The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development

Sci Rep. 2016 Jan 8:6:19050. doi: 10.1038/srep19050.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism
  • Amino Acid Sequence
  • Animals
  • Ataxia Telangiectasia Mutated Proteins / chemistry*
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Binding Sites
  • Brain / growth & development
  • Brain / metabolism*
  • DNA Damage
  • Gene Expression Regulation, Developmental
  • Humans
  • Models, Molecular
  • Neurogenesis / genetics*
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Structure, Secondary
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Vertebrates

Substances

  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins