The TLC (TRAM-LAG1-CLN8) domain is an about 200-residue domain found in a family of membrane-associated proteins related to yeast LAG1 and mammalian TRAM. It is predicted to contain five transmembrane α helices [1]. Although the role of the TLC domain is not known, four possible function have been suggested:

• it could catalyze the synthesis of ceramide-like moieties and/or activate lipid synthesis,
• it could protect proteins from proteolyis,
• it could be involved in lipid transport,
• or it could also act as a lipid sensor.

Some proteins known to contain a TLC domain are listed below:

• Vertebrate TRAM (translocation associated protein), a regulator of polypeptide translocation into the ER and appears to modulate the exposure of translocating proteins in the cytosol.
• Yeast Longevity-assurance protein 1 (LAG1), a regulator of longevity and ageing. It facilitates endoplasmic reticulum to Golgi transport of glycosylphosphatidylinositol (GPI)-anchored proteins.
• Mammalian CLN8, a multi-pass transmembrane protein, which is localized mainly to the endoplasmic reticulum (ER) and partially to the ER-Golgi intermediate compartment. In human, defects in CLN8 are a cause of progressive epilepsy with mental retardation (EPMR); also known as neuronal ceroid lipofuscinosis (NCL) type 8 and Northern epilepsy. In mouse, defects in CLN8 are the cause of the phenotype motor neuron degeneration (mnd), which is a naturally occuring NCL.

The profile we developed spans the entire TLC domain.