Protein: Derlin-1 (Degradation in endoplasmic reticulum protein 1) (Der1-like protein 1) (Q99J56)
Organism: Mus musculus (Mouse)
Function: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane. This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome. The channel has a lateral gate within the membrane which provides direct access to membrane proteins with no need to reenter the ER lumen first. May mediate the interaction between VCP and the misfolded protein. 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. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9BUN8}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q9BUN8}.
Sequence: MSDIGDWFRSIPAITRYWFAATVAVPLIGKLGIISPAYFFLWPEAFLYRFQIWRPFTATFYFPVGPGTGFLYLVNLYFLYQYSTRLEAGAFDGRPADYLFMLLFNWICIVITGLAMDMQLLMIPLIMSVLYVWAQLNRDLIVSFWFGTRFKACYLPWVILGFNYIIGGSVINELIGNLVGHLYFFLMFRYPMDLGGRNFLSTPQFLYRWLPSRRGGVSGFGVPPASMRRAADQNGGGGRHNWGQGFRLGDQ
InterPro domains: - IPR035952: Rhomboid-like superfamily (homologous_superfamily) [9-191]
- IPR007599: Derlin (family) [11-204]
Interaction partners: - E3 ubiquitin-protein ligase synoviolin
- Protein sel-1 homolog 1
- Transitional endoplasmic reticulum ATPase
- Ubiquitin recognition factor in ER-associated degradation protein 1
- E3 ubiquitin-protein ligase AMFR
- Protein OS-9
- Derlin-3
- Derlin-2
- Endoplasmic reticulum chaperone BiP
- Endoplasmic reticulum lectin 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0005126 (cytokine receptor binding), GO:0001664 (G protein-coupled receptor binding), GO:0042379 (chemokine receptor binding)
Biological Process (BP): GO:0008150 (biological process), GO:0009987 (cellular process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0051234 (establishment of localization), GO:0051641 (cellular localization), GO:0050794 (regulation of cellular process), GO:0051050 (positive regulation of transport), GO:0032879 (regulation of localization), GO:0033036 (macromolecule localization), GO:0048522 (positive regulation of cellular process), GO:0070727 (cellular macromolecule localization), GO:0051649 (establishment of localization in cell), GO:1903829 (positive regulation of protein localization), GO:0051049 (regulation of transport), GO:0051222 (positive regulation of protein transport), GO:0032388 (positive regulation of intracellular transport), GO:0060341 (regulation of cellular localization), GO:0006810 (transport), GO:0071702 (organic substance transport), GO:0090316 (positive regulation of intracellular protein transport), GO:0051223 (regulation of protein transport), GO:0032880 (regulation of protein localization), GO:0008104 (protein localization), GO:0032386 (regulation of intracellular transport), GO:1904951 (positive regulation of establishment of protein localization), GO:0070201 (regulation of establishment of protein localization), GO:0032386 (regulation of intracellular transport), GO:0033157 (regulation of intracellular protein transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005783 (endoplasmic reticulum), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0005769 (early endosome), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0005770 (late endosome), GO:0097708 (intracellular vesicle)