******************************************* * Microbodies C-terminal targeting signal * ******************************************* Microbodies are a class of small, single membraned organelles to which belong peroxisomes, glyoxysomes, and glycosomes. Microbody proteins are synthesized on free polysomes and imported into the organelle post-translationally. Unlike the import of proteins into mitochondria, chloroplasts or the ER/secretion pathway, import into microbodies does not generally require the removal of a presequence [1]. It has been experimentally shown [2,3,4] that, in some peroxisomal proteins, the targeting signal (PTS) resides in the last three amino acids of the C-terminus. This consensus sequence is known as 'S-K-L' (Ser-Lys-Leu), although some variations are allowed in all three positions. As the peroxisomal targeting signal also seems to be recognized by other microbodies, it is now [1] known as the C-terminal microbody targeting signal (CMTS). It must be noted that not all microbody proteins contain a CMTS; some seem to contain an internal CMTS-like sequence, but it is not yet known if it is active as such. Finally, a few proteins are synthesized with an N-terminal presequence which is cleaved off during import. Microbody proteins known or thought to contain a CMTS are listed below. - Mammalian D-amino acid oxidase. - Mammalian acyl-coenzyme A oxidase (but not the fungal enzymes). - Mammalian trifunctional fatty acid beta oxidation pathway enzyme. - Mammalian, insect, plants, and Aspergillus uricase. - Mammalian sterol carrier protein-2 high molecular form (SCP-X). - Mammalian long chain alpha-hydroxy acid oxidase. - Mammalian soluble epoxide hydrolase (sEH). - Firefly luciferase. - Plants glycolate oxidase. - Plants glyoxisomal isocitrate lyase. - Plants glyoxisomal malate synthase. - Trypanosoma glycosomal glucose-6-phosphate isomerase. - Trypanosoma glycosomal glyceraldehyde 3-phosphate dehydrogenase. - Yeast (H. polymorpha and Pichia pastoris) alcohol oxidase (AOX). - Yeast (H. polymorpha) dihydroxy-acetone synthase (DHAS). - Yeast (S. cerevisiae) carnitine o-acetyltransferase. - Yeast (S. cerevisiae) catalase A. - Yeast (S. cerevisiae) citrate synthase. - Yeast (S. cerevisiae) peroxisomal malate dehydrogenase. - Yeast (C. boidinii) peroxisomal protein PMP20. - Yeast (C. tropicalis) hydratase-dehydrogenase-epimerase (HDE) from fatty acid beta oxidation pathway. - Yeast (C. tropicalis) isocitrate lyase. -Consensus pattern: [SAGCN]-[RKH]-[LIVMAF]> -Last update: June 1994 / Pattern and text revised. [ 1] De Hoop M.J., Ab G. Biochem. J. 286:657-669(1992). [ 2] Gould S.J., Keller G.-A., Subramani S. J. Cell Biol. 107:897-905(1988). [ 3] Gould S.J., Keller G.-A., Hosken N., Wilkinson J., Subramani S. J. Cell Biol. 108:1657-1664(1989). [ 4] Gould S.J., Keller G.-A., Schneider M., Howell S.H., Garrard L.J., Goodman J.M., Distel B, Tabak H., Subramani S. EMBO J. 9:85-90(1990).