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Gene Review

HSPA4  -  heat shock 70kDa protein 4

Homo sapiens

Synonyms: APG-2, APG2, HEL-S-5a, HS24/P52, HSP70RY, ...
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Disease relevance of HSPA4


Psychiatry related information on HSPA4


High impact information on HSPA4

  • However, expression of the p53 gene and heat shock gene hsp 70 was not affected in these clones, indicating the existence of a specific regulatory linkage between c-fos and c-myc genes [7].
  • Cytoplasmic chaperones in precursor targeting to mitochondria: the role of MSF and hsp 70 [8].
  • A similar correlation for hsp60 and mycobacterial hsp70 did not achieve significance [9].
  • Still unclear, however, is exactly why most eukaryotic cells, in contrast to prokaryotic cells, express a novel form of hsp 70 (i.e., hsp 72) after experiencing stress [10].
  • In cells exposed to either an amino acid analog or sodium arsenite, two potent inducers of the stress response, newly synthesized proteins bind to but are not released from hsp 70 [11].

Chemical compound and disease context of HSPA4


Biological context of HSPA4


Anatomical context of HSPA4

  • Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5 [14].
  • While induction of hsp70 transcripts was observed in mouse TAMA26 Sertoli cells and NIH/3T3 fibroblasts on temperature shift from 37 degrees C to 42 degrees C (traditional heat shock) or from 32 degrees C to 39 degrees C, apg-2 transcripts were not induced under either condition [15].
  • Immunohistochemistry showed that hsp65 and hsp70 homologues were expressed in the synovial membrane in these patients but not in controls [9].
  • In addition to interacting with glucocorticoid receptors, the p56 protein of IM-9 cell cytosol is also found as part of a large heteromeric complex that contains both the 70-kDa and 90-kDa heat shock proteins (hsp70 and hsp90, respectively) [1].
  • We show that stimulation of murine and human macrophages with the heat shock proteins gp96 and hsp70 results in induction of inducible NO synthase and the production of NO [19].

Associations of HSPA4 with chemical compounds


Physical interactions of HSPA4


Regulatory relationships of HSPA4

  • Co-operative binding of hsp60 may promote transfer from hsp70 and correct folding of imported proteins in mitochondria [corrected] [26].

Other interactions of HSPA4

  • In addition, immunosuppressive and/or antiinflammatory activity of CsA can be executed via CyP-40 and hsp 70 complexed with SR, and following the interaction with CyP-related receptor of NK and with IL-8 [27].
  • In contrast, in the RVV group, 11 (45.8%) were hsp60-positive and eight (33.3%) were hsp70-positive [28].
  • By use of specific antibodies, we identified the fourth receptor subunit as a 59-kDa protein (p59); we did not obtain any evidence for the heat shock protein hsp70 being a receptor component [29].
  • Myeloma cells were transfected with the hsp70 gene under beta-actin gene promoter [30].
  • Analysis of whole cytosolic extracts by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography reveal an increased rate of radiolabeling for hsp70, hsp90, hsp100, ad hsp110, but no heat-inducible protein of smaller relative molecular mass is detected [1].

Analytical, diagnostic and therapeutic context of HSPA4

  • It was shown by electrophoresis and immunoblotting that a common sign of the cells which in vitro underwent such different harmful influences as ATP depletion, heat shock, oxidative stress, and SH reagent treatment was significant insolubilization of actin and 70-kDa heat-shock protein (hsp70) [31].
  • Patients with acute GVHD had a significant increase in IgM anti-hsp70 and/or anti-hsp90 early (30-90 days) after transplantation [32].
  • Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry [33].
  • In the present study, the synthesis of parasite heat shock proteins (hsp60, hsp70, and hsp90) was shown to be enhanced at a temperature of 39 C and the results of immunoprecipitation analysis indicated that parasite HSPs are highly immunogenic in T. cruzi-infected mice maintained at 36 C or room temperature (RT) [34].
  • The gene encoding a 70-kDa heat shock protein, hsp70, was not up-regulated (i.e., more highly expressed) as a part of the diapause program, nor was it up-regulated by desiccation stress, but it was up-regulated during recovery from cold shock [35].


  1. Hsp56: a novel heat shock protein associated with untransformed steroid receptor complexes. Sanchez, E.R. J. Biol. Chem. (1990) [Pubmed]
  2. Frequency of anti-hsp60, -65 and -70 antibodies in sera of patients with juvenile idiopathic arthritis. Zlacka, D., Vavrincova, P., Hien Nguyen, T.T., Hromadnikova, I. J. Autoimmun. (2006) [Pubmed]
  3. T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis. Salvetti, M., Buttinelli, C., Ristori, G., Carbonari, M., Cherchi, M., Fiorelli, M., Grasso, M.G., Toma, L., Pozzilli, C. J. Autoimmun. (1992) [Pubmed]
  4. Humoral immune response to the chlamydial heat shock proteins hsp60 and hsp70 in Chlamydia-associated chronic salpingitis with tubal occlusion. Dieterle, S., Wollenhaupt, J. Hum. Reprod. (1996) [Pubmed]
  5. Stress proteins in fungal diseases. Matthews, R.C., Maresca, B., Burnie, J.P., Cardona, A., Carratu, L., Conti, S., Deepe, G.S., Florez, A.M., Franceschelli, S., Garcia, E., Gargano, L.S., Kobayashi, G.S., McEwen, J.G., Ortiz, B.L., Oviedo, A.M., Polonelli, L., Ponton, J., Restrepos, A., Storlazzi, A. Med. Mycol. (1998) [Pubmed]
  6. Human olfactory receptor neurons express heat shock protein 70: age-related trends. Getchell, T.V., Krishna, N.S., Dhooper, N., Sparks, D.L., Getchell, M.L. The Annals of otology, rhinology, and laryngology. (1995) [Pubmed]
  7. Constitutive expression of c-fos antisense RNA blocks c-fos gene induction by interferon and by phorbol ester and reduces c-myc expression in F9 embryonal carcinoma cells. Levi, B.Z., Ozato, K. Genes Dev. (1988) [Pubmed]
  8. Cytoplasmic chaperones in precursor targeting to mitochondria: the role of MSF and hsp 70. Mihara, K., Omura, T. Trends Cell Biol. (1996) [Pubmed]
  9. Recognition of human 60 kD heat shock protein by mononuclear cells from patients with juvenile chronic arthritis. De Graeff-Meeder, E.R., van der Zee, R., Rijkers, G.T., Schuurman, H.J., Kuis, W., Bijlsma, J.W., Zegers, B.J., van Eden, W. Lancet (1991) [Pubmed]
  10. The constitutive and stress inducible forms of hsp 70 exhibit functional similarities and interact with one another in an ATP-dependent fashion. Brown, C.R., Martin, R.L., Hansen, W.J., Beckmann, R.P., Welch, W.J. J. Cell Biol. (1993) [Pubmed]
  11. Examining the function and regulation of hsp 70 in cells subjected to metabolic stress. Beckmann, R.P., Lovett, M., Welch, W.J. J. Cell Biol. (1992) [Pubmed]
  12. Heat shock proteins and heat shock protein-antibody complexes in placental tissues. Ziegert, M., Witkin, S.S., Sziller, I., Alexander, H., Brylla, E., Härtig, W. Infectious diseases in obstetrics and gynecology. (1999) [Pubmed]
  13. Okadaic acid markedly potentiates the heat-induced hsp 70 promoter activity. Chang, N.T., Huang, L.E., Liu, A.Y. J. Biol. Chem. (1993) [Pubmed]
  14. Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5. Fathallah, D.M., Cherif, D., Dellagi, K., Arnaout, M.A. J. Immunol. (1993) [Pubmed]
  15. Cloning of apg-2 encoding a novel member of heat shock protein 110 family. Kaneko, Y., Kimura, T., Kishishita, M., Noda, Y., Fujita, J. Gene (1997) [Pubmed]
  16. Molecular chaperones in protein folding and translocation. Clarke, A.R. Curr. Opin. Struct. Biol. (1996) [Pubmed]
  17. Invariant leu preceding turn motif phosphorylation site controls the interaction of protein kinase C with hsp70. Gao, T., Newton, A.C. J. Biol. Chem. (2006) [Pubmed]
  18. Allosteric regulation of hsp70 chaperones involves a conserved interdomain linker. Vogel, M., Mayer, M.P., Bukau, B. J. Biol. Chem. (2006) [Pubmed]
  19. Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. Panjwani, N.N., Popova, L., Srivastava, P.K. J. Immunol. (2002) [Pubmed]
  20. Specific activation of the human HSP70 promoter by copper sulfate in mosaic transgenic zebrafish. Seok, S.H., Park, J.H., Baek, M.W., Lee, H.Y., Kim, D.J., Uhm, H.M., Hong, J.J., Na, Y.R., Jin, B.H., Ryu, D.Y., Park, J.H. J. Biotechnol. (2006) [Pubmed]
  21. Role of nitric oxide in heat shock protein induced apoptosis of gammadeltaT cells. Atre, N., Thomas, L., Mistry, R., Pathak, K., Chiplunkar, S. Int. J. Cancer (2006) [Pubmed]
  22. Selective induction of chromosomal gene expression by human cytomegalovirus. Colberg-Poley, A.M., Santomenna, L.D. Virology (1988) [Pubmed]
  23. Induction of mitochondrial chaperonin, hsp60, by cadmium in human hepatoma cells. Hiranuma, K., Hirata, K., Abe, T., Hirano, T., Matsuno, K., Hirano, H., Suzuki, K., Higashi, K. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  24. Overexpressed heat shock protein 70 protects cells against DNA damage caused by ultraviolet C in a dose-dependent manner. Niu, P., Liu, L., Gong, Z., Tan, H., Wang, F., Yuan, J., Feng, Y., Wei, Q., Tanguay, R.M., Wu, T. Cell Stress Chaperones (2006) [Pubmed]
  25. Molecular events involved in transcriptional activation of heat shock genes become progressively refractory to heat stimulation during aging of human diploid fibroblasts. Liu, A.Y., Choi, H.S., Lee, Y.K., Chen, K.Y. J. Cell. Physiol. (1991) [Pubmed]
  26. Co-operative binding of hsp60 may promote transfer from hsp70 and correct folding of imported proteins in mitochondria [corrected]. Endo, T. FEBS Lett. (1991) [Pubmed]
  27. Some new aspects of molecular mechanisms of cyclosporin A effect on immune response. Zav'yalov, V.P., Denesyuk, A.I., Lundell, J., Korpela, T. APMIS (1995) [Pubmed]
  28. Detection of the human 70-kD and 60-kD heat shock proteins in the vagina: relation to microbial flora, vaginal pH, and method of contraception. Giraldo, P., Neuer, A., Ribeiro-Filho, A., Linhares, I., Witkin, S.S. Infectious diseases in obstetrics and gynecology. (1999) [Pubmed]
  29. Heterotetrameric structure of the human progesterone receptor. Rehberger, P., Rexin, M., Gehring, U. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  30. Transfection of NS0 myeloma fusion partner cells with HSP70 gene results in higher hybridoma yield by improving cellular resistance to apoptosis. Lasunskaia, E.B., Fridlianskaia, I.I., Darieva, Z.A., da Silva, M.S., Kanashiro, M.M., Margulis, B.A. Biotechnol. Bioeng. (2003) [Pubmed]
  31. Stress-induced insolubilization of certain proteins in ascites tumor cells. Kabakov, A.E., Gabai, V.L. Arch. Biochem. Biophys. (1994) [Pubmed]
  32. Antibodies to 70 kD and 90 kD heat shock proteins are associated with graft-versus-host disease in peripheral blood stem cell transplant recipients. Goral, J., Shenoy, S., Mohanakumar, T., Clancy, J. Clin. Exp. Immunol. (2002) [Pubmed]
  33. gammadelta T cells lyse autologous and allogenic oesophageal tumours: involvement of heat-shock proteins in the tumour cell lysis. Thomas, M.L., Samant, U.C., Deshpande, R.K., Chiplunkar, S.V. Cancer Immunol. Immunother. (2000) [Pubmed]
  34. Antibody response to heat shock proteins and histopathology in mice infected with Trypanosoma cruzi and maintained at elevated temperature. Arif, A.A., Gao, L., Davis, C.D., Helm, D.S. J. Parasitol. (1999) [Pubmed]
  35. Enhanced cold and desiccation tolerance in diapausing adults of Culex pipiens, and a role for Hsp70 in response to cold shock but not as a component of the diapause program. Rinehart, J.P., Robich, R.M., Denlinger, D.L. J. Med. Entomol. (2006) [Pubmed]
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