title: Poly-small ubiquitin-like modifier (PolySUMO)-binding proteins identified through a string search.
abstract: Polysumoylation is a crucial cellular response to stresses against genomic integrity or proteostasis. Like the small ubiquitin-like modifier (SUMO)-targeted ubiquitin ligase RNF4, proteins with clustered SUMO-interacting motifs (SIMs) can be important signal transducers downstream of polysumoylation. To identify novel polySUMO-binding proteins, we conducted a computational string search with a custom Python script. We found clustered SIMs in another RING domain protein Arkadia/RNF111. Detailed biochemical analysis of the Arkadia SIMs revealed that dominant SIMs in a SIM cluster often contain a pentameric VIDLT ((V/I/L/F/Y)(V/I)DLT) core sequence that is also found in the SIMs in PIAS family E3s and is likely the best-fitted structure for SUMO recognition. This idea led to the identification of additional novel SIM clusters in FLASH/CASP8AP2, C5orf25, and SOBP/JXC1. We suggest that the clustered SIMs in these proteins form distinct SUMO binding domains to recognize diverse forms of protein sumoylation.
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA. hsun@salk.edu
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Sun
authors.forename: Tony
authors.initials: T
authors.lastname: Hunter
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D058207:Sumoylation / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D025842:SUMO-1 Protein; C486067:RNF111 protein, human; C427283:Rnf111 protein, mouse; D044767:Ubiquitin-Protein Ligases