Fig. 3
From: Short linear motifs – ex nihilo evolution of protein regulation
The relationship between compact degenerate motifs, occurrence likelihoods and ex nihilo evolution. a The homeodomain of Drosophila Segmentation polarity homeobox protein engrailed (en) bound to a TAATTA subsite [119]. b The RRM of Transformer-2 protein homolog beta (TRA2B) bound to an AGAA exonic splicing enhancer (ESE) motif [120]. c The SH3 domain of Adapter molecule crk (CRK) bound to a PxxP motif from Rap guanine nucleotide exchange factor 1 (RAPGEF1) [121]. d The number of nucleotides or residues expected between instances of a motif occurring by chance in a sequence. A non-degenerate x-mer nucleotide motif instance would be expected to occur once every 4x nucleotides (e.g. a 6-mer every 46 or 4,096 nucleotides) and an non-degenerate x-mer protein motif would be expected to occur once every 20x amino acids (e.g. a 3-mer peptide motif every 203 or 8000 amino acids). The disparity in the length of the regions that contain these motifs (DNA, (pre-)mRNA and proteins) means that the number of random instances will vary by several fold across the three classes of biomolecule. Ranges are illustrative and are therefore approximate, based on over predictive consensuses (see motifs below) and use equal nucleotide (1/4) and amino acid (1/20) frequencies. Protein SLiMs: proline-directed phosphosite ([ST]P) [29]; D box degron (RxxLxx[ILMVK]) [69]; PxIxIT Calcineurin docking motif (Px[IVLF]x[IVLF][TSHEDQNKR]) [27]; SH3 domain-binding motif (PxxPx[KR]) [32]; PTAP late domain motif (P[TS]AP) [122]; and Fbw7 SCF degron([ILMVP]TPxx[ST]) [123]. RNA motif: A single RRM binding site (4 nucleotides) [124]; a single Zinc Finger recognition site (3 nucleotides) [125]; and an miRNA seed regions (6–8 nucleotides) [126]. DNA motifs: a single Zinc Finger recognition site (3 nucleotides) [127]; Homeobox domain (TAAT[GT][GT]) [128]; CAAT box ([TC]GATTGG[TC][TC][AG]) [129]; and P53 regulatory element (C[AT][AT]GNNNNNNC[AT][AT]G) [130]. e Simple model for motif acquisition by DNA, RNA and proteins (see text for details of model). f Potential mechanism of ex nihilo motif evolution illustrated using a hypothetical LxCxE pRB-binding motif (see text for details of model)