Transmembrane domains are composed of 15-30 hydrophobic residues and are found in proteins that span a membrane in a cell. A protein can have a single TM domain (e.g. Type I transmembrane receptors such as EGF receptor) or multiple TM domains (e.g. G-protein coupled receptors)

To span the hydrocarbon core of the membrane of ~3nm requires an alpha helix of ~20 uncharged predominantly apolar residues.

Membrane separates two aqueous compartments by a thin two dimensional lipid phase. Membrane proteins generally span this lipid phase and therefore needed to accomodate to the hydrophilic stretch on both sides of the membrane as well as to the hydrophobic environment in the core of the bilayer. The structure of the membrane embedded portions consist of either of transmembrane alpha helices often assembled in to helix bundles or of antiparralel beta sheets forming barrel shaped pores.

The length of the transmembrane helix may even correlate with the thickness of its membrane. Single spanning membrane proteins of the Endoplasmic reticulum(ER) and Golgi generally have shorter transmembrane domains than plasma membrane proteins.

Since cholestrol content and thus the thickness of the lipid bilayer also increases along with the secretory pathway, this might reflect a role of the transmembrane segments and proteins in lipid sorting.

In multi spanning membrane proteins the transmembrane helices are tightly bundled to compact , globular structure from which lipids are excluded.

There is no obvious statistical preference for a particular position within transmembrane sequences. Exceptions are aromatic amino acids, particularly tyrosine and tryptophan which are preferentially found at the ends of the trasnsmembrane segments.

Voltage gated channels
- Sodium channel, voltage gated, type IX, alpha subunit
- Calcium channel, voltage-dependent, L type, alpha-1C subunit
- Sodium channel, voltage gated, type IV, alpha subunit
- Calcium channel, voltage-dependent, L type, alpha-1S subunit
- Sodium channel, neuronal type I, alpha subunit etc.,

Transport/cargo proteins
- Solute carrier family 5 (sodium/glucose cotransporter), member 1
- SLC7A7
- Norepinephrine transporter protein 1, etc.,

Adenylate cyclases
- Adenylate cyclase 1-8

Membrane transport proteins
- CFTR
- Solute carrier family 4, sodium bicarbonate cotransporter, member 4
Cell surface receptors
- Limb region 1
- Acetylcholine receptor protein, alpha chain
- Calcitonin receptor

G protein coupled receptors
- Serotonin 5-HT-1F receptor
- Arginine vasopressin receptor 1B
- Frizzled 2
- 5-hydroxytryptamine receptor 2B
- Alpha 2A adrenergic receptor
- Alpha 1D adrenergic receptor
- Alpha 1B adrenergic receptor
- Alpha 1A adrenergic receptor
- Alpha 2B adrenergic receptor
- Angiotensin receptor 1 , etc.,