Alternative titles; symbols
HGNC Approved Gene Symbol: DERL3
Cytogenetic location: 22q11.23 Genomic coordinates (GRCh38): 22:23,834,503-23,839,006 (from NCBI)
Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. DERL3 is involved in the degradation of misfolded glycoproteins in the ER (Oda et al., 2006).
By virtue of their similarity to DERL1 (608813), Lilley and Ploegh (2004) identified DERL2 (610304) and DERL3, which are 70% identical to each other. By microarray analysis to identify ER stress-inducible genes in HeLa cells, Oda et al. (2006) cloned DERL3 and identified short and long variants. Northern blot analysis detected abundant DERL3 expression in placenta, pancreas, spleen, and small intestine, and much lower expression in other tissues examined. DERL3 appeared to be a 4-transmembrane protein with its N and C termini facing the cytosol.
Oda et al. (2006) found that DERL3 mRNA was induced in response to ER stress in human cell lines. Immunofluorescence analysis of HeLa cells revealed that DERL2 and DERL3 colocalized with SEC61B (609214), a component of the ER translocon. Overexpression of DERL2 or DERL3 accelerated the degradation of NHK, a misfolded glycoprotein substrate (107400.0024), and reducing DERL2 and DERL3 expression with short hairpin RNAs reduced the degradation of NHK. Both DERLs were able to bind nonglycosylated NHK, but this substrate was not degraded. Coimmunoprecipitation analysis indicated that both DERLs interacted with p97 (VCP; 601023) and EDEM1 (607673), components of the ER-associated protein degradation machinery. DERL2 and DERL3 also interacted with each other. Oda et al. (2006) concluded that DERL2 and DERL3 are regulated by the unfolded protein response and are required for ER-associated degradation of misfolded glycoproteins.
The International Radiation Hybrid Mapping Consortium mapped the DERL3 gene to chromosome 22 (RH80678).
Lilley, B. N., Ploegh, H. L. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429: 834-840, 2004. [PubMed: 15215855] [Full Text: https://doi.org/10.1038/nature02592]
Oda, Y., Okada, T., Yoshida, H., Kaufman, R. J., Nagata, K., Mori, K. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J. Cell Biol. 172: 383-393, 2006. [PubMed: 16449189] [Full Text: https://doi.org/10.1083/jcb.200507057]