Figure 7.

Phylogenetic distribution of VWA domain-containing proteins in the organisms with completed genomes is summarized in the diagram. Intracellular proteins are in blue; those with extracellular VWA domains are black. The most ancient VWA domain-containing proteins all seem to be intracellular (see list under early eukaryote). S. cerevisiae and S. pombe have all these genes except copines. With the exception of AAAVWA-ani, metazoan-specific VWA domains are extracellular. Mg chelatases may be of prokaryotic origin with subsequent transfer to plants in chloroplasts. They might also represent the ancestors of AAAVWA-euk, although, at the sequence level, they do not seem closely related. In present-day fungi and plants, it seems that all VWA domain proteins remain intracellular. In contrast, there have been significant expansions in extracellular proteins in Metazoa, a few being widely distributed (e.g., integrin β subunits) and others restricted as in chordates and C. elegans.