DERL1 cDNA Clone – Der1-Like Domain Family, Member 1 (Human)

The protein encoded by this gene is a member of the derlin family. Members of this family participate in the ER-associated degradation response and retrotranslocate misfolded or unfolded proteins from the ER lumen to the cytosol for proteasomal degradation. This protein recognizes substrate in the ER and works in a complex to retrotranslocate it across the ER membrane into the cytosol. This protein may select cystic fibrosis transmembrane conductance regulator protein (CFTR) for degradation as well as unfolded proteins in Alzheimer's disease. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

DERL1: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and the degradation substrate. In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein. Forms homo- and heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts with AMFR, VIMP/SELS, SEL1L, SYVN1 and VCP, as well as with SEL1L-SYVN1 and VCP-VIMP protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with the cytomegalovirus US11 protein. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with RNF103. Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR). Ubiquitous. Belongs to the derlin family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Chaperone; Membrane protein, integral; Membrane protein, multi-pass; Endoplasmic reticulum

Chromosomal Location of Human Ortholog: 8q24.13

Cellular Component: endoplasmic reticulum; integral to endoplasmic reticulum membrane; integral to membrane; membrane

Molecular Function: ATPase binding; MHC class I protein binding; protease binding; protein binding; ubiquitin protein ligase binding

Biological Process: ER-associated protein catabolic process; establishment of protein localization; intracellular transport of viral proteins in host cell; positive regulation of protein binding; positive regulation of protein ubiquitination; protein destabilization; protein homooligomerization; response to unfolded protein; retrograde protein transport, ER to cytosol; unfolded protein response