title: A proline-90 residue unique to SUMO-4 prevents maturation and sumoylation.
abstract: Four small ubiquitin-related modifier (SUMO) genes have been identified in humans. However, little is known about the basic biology of SUMO-4. Here, we report that SUMO-4 differs from SUMO-1, -2, and -3 in that the maturation process of SUMO-4 to active form containing C-terminal di-glycine residues is inhibited by a unique proline residue located at position 90 (Pro-90). Although, both the hydrolase and isopeptidase activities of SUMO peptidases are significantly diminished by Pro-90 as compared to Gln-90 (glutamine) in mutated SUMO genes, only the defective hydrolase activity appears to be biologically relevant. Native SUMO-4, thus, appears to be unable to form covalent isopeptide bonds with substrates. A biological role of SUMO-4, through non-covalent interactions is proposed.
authors.affiliation: Molecular Diabetes and Metabolism Section and the Harry B. and Aileen B. Gordon Diabetes Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. davido@bcm.tmc.edu
authors.forename: David
authors.initials: D
authors.lastname: Owerbach
authors.forename: Eileen M
authors.initials: EM
authors.lastname: McKay
authors.forename: Edward T H
authors.initials: ET
authors.lastname: Yeh
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Gabbay
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Bohren
mesh_terms: D001483:Base Sequence; D019759:Carbon-Nitrogen Lyases / Q000378:metabolism; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D005998:Glycine / Q000737:chemistry; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D009154:Mutation; D011392:Proline / Q000737:chemistry*; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; D011392:Proline; D006867:Hydrolases; D010450:Endopeptidases; D019759:Carbon-Nitrogen Lyases; C034300:isopeptidase; D005998:Glycine