title: QARIP: a web server for quantitative proteomic analysis of regulated intramembrane proteolysis.
abstract: Regulated intramembrane proteolysis (RIP) is a critical mechanism for intercellular communication and regulates the function of membrane proteins through sequential proteolysis. RIP typically starts with ectodomain shedding of membrane proteins by extracellular membrane-bound proteases followed by intramembrane proteolysis of the resulting membrane-tethered fragment. However, for the majority of RIP proteases the corresponding substrates and thus, their functions, remain unknown. Proteome-wide identification of RIP protease substrates is possible by mass spectrometry-based quantitative comparison of RIP substrates or their cleavage products between different biological states. However, this requires quantification of peptides from only the ectodomain or cytoplasmic domain. Current analysis software does not allow matching peptides to either domain. Here we present the QARIP (Quantitative Analysis of Regulated Intramembrane Proteolysis) web server which matches identified peptides to the protein transmembrane topology. QARIP allows determination of quantitative ratios separately for the topological domains (cytoplasmic, ectodomain) of a given protein and is thus a powerful tool for quality control, improvement of quantitative ratios and identification of novel substrates in proteomic RIP datasets. To our knowledge, the QARIP web server is the first tool directly addressing the phenomenon of RIP. The web server is available at http://webclu.bio.wzw.tum.de/qarip/. This website is free and open to all users and there is no login requirement.
authors.affiliation: Department of Genome Oriented Bioinformatics, Technische Universität München, Wissenschaftszentrum Weihenstephan, Maximus-von-Imhof Forum 3, 85354 Freising, Germany.
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Ivankov
authors.forename: Natalya S
authors.initials: NS
authors.lastname: Bogatyreva
authors.forename: Peter
authors.initials: P
authors.lastname: Hönigschmid
authors.forename: Bastian
authors.initials: B
authors.lastname: Dislich
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hogl
authors.forename: Peer-Hendrik
authors.initials: PH
authors.lastname: Kuhn
authors.forename: Dmitrij
authors.initials: D
authors.lastname: Frishman
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Lichtenthaler
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020407:Internet; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000032:analysis; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D040901:Proteomics; D012984:Software
chemical_list: D008565:Membrane Proteins; D010455:Peptides; D016282:Aspartic Acid Endopeptidases