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Updated: Aug 15, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
U2AF homology motifs: protein recognition in the RRM world
Clara L Kielkopf1, Stephan Lücke, Michael R Green
1Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. ckielkop@jhsph.edu
Abstract:
Recent structures of the heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) have revealed two unexpected examples of RNA recognition motif (RRM)-like domains with specialized features for protein recognition. These unusual RRMs, called U2AF homology motifs (UHMs), represent a novel class of protein recognition motifs. Defining a set of rules to distinguish traditional RRMs from UHMs is key to identifying novel UHM family members. Here we review the critical sequence features necessary to mediate protein-UHM interactions, and perform comprehensive database searches to identify new members of the UHM family. The resulting implications for the functional and evolutionary relationships among candidate UHM family members are discussed.
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