Sixtransmembrane

Sixtransmembrane refers to proteins or protein domains that span the lipid bilayer six times. This descriptor is used to classify membrane proteins by architecture rather than by a single evolutionary family. Six-transmembrane (6TM) proteins are found across bacteria, archaea, and eukaryotes and can participate in diverse biological roles.

Topologically, the six transmembrane helices create a compact membrane core with short cytoplasmic and/or extracellular loops. The orientation of the N- and C- termini varies among families, and the loops between helices often contribute to function, including ion binding sites, gating elements, or regulatory interfaces. Because the six-TM arrangement is a common solution for membrane transport and redox tasks, 6TM proteins appear in multiple, unrelated gene families.

In humans, a notable example is the STEAP family (six-transmembrane epithelial antigen of the prostate), which are metalloreductases involved in metal ion homeostasis and have been studied for roles in cancer biology. Other six-transmembrane proteins act as components of transport systems, channels, or accessory subunits in larger complexes. The six-TM topology is thought to arise through gene duplication and divergence, and researchers infer this topology from sequence hydrophobicity profiles and structural data.

Overall, sixtransmembrane describes a structural class of membrane proteins with six helices, encompassing a variety of functions and evolutionary lineages. It is a descriptive term used in structural biology and bioinformatics rather than a single, unified functional family.