Protein Families

A protein family is a group of proteins that have evolved from a common genetic ancestor.  These proteins have similarities in their three-dimensional structures and the functions they perform.  

Proteins within a family are called homologs.  

Orthologs are homologous proteins in different species that evolved from the same protein in a common ancestor. Generally, orthologous proteins perform similar functions in the different species.

Alpha hemoglobin in humans and alpha hemoglobin in mice are orthologous proteins. In contrast, paralogs are homologous proteins produced by gene duplication and can be present in the same or different species. Alpha and beta hemoglobin in humans are paralogous proteins.

A superfamily is composed of two or more families that have evolved from a more distant common ancestor than that of a protein family. Proteins in a superfamily have larger variations in structure and function.

Protein families can help us make a hypothesis about the function of a protein with a known amino acid sequence, but unknown shape or function. These proteins can be compared to other proteins in the family to help predict the three-dimensional structure and help determine the function of the protein.

Protein families often occur through gene duplication, when genetic mechanisms in an organism create an extra copy of a gene. The original copy of the gene and its duplicate copy can mutate and diverge in function as their gene sequences code for different amino acid sequences than their genetic ancestors.

Proteins within a family may have sequence identity as low as 30%, that is only 30% of the amino acid primary sequence may be identical; however, the overall protein structure and the domains within the protein are often incredibly similar.

For example, hemoglobin and myoglobin are proteins that are thought to have evolved by gene duplication. The α and β subunits of hemoglobin have only 49% amino acid sequence identity but have the same general pattern of secondary and tertiary protein structure, that is similar positions of their alpha helices and turns of their amino acid chain. 

The hemoglobin alpha subunit and myoglobin have only 26% sequence identity but also have similar secondary and tertiary structures. All three proteins can bind oxygen through a heme group as these homologous proteins are members of an oxygen-binding protein family.