Defining the RGG/RG motif

Mol Cell. 2013 Jun 6;50(5):613-23. doi: 10.1016/j.molcel.2013.05.021.


Motifs rich in arginines and glycines were recognized several decades ago to play functional roles and were termed glycine-arginine-rich (GAR) domains and/or RGG boxes. We review here the evolving functions of the RGG box along with several sequence variations that we collectively term the RGG/RG motif. Greater than 1,000 human proteins harbor the RGG/RG motif, and these proteins influence numerous physiological processes such as transcription, pre-mRNA splicing, DNA damage signaling, mRNA translation, and the regulation of apoptosis. In particular, we discuss the role of the RGG/RG motif in mediating nucleic acid and protein interactions, a function that is often regulated by arginine methylation and partner-binding proteins. The physiological relevance of the RGG/RG motif is highlighted by its association with several diseases including neurological and neuromuscular diseases and cancer. Herein, we discuss the evidence for the emerging diverse functionality of this important motif.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / metabolism
  • Apoptosis / physiology
  • Arginine / metabolism
  • DNA Damage
  • Fragile X Syndrome / metabolism
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Neoplasms / metabolism
  • Neuromuscular Diseases / metabolism
  • Protein Biosynthesis
  • Protein Interaction Domains and Motifs*
  • Proteins / chemistry*
  • Proteins / metabolism*


  • Proteins
  • Arginine