The same DDIs are used in different cellular contexts and in different organisms. The interacting domains (demonstrated and labeled in the left-most column) were mapped onto the interacting proteins (demonstrated and labeled in the two right columns). Edges connect between interacting domains/proteins. The proteins may be multidomain proteins, but only the relevant domain is demonstrated. (a) An example of the same DDI mapped onto two pairs of interacting proteins in yeast, which are involved in different processes, namely RNA export and RNA splicing. (b) An example of a subnetwork of four proteins whose interactions are attributed to the same DDIs in S. cerevisiae and in human. In yeast, the interacting proteins are involved in DNA mismatch repair and in human they are involved in meiotic recombination. The proteins MSH4 and MSH5 are not considered homologs of the proteins MSH2, MSH3, or MSH6 (based on the report by Altschul and coworkers  and on sequence comparison). (c) An example of two PPIs attributed to the same DDI in different processes in D. melanogaster and human; in fly it is involved in phospholipid biosynthesis and in human in vesicular trafficking. These examples emphasize the modularity of DDIs and their possible role as the 'building blocks' of the PPI networks. The Swiss-Prot accessions of the proteins are as follows: PABP: [P04147]; MEX67: [Q99257]; MSL1: [P40567]; RU2A: [Q08963]; MSH2: [P25847]; MSH3: [P25336]; MSH6: [Q03834]; MSH5: [O43196]; MSH4: [O15457]; SDCB1: [O00560]; and PIPA: [P13217]. DDI, domain-domain interaction; PPI, protein-protein interaction;. fly, D. melanogaster; yeast, S. cerevisiae.
Itzhaki et al. Genome Biology 2006 7:R125 doi:10.1186/gb-2006-7-12-r125