Cube-DB is a database of pre-evaluated conservation and specialization scores for residues in paralogous proteins belonging to multi-member families of human proteins. Protein family classification follows (largely) the classification suggested by HUGO Gene Nomenclature Committee. Sets of orhtologous protein sequences were generated by mutual-best-hit strategy using full vertebrate genomes available in Ensembl. The scores, described on documentation page, are assigned to each individual residue in a protein, and presented in the form of a table (html or downloadable xls formats) and mapped, when appropriate, onto the related structure (Jmol, Pymol, Chimera). Please check out or featured pages below, or click on "Browse" link on the right to get the full listing of available results.
Interferon-α receptor 2 specializes for the interaction with interferons termed IFNα, β and ω, in distinction to its cousin Interferon-γ receptor 1, with, well, IFNγ preference. Piehler and Schreiber analyzed the determinants of IFNAR2 specificity toward IFNα and IFNβ through an alanine scan of its binding site. Positions they found (through the measurement of thermodynamic and kinetic properties of the interaction) to have a strong impact on both IFNα and IFNβ binding are shown as spheres in the upper panel of the figure on the right. Positions with very little or no impact are shown in the lower panel. Independently, we can estimate which regions are specific for IFNAR2 by comparing it with IFNGR1 - the results are shown color coded according to the scale in the middle of the figure. The IFNAR2/IFNGR1 analysis page is accessible here.
Though HGNC did not include this interesting pair of duplicated genes in its standard list of protein families, we feature it here because the system provides a nice example of non-trivial functional specialization. After gene duplication 300 to 400 million years ago, lysozyme C gave rise to a gene that currently codes for α-lactalbumin, a protein expressed only in the lactating mammary gland. Lysozyme C is an enzyme, the function lost in lactalbumin. The latter however functions as a regulator of galctosyltransferase (which lysozyme C does not). The illustration shows a cluster of specific residues in α-lactalbumin (orange; contrasted with blue shades indicating nonspecific positions) at the interface with galactosyltransferase (green). The lactalbumin/lysozyme analysis page is accessible here.