{PDOC51555} {PS51556; SAM_MT_MG_PIX} {PS51560; SAM_MT_NNT1} {PS51581; SAM_GTMT} {PS51591; RNA_CAP01_NS5_MT} {PS51559; SAM_RMT2} {PS51600; SAM_GNMT} {PS51563; SAM_MTA70L_1} {PS51592; SAM_MTA70L_2} {PS51582; SAM_PEAMT} {PS51590; SAM_MT_MNV_L} {PS51589; SAM_MT56_VP3} {PS51612; SAM_MT_2O_PK} {PS51597; SAM_HNMT} {PS51615; SAM_MT_PUTRESCINE} {PS51625; SAM_MT_TRMB} {PS51626; SAM_MT_TRM1} {PS51610; SAM_CLNMT} {PS51620; SAM_TRM61} {PS51608; SAM_MT_UBIE} {PS51614; SAM_MT_ADRIFT} {PS51613; SAM_MT_RRMJ} {PS51627; SAM_MT_TRM11} {PS51555; SAM_MT12} {PS51585; SAM_MT_TPMT} {PS51678; SAM_MT_PRMT} {PS51679; SAM_MT_C5} {PS51680; SAM_MT_DRM} {PS51681; SAM_MT_NNMT_PNMT_TEMT} {PS51682; SAM_OMT_I} {PS51683; SAM_OMT_II} {PS51684; SAM_MT_TRM5_TYW2} {PS51685; SAM_MT_ERG6_SMT} {PS51686; SAM_MT_RSMB_NOP} {PS51687; SAM_MT_RNA_M5U} {PS51689; SAM_RNA_A_N6_MT} {PS51734; SAM_MPBQ_MSBQ_MT} {BEGIN} ************************************************************ * Class I SAM-dependent methyltransferases family profiles * ************************************************************ Methyltransferases (MTs) (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. The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids. MTs 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 MTs 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 MTs into 5 classes based on the structure of their catalytic domain (fold): - class I: Rossmann-like alpha/beta - 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 see - class VII: DNA/RNA-binding 3-helical bundle all alpha - class VIII: SSo0622-like alpha+beta - class IX: thymidylate synthetase alpha+beta The vast majority of MTs belong to the Rossmann-like fold (Class I) which consists in a seven-stranded beta sheet adjoined by alpha helices. The beta sheet contains a central topological switch-point resulting in a deep cleft in which SAM binds. Class I MTs display two conserved positions, the first one is a GxGxG motif (or at least a GxG motif) at the end of the first beta strand which is characteristic of a nucleotide-binding site and is hence used to bind the adenosyl part of SAM, the second conserved position is an acidic residue at the end of the second beta strand that forms one hydrogen bond to each hydroxyl of the SAM ribose part. The core of these enzymes is composed by about 150 amino acids that show very strong spatial conservation. Catechol O- MT (EC 2.1.1.6) is the canonical Class I MT considering that it consists in the exact consensus structural core with no extra domain (see ) [2]. Some enzymatic activities known to belong to the Class I superfamily: Profiles directed against domains: - C5-MTs (see ): DNA (cytosine-5-)-MT (EC 2.1.1.37) and tRNA (cytosine(38)-C(5))-MT (EC 2.1.1.204). - Domains rearranged MTs (DRMs) (EC=2.1.1.37). - Dot 1 MT (EC 2.1.1.43) (see ). - Eukaryotic and dsDNA viruses mRNA cap 0 MT (EC 2.1.1.56) (see ). - Flavivirus mRNA cap 0 and cap 1 MT (EC 2.1.1.56 and EC 2.1.1.57) [4,5,6]. - Mononegavirus L protein 2'-O-ribose MT domain, involved in the capping of viral mRNAs (cap 1 structure) [7,8]. - Protein arginine N-MTs (PRMTs) including histone-arginine N-MT (EC 2.1.1.125) and [Myelin basic protein]-arginine N-MT (EC 2.1.1.126). - RMT2 MTs: arginine N-MT 2 (EC 2.1.1.-) and guanidinoacetate N-MT (EC 2.1.1.2) [9,10]. - TRM1 tRNA (guanine(26)-N(2))-diMT (EC 2.1.1.216). - TRM5/TYW2 tRNA (guanine(37)-N(1))-MT (EC 2.1.1.228). - ERG6/SMT MTs: methylate sterol and triterpene. - RsmB/NOP MTs: RNA (cytosine-5-)-MTs. - RNA 5-methyluridine (m(5)U) MTs (EC 2.1.1.35, EC 2.1.1.189 and EC 2.1.1.190). - RrmJ mRNA (nucleoside-2'-O-)-MT (EC 2.1.1.57). - Adrift ribose 2'-O-MT (EC 2.1.1.-). - TrmB tRNA (guanine(46)-N(7))-MT (EC 2.1.1.33). Profiles directed against whole-length proteins: - Glycine and glycine/sarcosine N-methyltransferase (EC 2.1.1.20 and EC 2.1.1.156). - mRNA (2'-O-methyladenosine-N(6)-)-MT (EC 2.1.1.62) and other MT-A70-like MTs. - Phosphoethanolamine N-MT (PEAMT) (EC 2.1.1.103). - dsRNA viruses mRNA cap 0 MT (EC 2.1.1.56). - Poxvirus/kinetoplastid cap ribose 2'-O-MT. - NNT1 nicotinamide N-MT (EC 2.1.1.1). - NNMT/PNMT/TEMT MTs (see ): nicotinamide N-MT (EC 2.1.1.1), phenylethanolamine N-MT (EC 2.1.1.28) and amine N-MT (EC 2.1.1.49). - HNMT histamine N-MT (EC 2.1.1.8). - Putrescine N-MT (EC 2.1.1.53). - CLNMT calmodulin-lysine N-MT (EC 2.1.1.60). - TRM61 tRNA (adenine(57)-N(1)/adenine(58)-N(1) or adenine(58)-N(1))-MT (EC 2.1.1.219 or EC 2.1.1.220). - UbiE 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase (EC 2.1.1.201). - Tocopherol O-MT (EC 2.1.1.95). The Synechocystis homologue has not a tocopherol MT but a MPBQ/MSBQ activity (EC 2.1.1.295) (see below) [11,12]. - 2-methyl-6-phytyl-1,4-benzoquinone/2-methyl-6-solanyl-1,4-benzoquinone MT (MPBQ/MSBQ MT) (EC 2.1.1.295) [12]. - Cation-dependent O-MT includes caffeoyl-CoA O-MT (CCoAOMT) (EC 2.1.1.104) that is involved in plant defense, catechol O-MT (COMT) (EC 2.1.1.6) that plays an important role in the central nervous system in the mammalian organism, and a family of bacterial OMTs that may be involved in antibiotic production. - Cation-independent O-MT includes caffeic acid OMTs that are able to methylate the monolignol precursors caffeic acid (EC 2.1.1.68), caffeyl aldehyde, or caffeyl alcohol, acetylserotonin OMT (EC 2.1.1.4) and acetylserotonin OMT-like (EC 2.1.1.-). - Magnesium protoporphyrin IX MT (EC 2.1.1.11). - rRNA adenine N(6)-MT and adenine N(6), N(6)-diMT. - TRM11 MTs: tRNA (guanine(10)-N2)-MT (EC 2.1.1.214) and homologs (EC 2.1.1.-). - Methionine S-MT (EC 2.1.1.12). - TPMT MTs: thiopurine S-MT (EC 2.1.1.67), thiol S-MT (EC 2.1.1.9) and thiocyanate MT (EC 2.1.1.n4). The profiles we developed cover the entire domains or families. -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. -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. -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. -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. -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. -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. -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. -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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2013 / Profile added and 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] Egloff M.P., Benarroch D., Selisko B., Romette J.L., Canard B. "An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization." EMBO J. 21:2757-2768(2002). PubMed=12032088; DOI=10.1093/emboj/21.11.2757 [ 5] Zhou Y., Ray D., Zhao Y., Dong H., Ren S., Li Z., Guo Y., Bernard K.A., Shi P.Y., Li H. "Structure and function of flavivirus NS5 methyltransferase." J. Virol. 81:3891-3903(2007). PubMed=17267492; DOI=10.1128/JVI.02704-062 [ 6] Geiss B.J., Thompson A.A., Andrews A.J., Sons R.L., Gari H.H., Keenan S.M., Peersen O.B. "Analysis of flavivirus NS5 methyltransferase cap binding." J. Mol. Biol. 385:1643-1654(2009). PubMed=19101564; DOI=10.1016/j.jmb.2008.11.058 [ 7] Bujnicki J.M., Rychlewski L. "In silico identification, structure prediction and phylogenetic analysis of the 2'-O-ribose (cap 1) methyltransferase domain in the large structural protein of ssRNA negative-strand viruses." Protein Eng. 15:101-108(2002). PubMed=11917146 [ 8] Ferron F., Longhi S., Henrissat B., Canard B. "Viral RNA-polymerases -- a predicted 2'-O-ribose methyltransferase domain shared by all Mononegavirales." Trends Biochem. Sci. 27:222-224(2002). PubMed=12076527 [ 9] Komoto J., Yamada T., Takata Y., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. "Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes." Biochemistry 43:14385-14394(2004). PubMed=15533043; DOI=10.1021/bi0486785 [10] Komoto J., Huang Y., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F. "Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase." J. Mol. Biol. 320:223-235(2002). PubMed=12079381; DOI=10.1016/S0022-2836(02)00448-5 [11] Endrigkeit J., Wang X., Cai D., Zhang C., Long Y., Meng J., Jung C. "Genetic mapping, cloning, and functional characterization of the BnaX.VTE4 gene encoding a gamma-tocopherol methyltransferase from oilseed rape." Theor. Appl. Genet. 119:567-575(2009). PubMed=19479236; DOI=10.1007/s00122-009-1066-6 [12] Cheng Z., Sattler S., Maeda H., Sakuragi Y., Bryant D.A., DellaPenna D. "Highly divergent methyltransferases catalyze a conserved reaction in tocopherol and plastoquinone synthesis in cyanobacteria and photosynthetic eukaryotes." Plant Cell 15:2343-2356(2003). PubMed=14508009; DOI=10.1105/tpc.013656 [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}