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Gene Review

DNAJA1  -  DnaJ (Hsp40) homolog, subfamily A, member 1

Homo sapiens

Synonyms: DJ-2, DNAJ2, DjA1, DnaJ homolog subfamily A member 1, DnaJ protein homolog 2, ...
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Disease relevance of DNAJA1

  • Within the ulcerated plaque group, there was a correlation between degree of stenosis and high HDJ-2 mRNA expression (r = 0.896, P =.016) [1].

Psychiatry related information on DNAJA1


High impact information on DNAJA1

  • Overexpression of wild-type HDJ-2/HSDJ in HeLa cells decreases the frequency of ataxin-1 aggregation [3].
  • Furthermore, we demonstrated that the J-domain of two human DnaJ homologs, HSJ1 or DNAJ2, could substitute functionally for the amino-terminus of TAg in promoting viral DNA replication [4].
  • Unexpectedly, dj2, but not dj1, together with hsc70 refolded the protein efficiently [5].
  • To investigate roles of dj2 and dj1, we developed a system of chaperone depletion from and readdition to rabbit reticulocyte lysates [5].
  • We propose that dj2 is the functional partner DnaJ homologue of hsc70 in the mammalian cytosol [5].

Chemical compound and disease context of DNAJA1

  • The level of expression of HDJ-2 mRNA was also correlated to the presence of plaque ulceration and the degree of luminal stenosis associated with the lesion [1].

Biological context of DNAJA1


Anatomical context of DNAJA1

  • Overexpression of HDJ-2/HSDJ did not modify inclusion formation in PC12 and SH-SY5Y cells but increased inclusion formation in COS-7 cells [2].
  • Simultaneous depletion of dj2 and dj3 from rabbit reticulocyte lysate markedly reduced mitochondrial import of pre-ornithine transcarbamylase and refolding of guanidine-denatured luciferase [9].
  • These results indicate that HSDJ is involved in an early step(s) of protein import into mitochondria [10].
  • HSDJ mRNA was heat-induced in cultured cells [10].
  • Increased HDJ-2 expression in carotid artery plaques was independent of hsp70 (Pearson correlation, r = 0.11; Bartlett chi(2) analysis, P =.71) [1].

Associations of DNAJA1 with chemical compounds

  • Transiently expressed HSDJ was also prenylated, whereas its mutant C394S in which cysteine of the "CaaX box" was mutated to serine, was not [10].
  • Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone [11].
  • Hdj2 inactivation paralleled the oxidation of cysteine thiols and concomitant release of coordinated zinc, suggesting a role of cysteine residues in the zinc finger domain of Hdj2 as a redox sensor of chaperone-mediated protein-folding machinery [12].
  • Treatment with tipifarnib suppressed FTase (but not geranylgeranyltransferase I) in bone marrow and peripheral blood mononuclear cells and also inhibited the farnesylation of HDJ-2 in unfractionated mononuclear cells and purified myeloma cells [13].
  • L-778,123 inhibited HDJ2 prenylation for the duration of the drug infusion in a dose-dependent manner, but seemed to plateau above 560 mg/m(2)/day [14].

Regulatory relationships of DNAJA1

  • Mechanistically, peptide-K inhibited, while peptide-Phi enhanced, HDJ2-induced stimulation of Hsc70 ATPase activity in vitro [15].

Other interactions of DNAJA1

  • In a reconstituted system, both hsc70-dj2 and hsc70-dj3 were effective in protein refolding [9].
  • Our results, together with the current structural information of the Hsp40 C-terminal and J-domains, were used to generate models of the internal structural organization of DjA1 and DjB4 [16].
  • CONCLUSION: These results demonstrate that expression of HDJ-2 is significantly increased in atherosclerotic carotid artery plaques as compared with hsp60 and hsp70 and correlates with luminal stenosis in ulcerated atherosclerotic carotid artery plaques [1].
  • A subset of the neuronal intranuclear inclusions stained positively for the chaperones Hsp90alpha and HDJ-2, a member of the Hsp40 family [17].
  • Small and large NIIs contained ataxin-7, human DnaJ homologue 2 (HDJ-2) and proteasome subunit 19S [18].

Analytical, diagnostic and therapeutic context of DNAJA1

  • In addition, Western blot analysis showed that expression of HDJ-2 was also not affected by heat shock [19].
  • We have also shown that the expression of HDJ-2 is highly elevated in kidney allograft biopsies of kidneys undergoing rejection [Y.G. Alevy, D. Brennan, S. Durriya, T. Howard, T. Mohanakumar, Increased expression of the HDJ-2 heat shock protein in biopsies of human rejected kidneys, Transplantation 61 (1996) 963-967] [19].
  • We identified a specific interaction of Hdj2 with the cellular redox enzyme thioredoxin using a yeast two-hybrid assay and a coimmunoprecipitation assay, thereby investigating how the redox environment of the cell regulates Hdj2 function [12].
  • RESULTS: The expression of heat shock protein HDJ-2 was significantly higher in samples from lung transplant recipients undergoing rejection when compared with recipients without rejection or infection [20].
  • In contrast, drug-induced increases in the slower migrating, unprocessed species of the chaperone protein HDJ-2 and the intranuclear intermediate filament protein lamin A were detected in all four cell lines after treatment with either agent [21].


  1. Increased expression of HDJ-2 (hsp40) in carotid artery atherosclerosis: a novel heat shock protein associated with luminal stenosis and plaque ulceration. Nguyen, T.Q., Jaramillo, A., Thompson, R.W., Dintzis, S., Oppat, W.F., Allen, B.T., Sicard, G.A., Mohanakumar, T. J. Vasc. Surg. (2001) [Pubmed]
  2. Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease. Wyttenbach, A., Carmichael, J., Swartz, J., Furlong, R.A., Narain, Y., Rankin, J., Rubinsztein, D.C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  3. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T., Zoghbi, H.Y. Nat. Genet. (1998) [Pubmed]
  4. DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication. Campbell, K.S., Mullane, K.P., Aksoy, I.A., Stubdal, H., Zalvide, J., Pipas, J.M., Silver, P.A., Roberts, T.M., Schaffhausen, B.S., DeCaprio, J.A. Genes Dev. (1997) [Pubmed]
  5. 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]
  6. Cloning of a unique human homologue of the Escherichia coli DNAJ heat shock protein. Chellaiah, A., Davis, A., Mohanakumar, T. Biochim. Biophys. Acta (1993) [Pubmed]
  7. A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation, and transrepression defects of a glucocorticoid receptor zinc finger mutant. Tang, Y., Ramakrishnan, C., Thomas, J., DeFranco, D.B. Mol. Biol. Cell (1997) [Pubmed]
  8. Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial. Karp, J.E., Lancet, J.E., Kaufmann, S.H., End, D.W., Wright, J.J., Bol, K., Horak, I., Tidwell, M.L., Liesveld, J., Kottke, T.J., Ange, D., Buddharaju, L., Gojo, I., Highsmith, W.E., Belly, R.T., Hohl, R.J., Rybak, M.E., Thibault, A., Rosenblatt, J. Blood (2001) [Pubmed]
  9. Human DnaJ homologs dj2 and dj3, and bag-1 are positive cochaperones of hsc70. Terada, K., Mori, M. J. Biol. Chem. (2000) [Pubmed]
  10. HSDJ, a human homolog of DnaJ, is farnesylated and is involved in protein import into mitochondria. Kanazawa, M., Terada, K., Kato, S., Mori, M. J. Biochem. (1997) [Pubmed]
  11. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Stenoien, D.L., Cummings, C.J., Adams, H.P., Mancini, M.G., Patel, K., DeMartino, G.N., Marcelli, M., Weigel, N.L., Mancini, M.A. Hum. Mol. Genet. (1999) [Pubmed]
  12. Redox-regulated cochaperone activity of the human DnaJ homolog Hdj2. Choi, H.I., Lee, S.P., Kim, K.S., Hwang, C.Y., Lee, Y.R., Chae, S.K., Kim, Y.S., Chae, H.Z., Kwon, K.S. Free Radic. Biol. Med. (2006) [Pubmed]
  13. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma. Alsina, M., Fonseca, R., Wilson, E.F., Belle, A.N., Gerbino, E., Price-Troska, T., Overton, R.M., Ahmann, G., Bruzek, L.M., Adjei, A.A., Kaufmann, S.H., Wright, J.J., Sullivan, D., Djulbegovic, B., Cantor, A.B., Greipp, P.R., Dalton, W.S., Sebti, S.M. Blood (2004) [Pubmed]
  14. A phase I and pharmacological study of the farnesyl protein transferase inhibitor L-778,123 in patients with solid malignancies. Britten, C.D., Rowinsky, E.K., Soignet, S., Patnaik, A., Yao, S.L., Deutsch, P., Lee, Y., Lobell, R.B., Mazina, K.E., McCreery, H., Pezzuli, S., Spriggs, D. Clin. Cancer Res. (2001) [Pubmed]
  15. Differential inhibition of Hsc70 activities by two Hsc70-binding peptides. Thulasiraman, V., Yun, B.G., Uma, S., Gu, Y., Scroggins, B.T., Matts, R.L. Biochemistry (2002) [Pubmed]
  16. Low resolution structural study of two human HSP40 chaperones in solution. DJA1 from subfamily A and DJB4 from subfamily B have different quaternary structures. Borges, J.C., Fischer, H., Craievich, A.F., Ramos, C.H. J. Biol. Chem. (2005) [Pubmed]
  17. Protein surveillance machinery in brains with spinocerebellar ataxia type 3: redistribution and differential recruitment of 26S proteasome subunits and chaperones to neuronal intranuclear inclusions. Schmidt, T., Lindenberg, K.S., Krebs, A., Schöls, L., Laccone, F., Herms, J., Rechsteiner, M., Riess, O., Landwehrmeyer, G.B. Ann. Neurol. (2002) [Pubmed]
  18. Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content. Takahashi, J., Fujigasaki, H., Zander, C., El Hachimi, K.H., Stevanin, G., Dürr, A., Lebre, A.S., Yvert, G., Trottier, Y., Thé, H., Hauw, J.J., Duyckaerts, C., Brice, A. Brain (2002) [Pubmed]
  19. Characterization of HDJ-2, a human 40 kD heat shock protein. Davis, A.R., Alevy, Y.G., Chellaiah, A., Quinn, M.T., Mohanakumar, T. Int. J. Biochem. Cell Biol. (1998) [Pubmed]
  20. Increased expression of HDJ-2 (heat shock protein 40) and heat shock protein 70 in biopsy specimens of transplanted human lungs. Rizzo, M., Alevy, Y.G., Sundaresan, S., Lynch, J., Trulock, E.P., Cooper, J.D., Patterson, G.A., Mohanakumar, T. J. Heart Lung Transplant. (1998) [Pubmed]
  21. Comparison of potential markers of farnesyltransferase inhibition. Adjei, A.A., Davis, J.N., Erlichman, C., Svingen, P.A., Kaufmann, S.H. Clin. Cancer Res. (2000) [Pubmed]
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