Motif Analysis of Amino-Acid Sequences by a Quantification Method: Application to Phosphorylation Signals of Protein Kinase C and cAMP-Dependent Protein Kinase

摘要

Prediction of protein function using amino-acid sequence motifs is based on the observation that the functionally important region is strongly conserved in short segments of amino-acid sequences.Although the consensus sequence has been used to describe such a functional signal,the actual sequence differs from it to a greater or lesser degree,and the consensus sequence only describes the signal qualitatively.In the present report,we study phosphorylation signals of protein kinase C (PKC) and cAMP-dependent protein kinase (PKA).PKC phosphorylates solely Ser or Thr residues.The consensus sequence is given by (R/K_(1-3),X_(2-0)-S/T-(X_(2-0),R/K_(1-3)),where X denotes no particular amino acid.PKA also phosphorylates Ser or Thr,but its consensus sequence is described by R-R/K-X-S/T.We analyzed such signals by a quantification method,and estimated the strength of the signal quantitatively.This approach was applied to several proteins and peptide analogues,and the replacement effect of amino acids upon catalytic activities of phosphorylation was explained in terms of the strength of the signal (sample score of peptide sequence).