E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (  , ). In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting reticulophagy of endoplasmic reticulum sheets . Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha (, ). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response . Regulates inflammation in response to endoplasmic reticulum stress by promoting reticulophagy, leading to inhibit the activity of the NF-kappa-B transcription factor (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role of these modifications is however unclear: as both DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain whether ufmylation of these proteins is a collateral effect or is required for ufmylation (, ). Catalyzes ufmylation of various subunits of the ribosomal complex or associated components, such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By similarity). Anchors CDK5RAP3 in the cytoplasm, preventing its translocation to the nucleus which allows expression of the CCND1 cyclin and progression of cells through the G1/S transition . Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 . Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear receptor-mediated transcription . Required for hematopoietic stem cell function and hematopoiesis (By similarity). Required for cardiac homeostasis (By similarity).
Subcellular locations: Endoplasmic reticulum membrane, Cytoplasm, Cytosol, Nucleus, Chromosome
Recruited to double-strand breaks by the MRE11-RAD50-NBN (MRN) complex following DNA damage.
Ubiquitously expressed, with a high expression in liver (at protein level) . Low expression in several invasive hepatocellular carcinomas, such Hep-G2, Hep 3B2.1-7, HLE and PLC .