Small Ubiquitin-like Modifier 1 (SUMO1), also known as Sentrin, UBL1, and SMT3C, is synthesized as a 101 amino acid (aa) propeptide with a predicted molecular weight of 11.5 kDa. Human SUMO1 is the most unique of the four identified SUMO proteins and shares only 44%, 47%, and 41% aa sequence identity with SUMO2, SUMO3, and SUMO4, respectively. In contrast, human SUMO1 shares 100% aa sequence identity with the mouse ortholog. 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. All SUMO proteins share a conserved ubiquitin domain and a C-terminal diglycine cleavage/attachment site. Following cleavage of a four aa C-terminal prosegment, the C-terminal glycine residue of SUMO1 is enzymatically attached to a lysine residue on a target protein. In humans, SUMO1 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. SUMOylation can occur without the requirement of a specific SUMO ligase (E3), where SUMO1 is transferred directly from UBE2I/Ubc9 to specific substrates. In Alzheimer's disease models SUMO1 has been shown to influence the generation of amyloid-β peptide by promoting the accumulation of BACE-1. Covalent modification of PTEN by SUMO1 is thought to regulate tumorigenesis by retaining PTEN at the plasma membrane, an effect that suppresses PI 3-Kinase/Akt-dependent tumor growth. All SUMO isoforms are translated with additional C-terminal residues that have to be removed to generate the active protein. Pro-SUMO-1 (101 amino acids) is the inactive precursor of SUMO-1 (97 amino acids) and is processed at the C-terminus by SUMO-1 specific proteases (SENPs). The resulting SUMO-1 protein has the conserved C-terminal Gly-Gly residues that function inactivation and conjugation reactions.