Orthologous domains in multidomain proteins. Most molybdopterin biosynthesis proteins in metazoa and plants contain four domains (two molybdopterin-binding domains, PF00994 [green], and one PF03453 [blue] and PF03453 [red] domain). This domain arrangement appears to have been constructed by joining a common cassette of PF00994, PF03453, and PF03453 to another copy of PF00994. The three-domain cassette is intact, and all domains are orthologous in the same order. (A) Metazoa-plant orthologs of the central domain of the cassette. (B) Orthology of the additional PF00994 domain. Oddly, here only the chordate lineage of metazoa appears orthologous to the plant domain. The Drosophila protein CIN_DROME cannot be considered orthologous to GEPH_HUMAN in this domain despite having the same domain architecture. This indicates that the N-terminal domain in the arthropod and metazoan proteins derive from paralogous domains, which were added to the cassette independently in each lineage. The additional PF00994 domain was also added independently in the plant protein CNX1_ARATH, but here the orthologous domain was used.
