{PDOC50922} {PS50922; TLC} {BEGIN} ********************** * 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 alpha 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: August 2003 / First entry. [ 1] Winter E., Ponting C.P. "TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains?" Trends Biochem. Sci. 27:381-383(2002). PubMed=12151215 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}