{PDOC51565} {PS51565; SAM_MT85_SETD3} {PS51566; SAM_MT43_TRX_MLL} {PS51567; SAM_MT43_SUVAR420_1} {PS51570; SAM_MT43_SUVAR420_2} {PS51568; SAM_MT43_SET2_1} {PS51578; SAM_MT43_SET2_2} {PS51571; SAM_MT43_PR_SET} {PS51573; SAM_MT43_SUVAR39_1} {PS51575; SAM_MT43_SUVAR39_2} {PS51579; SAM_MT43_SUVAR39_3} {PS51576; SAM_MT43_EZ} {PS51577; SAM_MT43_SET7} {PS51572; SAM_MT43_1} {PS51574; SAM_MT43_2} {PS51580; SAM_MT43_3} {PS51583; SAM_MT127} {PS51611; SAM_MT59} {BEGIN} ************************************************************ * Class V 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. 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 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 Class V proteins contain the SET domain (see ) usually flanked by other domains forming the so-called pre- and post-SET regions. Except the members of the STD3 family which N-methylate histidine in beta-actin (EC 2.1.1.85) (see ) [4,5], enzymes belonging to this class N-methylate lysine in proteins. Most of them are histone methyltransferases (EC 2.1.1.43) like the histone H3-K9 methyltransferase dim-5 (see ) or the histone H3-K4 methyltransferase SETD7 (see ) [3,6]. Some others methylate the large subunit of the enzyme ribulose-bisphosphate-carboxylase/oxygenase (RuBisCO) (EC 2.1.1.127) in plants; in these enzymes the SET domain is interrupted by a novel domain [4]. Cytochrome c lysine N-methyltransferases (EC 2.1.1.59) do not possess a SET domain, or at least not a SET domain detected by any of the detection methods; however they do display a SET-like region and for this reason they are also assigned to this class [7]. Some enzymatic activities known to belong to the Class V superfamily: - SETD3 actin-histidine N-methyltransferase (EC 2.1.1.85). Orthologues of the protein SETD3 are present in animals, plants and certain fungi, but not in the proteomes of the amoeboflagellate Neisseria gruberi and yeast species. - TRX/MLL histone-lysine N-methyltransferase (EC 2.1.1.43). - Suvar4-20 histone-lysine N-methyltransferase (EC 2.1.1.43). - SET2 histone-lysine N-methyltransferase (EC 2.1.1.43). - PR/SET histone-lysine N-methyltransferase (EC 2.1.1.43). - Suvar3-9 histone-lysine N-methyltransferase (EC 2.1.1.43). - EZ histone-lysine N-methyltransferase (EC 2.1.1.43). - SET7 histone-lysine N-methyltransferase (EC 2.1.1.43). - Plant LSMT protein-lysine methyltransferase. LSMT homologs from plants display different substrate specificities, with targets involved in carbon metabolism. - [Cytochrome c]-lysine N-methyltransferase (EC 2.1.1.59). The profiles we developed to identify Class V 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. -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 2019 / Profile 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] Wilkinson A.W., Diep J., Dai S., Liu S., Ooi Y.S., Song D., Li T.-M., Horton J.R., Zhang X., Liu C., Trivedi D.V., Ruppel K.M., Vilches-Moure J.G., Casey K.M., Mak J., Cowan T., Elias J.E., Nagamine C.M., Spudich J.A., Cheng X., Carette J.E., Gozani O. "SETD3 is an actin histidine methyltransferase that prevents primary dystocia." Nature 565:372-376(2019). PubMed=30626964; DOI=10.1038/s41586-018-0821-8 [ 5] Kwiatkowski S., Seliga A.K., Vertommen D., Terreri M., Ishikawa T., Grabowska I., Tiebe M., Teleman A.A., Jagielski A.K., Veiga-da-Cunha M., Drozak J. "SETD3 protein is the actin-specific histidine N-methyltransferase." Elife 7:0-0(2018). PubMed=30526847; DOI=10.7554/eLife.37921 [ 6] Yeates T.O. "Structures of SET domain proteins: protein lysine methyltransferases make their mark." Cell 111:5-7(2002). PubMed=12372294 [ 7] Porras-Yakushi T.R., Whitelegge J.P., Clarke S. "Yeast ribosomal/cytochrome c SET domain methyltransferase subfamily: identification of Rpl23ab methylation sites and recognition motifs." J. Biol. Chem. 282:12368-12376(2007). PubMed=17327221; DOI=10.1074/jbc.M611896200 [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}