Ptc and Disp, two key proteins the Hh pathway, in their evolutionary context.

(A) A phylogenetic tree of proteins related to Patched, limited to proteins that are full-length (i.e., those that contain all 12 transmembrane segments), is shown. The tree is color-coded according to the taxonomy of the organisms in which the respective proteins are found. Note one particular family of deeply branching bacterial Ptc homologs, the HpnN family, which encodes a transporter that is predicted to be associated with hopanoid biosynthesis. (B) A typical hopanoid is shown, next to cholesterol, a typical sterol. (C) Sequence alignment of selected HpnN family members with the most common reciprocal-best-match, the Disp family, is shown. Only six sequences are shown (three bacterial and three eukaryotic proteins); the alignment is restricted to transmembrane segments 2 to 6, which form the so-called SSD. (D) and (E) Evidence is shown for a functional association between HpnN-family transporters and HpnF; the latter being the enzyme that catalyzes the first step of hopanoid biosynthesis. Both genes tend to be either present or absent together in a given genome in proteobacteria and occasionally occur in direct chromosomal proximity.