HGNC Approved Gene Symbol: DNAJB14
Cytogenetic location: 4q23 Genomic coordinates (GRCh38): 4:99,896,248-99,946,618 (from NCBI)
DNAJ proteins, like DNAJB14, belong to the HSP40 (see DNAJB1, 604572) class of cochaperones and associate specifically with HSP70 ATPases (e.g., HSPA4; 601113) to stimulate protein folding and remodeling reactions in the endoplasmic reticulum (summary by Goodwin et al., 2011).
By screening a short hairpin RNA (shRNA) library for genes required for SV40 infection in HeLa cells, Goodwin et al. (2011) identified DNAJB14. DNAJB14 is predicted to have a C-terminal transmembrane domain. Epitope-tagged constructs showed that human DNAJB14 and DNAJB12 (608376) colocalized with an endoplasmic reticulum (ER) marker in transfected HeLa cells. Detergent partitioning demonstrated that both DNAJ proteins were integral membrane proteins.
Goodwin et al. (2011) found that knockdown of DNAJB12 or DNAJB14 dramatically inhibited SV40 infection and nuclear expression of SV40 large T antigen, an early viral gene product. Knockdown of these and other DNAJ genes had no effect on infection of HeLa cells by adenovirus or HPV16, which do not traffic through the ER. Expression of mutant DNAJB12 or DNAJB14 proteins that were resistant to shRNA-mediated silencing largely restored SV40 infection of HeLa cells.
Goodwin et al. (2014) found that overexpression of DNAJB12 or DNAJB14 in HeLa, monkey CV1, or human foreskin fibroblasts resulted in formation of elaborate single-walled membranous structures beneath the nuclear envelope. They named these structures DNAJ-associated nuclear globular structures, or DJANGOS. DJANGOS appeared as tightly-packed tubes, sheets, and multilayered concentric whorls of uniform size. DJANGOS contain DNAJB12, DNAJB14, HSC70 (HSPA8; 600816), and markers of the ER lumen and ER and nuclear membranes. A section of double membrane connected DJANGOS to abnormal nuclear pores that bound the outer nuclear membrane only. DJANGOS broke down rapidly during cell division and reformed synchronously in daughter cell nuclei. Mutation and knockdown studies showed that a functional J domain in DNAJB12 or DNAJB14, and active HSC70, were required for DJANGOS formation.
Hartz (2017) mapped the DNAJB14 gene to chromosome 4q23 based on an alignment of the DNAJB14 sequence (GenBank AK024343) with the genomic sequence (GRCh38).
Goodwin, E. C., Lipovsky, A., Inoue, T., Magaldi, T. G., Edwards, A. P. B., Van Goor, K. E. Y., Paton, A. W., Paton, J. C., Atwood, W. J., Tsai, B., DiMaio, D. BiP and multiple DNAJ molecular chaperones in the endoplasmic reticulum are required for efficient simian virus 40 infection. MBio 2: e00101-11, 2011. Note: Electronic Article. [PubMed: 21673190] [Full Text: https://doi.org/10.1128/mBio.00101-11]
Goodwin, E. C., Motamedi, N., Lipovsky, A., Fernandez-Busnadiego, R., DiMaio, D. Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus by membranes associated with a novel nuclear pore structure. PLoS One 9: e94322, 2014. Note: Electronic Article. [PubMed: 24732912] [Full Text: https://doi.org/10.1371/journal.pone.0094322]
Hartz, P. A. Personal Communication. Baltimore, Md. 05/22/2017.