Gene Symbol: DNAJA3
Description: DnaJ heat shock protein family (Hsp40) member A3
Alias: HCA57, TID1, hTID-1, dnaJ homolog subfamily A member 3, mitochondrial, DnaJ (Hsp40) homolog, subfamily A, member 3, dnaJ protein Tid-1, hepatocellular carcinoma-associated antigen 57, tumorous imaginal discs protein Tid56 homolog
Species: human
Products:     DNAJA3

Top Publications

  1. 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
    ..mTid-1 were isolated, two of which correspond to the recently identified hTid-1(L) and hTid-1(S) forms of the human TID1 gene that exhibit opposing effects on apoptosis...
  2. Schaaf C, Benzing J, Schmitt T, Erz D, Tewes M, Bartram C, et al. Novel interaction partners of the TPR/MET tyrosine kinase. FASEB J. 2005;19:267-9 pubmed
    ..Participation in apoptosis-regulating mechanisms through interaction with DAPK-3 and cell cycle control via binding to nuclear proteins such as CENPC and SMC-1 are possible new aspects of intracellular MET signaling. ..
  3. Syken J, Macian F, Agarwal S, Rao A, Munger K. TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells. Oncogene. 2003;22:4636-41 pubmed
    ..described two human DnaJ proteins, hTid-1L and hTid-1S, which are derived from alternative splicing of the TID1 gene, the human homologue of the Drosophila tumor suppressor lethal(2) tumorous imaginal discs, and showed that ..
  4. Schilling B, De Medina T, Syken J, Vidal M, M nger K. A novel human DnaJ protein, hTid-1, a homolog of the Drosophila tumor suppressor protein Tid56, can interact with the human papillomavirus type 16 E7 oncoprotein. Virology. 1998;247:74-85 pubmed publisher
    ..The ability of HPV E7 to interact with a cellular DnaJ protein suggests that these two viral oncoproteins may target common regulatory pathways through J-domains...
  5. Wakabayashi Y, Mao J, Brown K, Girardi M, Balmain A. Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the Patched gene in FVB mice. Nature. 2007;445:761-5 pubmed
    ..The Ptch polymorphism affects Hras-induced apoptosis, and binding to Tid1, the mouse homologue of the Drosophila l(2)tid tumour suppressor gene...
  6. Trentin G, He Y, Wu D, Tang D, Rozakis Adcock M. Identification of a hTid-1 mutation which sensitizes gliomas to apoptosis. FEBS Lett. 2004;578:323-30 pubmed
    ..We report the first case of a tumor-associated mutation at the human TID1 locus, which was identified in the SF767 glioma cell line giving rise to aberrantly high levels of a hTid-1(L) ..
  7. Edwards K, Munger K. Depletion of physiological levels of the human TID1 protein renders cancer cell lines resistant to apoptosis mediated by multiple exogenous stimuli. Oncogene. 2004;23:8419-31 pubmed
    ..These results suggest that hTID1 functions as an important cell death regulator and raise the interesting possibility that hTID1 could exert tumor suppressor activity. ..
  8. Linnoila J, Wang Y, Yao Y, Wang Z. A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junction. Neuron. 2008;60:625-41 pubmed publisher
    ..We used two-hybrid screens to identify a protein, tumorous imaginal discs (Tid1), that binds to the cytoplasmic domain of muscle-specific kinase (MuSK), a major component of the agrin receptor...
  9. 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
    ..In this study, we show that the tumor suppressor Tid1 forms a complex with p53 under hypoxic conditions that directs p53 translocation to the mitochondria and the ..

More Information


  1. Sarkar S, Pollack B, Lin K, Kotenko S, Cook J, Lewis A, et al. hTid-1, a human DnaJ protein, modulates the interferon signaling pathway. J Biol Chem. 2001;276:49034-42 pubmed
    ..Drosophila Tid56 and its human homologue hTid-1 represent members of the DnaJ family of molecular chaperones. The TID1 gene encodes two splice variants hTid-1(S) and hTid-1(L)...
  2. 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. ..
  3. Cheng H, Cenciarelli C, Tao M, Parks W, Cheng Mayer C. HTLV-1 Tax-associated hTid-1, a human DnaJ protein, is a repressor of Ikappa B kinase beta subunit. J Biol Chem. 2002;277:20605-10 pubmed
    ..Collectively, our data suggest that hTid-1, in association with heat shock proteins, exerts a negative regulatory effect on the NF-kappaB activity induced by various extracellular and intracellular activators including HTLV-1 Tax. ..
  4. Sinha D, Joshi N, Chittoor B, Samji P, D Silva P. Role of Magmas in protein transport and human mitochondria biogenesis. Hum Mol Genet. 2010;19:1248-62 pubmed publisher
    ..Together, we propose a model showing how Magmas:DnaJC19 subcomplex is associated with TIM23 complex and thus regulates mitochondrial import process. ..
  5. Kim S, Hayashi M, Lo J, Fearns C, Xiang R, Lazennec G, et al. Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8. Cancer Res. 2005;65:8784-91 pubmed
    b>Tid1 is the human homologue of the Drosophila tumor suppressor, Tid56. Reducing the expression of Tid1 in MDA-MB231 breast cancer cells enhanced their migration without affecting their survival or growth rate...
  6. Yin X, Rozakis Adcock M. Genomic organization and expression of the human tumorous imaginal disc (TID1) gene. Gene. 2001;278:201-10 pubmed
    ..Here we report the cloning and characterization of the genomic structure of the human TID1 gene (hTID1), which is located on chromosome 16p13.3. hTID1 is approximately 34 kb and is composed of 12 exons...
  7. Kurzik Dumke U, Czaja J. Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC. Cell Signal. 2007;19:1973-85 pubmed
  8. Bae M, Jeong J, Kim S, Kim S, Kang H, Kim D, et al. Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha. Cancer Res. 2005;65:2520-5 pubmed
    ..These findings propose that Tid-1(L) may play a critical role in pVHL-mediated tumor suppression by modulating the pVHL-dependent HIF-1alpha stability. ..
  9. Chen C, Chiou S, Huang C, Jan C, Lin S, Hu W, et al. Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma. J Pathol. 2009;219:347-55 pubmed publisher
    Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival...
  10. Kurzik Dumke U, Hörner M, Czaja J, Nicotra M, Simiantonaki N, Koslowski M, et al. Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor. Int J Mol Med. 2008;21:19-31 pubmed
  11. Syken J, De Medina T, Munger K. TID1, a human homolog of the Drosophila tumor suppressor l(2)tid, encodes two mitochondrial modulators of apoptosis with opposing functions. Proc Natl Acad Sci U S A. 1999;96:8499-504 pubmed
    Mitochondria have emerged as central regulators of apoptosis. Here, we show that TID1, a human homolog of the Drosophila tumor suppressor lethal (2) tumorous imaginal discs, l(2)tid, encodes two mitochondrial matrix proteins, designated ..
  12. Liu H, MacDonald J, Hryciw T, Li C, Meakin S. Human tumorous imaginal disc 1 (TID1) associates with Trk receptor tyrosine kinases and regulates neurite outgrowth in nnr5-TrkA cells. J Biol Chem. 2005;280:19461-71 pubmed
    The human tumorous imaginal disc 1 (TID1) proteins including TID1(L) and TID1(S), members of the DnaJ domain protein family, are involved in multiple intracellular signaling pathways such as apoptosis induction, cell proliferation, and ..
  13. Kim S, Chao T, Xiang R, Lo J, Campbell M, Fearns C, et al. Tid1, the human homologue of a Drosophila tumor suppressor, reduces the malignant activity of ErbB-2 in carcinoma cells. Cancer Res. 2004;64:7732-9 pubmed
    ..We discovered that this domain of ErbB-2 interacts with Tid1 protein, the human counterpart of the Drosophila tumor suppressor Tid56, whose null mutation causes lethal ..
  14. Cheng H, Cenciarelli C, Nelkin G, Tsan R, Fan D, Cheng Mayer C, et al. Molecular mechanism of hTid-1, the human homolog of Drosophila tumor suppressor l(2)Tid, in the regulation of NF-kappaB activity and suppression of tumor growth. Mol Cell Biol. 2005;25:44-59 pubmed
    ..Collectively, the data suggest that hTid-1 represses the activity of NF-kappaB through physical and functional interactions with the IKK complex and IkappaB and, in doing so, it modulates cell growth and death. ..
  15. Kumada K, Fuse N, Tamura T, Okamori C, Kurata S. HSP70/DNAJA3 chaperone/cochaperone regulates NF-κB activity in immune responses. Biochem Biophys Res Commun. 2019;: pubmed publisher
    ..Our previous study revealed that the Droj2/DNAJA3 cochaperone contributes to the NF-κB pathway in Drosophila and humans...
  16. Patra M, Weiss C, Abu Libdeh B, Ashhab M, Abuzer S, Elpeleg O, et al. A novel variant of the human mitochondrial DnaJ protein, Tid1, associates with a human disease exhibiting developmental delay and polyneuropathy. Eur J Hum Genet. 2019;: pubmed publisher
    ..Exome analysis disclosed a homozygous variant, c.452G>C (p.(Arg151Thr)), in TID1, encoding a mitochondrial J-protein chaperone that is known for its function in assisting the Hsp70 chaperone, ..
  17. Nimonkar A, Dombrowski C, Siino J, Stasiak A, Stasiak A, Kowalczykowski S. Saccharomyces cerevisiae Dmc1 and Rad51 proteins preferentially function with Tid1 and Rad54 proteins, respectively, to promote DNA strand invasion during genetic recombination. J Biol Chem. 2012;287:28727-37 pubmed publisher
    The Saccharomyces cerevisiae Dmc1 and Tid1 proteins are required for the pairing of homologous chromosomes during meiotic recombination...
  18. Beck J, Mufson E, Counts S. Evidence for Mitochondrial UPR Gene Activation in Familial and Sporadic Alzheimer's Disease. Curr Alzheimer Res. 2016;13:610-4 pubmed
    ..40-60% increase in expression levels of select genes activated by the mtUPR, including mitochondrial chaperones dnaja3, hspd1, and hspe1, mitochondrial proteases clpp and yme1l1, and txn2, a mitochondrial-specific oxidoreductase...
  19. Vahedi S, Chueh F, Chandran B, Yu C. Lymphocyte-specific protein tyrosine kinase (Lck) interacts with CR6-interacting factor 1 (CRIF1) in mitochondria to repress oxidative phosphorylation. BMC Cancer. 2015;15:551 pubmed publisher
    ..Reduced interaction between CRIF1 and Tid1, another key component of intramitochondrial translational machinery, in Jurkat further supports the role of ..
  20. Cheng L, Hung K, Lee T, Huang C, Chiu W, Lo J, et al. Mitochondrial co-chaperone protein Tid1 is required for energy homeostasis during skeletal myogenesis. Stem Cell Res Ther. 2016;7:185 pubmed
    b>Tid1 is a mitochondrial co-chaperone protein and its transcript is abundantly expressed in skeletal muscle tissues. However, the physiological function of Tid1 during skeletal myogenesis remains unclear...
  21. Chan Y, Bishop D. Purification of Saccharomyces cerevisiae Homologous Recombination Proteins Dmc1 and Rdh54/Tid1 and a Fluorescent D-Loop Assay. Methods Enzymol. 2018;600:307-320 pubmed publisher
    ..The same method may be used for purification of recombinant Rdh54 (a.k.a. Tid1) and other HR proteins with minor adjustments...
  22. Wang L, Tam J, Liu D. Biochemical and functional characterization of Epstein-Barr virus-encoded BARF1 protein: interaction with human hTid1 protein facilitates its maturation and secretion. Oncogene. 2006;25:4320-31 pubmed
    ..Interestingly, coexpression of BARF1 with hTid1 demonstrated that hTid1 could promote secretion of BARF1, suggesting that hTid1 may act as a chaperone to facilitate the folding, processing and maturation of BARF1. ..
  23. Lo J, Zhou H, Fearns C, Reisfeld R, Yang Y, Lee J. Tid1 is required for T cell transition from double-negative 3 to double-positive stages. J Immunol. 2005;174:6105-12 pubmed
    b>Tid1, a DnaJ cochaperone protein, is the mammalian homologue of the Drosophila tumor suppressor Tid56 whose antitumor function is most likely mediated through its capacity to regulate cell differentiation in imaginal discs...
  24. Yano M. ABCB10 depletion reduces unfolded protein response in mitochondria. Biochem Biophys Res Commun. 2017;486:465-469 pubmed publisher
    ..depletion significantly decreased expression of UPRmt-related mitochondrial chaperones (HSPD1 and DNAJA3), and a mitochondrial protease (LONP1)...
  25. Momiuchi Y, Kumada K, Kuraishi T, Takagaki T, Aigaki T, Oshima Y, et al. The Role of the Phylogenetically Conserved Cochaperone Protein Droj2/DNAJA3 in NF-κB Signaling. J Biol Chem. 2015;290:23816-25 pubmed publisher
    ..Here we demonstrate that a cochaperone protein, Droj2/DNAJA3, is involved in the activation of canonical NF-κB signaling in flies and in human cultured cells...
  26. Lee B, Ahn Y, Kang S, Park Y, Jeon Y, Rho J, et al. Stoichiometric expression of mtHsp40 and mtHsp70 modulates mitochondrial morphology and cristae structure via Opa1L cleavage. Mol Biol Cell. 2015;26:2156-67 pubmed publisher
  27. Trinh D, Elwi A, Kim S. Direct interaction between p53 and Tid1 proteins affects p53 mitochondrial localization and apoptosis. Oncotarget. 2010;1:396-404 pubmed
    ..We previously demonstrated that Tid1 interacts with p53, resulting in mitochondrial translocation of the complex and induction of intrinsic apoptosis [1]..
  28. Dhennin Duthille I, Nyga R, Yahiaoui S, Gouilleux Gruart V, Regnier A, Lassoued K, et al. The tumor suppressor hTid1 inhibits STAT5b activity via functional interaction. J Biol Chem. 2011;286:5034-42 pubmed publisher
    ..Our findings define hTid1 as a novel partner and negative regulator of STAT5b. ..
  29. Shinohara M, Gasior S, Bishop D, Shinohara A. Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination. Proc Natl Acad Sci U S A. 2000;97:10814-9 pubmed
    ..Previous studies suggested that normal Dmc1 loading depends on Rad51. We show here that a mutation in TID1/RDH54, encoding a RAD54 homolog, reduces Rad51-Dmc1 colocalization relative to WT...
  30. Kurzik Dumke U, Hörner M, Nicotra M, Koslowski M, Natali P. In vivo evidence of htid suppressive activity on ErbB-2 in breast cancers over expressing the receptor. J Transl Med. 2010;8:58 pubmed publisher
    ..Our findings provide in vivo evidence that htid is a tissue independent and evolutionarily conserved suppressor of ErbB-2. ..
  31. Lu B, Garrido N, Spelbrink J, Suzuki C. Tid1 isoforms are mitochondrial DnaJ-like chaperones with unique carboxyl termini that determine cytosolic fate. J Biol Chem. 2006;281:13150-8 pubmed
    b>Tid1 is a human homolog of bacterial DnaJ and the Drosophila tumor suppressor Tid56 that has two alternatively spliced isoforms, Tid1-long and -short (Tid1-L and -S), which differ only at their carboxyl termini...
  32. Copeland E, Balgobin S, Lee C, Rozakis Adcock M. hTID-1 defines a novel regulator of c-Met Receptor signaling in renal cell carcinomas. Oncogene. 2011;30:2252-63 pubmed publisher
    ..Given the prevalence of HGF/MetR pathway activation in human cancers, targeted inhibition of hTid-1 may be a useful therapeutic in the management of MetR-dependent malignancies. ..
  33. Hayashi M, Imanaka Yoshida K, Yoshida T, Wood M, Fearns C, Tatake R, et al. A crucial role of mitochondrial Hsp40 in preventing dilated cardiomyopathy. Nat Med. 2006;12:128-32 pubmed
    ..Here we report that the mitochondrial chaperone Hsp40, also known as Dnaja3 or Tid1, is differentially expressed during cardiac development and pathological hypertrophy...
  34. Lo J, Hayashi M, Woo Kim S, Tian B, Huang J, Fearns C, et al. Tid1, a cochaperone of the heat shock 70 protein and the mammalian counterpart of the Drosophila tumor suppressor l(2)tid, is critical for early embryonic development and cell survival. Mol Cell Biol. 2004;24:2226-36 pubmed
    b>Tid1 is the mammalian counterpart of the Drosophila tumor suppressor Tid56 and is also a DnaJ protein containing a conserved J domain through which it interacts with the heat shock protein 70 (Hsp70) family of chaperone proteins...
  35. Shodhan A, Novatchkova M, Loidl J. BIME2, a novel gene required for interhomolog meiotic recombination in the protist model organism Tetrahymena. Chromosome Res. 2017;25:291-298 pubmed publisher
    ..Bime2 distantly resembles budding yeast Rdh54/Tid1 and the vertebrate Rad54B helicases and may have similar functions in promoting or stabilizing Dmc1 nucleoprotein ..
  36. Wang Y, Han K, Pang X, Vaughan H, Qu W, Dong X, et al. Large scale identification of human hepatocellular carcinoma-associated antigens by autoantibodies. J Immunol. 2002;169:1102-9 pubmed
    ..These results indicate a broad range expression of autoantigens in HCC patients. Our findings open an avenue for the study of autoantigens in the transformation, metastasis, and immune evasion in HCC. ..
  37. Ng A, Baird S, Screaton R. Essential role of TID1 in maintaining mitochondrial membrane potential homogeneity and mitochondrial DNA integrity. Mol Cell Biol. 2014;34:1427-37 pubmed publisher
    The tumorous imaginal disc 1 (TID1) protein localizes mainly to the mitochondrial compartment, wherein its function remains largely unknown...
  38. Chen C, Jan C, Lo J, Yang S, Chang Y, Pan S, et al. Tid1-L inhibits EGFR signaling in lung adenocarcinoma by enhancing EGFR Ubiquitinylation and degradation. Cancer Res. 2013;73:4009-19 pubmed publisher
    Tid1 (DNAJA3), a DnaJ cochaperone, may promote degradation of oncogenic kinases. Tid1 has 2 isoforms, Tid1-L and Tid1-S, that may function differently...
  39. Elwi A, Lee B, Meijndert H, Braun J, Kim S. Mitochondrial chaperone DnaJA3 induces Drp1-dependent mitochondrial fragmentation. Int J Biochem Cell Biol. 2012;44:1366-76 pubmed publisher
    ..Here we report that altered levels of DnaJA3 (Tid1/mtHsp40) a mitochondrial member of the DnaJ protein family, and heat shock protein (Hsp) co-chaperone of ..
  40. Goswami A, Samaddar M, Sinha D, Purushotham J, D Silva P. Enhanced J-protein interaction and compromised protein stability of mtHsp70 variants lead to mitochondrial dysfunction in Parkinson's disease. Hum Mol Genet. 2012;21:3317-32 pubmed publisher
    ..Taken together, our findings provide evidence in favor of direct involvement of mtHsp70 as a susceptibility factor in PD. ..
  41. Hageman J, van Waarde M, Zylicz A, Walerych D, Kampinga H. The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities. Biochem J. 2011;435:127-42 pubmed publisher
  42. Niu G, Zhang H, Liu D, Chen L, Belani C, Wang H, et al. Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex. J Biol Chem. 2015;290:18102-10 pubmed publisher
    ..However, the role of their co-chaperones in autophagy regulation has not been well defined. We here show that Tid1, a DnaJ co-chaperone for Hsp70 and the mammalian homologue of the Drosophila tumor suppressor Tid56, is a key ..
  43. Choi J, Choi D, Sohn K, Kwak S, Suk J, Lim J, et al. Absence of a human DnaJ protein hTid-1S correlates with aberrant actin cytoskeleton organization in lesional psoriatic skin. J Biol Chem. 2012;287:25954-63 pubmed publisher
  44. Jan C, Yu C, Hung M, Harn H, Nieh S, Lee H, et al. Tid1, CHIP and ErbB2 interactions and their prognostic implications for breast cancer patients. J Pathol. 2011;225:424-37 pubmed publisher
    ..Human tumourous imaginal disc 1 (Tid1, DnaJa3), a co-chaperone of heat shock protein 70 (Hsp70), also suppresses ErbB2 expression in breast cancer cell lines...
  45. Xu W, Liu L, Hornby D. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-α pathway to PCSK9-mediated LDLR degradation pathway. Molecules. 2012;17:12086-101 pubmed publisher
    ..The novel pathway described here will open new avenues for exploring novel disease treatments. ..
  46. Cheng H, Cenciarelli C, Shao Z, Vidal M, Parks W, Pagano M, et al. Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70. Curr Biol. 2001;11:1771-5 pubmed
    ..In the presence of Tax, hTid-1 and its associated Hsp70 are sequestered within a cytoplasmic "hot spot" structure, a subcellular distribution that is characteristic of Tax in HEK cells. ..
  47. Sasaki S, Nakamura T, Arakawa H, Mori M, Watanabe T, Nagawa H, et al. Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer. Oncogene. 2002;21:5024-30 pubmed
    ..Finally, hRFI protein was shown to be cleaved within the DEDD sequence spanning residues 230-233 by caspase-3 during the apoptotic induction. ..
  48. Rodriguez M, Yu X, Chen J, Songyang Z. Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains. J Biol Chem. 2003;278:52914-8 pubmed
    ..Structural analysis of BRCA1 BRCT repeats also predicted conserved residues that may form the phosphopeptide-binding pocket. Thus, the BRCT repeats are a new family of phosphopeptide-binding domains in DNA damage responses. ..