Actin is an abundant intracellular protein in eukaryotic cells. In muscle cells, for example, actin constitutes 10 percent by weight of the total cellular protein; even in nonmuscle cells, actin makes up 1–5 percent of the cellular protein. The cytosolic concentration of actin in nonmuscle cells ranges from 0.1 to 0.4 mM; in special structures such as microvilli, however, the local actin concentration can be as high as 5 mM. To grasp how much actin is present in cells, consider a typical liver cell, which has 2 × 104 insulin receptor molecules but approximately 5 × 108, or half a billion, actin molecules. Because they form structures that extend across large parts of the cell interior, cytoskeletal proteins are among the most abundant proteins in a cell.
Actin is encoded by a large family of genes that gives rise to some of the most conserved proteins within and across species. In those cases in which it has been examined, genetic analysis shows that actin plays an essential role in cells. The protein sequences of actins from amoebae and from animals are identical at 80 percent of their amino acid positions, despite about a billion years of evolution. The multiple actin genes found in modern eukaryotes are related to a bacterial gene, MreB, whose product forms filaments that are important in bacterial cell-wall synthesis. Some single-celled eukaryotes, such as yeasts and amoebae, have one or two ancestral actin genes, whereas multicellular organisms often contain multiple actin genes. For instance, humans have six actin genes, and some plants have more than sixty actin genes (although most are pseudogenes, which do not encode functional actin proteins). Each functional actin gene encodes a different isoform of the protein. Actin isoforms have historically be classified into three groups based on their overall charge: the α-actins, β-actins, and γ-actins. In vertebrates, four actin isoforms are present in specific types of muscle cells, and two isoforms are found in nonmuscle cells. These six isoforms differ at only about 25 of the 375 residues in the complete protein, or show about 93 percent identity. Although these differences may seem minor, the three types of isoforms have different functions: α-actins are associated with various contractile structures, γ-actin accounts for filaments in stress fibers, and β-actin is enriched in the cell cortex and leading edge of motile cells.