PROSITE documentation PDOC51555
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 α/β
class II: TIM β/α-barrel α/β
class III: tetrapyrrole methylase α/β
class IV: SPOUT α/β see <
class V: SET domain all β see <
A more recent paper [
3] based on a study of the Saccharomyces cerevisiae
methyltransferome argues for four more folds:
class VI: transmembrane all α see <
class VII: DNA/RNA-binding 3-helical bundle all α
class VIII: SSo0622-like α+β
class IX: thymidylate synthetase α+β
The vast majority of MTs belong to the Rossmann-like fold (Class I) which
consists in a seven-stranded β sheet adjoined by α helices. The β
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 β 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 β 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
126.96.36.199) is the canonical Class I MT considering that it consists in
the exact consensus structural core with no extra domain (see <PDB: 1VID>) [ 2].
Some enzymatic activities known to belong to the Class I superfamily:
Profiles directed against domains:
C5-MTs (see <
PDOC00089>): DNA (cytosine-5-)-MT (EC 188.8.131.52) and tRNA
(cytosine(38)-C(5))-MT (EC 184.108.40.206).
Domains rearranged MTs (DRMs) (EC=
Dot 1 MT (EC
220.127.116.11) (see < PDOC51569>).
Eukaryotic and dsDNA viruses mRNA cap 0 MT (EC
18.104.22.168) (see < PDOC51562>).
Flavivirus mRNA cap 0 and cap 1 MT (EC
22.214.171.124 and EC 126.96.36.199) [ 4, 5, 6].
Mononegavirus L protein 2'-O-ribose MT domain, involved in the capping of
viral mRNAs (cap 1 structure) [
Protein arginine N-MTs (PRMTs) including histone-arginine N-MT
188.8.131.52) and [Myelin basic protein]-arginine N-MT (EC 184.108.40.206).
RMT2 MTs: arginine N-MT 2 (EC 2.1.1.-) and guanidinoacetate N-MT
220.127.116.11) [ 9, 10].
TRM1 tRNA (guanine(26)-N(2))-diMT (EC
TRM5/TYW2 tRNA (guanine(37)-N(1))-MT (EC
ERG6/SMT MTs: methylate sterol and triterpene.
RsmB/NOP MTs: RNA (cytosine-5-)-MTs.
RNA 5-methyluridine (m(5)U) MTs (EC
18.104.22.168, EC 22.214.171.124 and EC
RrmJ mRNA (nucleoside-2'-O-)-MT (EC
Adrift ribose 2'-O-MT (EC 2.1.1.-).
TrmB tRNA (guanine(46)-N(7))-MT (EC
Profiles directed against whole-length proteins:
Glycine and glycine/sarcosine N-methyltransferase (EC
126.96.36.199 and EC
mRNA (2'-O-methyladenosine-N(6)-)-MT (EC
188.8.131.52) and other MT-A70-like
Phosphoethanolamine N-MT (PEAMT) (EC
dsRNA viruses mRNA cap 0 MT (EC
Poxvirus/kinetoplastid cap ribose 2'-O-MT.
NNT1 nicotinamide N-MT (EC
NNMT/PNMT/TEMT MTs (see <
PDOC00844>): nicotinamide N-MT (EC 184.108.40.206),
phenylethanolamine N-MT (EC 220.127.116.11) and amine N-MT (EC 18.104.22.168).
HNMT histamine N-MT (EC
Putrescine N-MT (EC
CLNMT calmodulin-lysine N-MT (EC
TRM61 tRNA (adenine(57)-N(1)/adenine(58)-N(1) or adenine(58)-N(1))-MT
22.214.171.124 or EC 126.96.36.199).
UbiE 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase (EC
Tocopherol O-MT (EC
188.8.131.52). The Synechocystis homologue has not a
tocopherol MT but a MPBQ/MSBQ activity (EC 184.108.40.2065) (see below) [ 11, 12].
(MPBQ/MSBQ MT) (EC
220.127.116.115) [ 12].
Cation-dependent O-MT includes caffeoyl-CoA O-MT (CCoAOMT) (EC
that is involved in plant defense, catechol O-MT (COMT) (EC 18.104.22.168) 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
Cation-independent O-MT includes caffeic acid OMTs that are able to
methylate the monolignol precursors caffeic acid (EC
aldehyde, or caffeyl alcohol, acetylserotonin OMT (EC 22.214.171.124) and
acetylserotonin OMT-like (EC 2.1.1.-).
Magnesium protoporphyrin IX MT (EC
rRNA adenine N(6)-MT and adenine N(6), N(6)-diMT.
TRM11 MTs: tRNA (guanine(10)-N2)-MT (EC
126.96.36.199) and homologs
Methionine S-MT (EC
TPMT MTs: thiopurine S-MT (EC
188.8.131.52), thiol S-MT (EC 184.108.40.206) and
thiocyanate MT (EC 2.1.1.n4).
The profiles we developed cover the entire domains or families.
October 2013 / Profile added and text revised.
PROSITE methods (with tools and information) covered by this documentation:
PS51591; mRNA cap 0 and cap 1 methyltransferase (EC 220.127.116.11 and EC 18.104.22.168) domain profile (MATRIX)
PS51610; Calmodulin-lysine N-methyltransferase (EC 22.214.171.124) family profile (MATRIX)
PS51600; Glycine N-methyltransferase (EC 126.96.36.199 and EC 188.8.131.52) family profile (MATRIX)
PS51581; SAM-dependent methyltransferase gamma-tocopherol (gTMT)-type family profile (MATRIX)
PS51597; Histamine N-methyltransferase (EC 184.108.40.206) family profile (MATRIX)
PS51734; MPBQ/MBSQ family SAM-binding methyltransferase profile (MATRIX)
PS51555; Methionine S-methyltransferase (EC 220.127.116.11) family profile (MATRIX)
PS51589; Viral protein 3 containing mRNA (guanine-N(7)-)-methyltransferase family profile (MATRIX)
PS51563; mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase (EC 18.104.22.168) family profile (MATRIX)
PS51592; mRNA (2'-O-methyladenosine-N(6)-)-methyltransferase-like (MT-A70-like) family profile (MATRIX)
PS51612; Poxvirus/kinetoplastid-type ribose 2'-O-methyltransferase (EC 22.214.171.124) family profile (MATRIX)
PS51614; Adrift-type ribose 2'-O-methyltransferase (EC 2.1.1.-) domain profile (MATRIX)
PS51679; C-5 cytosine-specific DNA methylase (Dnmt) domain profile (MATRIX)
PS51680; SAM-dependent methyltransferase DRM-type domain profile (MATRIX)
PS51685; SAM-dependent methyltransferase Erg6/SMT-type domain profile (MATRIX)
PS51556; Magnesium protoporphyrin IX methyltransferase (EC 126.96.36.199) family profile (MATRIX)
PS51590; Mononegavirus L protein 2'-O-ribose methyltransferase domain profile (MATRIX)
PS51681; SAM-dependent methyltransferase NNMT/PNMT/TEMT-type profile (MATRIX)
PS51560; Nicotinamide N-methyltransferase (EC 188.8.131.52) family profile (MATRIX)
PS51678; SAM-dependent methyltransferase PRMT-type domain profile (MATRIX)
PS51615; Putrescine N-methyltransferase (EC 184.108.40.206) family profile (MATRIX)
PS51687; SAM-dependent methyltransferase RNA m(5)U-type domain profile (MATRIX)
PS51613; RrmJ-type ribose 2'-O-methyltransferase (EC 220.127.116.11) domain profile (MATRIX)
PS51686; SAM-dependent MTase RsmB/NOP-type domain profile (MATRIX)
PS51585; Thiopurine or thiol or thiocyanate S-methyltransferase (TPMT) family profile (MATRIX)
PS51626; Trm1 methyltransferase domain profile (MATRIX)
PS51627; tRNA methyltransferase 11 (TRM11) (EC 2.1.1.-) family profile (MATRIX)
PS51684; SAM-dependent methyltransferase TRM5/TYW2-type domain profile (MATRIX)
PS51625; SAM-dependent methyltransferase TRMB-type domain profile (MATRIX)
PS51608; UbiE family SAM-binding methyltransferase profile (MATRIX)
PS51682; SAM-dependent O-methyltransferase class I-type profile (MATRIX)
PS51683; SAM-dependent O-methyltransferase class II-type profile (MATRIX)
PS51582; Phosphoethanolamine N-methyltransferase (PEAMT) (EC 18.104.22.168) family profile (MATRIX)
PS51559; Arginine and arginine-like N-methyltransferase domain profile (MATRIX)
PS51689; rRNA adenine N(6)-methyltransferase family profile (MATRIX)
PS51620; tRNA (adenine(57)-N(1)/adenine(58)-N(1) or adenine(58)-N(1)) (EC 22.214.171.124 or EC 126.96.36.199) family profile (MATRIX)
1 Authors Kozbial P.Z., Mushegian A.R.
Title Natural history of S-adenosylmethionine-binding proteins.
Source BMC Struct. Biol. 5:19-19(2005).
PubMed ID 16225687
2 Authors Schubert H.L., Blumenthal R.M., Cheng X.
Title Many paths to methyltransfer: a chronicle of convergence.
Source Trends. Biochem. Sci. 28:329-335(2003).
PubMed ID 12826405
3 Authors Wlodarski T., Kutner J., Towpik J., Knizewski L., Rychlewski L., Kudlicki A., Rowicka M., Dziembowski A., Ginalski K.
Title Comprehensive structural and substrate specificity classification of the Saccharomyces cerevisiae methyltransferome.
Source PLoS One. 6:E23168-E23168(2011).
PubMed ID 21858014
4 Authors Egloff M.P., Benarroch D., Selisko B., Romette J.L., Canard B.
Title An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization.
Source EMBO J. 21:2757-2768(2002).
PubMed ID 12032088
5 Authors Zhou Y., Ray D., Zhao Y., Dong H., Ren S., Li Z., Guo Y., Bernard K.A., Shi P.Y., Li H.
Title Structure and function of flavivirus NS5 methyltransferase.
Source J. Virol. 81:3891-3903(2007).
PubMed ID 17267492
6 Authors Geiss B.J., Thompson A.A., Andrews A.J., Sons R.L., Gari H.H., Keenan S.M., Peersen O.B.
Title Analysis of flavivirus NS5 methyltransferase cap binding.
Source J. Mol. Biol. 385:1643-1654(2009).
PubMed ID 19101564
7 Authors Bujnicki J.M., Rychlewski L.
Title 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.
Source Protein Eng. 15:101-108(2002).
PubMed ID 11917146
8 Authors Ferron F., Longhi S., Henrissat B., Canard B.
Title Viral RNA-polymerases -- a predicted 2'-O-ribose methyltransferase domain shared by all Mononegavirales.
Source Trends Biochem. Sci. 27:222-224(2002).
PubMed ID 12076527
9 Authors Komoto J., Yamada T., Takata Y., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F.
Title Catalytic mechanism of guanidinoacetate methyltransferase: crystal structures of guanidinoacetate methyltransferase ternary complexes.
Source Biochemistry 43:14385-14394(2004).
PubMed ID 15533043
10 Authors Komoto J., Huang Y., Takata Y., Yamada T., Konishi K., Ogawa H., Gomi T., Fujioka M., Takusagawa F.
Title Crystal structure of guanidinoacetate methyltransferase from rat liver: a model structure of protein arginine methyltransferase.
Source J. Mol. Biol. 320:223-235(2002).
PubMed ID 12079381
11 Authors Endrigkeit J., Wang X., Cai D., Zhang C., Long Y., Meng J., Jung C.
Title Genetic mapping, cloning, and functional characterization of the BnaX.VTE4 gene encoding a gamma-tocopherol methyltransferase from oilseed rape.
Source Theor. Appl. Genet. 119:567-575(2009).
PubMed ID 19479236
12 Authors Cheng Z., Sattler S., Maeda H., Sakuragi Y., Bryant D.A., DellaPenna D.
Title Highly divergent methyltransferases catalyze a conserved reaction in tocopherol and plastoquinone synthesis in cyanobacteria and photosynthetic eukaryotes.
Source Plant Cell 15:2343-2356(2003).
PubMed ID 14508009
E1 Title https://enzyme.expasy.org/EC/2.1.1.-
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