PROSITE documentation PDOC50922
TLC domain profile


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.

Last update:

August 2003 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

TLC, PS50922; TLC domain profile  (MATRIX)


1AuthorsWinter E. Ponting C.P.
TitleTRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?
SourceTrends Biochem. Sci. 27:381-383(2002).
PubMed ID12151215

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