Human 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 (1-3). 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 (4,5). In yeast, the SUMO-activating (E1) enzyme is Aos1/Uba2p (6). 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-beta peptide by promoting the accumulation of BACE-1 (7). Covalent modification of Phosphatase and Tensin Homolog Deleted on Chromosome (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 (8).
All SUMO isoforms are translated with additional C-terminal residues that have to be removed to generate the active protein. Pro-SUMO1 (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 SUMO1 protein has the conserved C-terminal Gly-Gly residues that function inactivation and conjugation reactions. This protein can be used as a negative control in sumoylation reactions or as a substrate for SENPs. NCBI Accession # NM_003352.
