Figure 2.

Presumed topology of NCBTs and Slc4-like transporters. Presumed topology of the electrogenic Na/HCO₃ cotransporter NBCe1 (A), representing a probable common structure for all five mammalian NCBTs and most nonmammalian NCBTs. The model shows the extended cytosolic amino- and carboxy-terminal domains (Nt and Ct) linked via a transmembrane domain (TMD) that includes 14 transmembrane spans (TMs), one of which is thought to be an extended region (E) rather than an α-helix. In mammalian NCBTs, the third extracellular loop (EL3) between TMs 5 and 6 usually includes multiple cysteine residues (C) and multiple putative glycosylation sites (Y). A sequence alignment displaying these features for human NCBTs is provided in Appendix I. Pictorial depiction of NBCe1 domain sequences aligned against homologous regions of nonvertebrate Slc4-like transporters (B). Horizontal purple bars represent protein sequence laid out from Nt to Ct. Gaps in sequence alignment are depicted as horizontal lines. Vertical bars represent position of α-helical TMs. Note the shorter Nt and EL3 in nonvertebrates. The amoebal Slc4-like transporter includes an extended Nt (yellow region), but it shares no significant sequence identity with the extended Nt of vertebrate Slc4s. The sequence of nonmammalian Slc4-like protein is provided in Appendix II.