DDRGK1
Description
The DDRGK1 (DDRGK domain containing 1) is a protein-coding gene located on chromosome 20.
DDRGK1 acts as a substrate adapter for ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to substrate proteins, which plays a key role in reticulophagy (also called ER-phagy). In response to endoplasmic reticulum stress, DDRGK1 promotes the recruitment of the E3 UFM1-protein ligase UFL1 to the endoplasmic reticulum membrane. In turn, UFL1 mediates ufmylation of proteins such as RPN1 and RPL26/uL24, promoting reticulophagy of endoplasmic reticulum sheets. Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) by regulating ERN1/IRE1-alpha stability. Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis or inflammatory response. DDRGK1 is required for TRIP4 ufmylation, thereby regulating nuclear receptors-mediated transcription. DDRGK1 may play a role in NF-kappa-B-mediated transcription through regulation of the phosphorylation and the degradation of NFKBIA, the inhibitor of NF-kappa-B. DDRGK1 plays a role in cartilage development through SOX9, inhibiting the ubiquitin-mediated proteasomal degradation of this transcriptional regulator.
DDRGK1 is also known as C20orf116, SEMDSH, UFBP1, dJ1187M17.3.
