol. (1998) [Pubmed]
  4. Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR. Rubenstein, R.C., Zeitlin, P.L. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  5. Overexpression of the heat shock protein HSP70 family and p53 protein and prognosis for patients with gastric cancer. Maehara, Y., Oki, E., Abe, T., Tokunaga, E., Shibahara, K., Kakeji, Y., Sugimachi, K. Oncology (2000) [Pubmed]
  6. Treatment with extracellular HSP70/HSC70 protein can reduce polyglutamine toxicity and aggregation. Novoselova, T.V., Margulis, B.A., Novoselov, S.S., Sapozhnikov, A.M., van der Spuy, J., Cheetham, M.E., Guzhova, I.V. J. Neurochem. (2005) [Pubmed]
  7. Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis. DeLuca-Flaherty, C., McKay, D.B., Parham, P., Hill, B.L. Cell (1990) [Pubmed]
  8. HLA-DR4 and HLA-DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70-kD heat shock proteins. Auger, I., Escola, J.M., Gorvel, J.P., Roudier, J. Nat. Med. (1996) [Pubmed]
  9. Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene transcription in NG108-15 neuroblastoma x glioma cells. Miles, M.F., Diaz, J.E., DeGuzman, V.S. J. Biol. Chem. (1991) [Pubmed]
  10. Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain. Kawagoe, J., Abe, K., Kogure, K. J. Neurochem. (1993) [Pubmed]
  11. Reduction of HSP70 and HSC70 mRNA inductions by bifemelane hydrochloride after transient ischemia in gerbil brain. Aoki, M., Abe, K., Liu, X.H., Lee, T.H., Kato, H., Kogure, K. Neurosci. Lett. (1993) [Pubmed]
  12. Heat shock cognate 70 mutations in sporadic breast carcinoma. Bakkenist, C.J., Koreth, J., Williams, C.S., Hunt, N.C., McGee, J.O. Cancer Res. (1999) [Pubmed]
  13. Comparison of gene expression profile between human chondrons and chondrocytes: a cDNA microarray study. Zhang, Z., Fan, J., Becker, K.G., Graff, R.D., Lee, G.M., Francomano, C.A. Osteoarthr. Cartil. (2006) [Pubmed]
  14. GrpE-like regulation of the hsc70 chaperone by the anti-apoptotic protein BAG-1. Höhfeld, J., Jentsch, S. EMBO J. (1997) [Pubmed]
  15. The Hdj-2/Hsc70 chaperone pair facilitates early steps in CFTR biogenesis. Meacham, G.C., Lu, Z., King, S., Sorscher, E., Tousson, A., Cyr, D.M. EMBO J. (1999) [Pubmed]
  16. Identification of novel nuclear export and nuclear localization-related signals in human heat shock cognate protein 70. Tsukahara, F., Maru, Y. J. Biol. Chem. (2004) [Pubmed]
  17. The human DnaJ homologue dj2 facilitates mitochondrial protein import and luciferase refolding. Terada, K., Kanazawa, M., Bukau, B., Mori, M. J. Cell Biol. (1997) [Pubmed]
  18. Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells: superiority of HSP60. Bethke, K., Staib, F., Distler, M., Schmitt, U., Jonuleit, H., Enk, A.H., Galle, P.R., Heike, M. J. Immunol. (2002) [Pubmed]
  19. Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors. Lee, D.W., Zhao, X., Zhang, F., Eisenberg, E., Greene, L.E. J. Cell. Sci. (2005) [Pubmed]
  20. Molecular and functional characterization of HSC54, a novel variant of human heat-shock cognate protein 70. Tsukahara, F., Yoshioka, T., Muraki, T. Mol. Pharmacol. (2000) [Pubmed]
  21. Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70. Carrello, A., Allan, R.K., Morgan, S.L., Owen, B.A., Mok, D., Ward, B.K., Minchin, R.F., Toft, D.O., Ratajczak, T. Cell Stress Chaperones (2004) [Pubmed]
  22. HSP70 binding sites in the tumor suppressor protein p53. Fourie, A.M., Hupp, T.R., Lane, D.P., Sang, B.C., Barbosa, M.S., Sambrook, J.F., Gething, M.J. J. Biol. Chem. (1997) [Pubmed]
  23. The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator. Alberti, S., Böhse, K., Arndt, V., Schmitz, A., Höhfeld, J. Mol. Biol. Cell (2004) [Pubmed]
  24. Stathmin interaction with HSC70 family proteins. Manceau, V., Gavet, O., Curmi, P., Sobel, A. Electrophoresis (1999) [Pubmed]
  25. Heat shock factor-1 and the heat shock cognate 70 protein associate in high molecular weight complexes in the cytoplasm of NIH-3T3 cells. Nunes, S.L., Calderwood, S.K. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  26. Sodium 4-phenylbutyrate downregulates HSC70 expression by facilitating mRNA degradation. Rubenstein, R.C., Lyons, B.M. Am. J. Physiol. Lung Cell Mol. Physiol. (2001) [Pubmed]
  27. Impact of heavy metals and organochlorines on hsp70 and hsc70 gene expression in black sea bream fibroblasts. Deane, E.E., Woo, N.Y. Aquat. Toxicol. (2006) [Pubmed]
  28. Functional divergence between co-chaperones of Hsc70. Tzankov, S., Wong, M.J., Shi, K., Nassif, C., Young, J.C. J. Biol. Chem. (2008) [Pubmed]
  29. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. Takayama, S., Xie, Z., Reed, J.C. J. Biol. Chem. (1999) [Pubmed]
  30. Role of cyclin G-associated kinase in uncoating clathrin-coated vesicles from non-neuronal cells. Greener, T., Zhao, X., Nojima, H., Eisenberg, E., Greene, L.E. J. Biol. Chem. (2000) [Pubmed]
  31. Heat shock 70-kDa protein 8 isoform 1 is expressed on the surface of human embryonic stem cells and downregulated upon differentiation. Son, Y.S., Park, J.H., Kang, Y.K., Park, J.S., Choi, H.S., Lim, J.Y., Lee, J.E., Lee, J.B., Ko, M.S., Kim, Y.S., Ko, J.H., Yoon, H.S., Lee, K.W., Seong, R.H., Moon, S.Y., Ryu, C.J., Hong, H.J. Stem Cells (2005) [Pubmed]
  32. Platelet adhesion to collagen under flow causes dissociation of a phosphoprotein complex of heat-shock proteins and protein phosphatase 1. Polanowska-Grabowska, R., Simon, C.G., Falchetto, R., Shabanowitz, J., Hunt, D.F., Gear, A.R. Blood (1997) [Pubmed]
  33. Identification of two molecular chaperons (HSX70, HSC70) in mature human erythrocytes. Gromov, P.S., Celis, J.E. Exp. Cell Res. (1991) [Pubmed]
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