Ubiquitin-like (UBL) post-translational modifiers are covalently linked to most, if not all, target protein(s) through an enzymatic cascade analogous to ubiquitylation, consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. Ubiquitin-fold modifier 1 (Ufm1) a ubiquitin-like protein is activated by a novel E1-like enzyme, Uba5, by forming a high-energy thioester bond. Activated Ufm1 is then transferred to its cognate E2-like enzyme, Ufc1, in a similar thioester linkage. This family represents the E2-like enzyme which catalyses the second step in ufmylation [, ].
This entry represents Ufm1 (ubiquitin-fold modifier), which is a ubiquitin-like protein with structural similarities to ubiquitin [, ]. Ufm1 is one of a number of ubiquitin-like modifiers that conjugate to target proteins in cells through Uba5 (E1) and Ufc1 (E2). The Ufm1-system is conserved in metazoa and plants, suggesting it has a potential role in multicellular organisms []. Human Ufm1 is synthesized as a precursor consisting of 85 amino-acid residues. Prior to activation by Uba5, the extra amino acids at the C-terminal region of Ufm1 are removed to expose Gly, which is necessary for conjugation to target molecule(s). C-terminal processing of Ufm1 requires two specific cysteine peptidases (): UfSP1 and UfSP2; both peptidases are also able to release Ufm1 from Ufm1-conjugated cellular proteins. UfSP2 is present in most, if not all, of multi-cellular organisms including plant, nematode, fly, and mammal, whereas UfSP1 is not present in plants and nematodes [].
