Panel A illustrates hierarchical classification of human membrane proteins according to topology, targeting mechanism, and membrane orientation, alongside schematic representations of single-pass and multipass membrane protein types with cytosolic or exoplasmic termini. Panel B presents bar graphs showing distributions of multipass membrane proteins by transmembrane-domain numbers, highlighting odd-number dominance in Nexo proteins and even-number dominance in Ncyt proteins with representative protein-family examples.
Topology classification of the human membrane proteome. (A) Left: classification of the 4,863 human membrane proteins by topology. The innermost ring shows the split between single-pass (blue) and multipass (red) proteins. The middle ring divides each group by targeting mechanism: proteins with a cleavable SS (green) versus those using signal or TA (yellow). The outer ring subdivides proteins by orientation (N terminus exoplasmic, Nexo, purple; N terminus cytosolic, Ncyt, green). Right: schematic diagrams of single-pass and multipass proteins that are classified as Type I (cleavable signal, Nexo), Type II (Ncyt SA), Type III (Nexo SA), or Type IV (TA, Ncyt, short C-terminal tail ≤50 aa). (B) Distribution of multipass by the number of TMDs. Nexo multipass proteins (left graph) are strongly biased toward odd TMD numbers, with 7-TMD proteins dominating. Ncyt multipass proteins (right graph) show a strong bias toward even TMD numbers. Notable examples of protein families within each category are indicated.