The selected hetero-interactions. The gene ID refers to that of the DOGAN genome database of P. horikoshii OT3 . Ortholog classification was performed using the Sequence Similarity Database (SDDB)  of the Kyoto Encyclopedia of Genes and Genomes (KEGG) [48,49]. Proteins are classified and color-coded by ortholog level. The arrow in each interaction indicates the direction of bait protein to prey protein in the mammalian two-hybrid assay. The luciferase reporter activity of an interaction is indicated by thin lines (level 2) or thick lines (level 3). Annotations were derived using the SSDB  with entries for the P. horikoshii OT3 genome in KEGG [48,49] or the Database of Genomes Analyzed in NITE (DOGAN) . Interactions marked with an asterisk indicate the existence of interlogs in other organisms. The protein pairs marked with red frames were encoded as operons on the P. horikoshii OT3 genome. 'a' marks proteins unique to Pyrococcus without orthologs in other archaeal species.