Conservation Analysis and Structure Prediction of the SH2 Family of
Phosphotyrosine Binding Domains
Robert B. Russell, Jason Breed & Geoffrey J. Barton
From FEBS Lett., 304, 15-20, 1992.
Abstract
Src homology 2 (SH2) regions are short (approximately 100 amino acids), non-catalytic domains
conserved among a wide variety of proteins involved in cytoplasmic signaling induced by growth
factors. It is thought that SH2 domains play an important role in the intracellular response to growth
factor stimulation by binding to phosphotyrosine containing proteins. In this paper we apply the
techniques of multiple sequence alignment, secondary structure prediction and conservation analysis
to 67 SH2 domain amino acid sequences. This combined approach predicts seven core secondary
structure regions with the pattern beta-alpha-beta-beta-beta-beta-alpha, identifies those residues
most likely to be buried in the hydrophobic core of the native SH2 domain, and highlights patterns of
conservation indicative of secondary structural elements. Residues likely to be involved in
phosphotyrosine binding are shown and orientations of the predicted secondary structures suggested
which could enable such residues to cooperate in phosphate binding. We propose a consensus pattern
that encapsulates the principal conserved features of the SH2 domains. Comparison of the proposed
SH2 domain of akt to this pattern shows only 12/40 matches, suggesting that this domain may not
exhibit SH2-like properties.