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Fig. 11. A model for the evolution of STATs and their DNA binding sites. The
model proposes an ancestral, constitutively dimeric protein (GAA). It has a
GAA-binding half site and binds DNA co-operatively. This latter feature
favoured the evolution of tandem, dyad-binding sites of the form (GAAnTTC)n.
The junctions between these sites (shown at A) constitute potential binding
sites for a protein recognising the reversed order sequence TTCnGAA. STAT
proteins are proposed to have arisen, by the recruitment of a site of tyrosine
phosphorylation (Y) and an SH2 domain (SH2), to bind such junctional
sequences.