Urm1 couples sulfur transfer to ubiquitin-like protein function in oxidative stress

Dual Role of the Molybdenum Cofactor Biosynthesis Protein MOCS3 in tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Humans

“…MOCS2A subsequently interacts with MOCS2B, which binds cPMP and generates MPT after the transfer of two sulfur atoms from two MOCS2A proteins (8). The major difference between the activation of Ub and the second step of the Moco biosynthesis is found in the underlying sulfur chemistry, because Ub activation involves thioester formation, and the thiocarboxylate formation is based on persulfide group transfer (12).…”

“…It was shown that human URM1 is conjugated to lysine residues of target proteins in its own pathway and that oxidative stress enhances protein urmylation in mammalian cells. However, mechanisms underlying the dual function in protein conjugation and sulfur transfer are still controversially discussed, because on the one hand in cofactor biosynthesis persulfide formation is essential and on the other hand thioester formation is needed for Ub conjugation (12,23). Therefore, the mechanism of both conjugation and thiocarboxylation by Ubls has to be further elucidated.…”

The dual role of ubiquitin-like protein Urm1 as a protein modifier and sulfur carrier

“…The shaded areas show the overlapping parts of these pathways, revealing that Urm1 has features similar to ubiquitin and ThiS in the activation and conjugation process. This figure is a combination of the excellent work done by Petroski et al (2011) and Pedrioli et al (2008). No E2 or E3 for Urm1 has been detected, so the existence of an Urm1-E2 intermediate is still hypothetical.…”

“…deubiquitinating enzymes, or prevent the translocation of CAS to the nucleus, evidence for this is still lacking (Petroski et al, 2011).…”

“…Urm1 seems to occupy an important place in the evolutionary link between prokaryotic sulfur carrier proteins and eukaryotic UBLs (Fig. 1) and is regarded as a molecular fossil (Xu et al, 2006;Pedrioli et al, 2008;Petroski et al, 2011;Van der Veen et al, 2011).…”