Genomic encoding

The abundance of many protein kinases in cells is an indication of the great importance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase genes have been recognized in yeast, and it is estimated that the human genome encodes more than 1000 different protein kinases. Tyrosine kinases (protein kinases that phosphorylate Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases). Tyrosine kinases are components of signaling pathways involved in cell-cell communication (see Chapter 34). 

Peptidases are found in all forms of life. There are about 612 peptidases in humans, plus an additional 385 proteins that are homologous to peptidases but either have no or different catalytic activity. In general, 2% of all genes in a genome encode peptidases. 

PTKs can be subdivided into two large families, receptor tyrosine kinases (RTKs) and non-RTKs. The human genome encodes for a total of 90 tyrosine kinases of which 32 are nonreceptor PTKs that can be placed in 10 subfamilies (Fig. 1). All nonreceptor PTKs share a common kinase domain and usually contain several additional domains that mediate interactions with protein-binding partners, membrane lipids, or DNA (Table 1). These interactions may affect cellular localization and the activation status of the kinase or attract substrate proteins for phosphorylation reactions. 

Hydroxylation is the chief reaction involved in phase 1. The responsible enzymes are called monooxygenases or cytochrome P450s the human genome encodes at least 14 families of these enzymes. Estimates of the number of distinct cytochrome P450s in human tissues range from approximately 35 to 60. The reaction catalyzed by a monooxygenase (cytochrome P450) is as follows ... 

HCV is a single-stranded RNA virus of the Flaviviridae family. It has a 9.4-kb positive-sense genome encoding a polyprotein precursor of 3011 amino acids. Individual isolates of HCV consist of closely related yet heterogeneous populations... 

We have seen that the protein Grb2 in the insulin signaling pathway (Fig. 12-6) binds through its SH2 domain to other proteins that contain exposed (P)-Tyr residues. The human genome encodes at least 87 SH2-containing proteins, many already known to participate in signaling. The (P)-Tyr residue is bound in a deep... 

PTB domains (phosphotyrosine-binding domains) also bind (P)-Tyr in partner proteins, but their critical sequences and three-dimensional structures distinguish them from SH2 domains. The human genome encodes 24 proteins that contain PTB domains, including IRS-1, which we have already met in its role as a scaffold protein in insulin-signal transduction (Fig. 12-6). 

Plants respond to many environmental stimuli, and employ hormones and growth factors to coordinate the development and metabolic activities of their tissues. Plant genomes encode hundreds of signaling proteins, including some very similar to those used in signal transductions in mammalian cells. 

Chloroplasts contain large 120- to 169-kb circular genomes encoding about 100 proteins (Chapter 23). A characteristic feature of most chloroplast DNA is the presence of long inverted repeat sequences (10,058 bp in the liverwort, 25,339 bp in tobacco).463 464 These are separated by 19,813 and 81,095 bp single copy regions in the liverwort and by similar sized regions in tobacco. Plastid DNA exists as a mixture of monomeric molecules with smaller amounts of dimers, trimers, and tetramers.464... 

It is estimated that 20-30% of all genes in most genomes encode membrane proteins [157], However, only a small number of detailed structures have been obtained for membrane proteins because of technical difficulties in experiments such as high quality crystal growth. Therefore, it is desirable to develop a method for predicting membrane protein structures by computer simulations. 

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