Alternative titles; symbols
HGNC Approved Gene Symbol: DNAJC10
Cytogenetic location: 2q32.1 Genomic coordinates (GRCh38) : 2:182,716,257-182,794,464 (from NCBI)
By screening databases for sequences sharing homology with the thioredoxin (187700) active site, followed by 5-prime and 3-prime RACE of testis and adrenal gland cDNA libraries, Cunnea et al. (2003) cloned full-length ERDJ5. The deduced 793-amino acid protein has a calculated molecular mass of about 91 kD. ERDJ5 contains an N-terminal hydrophobic sequence, followed by a type III DnaJ domain, 4 thioredoxin-like domains, and a C-terminal KDEL endoplasmic reticulum (ER) retention signal. Northern blot analysis detected a major 4.4-kb transcript in all tissues examined. Highest levels were in pancreas and testis, and intermediate levels were in heart, liver, spleen, prostate, and ovary. Several smaller transcripts were also observed. In situ hybridization in mice detected strong expression in prostate; adrenal cortex and medulla; several areas of the central nervous system, particularly neurons of the hippocampus and granular cell layer of the cerebellar cortex; epididymis; stratified epithelium of the alimentary tract; and intestinal mucosa.
Hosoda et al. (2003) cloned mouse Erdj5, which they designated Jpdi. The deduced 793-amino acid protein shares about 90% amino acid identity with human ERDJ5. Northern blot analysis of mouse tissues detected 4.0- and 3.3-kb transcripts in all tissues examined, with highest expression in heart, liver, kidney, and testis, and lower expression in spleen and skeletal muscle. The 4.0-kb transcript was predominant in all tissues except testis. Immunolocalization of Erdj5 in transfected mouse fibroblasts detected colocalization of Erdj5 with protein disulfide isomerase (PDI; 176790) in a classic ER distribution. Erdj5 and Pdi also colocalized within purified HeLa cell microsomes. Endoglycosidase H treatment revealed that Erdj5 is modified by N-linked glycosylation.
Cunnea et al. (2003) determined that ERDJ5 interacted in vitro with BIP (HSPA5; 138120) through its DnaJ domain in an ATP-dependent manner. Endogenous ERDJ5 expression was induced in embryonic kidney cells treated with a panel of common unfolded protein response inducers. Heat shock and serum deprivation did not induce ERDJ5 expression.
Hosoda et al. (2003) characterized the interaction between mouse Erdj5 and Bip. Binding depended upon an intact HPD tripeptide motif in the J domain of Erdj5. The ATPase activity of Bip was enhanced about 2-fold by the addition of the J domain of Erdj5.
Ushioda et al. (2008) found that the ER-resident protein ERDJ5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins, and accelerated ER-associated degradation (ERAD) through its physical and functional associations with EDEM (607673) and the ER-resident chaperone BIP (138120). Thus, Ushioda et al. (2008) concluded that ERDJ5 is a member of a supramolecular ERAD complex that recognizes and unfolds misfolded proteins for their efficient retrotranslocation.
Cunnea et al. (2003) determined that the ERDJ5 gene contains 24 exons and spans about 62 kb.
By genomic sequence analysis, Cunnea et al. (2003) mapped the ERDJ5 gene to chromosome 2p23.1-p22.1.
Cunnea, P. M., Miranda-Vizuete, A., Bertoli, G., Simmen, T., Damdimopoulos, A. E., Hermann, S., Leinonen, S., Huikko, M. P., Gustafsson, J.-A., Sitia, R., Spyrou, G. ERdj5, an endoplasmic reticulum (ER)-resident protein containing DnaJ and thioredoxin domains, is expressed in secretory cells or following ER stress. J. Biol. Chem. 278: 1059-1066, 2003. [PubMed: 12411443] [Full Text: https://doi.org/10.1074/jbc.M206995200]
Hosoda, A., Kimata, Y., Tsuru, A., Kohno, K. JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J-domain and thioredoxin-like motifs. J. Biol. Chem. 278: 2669-2676, 2003. [PubMed: 12446677] [Full Text: https://doi.org/10.1074/jbc.M208346200]
Ushioda, R., Hoseki, J., Araki, K., Jansen, G., Thomas, D. Y., Nagata, K. ERdj5 is required as a disulfide reductase for degradation of misfolded proteins in the ER. Science 321: 569-572, 2008. [PubMed: 18653895] [Full Text: https://doi.org/10.1126/science.1159293]