Human Small Ubiquitin-like Modifier 3 (SUMO3), also known as SMT3A, is synthesized as a 103 amino acid (aa), propeptide with a predicted 11.5 kDa. SUMO3 contains a two aa C-terminal prosegment. Poly-SUMO3 represents chains of wild-type recombinant human SUMO3 molecules linked via lysine residue 11, which is the point of attachment for the C-terminal glycine residue of the preceding SUMO3. SUMO3 monomers and dimers have been removed from the chain mixture. Human SUMO3 shares 83% sequence identity with mouse SUMO3. Di-SUMO3 can be used as a substrate for SUMO-specific isopeptidases (SENPs) and DeSUMOylating Isopeptidase 1 (DeSI-1) that cleave the isopeptide linkage between two SUMO3 molecules. It can also be used to investigate mechanisms of binding and recognition by SUMO-activating (E1) enzymes, SUMO-conjugating (E2) enzymes, SUMO ligases (E3s), and other proteins that contain SUMO binding domains.
SUMOs are a family of small, related proteins that can be enzymatically attached to a target protein by a post-translational modification process termed SUMOylation. Unlike SUMO1 which is usually conjugated to proteins as a monomer, SUMO2 and SUMO3 form high molecular weight polymers on proteins. All SUMO proteins share a conserved Ubiquitin domain and a C-terminal diglycine cleavage/attachment site. Following prosegment cleavage, the C-terminal glycine residue of SUMO3 is enzymatically attached to a lysine residue on a target protein. In humans, SUMO3 is conjugated to a variety of molecules in the presence of the SAE1/UBA2 SUMO-activating (E1) enzyme and the UBE2I/Ubc9 SUMO-conjugating (E2) enzyme. In yeast, the SUMO-activating (E1) enzyme is Aos1/Uba2p.