Derlin 3 (DERL3)

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.Immunofluorescence analysis of HeLa cells revealed that DERL2 and DERL3 colocalized with SEC61B , a component of the ER translocon. Overexpression of DERL2 or DERL3 accelerated the degradation of NHK, a misfolded glycoprotein substrate, 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) and EDEM1, components of the ER-associated protein degradation machinery.