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Phylogenetic tree for human two-pore channels (TPCs) and their relationship with voltage-gated Ca2+ channels (VGCCs) and transient receptor potential (TRP) members. It is likely that VGCCs have arisen from two rounds of tandem duplication in evolution. Thus, TPCs, having 12 transmembrane domains (12TM) may be considered ancient intermediate proteins between TRP channels (6TM), such as CatSpers in sperm or mucolipins or polycystins, and VGCCs (24TM).
