MMS2like

MMS2like refers to a family of ubiquitin-conjugating enzyme variant (UEV) proteins that resemble the yeast Mms2 protein. Members of this family are typically catalytically inactive due to missing active-site residues and function as non-catalytic adaptors in ubiquitin signaling. In many organisms, MMS2-like proteins form complexes with the ubiquitin-conjugating enzyme Ubc13 (UBE2N) to promote the formation of K63-linked polyubiquitin chains, which regulate non-proteolytic signaling pathways such as DNA damage tolerance.

In the context of DNA damage response, MMS2-like proteins participate in the error-free bypass pathway by facilitating the assembly of K63-linked ubiquitin chains on chromatin, enabling template switching and proper replication past lesions. This function often requires collaboration with other factors, and the exact partners can vary by species. For example, in yeast, the MMS2-Ubc13 complex works with Rad5/Rad18 to promote error-free lesion bypass.

Distribution and gene nomenclature for MMS2-like proteins vary across species. In yeast, MMS2 is the exemplar gene, while in humans orthologous proteins include UBE2V1 and UBE2V2. These proteins share the conserved UEV fold but lack catalytic activity, and they are essential for specific ubiquitin signaling pathways that influence DNA repair and, in some contexts, broader signaling networks.

Structure and evolution of MMS2-like proteins are characterized by a conserved ubiquitin-conjugating enzyme variant fold that enables interaction with Ubc13. Their evolutionary conservation across eukaryotes reflects a preserved role as ubiquitin chain assembly adaptors rather than enzymes, underscoring their importance in regulated ubiquitination processes.