hsp40 heat shock proteins


Summary: A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.

Top Publications

  1. Dittmar K, Banach M, Galigniana M, Pratt W. The role of DnaJ-like proteins in glucocorticoid receptor.hsp90 heterocomplex assembly by the reconstituted hsp90.p60.hsp70 foldosome complex. J Biol Chem. 1998;273:7358-66 pubmed
    ..hsp90 heterocomplex assembled in reticulocyte lysate. We conclude that hsp40 is a component of the multiprotein hsp90-based chaperone system where it potentiates GR.hsp90 heterocomplex assembly. ..
  2. Chan H, Warrick J, Gray Board G, Paulson H, Bonini N. Mechanisms of chaperone suppression of polyglutamine disease: selectivity, synergy and modulation of protein solubility in Drosophila. Hum Mol Genet. 2000;9:2811-20 pubmed
    ..These findings have implications for these and other human neurodegenerative diseases associated with abnormal protein aggregation. ..
  3. Meyer A, Hoover L, Craig E. The cytosolic J-protein, Jjj1, and Rei1 function in the removal of the pre-60 S subunit factor Arx1. J Biol Chem. 2010;285:961-8 pubmed publisher
  4. Johnson J, Ahrendt E, Braun J. CSPalpha: the neuroprotective J protein. Biochem Cell Biol. 2010;88:157-65 pubmed publisher
    ..Here we highlight recent advances in our understanding of the critical role that CSPalpha plays in governing exocytotic secretory functions. ..
  5. Lin S, Hsueh C, Yu S, Su C, Shum W, Yeh K, et al. HLJ1 is a novel caspase-3 substrate and its expression enhances UV-induced apoptosis in non-small cell lung carcinoma. Nucleic Acids Res. 2010;38:6148-58 pubmed publisher
    ..Further experiments revealed a non-typical caspase-3 cleavage site (MEID) at amino acid 125-128 of HLJ1. Our results collectively suggest that HLJ1 is a novel substrate of caspase-3 during the UV-induced apoptotic process...
  6. Stolz A, Wolf D. Endoplasmic reticulum associated protein degradation: a chaperone assisted journey to hell. Biochim Biophys Acta. 2010;1803:694-705 pubmed publisher
    ..This review summarizes our up to date knowledge of chaperone classes and chaperone function in endoplasmic reticulum associated degradation of protein waste. ..
  7. Tukaj S, Kotlarz A, Jozwik A, Smolenska Z, Bryl E, Witkowski J, et al. Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patients. Cell Stress Chaperones. 2010;15:555-66 pubmed publisher
    ..This is also the first description of immunomodulatory effect of human Hsp40s on T cells and cytokine secretion in RA, suggesting that Hsp40s act as natural anti-inflammatory agents in RA. ..
  8. Walker V, Wong M, Atanasiu R, Hantouche C, Young J, Shrier A. Hsp40 chaperones promote degradation of the HERG potassium channel. J Biol Chem. 2010;285:3319-29 pubmed publisher
    ..We propose a novel role for the DJA proteins in regulating degradation and suggest that they act at a critical point in secretory pathway quality control. ..
  9. Claeys K, Sozanska M, Martin J, Lacene E, Vignaud L, Stockholm D, et al. DNAJB2 expression in normal and diseased human and mouse skeletal muscle. Am J Pathol. 2010;176:2901-10 pubmed publisher
    ..Therefore, we propose a role for DNAJB2 in protein turnover processes in skeletal muscle. ..

More Information


  1. Koffeman E, Genovese M, Amox D, Keogh E, Santana E, Matteson E, et al. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II. Arthritis Rheum. 2009;60:3207-16 pubmed publisher
    ..Tolerization to dnaJP1 leads to immune deviation and a trend toward clinical efficacy. Susceptibility to treatment relies on the coexpression of molecules that can down-regulate adaptive immunity. ..
  2. Külzer S, Rug M, Brinkmann K, Cannon P, Cowman A, Lingelbach K, et al. Parasite-encoded Hsp40 proteins define novel mobile structures in the cytosol of the P. falciparum-infected erythrocyte. Cell Microbiol. 2010;12:1398-420 pubmed publisher
    ..We suggest that these J-dots are involved in trafficking of parasite-encoded proteins through the cytosol of the infected erythrocyte. ..
  3. Riemer J, Appenzeller Herzog C, Johansson L, Bodenmiller B, Hartmann Petersen R, Ellgaard L. A luminal flavoprotein in endoplasmic reticulum-associated degradation. Proc Natl Acad Sci U S A. 2009;106:14831-6 pubmed publisher
    ..Our data show that ERFAD facilitates the dislocation of certain ERAD substrates to the cytosol, and we discuss the findings in relation to a potential redox function of the protein. ..
  4. Kampinga H, Craig E. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol. 2010;11:579-92 pubmed publisher
    ..Some target HSP70 activity to clients at precise locations in cells and others bind client proteins directly, thereby delivering specific clients to HSP70 and directly determining their fate. ..
  5. Kajander T, Sachs J, Goldman A, Regan L. Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90: computational analysis and protein engineering. J Biol Chem. 2009;284:25364-74 pubmed publisher
    ..Finally we present the crystal structure of TPR2A in complex with its non-cognate Hsp70 ligand, which provides insight on the origins of specificity in TPR domain-peptide recognition. ..
  6. Roth M, Zhong J, Tamm M, Szilard J. Mesothelioma cells escape heat stress by upregulating Hsp40/Hsp70 expression via mitogen-activated protein kinases. J Biomed Biotechnol. 2009;2009:451084 pubmed publisher
    ..Thus hyperthermia combined with suppression of p38 MAPK or Hsp40 may represent a novel approach to improve mesothelioma therapy. ..
  7. Goodman A, Fornek J, Medigeshi G, Perrone L, Peng X, Dyer M, et al. P58(IPK): a novel "CIHD" member of the host innate defense response against pathogenic virus infection. PLoS Pathog. 2009;5:e1000438 pubmed publisher
  8. Hageman J, Rujano M, van Waarde M, Kakkar V, Dirks R, Govorukhina N, et al. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol Cell. 2010;37:355-69 pubmed publisher
    ..Combined, our data provide a functional link between HDACs and DNAJs in suppressing cytotoxic protein aggregation. ..
  9. Dorn K, Willmund F, Schwarz C, Henselmann C, Pohl T, Hess B, et al. Chloroplast DnaJ-like proteins 3 and 4 (CDJ3/4) from Chlamydomonas reinhardtii contain redox-active Fe-S clusters and interact with stromal HSP70B. Biochem J. 2010;427:205-15 pubmed publisher
    ..550-2800 kDa, which appeared to contain RNA. We speculate that the CDJ3-5 proteins might represent redox switches that act by recruiting HSP70B for the reorganization of regulatory protein complexes...
  10. Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin J, et al. A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 2008;133:978-93 pubmed publisher
    ..Our study reveals a novel regulatory mechanism of cardiac hypertrophy through which the nucleocytoplasmic shuttling of class II HDACs is modulated by their redox modification in a Trx1-sensitive manner. ..
  11. Bernal Bayard J, Cardenal Muñoz E, Ramos Morales F. The Salmonella type III secretion effector, salmonella leucine-rich repeat protein (SlrP), targets the human chaperone ERdj3. J Biol Chem. 2010;285:16360-8 pubmed publisher
  12. Saulnier D, de Decker S, Haffner P. Real-time PCR assay for rapid detection and quantification of Vibrio aestuarianus in oyster and seawater: a useful tool for epidemiologic studies. J Microbiol Methods. 2009;77:191-7 pubmed publisher
    ..aestuarianus in pathogenesis and epidemiologic studies, as well as for designing appropriate prophylactic control measures. ..
  13. Fiaux J, Horst J, Scior A, Preissler S, Koplin A, Bukau B, et al. Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction. J Biol Chem. 2010;285:3227-34 pubmed publisher
    ..Taken together, we present a novel mechanism for converting Zuotin and Ssz chaperones into a functionally active dimer. ..
  14. Lotz G, Legleiter J, Aron R, Mitchell E, Huang S, Ng C, et al. Hsp70 and Hsp40 functionally interact with soluble mutant huntingtin oligomers in a classic ATP-dependent reaction cycle. J Biol Chem. 2010;285:38183-93 pubmed publisher
    ..Thus, Hsp70 and Hsp40 (DNAJB1) dynamically target specific subsets of soluble oligomers in a classic ATP-dependent reaction cycle, supporting a pathogenic role for these structures in HD. ..
  15. Qian J, Perchiniak E, Sun K, Groden J. The mitochondrial protein hTID-1 partners with the caspase-cleaved adenomatous polyposis cell tumor suppressor to facilitate apoptosis. Gastroenterology. 2010;138:1418-28 pubmed publisher
    ..These data suggest that the amino-terminal segment of APC promotes cell sensitivity to apoptosis modulated through its binding to 40- and 43-kilodalton hTID-1 isoforms. ..
  16. Weeks S, Shield W, Sahi C, Craig E, Rospert S, Miller D. A targeted analysis of cellular chaperones reveals contrasting roles for heat shock protein 70 in flock house virus RNA replication. J Virol. 2010;84:330-9 pubmed publisher
    ..These results identify hsp70 chaperones as critical regulators of FHV RNA replication and indicate that cellular chaperones can have both positive and negative regulatory effects on virus replication. ..
  17. Pollock F, Morris P, Willis B, Bourne D. Detection and quantification of the coral pathogen Vibrio coralliilyticus by real-time PCR with TaqMan fluorescent probes. Appl Environ Microbiol. 2010;76:5282-6 pubmed publisher
    ..Moreover, inhibition by DNA and cells derived from bacteria other than V. coralliilyticus was minimal. This assay represents a novel approach to coral disease diagnosis that will advance the field of coral disease research. ..
  18. Kota P, Summers D, Ren H, Cyr D, Dokholyan N. Identification of a consensus motif in substrates bound by a Type I Hsp40. Proc Natl Acad Sci U S A. 2009;106:11073-8 pubmed publisher
    ..Based on our results, and given that Ydj1p and its human ortholog Hdj2 are functionally interchangeable, we hypothesize that our results can be extended to understanding human diseases. ..
  19. Chen C, Lin H, Chuang S, Lin S, Chen J. Acidic stress facilitates tyrosine phosphorylation of HLJ1 to associate with actin cytoskeleton in lung cancer cells. Exp Cell Res. 2010;316:2910-21 pubmed publisher
    ..We propose that acidic stress increases the association between HLJ1 and ?-actin to modulate migration of human lung cancer cells. ..
  20. Martínez Alonso M, Toledo Rubio V, Noad R, Unzueta U, Ferrer Miralles N, Roy P, et al. Rehosting of bacterial chaperones for high-quality protein production. Appl Environ Microbiol. 2009;75:7850-4 pubmed publisher
    ..Thus, undesired side effects of bacterial folding modulators can be avoided by appropriate rehosting in heterologous cell expression systems. ..
  21. Papalas J, Vollmer R, Gonzalez Gronow M, Pizzo S, Burchette J, Youens K, et al. Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma. Mod Pathol. 2010;23:134-43 pubmed publisher
  22. Horne B, Li T, Genevaux P, Georgopoulos C, Landry S. The Hsp40 J-domain stimulates Hsp70 when tethered by the client to the ATPase domain. J Biol Chem. 2010;285:21679-88 pubmed publisher
    ..The results suggest that the Jd shifts DnaK to a client-bound form by stimulating the DnaK ATPase but only when the Jd is brought to DnaK by a client-Hsp40 complex. ..
  23. Hosoda A, Tokuda M, Akai R, Kohno K, Iwawaki T. Positive contribution of ERdj5/JPDI to endoplasmic reticulum protein quality control in the salivary gland. Biochem J. 2009;425:117-25 pubmed publisher
    ..This effect was dependent on the thioredoxin-like motifs of ERdj5. Thus we suggest that ERdj5 contributes to ER protein quality control in the salivary gland. ..
  24. Sielaff B, Tsai F. The M-domain controls Hsp104 protein remodeling activity in an Hsp70/Hsp40-dependent manner. J Mol Biol. 2010;402:30-7 pubmed publisher
    ..Our results demonstrate that the M-domain controls Hsp104 protein remodeling activities in an Hsp70/Hsp40-dependent manner, which is required to unleash Hsp104 protein disaggregating activity. ..
  25. Zhang H, Schmidt B, Sun F, Condliffe S, Butterworth M, Youker R, et al. Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis. J Biol Chem. 2006;281:11312-21 pubmed
  26. Trentin G, Yin X, Tahir S, Lhotak S, Farhang Fallah J, Li Y, et al. A mouse homologue of the Drosophila tumor suppressor l(2)tid gene defines a novel Ras GTPase-activating protein (RasGAP)-binding protein. J Biol Chem. 2001;276:13087-95 pubmed
    ..These findings raise the possibility that Tid chaperone proteins may play a role in governing the conformation, activity, and/or subcellular distribution of GAP, thereby influencing its biochemical and biological activity within cells. ..
  27. Lu X, Kakkar V. The role of heat shock protein (HSP) in atherosclerosis: Pathophysiology and clinical opportunities. Curr Med Chem. 2010;17:957-73 pubmed
    ..The role of these HSPs, their protective vs. immunogenic properties with special emphasis on their potential as targets to develop therapeutic agent against atherosclerosis will be discussed. ..
  28. Nian R, Kim D, Tan L, Kim C, Choe W. Synergistic coordination of polyethylene glycol with ClpB/DnaKJE bichaperone for refolding of heat-denatured malate dehydrogenase. Biotechnol Prog. 2009;25:1078-85 pubmed publisher
  29. Burré J, Sharma M, Tsetsenis T, Buchman V, Etherton M, Südhof T. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010;329:1663-7 pubmed publisher
    ..Thus, synucleins may function to sustain normal SNARE-complex assembly in a presynaptic terminal during aging. ..
  30. Minami Y, Kawasaki H, Minami M, Tanahashi N, Tanaka K, Yahara I. A critical role for the proteasome activator PA28 in the Hsp90-dependent protein refolding. J Biol Chem. 2000;275:9055-61 pubmed
    ..Kinetics of substrate binding support the idea that PA28 acts as the molecular link between the Hsp90-dependent capture of unfolded proteins and the Hsc70- and ATP-dependent refolding process. ..
  31. Rokney A, Shagan M, Kessel M, Smith Y, Rosenshine I, Oppenheim A. E. coli transports aggregated proteins to the poles by a specific and energy-dependent process. J Mol Biol. 2009;392:589-601 pubmed publisher
    ..Moreover, the results show that the processing of aggregated proteins by the protein quality control system is a multi-step process with distinct spatial and temporal controls. ..
  32. Adachi M, Liu Y, Fujii K, Calderwood S, Nakai A, Imai K, et al. Oxidative stress impairs the heat stress response and delays unfolded protein recovery. PLoS ONE. 2009;4:e7719 pubmed publisher
    ..These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance. ..
  33. Ye C, Li H. HSP40 ameliorates impairment of insulin secretion by inhibiting huntingtin aggregation in a HD pancreatic beta cell model. Biosci Biotechnol Biochem. 2009;73:1787-92 pubmed
    ..These results suggest that impairment of beta cells is mostly linked with the aggregate formation of mutant huntingtin, and that HSP40 ameliorates the malfunction of pancreatic beta cells by inhibiting aggregation. ..
  34. Mokry D, Manandhar S, Chicola K, Santangelo G, Schmidt W. Heterologous expression studies of Saccharomyces cerevisiae reveal two distinct trypanosomatid CaaX protease activities and identify their potential targets. Eukaryot Cell. 2009;8:1891-900 pubmed publisher
    ..brucei CaaX protease specificity. ..
  35. Watson E, Mattar P, Schuurmans C, Cross J. Neural stem cell self-renewal requires the Mrj co-chaperone. Dev Dyn. 2009;238:2564-74 pubmed publisher
    ..Regardless, Mrj plays an important role in neural stem cell self-renewal. ..
  36. Mendelev N, Witherspoon S, Li P. Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways. Exp Neurol. 2009;220:328-34 pubmed publisher
    ..We conclude that SelH protects neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, by preventing mitochondrial depolarization, and by promoting cell survival pathways. ..
  37. Ptak C, Anderson A, Scott R, Van de Vosse D, Rogers R, Sydorskyy Y, et al. A role for the karyopherin Kap123p in microtubule stability. Traffic. 2009;10:1619-34 pubmed publisher
    ..We propose that Kap123p and Caj1p, a member of the Hsp40 family of proteins, together play an essential role in normal microtubule function. ..
  38. Elias M, Archibald J. The RJL family of small GTPases is an ancient eukaryotic invention probably functionally associated with the flagellar apparatus. Gene. 2009;442:63-72 pubmed publisher
    ..These independent fusions suggest that RJL proteins may generally function via regulating the DnaJ-Hsp70 module. ..
  39. Wieten L, van der Zee R, Goedemans R, Sijtsma J, Serafini M, Lubsen N, et al. Hsp70 expression and induction as a readout for detection of immune modulatory components in food. Cell Stress Chaperones. 2010;15:25-37 pubmed publisher
    ..These assay systems are generally applicable to identify compounds that affect the Hsp level in cells of the immune system. ..
  40. Zhang H, Ye X, Su Y, Yuan J, Liu Z, Stein D, et al. Coxsackievirus B3 infection activates the unfolded protein response and induces apoptosis through downregulation of p58IPK and activation of CHOP and SREBP1. J Virol. 2010;84:8446-59 pubmed publisher
    ..Taken together, these data suggest that CVB3 infection activates UPR pathways and induces ER stress-mediated apoptosis through the suppression of P58(IPK) and induction/activation of CHOP, SREBP1, and caspase-12. ..
  41. Xu F, Proft J, Gibbs S, Winkfein B, Johnson J, Syed N, et al. Quercetin targets cysteine string protein (CSPalpha) and impairs synaptic transmission. PLoS ONE. 2010;5:e11045 pubmed publisher
  42. Couturier M, Buccellato M, Costanzo S, Bourhis J, Shu Y, Nicaise M, et al. High affinity binding between Hsp70 and the C-terminal domain of the measles virus nucleoprotein requires an Hsp40 co-chaperone. J Mol Recognit. 2010;23:301-15 pubmed publisher
    ..As such, hsp40 is an essential variable in understanding the outcome of MeV-hsp70 interactions. ..
  43. Wen K, Damania B. Hsp90 and Hsp40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1. Oncogene. 2010;29:3532-44 pubmed publisher
    ..Finally, we report that the Hsp90 inhibitors, 17-AAG and 17-DMAG, can suppress the proliferation of KSHV-positive PEL cell lines and exhibited IC(50) values of 50 nM and below. ..
  44. Mapa K, Sikor M, Kudryavtsev V, Waegemann K, Kalinin S, Seidel C, et al. The conformational dynamics of the mitochondrial Hsp70 chaperone. Mol Cell. 2010;38:89-100 pubmed publisher
  45. Terada K, Oike Y. Multiple molecules of Hsc70 and a dimer of DjA1 independently bind to an unfolded protein. J Biol Chem. 2010;285:16789-97 pubmed publisher
    ..Instead, these results suggest the importance of the bivalent binding of DjA1 dimer that limits unfavorable transitions of substrate conformations in protein folding. ..
  46. Ahn B, Trinh D, Zajchowski L, Lee B, Elwi A, Kim S. Tid1 is a new regulator of p53 mitochondrial translocation and apoptosis in cancer. Oncogene. 2010;29:1155-66 pubmed publisher
  47. Pesce E, Cockburn I, Goble J, Stephens L, Blatch G. Malaria heat shock proteins: drug targets that chaperone other drug targets. Infect Disord Drug Targets. 2010;10:147-57 pubmed
    ..This review critically evaluates the potential of Hsps as malaria drug targets, as well as the use of chaperones as aids in the heterologous expression of other potential malarial drug targets. ..
  48. Li J, Qian X, Sha B. Heat shock protein 40: structural studies and their functional implications. Protein Pept Lett. 2009;16:606-12 pubmed
    ..This review provides a discussion of recent structural studies of Hsp40s and their functional implications. ..
  49. Perales Calvo J, Muga A, Moro F. Role of DnaJ G/F-rich domain in conformational recognition and binding of protein substrates. J Biol Chem. 2010;285:34231-9 pubmed publisher
    ..These data indicate that DnaJ distinguishes the substrate conformation and is able to adapt the use of the G/F-rich region to form stable substrate complexes...
  50. Datta R, Shah G, Rubbelke T, Waheed A, Rauchman M, Goodman A, et al. Progressive renal injury from transgenic expression of human carbonic anhydrase IV folding mutants is enhanced by deficiency of p58IPK. Proc Natl Acad Sci U S A. 2010;107:6448-52 pubmed publisher
    ..These data indicate that expression of the RP17-associated folding mutants of hCAIV can adversely affect tissues beyond the retina and their in vivo proteotoxicity is sensitive to modulation of the protein folding environment of the ER. ..
  51. Olivares Fuster O, Terhune J, Shoemaker C, Arias C. Cloning, expression, and immunogenicity of Flavobacterium columnare heat shock protein dnaJ. J Aquat Anim Health. 2010;22:78-86 pubmed publisher
    ..coli lysates. Although HSPs have been shown to be immunodominant and good candidates for subunit vaccines in other animals, DnaJ failed to protect against columnaris disease in channel catfish. ..
  52. Chang T, Yu S, Lin S, Hsiao Y, Chang G, Yang P, et al. Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating enhancer binding protein 2alpha complex formation. Cancer Res. 2010;70:1656-67 pubmed publisher
    ..Our findings suggest that HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2alpha to the MMP-2 promoter. ..
  53. Gorleku O, Chamberlain L. Palmitoylation and testis-enriched expression of the cysteine-string protein beta isoform. Biochemistry. 2010;49:5308-13 pubmed publisher
    ..Subsequent analysis of chimeric proteins reveals that regions upstream of the cysteine-string domains of CSPalpha and CSPbeta underlie this difference in palmitoylation efficiency between the two isoforms. ..