LYRM4, also called ISD11, is a eukaryote-specific component of the mitochondrial biogenesis of Fe-S clusters which are essential cofactors in multiple processes, including oxidative phosphorylation []. It is required for nuclear and mitochondrial iron-sulfur protein biosynthesis by forming a complex with, and stabilizing, the sulfur donor NFS1 []. LYRM4 belongs to the Complex1_LYR-like superfamily that consists of proteins of diverse functions that are exclusively found in eukaryotes and contain the conserved tripeptide 'LYR' close to the N terminus.
This entry includes adenylyltransferase and sulfurtransferase MOCS3 and its homologue, Uba4, from yeasts.In budding yeasts, Uba4 receives sulphur from Nfs1 and Tum1 []. Uba4 then forms an acyl adenylate intermediate with the C-terminal of the Urm1 protein, and then forms an acyl disulfide bond between Uba4 Cys397 and the Urm1 C-terminal glycin []. Subsequently, the activated Urm1 acts as a sulphur carrier in the process of eukaryotic transfer RNA (tRNA) thiolation []. MOCS3 plays a central role in 2-thiolation of mcm5S2U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) []. It is also essential during biosynthesis of the molybdenum cofactor [, ]. MOCS3 acts by mediating the C-terminal thiocarboxylation of sulfur carriers Urm1 and MOCS2A (the small subunit of molybdopterin synthase) [, , , ].
