title: The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development.
abstract: ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM.
authors.affiliation: Department of Biology, University of St. Thomas, Houston, TX, USA.
authors.forename: Lukas
authors.initials: L
authors.lastname: Cara
authors.affiliation: Department of Biology, University of St. Thomas, Houston, TX, USA.
authors.forename: Medina
authors.initials: M
authors.lastname: Baitemirova
authors.affiliation: Department of Mathematics, Computer Science and Cooperative Engineering, University of St. Thomas, Houston, TX, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Follis
authors.affiliation: Department of Biology, University of St. Thomas, Houston, TX, USA.
authors.forename: Maia
authors.initials: M
authors.lastname: Larios-Sanz
authors.affiliation: Department of Biology, University of St. Thomas, Houston, TX, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Ribes-Zamora
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D004249:DNA Damage; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008958:Models, Molecular; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014714:Vertebrates
chemical_list: C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins