UFM1-specific ligase 1 (UFL1)

UFM1-specific ligase 1 (UFL1) is the sole known E3 ligase responsible for catalyzing UFM1 (ubiquitin-fold modifier 1) conjugation (ufmylation) to protein substrates in eukaryotic cells, a process essential for regulating endoplasmic reticulum (ER) homeostasis, stress responses, hematopoiesis, and multiple other biological processes[1][2][3]. UFL1 forms a complex with adaptor proteins such as DDRGK1 and CDK5RAP3 to exert its E3 ligase activity, acting as a scaffold-type ligase, and is usually anchored on the cytoplasmic ER membrane[1][2][3]. UFL1 deficiency leads to complete loss of ufmylation, hematopoietic failure, and embryonic lethality in animal models, highlighting its essential role in cell survival and organ development, and connecting UFL1 to diseases such as cancer, inflammatory conditions, and ER-stress pathologies[1][3]. No drugs currently target UFL1 directly, but its unique and central role in the UFMylation pathway makes it a potential therapeutic target under investigation[1][3].

Other names

E3 UFM1-protein ligase 1KIAA0776MAXERRCADNLBPE3 UFM1-protein transferase 1Multiple alpha-helix protein located at ERNovel LZAP-binding proteinRegulator of C53/LZAP and DDRGK1Regulator of CDK5RAP3 and DDRGK1LZAP-binding protein

Scaffold for E2 (UFC1) and substrate recruitment to catalyze UFM1 transfer (protein ufmylation)