{PDOC51598} {PS51598; SAM_CHO2} {PS51599; SAM_PEMT_PEM2} {PS51564; SAM_ICMT} {BEGIN} ************************************************************* * Class VI SAM-dependent methyltransferases family profiles * ************************************************************* Methyltransferases (EC 2.1.1.-) constitute an important class of enzymes present in every life form. They transfer a methyl group most frequently from S-adenosyl L-methionine (SAM or AdoMet) to a nucleophilic acceptor such as nitrogen, oxygen, sulfur or carbon leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule [1,2,3]. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. Methyltransferases are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing [1,2,3]. More than 230 different enzymatic reactions of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor [E1]. A review published in 2003 [2] divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold): - class I: Rossmann-like alpha/beta see - class II: TIM beta/alpha-barrel alpha/beta - class III: tetrapyrrole methylase alpha/beta - class IV: SPOUT alpha/beta see - class V: SET domain all beta see A more recent paper [3] based on a study of the Saccharomyces cerevisiae methyltransferome argues for four more folds: - class VI: transmembrane all alpha - class VII: DNA/RNA-binding 3-helical bundle all alpha - class VIII: SSo0622-like alpha+beta - class IX: thymidylate synthetase alpha+beta So far, methyltransferases that have been assigned to Class VI (transmembrane) are all multi-pass proteins [3] and they all have been localized to the endoplamic reticulum membrane [3,4,5]. Some methyltransferases belonging to this class have been implicated in the formation of phosphatidylcholine (PC) from phosphatidylethanolamine (PE) [6] and others to the carboxy-methylation of proteins containing a C-terminal CAAX motif [5]. Some enzymatic activities known to belong to the Class VI superfamily: - CHO2 phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17). - PEMT/PEM2 methyltransferases: phosphatidylethanolamine N-methyltransferase (EC 2.1.1.17) and phosphatidyl-N-methylethanolamine N-methyltransferase (EC 2.1.1.71). - Protein-S-isoprenylcysteine O-methyltransferase (EC 2.1.1.100). The profiles we developed to identify Class VI SAM-dependent methyltransferases families are directed against whole length proteins. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: May 2013 / Text revised. [ 1] Kozbial P.Z., Mushegian A.R. "Natural history of S-adenosylmethionine-binding proteins." BMC Struct. Biol. 5:19-19(2005). PubMed=16225687; DOI=10.1186/1472-6807-5-19 [ 2] Schubert H.L., Blumenthal R.M., Cheng X. "Many paths to methyltransfer: a chronicle of convergence." Trends. Biochem. Sci. 28:329-335(2003). PubMed=12826405 [ 3] Wlodarski T., Kutner J., Towpik J., Knizewski L., Rychlewski L., Kudlicki A., Rowicka M., Dziembowski A., Ginalski K. "Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome." PLoS One. 6:E23168-E23168(2011). PubMed=21858014; DOI=10.1371/journal.pone.0023168 [ 4] Zinser E., Sperka-Gottlieb C.D., Fasch E.V., Kohlwein S.D., Paltauf F., Daum G. "Phospholipid synthesis and lipid composition of subcellular membranes in the unicellular eukaryote Saccharomyces cerevisiae." J. Bacteriol. 173:2026-2034(1991). PubMed=2002005 [ 5] Romano J.D., Schmidt W.K., Michaelis S. "The Saccharomyces cerevisiae prenylcysteine carboxyl methyltransferase Ste14p is in the endoplasmic reticulum membrane." Mol. Biol. Cell. 9:2231-2247(1998). PubMed=9693378 [ 6] de Kroon A.I., Koorengevel M.C., Vromans T.A., de Kruijff B. "Continuous equilibration of phosphatidylcholine and its precursors between endoplasmic reticulum and mitochondria in yeast." Mol. Biol. Cell. 14:2142-2150(2003). PubMed=12802081; DOI=10.1091/mbc.E02-08-0460 [E1] https://enzyme.expasy.org/EC/2.1.1.- -------------------------------------------------------------------------------- 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}