Figure 4. Structural features of the N-termini of the GRKa/4/5/6 group.

The N-terminal α-helix present in all GRKs (Fig. 3), in the GRKa/4/5/6 clade is followed by several glycines that break secondary structure and highly conserved sequence containing (in this order) 1–3 positively charged residues, glycine, a positively charged residue, serine, two positive charged residues, tryptophan, and 1–2 positively charged residues. The absence of this sequence and/or N-terminal helix, which is remarkably conserved from Trichoplax to human, in some predicted GRK sequences (platypus GRK6, finch GRK5, dog, horse, panda, and platypus GRK4, and GRKa from tick and jumping ant) likely indicates that these parts of corresponding genes were missed or erroneously annotated. GRKa from opisthokont Capsaspora owczarzaki appears to have rudimentary versions of the helix and positive patch. Highlighting: the α-helix, conserved hydrophobic residues in green, other conserved residues in yellow; the positive patch: positively charged residues are shown in bold blue, conserved glycine, and serine are highlighted in yellow, conserved tryptophan in blue. (seq) indicates a sequences interposing between the receptor-binding N-terminal and α-helix a stretch of glycines followed by a conserved hydrophobic motive. These sequences were removed to avoid long gaps. Considering that the N-terminal sequences in human GRK5/6 and Trichoplax GRKa are nearly identical, it appears likely that these sequences simply resulted from mispredictions. Apparent insert in C. owczarzaki GRK is shown in red as X, which stands for the sequence LFLTHFC. Species abbreviations are as in Fig. 1.