Fig. 8

(Parts a, b, c, d, and e). Common topologies and conserved features within the 4TM dataset. Part a The Miscellaneous class includes proteins that have been characterized into subgroups through similar functional activities. Common features include intracellular termini and conserved cysteine residues (yellow outlined in red ovals) in the extracellular loops that either engage in forming disulphide bonds (e.g. claudins and tetraspanins) or interact and form bonds with other proteins (i.e. connexins). Tetraspanins have 4-6 conserved cysteine residues as well as a conserved CCG (cysteine-cysteine-glycine) motif in the large extracellular loop 2. Part b The example here, MS4A2, is one of the two identified receptors and a member of the MS4A protein family, in which 16 members are characterized by 4TMs, a CD20 domain, and an in N-terminus. Part c The Transporter class includes 66 proteins, of which 65 have an in N-terminus and conserved cysteine residues in the extracellular loops are common. TMEM205 is the sole transporter with the opposite topology, and is interesting due to its use of novel mechanisms in cisplatin (chemotherapy) resistance [82]. Part d Of the 45 Enzyme class proteins, all except five maintain an N-terminus intracellular location. ZDHHC-3 is a typical protein of the ZDHHC protein family, characterized by 4TMs, a conserved DHHC domain, and a conserved DPG (aspartate-proline-glycine) motif as well as a TTxE (threonine-threonine-asparagine-glutamate) motif. Part e The Dual function class contains 47 proteins and all 46 proteins of the neurotransmitter gated ion channel family (NGIC) are included here. The NGIC family has a long extracellular N-terminus that contains several important binding sites as well as two conserved cysteine residues that participate in disulphide bonds. The NGIC family is unique in that it has extracellular N- and C-termini and also has signal peptides predicted in 40 of the proteins