Guanosine cyclic 3',5'-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families.
The amino acid sequence of bovine lung cGMP-dependent protein kinase has been determined by degradation and alignment of two primary overlapping sets of peptides generated by cleavage at methionyl or arginyl residues. The protein contains 670 residues in a single N alpha-acetylated chain corresponding to a molecular weight of 76 331. The function of the molecule is considered in six segments of sequence which may correspond to four folding domains. From the amino terminus, the first segment is related to the dimerizing property of the protein. The second and third segments appear to have evolved from an ancestral tandem internal gene duplication, generating twin cGMP-binding domains which are homologous to twin domains in the regulatory subunits of cAMP-dependent protein kinase and to the cAMP-binding domain of the catabolite gene activator of Escherichia coli. The fourth and fifth segments may comprise one domain which is homologous to the catalytic subunits of cAMP-dependent protein kinase, of calcium-dependent phosphorylase b kinase, and of certain oncogenic viral protein tyrosine kinases. The regulatory, amino-terminal half of cGMP-dependent protein kinase appears to be related to a family of smaller proteins that bind cAMP for diverse purposes, whereas the catalytic, carboxyl-terminal half is related to a family of protein kinases of varying specificity and varying sensitivity to regulators. These data suggest that ancestral gene splicing events may have been involved in the fusion of two families of proteins to generate the allosteric character of this chimeric enzyme.
D000595:Amino Acid Sequence; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D003488:Cyanogen Bromide; D006152:Cyclic GMP / Q000494:pharmacology; D010450:Endopeptidases; D007202:Indicators and Reagents; D008168:Lung / Q000201:enzymology*; D010446:Peptide Fragments / Q000032:analysis; D011487:Protein Conformation; D011494:Protein Kinases / Q000302:isolation & purification
D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D010446:Peptide Fragments; D011494:Protein Kinases; D010450:Endopeptidases; D006152:Cyclic GMP; D003488:Cyanogen Bromide