DERL1

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.

Full Name

Der1-like domain family, member 1

Function

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 misfolded protein (PubMed:15215856).

Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908).

By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).

(Microbial infection) 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.

Biological Process

Endoplasmic reticulum unfolded protein response Source: UniProtKB
ERAD pathway Source: ParkinsonsUK-UCL
ER-associated misfolded protein catabolic process Source: ParkinsonsUK-UCL
Establishment of protein localization Source: UniProtKB
Positive regulation of protein binding Source: ParkinsonsUK-UCL
Positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
Protein destabilization Source: UniProtKB
Protein folding Source: Reactome
Protein ubiquitination Source: Reactome
Response to unfolded protein Source: MGI
Retrograde protein transport, ER to cytosol Source: UniProtKB
Transmembrane transport Source: Reactome
Ubiquitin-dependent ERAD pathway Source: UniProtKB
Viral process Source: UniProtKB-KW

Cellular Location

Endoplasmic reticulum membrane

Topology

Cytoplasmic: 2-22
Helical: 23-43
Lumenal: 44-59
Helical: 60-80
Cytoplasmic: 81-105
Helical: 106-126
Lumenal: 127-154
Helical: 155-175
Cytoplasmic: 176-251