The region of a transmembrane protein that actually spans the membrane. Transmembrane regions are usually hydrophobic in order to be thermodynamically compatible with the lipid bilayer portion of the membrane. They may consist of either alpha-helical or beta-strand secondary structure elements, but in either case the external residues (the ones facing the membrane) are invariably hydrophobic while the internal residues may be hydrophilic (as in the case of a pore or channel) or polar. One common transmembrane structural domain is the seven-helix bundle seen in numerous channel proteins.

This definition is in context to Bioinformatic. See more contextual defintions for Transmembrane Region.