DERL1
Description
The DERL1 (derlin 1) is a protein-coding gene located on chromosome 8.
Derlin-1, also known as degradation in endoplasmic reticulum protein 1, is a membrane protein encoded by the DERL1 gene in humans. It is located in the endoplasmic reticulum (ER) membrane and plays a role in retrotranslocation of misfolded proteins and ER stress. Derlin-1 is widely expressed in various tissues, including thyroid, fat, and bone marrow. It belongs to the Derlin family of proteins, which are components of the ERAD pathway. Derlins mediate the degradation of misfolded lumenal proteins within the ER, earning them the name 'der' for 'Degradation in the ER'. Derlin-1 is a mammalian homologue of the yeast DER1 protein, involved in the yeast ERAD pathway. It is also a member of the rhomboid-like clan of polytopic membrane proteins. Overexpression of derlin-1 is associated with several cancers, including colon cancer, breast cancer, bladder cancer, and non-small cell lung cancer. The DERL1 gene was discovered in 2004 by two independent research groups while exploring the retrotranslocation machinery in the ER. Professor Tom A. Rapoport and his group at Harvard Medical School provided evidence for the existence of DERL1.
Derlin-1 is a component of the endoplasmic reticulum-associated degradation (ERAD) pathway, responsible for degrading misfolded proteins in the lumen of the endoplasmic reticulum (ER). It forms a tetrameric channel that spans the ER membrane, allowing misfolded proteins to be retrotranslocated from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome. This channel also has a lateral gate within the membrane that provides direct access to membrane proteins, bypassing the need to reenter the ER lumen. Derlin-1 may mediate the interaction between VCP and misfolded proteins. It is also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the ER and reroutes them to the cytosol for degradation. Derlin-1 indirectly regulates the insulin-like growth factor receptor signaling pathway by controlling the steady-state expression of the IGF1R receptor.
DERL1 is also known as DER-1, DER1, derlin-1.
