title: De-novo protein function prediction using DNA binding and RNA binding proteins as a test case.
abstract: Of the currently identified protein sequences, 99.6% have never been observed in the laboratory as proteins and their molecular function has not been established experimentally. Predicting the function of such proteins relies mostly on annotated homologs. However, this has resulted in some erroneous annotations, and many proteins have no annotated homologs. Here we propose a de-novo function prediction approach based on identifying biophysical features that underlie function. Using our approach, we discover DNA and RNA binding proteins that cannot be identified based on homology and validate these predictions experimentally. For example, FGF14, which belongs to a family of secreted growth factors was predicted to bind DNA. We verify this experimentally and also show that FGF14 is localized to the nucleus. Mutating the predicted binding site on FGF14 abrogated DNA binding. These results demonstrate the feasibility of automated de-novo function prediction based on identifying function-related biophysical features.
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Sapir
authors.initials: S
authors.lastname: Peled
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Olga
authors.initials: O
authors.lastname: Leiderman
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Rotem
authors.initials: R
authors.lastname: Charar
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Gilat
authors.initials: G
authors.lastname: Efroni
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Yaron
authors.identifier: 0000-0002-8017-948X
authors.initials: Y
authors.lastname: Shav-Tal
authors.affiliation: The Goodman Faculty of Life Sciences, Nanotechnology building, Bar Ilan University, Ramat Gan 52900, Israel.
authors.forename: Yanay
authors.initials: Y
authors.lastname: Ofran
mesh_terms: D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016208:Databases, Factual; D005346:Fibroblast Growth Factors; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors; D012313:RNA; D004247:DNA