SII-SWORD/CoKE huggingface dataset:
Actin-histidine N-methyltransferase SETD3 (SETD3)
Type: Family

SETD3 is a protein-histidine N-methyltransferase that specifically mediates methylation of actin at 'His-73' . It was initially reported to have histone methyltransferase activity and methylate 'Lys-4' and 'Lys-36' of histone H3 (H3K4me and H3K36me). However, this conclusion was based on mass spectrometry data wherein mass shifts were inconsistent with a bona fide methylation event. In vitro, the protein-lysine methyltransferase activity is weak compared to the protein-histidine methyltransferase activity .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.

A review published in 2003 divides all methyltransferases into 5 classes based on the structure of their catalytic domain (fold):

class I: Rossmann-like alpha/beta

class II: TIM β/α-barrel alpha/beta

class III: tetrapyrrole methylase alpha/beta

class IV: SPOUT alpha/beta

class V: SET domain all beta

A more recent paper 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

Class V proteins contain the SET domain 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) , 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 or the histone H3-K4 methyltransferase SETD7 . 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 . 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 .
Mononegavirus L protein 2-O-ribose methyltransferase (Mononega_L_MeTrfase)
Type: Domain

Large structural protein L or protein L from Mononegavirales is responsible for the replication and transcription of the viral genome as well as all posttranscriptional modifications of viral mRNAs . The template is composed of the viral RNA tightly encapsulated by the nucleoprotein (N). The protein can function either as transcriptase or as replicase. The transcriptase synthesises subsequently subgenomic RNAs, assuring their capping and polyadenylation by a stuttering mechanism. The replicase mode is dependent on intracellular N protein concentration. In this mode, the polymerase replicates the whole viral genome without recognising the transcriptional signals .

The large structural protein carries three enzymatic activities: RNA-directed RNA polymerase (

), mRNA (guanine-N(7)-)-methyltransferase (

), and mRNA guanylyltransferase (

). This entry represents the methyltransferase domain.
Histone-lysine N-methyltransferase, SET2, plant (Hist-Lys_N-MeTrfase_SET2_plant)
Type: Family

ASHR3 protein, a member of this family, interacts with the putative basic helix-loop-helix transcription factor ABORTED MICROSPORES (AMS), which is involved in anther and stamen development in Arabidopsis. This interaction is mediated by the PHD finger and the SET domain of ASHR3 .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone-lysine N-methyltransferase, Set2, fungi (Set2_fungi)
Type: Family

This enzyme methylates histone H3 to form H3K36me. It is involved in transcription elongation as well as in transcription repression . The methyltransferase activity requires the recruitment to the RNA polymerase II, which is CTK1 dependent . It has been shown that this enzyme interacts with the RNA polymerase II hyperphosphorylated CTD and also with CYC8 in Saccharomyces cerevisiae .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone-lysine N-methyltransferase DOT1 domain (DOT1_dom)
Type: Domain

This entry represents the DOT1 domain.

The Dot1 protein (Dot1p) is an histone-lysine N-methyltransferase (

) that methylates lysine 79 (Lys-79) of histone H3. It was first
identified as a Disruptor Of Telomeric silencing in yeast where Dot1p is implicated in gene silencing and localization of the Silent Information Regulator (SIR) complex; in higher eukaryotes the methylation carried out by this enzyme may be used for differentiating chromatin domains. Unlike other histone-lysine methyltransferases (HKMTs), Dot1p displays a Rossmann-like (Class I) S-adenosyl-L-methyionine (SAM)-dependent MT fold while other HKMTs contain the SET domain and hence belong to a whole different structural class .

Whereas most HKMTs, such as Suvar3-9 methylate Lys on the N-terminal tails of histones that stick out from the nucleosome, Dot1p substrate (Lys-79 of histone H3) is located in the conserved histone core, in a short turn connecting the first and second helices, exposed on the nucleosome disk
surface . In order for Lys-79 of H3 to be methylated by Dot1p, another lysine, Lys-123 of histone H2B, needs to be ubiquitinated. A possible reason put forward for this requirement is that the ubiquitination may create a space between adjacent nucleosomes, permitting access of Dot1p to its substrate . In yeast, different states of methylation on Lys-79 of histone H3 (unmodified, mono-, di- and trimethylated) co-exist at the same time, but no clear function is associated with these different methylation states .

The structure of the evolutionary conserved core of Dot1p, the DOT1 domain, has first been described for the yeast Dot1p in complex with
S-adenosyl-L-homocysteine (AdoHcy) and then for the human Dot1-like protein (Dot1Lp) in complex with SAM. The DOT1 domain is about 300-350 amino acids long and is usually located at either of the extremities of the protein sequence: it stands at the C terminus of the yeast Dot1p and at the N terminus of the human Dot1Lp . DOT1 displays a rather elongated structure and can be subdivided into two parts: the N- and the C-terminal subdomains . The N-terminal part is made up of five α-helices and two pairs of short β-strand hairpins. The C-terminal part displays a Rossmann-like fold: it consists in a seven-stranded β-sheet tucked by five α-helices (three helices on one
side of the sheet and two on the other), the sheet contains a central topological switchpoint resulting in a deep pocket where SAM is bound. The two
subdomains are linked covalently by a loop. Altogether the SAM binding pocket is formed by five segments of the DOT1 domain of which four are located in the C-terminal substructure of the DOT1 domain and one in the loop connecting both parts; two of these segments are conserved across different Class I SAM-dependent MTs .
Suv4-20 family, animal (Suv4-20_animal)
Type: Family

This entry includes Suv4-20 family members from eukaryotes, including Suv4-20 from insects and SUV420H1/SUV420H2 from mammals.

Post-translational modification of the core histones H2A, H2B, H3 and H4 play an important part in chromatin biology. Histone H4 lysine 20 methylation (H4K20me) is critical for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction . Suv4-20 family members are a group of histone H4K20 methyltransferases that play an important role in epigenetic regulation. Lower eukaryotes have a single Suv4-20, while mammals have two closely related Suv4-20 paralogs, SUV420H1 and SUV420H2 . In mammals H4K20me2 is generated primarily by SUV420H1/KMT5B (which can also produce H4K20me3), while H4K20me3 is mostly generated by SUV420H2/KMT5C .
tRNA (guanine(37)-N(1))-methyltransferase, eukaryotic (tRNA_Gua_MeTrfase_euk)
Type: Family

This entry represents RNA (guanine(37)-N(1))-methyltransferase from eukaryotes. This enzyme specifically methylates the N1 position of guanosine-37 in various cytoplasmic and mitochondrial tRNAs .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone H3-K9 methyltransferase, plant (H3-K9-MeTrfase_plant)
Type: Family

In general, members of this family methylate 'Lys-9' of histone H3. It also methylates 'Lys-27' of histone H3 and 'Lys-20' of H4, and cytosine . H3 'Lys-9' methylation represents a specific tag for epigenetic transcriptional repression .

This enzyme plays a central role in gene silencing . The silencing mechanism via DNA CpNpG methylation requires the targeting of chromomethylase CMT3 to methylated histones, probably through an interaction with an heterochromatin protein 1-like adapter. Arabidopsis homologue SUVH4 is directly required for the maintenance of the DNA CpNpG and asymmetric methylation. It is also involved in the silencing of transposable elements .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
tRNA (uracil-5-)-methyltransferase (tRNA_(uracil-5-)_MeTrfase)
Type: Family

This family consists of proteins believed to act as tRNA (uracil-5-)-methyltransferase (

). They catalyse the formation of 5-methyl-uridine at position 54 (m5U54) in tRNA and may have a role in tRNA stabilisation or maturation .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Histone-lysine N-methyltransferase SETDB1 (Hist-Lys_N-MeTrfase_SETDB1)
Type: Family

SETDB1 is a member of the histone-lysine N-methyltransferase Suvar3-9 subfamily. Members of this subfamily trimethylate 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones . This enzyme mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. H3 'Lys-9' trimethylation is coordinated with DNA methylation. It probably forms a complex with MBD1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Protein arginine N-methyltransferase (Arg_MeTrfase)
Type: Family

Protein arginine methyltransferases (PRMTs) are enzymes that transfer methyl groups to the arginine residues of histones and other proteins. Arginine methylation is an important posttranslational modification process that plays functional roles in transcriptional control, splicing, DNA repair, and signaling .
Calmodulin-lysine N-methyltransferase (CaM-Lys-N-MeTrfase)
Type: Family

Members of this family are calmodulin-lysine N-methyltransferase (

) that catalyse the trimethylation of 'Lys-116' in calmodulin . The enzyme is cytosolic and is found at high levels in tissues with high levels of calmodulin .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
Putrescine N-methyltransferase (Putrescine_N-MeTfrase)
Type: Family

This entry represents putrescine N-methyltransferase (

), which catalyses S-adenosylmethionine (SAM)-dependent methylation of putrescine in tropane alkaloid biosynthesis. The protein displays little amino acid similarity to other plant methyltransferases, and probably evolved from spermidine synthase .
Poxvirus/kinetoplastid-type cap-specific nucleoside 2-O-methyltransferase (Pox/kineto_cap_MeTfrase)
Type: Family

Members of this family are mRNA (nucleoside-2'-O-)-methyltransferases (

). They are found in Poxvirus and in kinetoplastids (a group of single-cell flagellate protozoa). These enzymes are required for the formation of the 5' cap structure of mRNA .
Histone-lysine N-methyltransferase SMYD3 (Hist-Lys_N-MeTrfase_SMYD3)
Type: Family

This family of enzymes specifically methylate 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation . It plays an important role in transcriptional activation as a member of an RNA polymerase complex. It also binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.
TARBP1 (TARBP1)
Type: Family

This family includes TAR RNA-binding protein 1 (TARBP1), which is a probable S-adenosyl-L-methionine-dependent methyltransferase that methylates RNA molecules such as tRNAs. During infection by HIV-1, it binds to the loop region of TAR RNA, a region also bound by RNA polymerase II .
Adrift-type ribose 2-O-methyltransferase domain (Adrift-typ_MeTrfase)
Type: Domain

In higher eukaryotes, including insects, vertebrates and their viruses, mRNA and snRNA 5'-ends are modified by the addition of methyl groups to the first and/or the second transcribed nucleotides. Methylation of the ribose on the second transcribed position is termed cap2, and the enzyme responsible is the cap-specific mRNA (nucleoside-2'-O-)-methyltransferase or cap methyltransferase 2 . In Drosophila, this protein was originally known as adrift, and was isolated as a gene required for pathfinding on the segmental nerve .
tRNA methyltransferase 10 homolog C, TRM10-type domain (Trm10_C_MTase_dom)
Type: Domain

Mitochondrial RNase P (mtRNase P) cleaves tRNA molecules in their 5'-ends and consists of 3 components: a tRNA methyltransferase (MRPP1/TRMT10), a dehydrogenase/reductase-family member (MRPP2/HSD17B10), and MRPP3 (KIAA03910) .

This entry includesTRMT10C, which is a metazoa homologue to yeast TRM10, a tRNA m1G methyltransferase responsible for modification at position 9. In humans there are three TRM10 orthologues. Mutations in TRMT10C cause mitochondrial disease . Mitochondrial ribonuclease P protein 1 homolog from Drosophila melanogaster is also included in this group.

This entry represents the SAM-dependent methyltransferase TRM10-type domain.
Cytochrome c lysine N-methyltransferase 1 (Ctm1)
Type: Family

Ctm1 is a methyltransferase which mediates trimethylation of 'Lys-78' of cytochrome c (CYC1) in budding yeasts .
RrmJ-type ribose 2-O-methyltransferase domain (RrmJ-type_MeTrfase)
Type: Domain

This domain is found in cap-specific mRNA (nucleoside-2-O-)-methyltransferase 1, which is a S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs . It methylates the ribose of the first nucleotide of a m7GpppG-capped mRNA to produce m7GpppNmp (cap1). Cap1 modification is linked to higher levels of translation. It may be involved in the interferon response pathway . This group also includes

, which is thought to be inactive as it lacks the conserved Lys active site in position 367.
Methyltransferase NNMT/PNMT/TEMT, conserved site (NNMT/PNMT/TEMT_CS)
Type: Conserved_site

Several cytoplasmic vertebrate methyltransferases are evolutionary related , including nicotinamide N-methyltransferase (

) (NNMT); phenylethanolamine N-methyltransferase (

) (PNMT); and thioether S-methyltransferase (

) (TEMT). NNMT catalyses the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for the biotransformation of many drugs and xenobiotic compounds. PNMT catalyses the last step in catecholamine biosynthesis, the conversion of noradrenalin to adrenalin; and TEMT catalyses the methylation of dimethyl sulphide into trimethylsulphonium. These three enzymes use S-adenosyl-L-methionine as the methyl donor. They are proteins of 30 to 32kDa.

This entry represents the most conserved region, a stretch of 16 residues which are located in the N-terminal section of these enzymes.
tRNA (uracil-5-)-methyltransferase homolog B, chordates (TRM2B_chor)
Type: Family

This entry includes tRNA (uracil-5-)-methyltransferase homologue B (

) found in chordates. This mitochondrial enzyme catalyses the formation of 5-methyl-uridine at position 54 (m5U54) in all tRNAs , and specifically methylates the uridine in position 429 of 12S rRNA (m5U429) .

Methyltransferases (EC [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 oxygen leading to S-adenosyl-L-homocysteine (AdoHcy) and a methylated molecule . All these enzymes have in common a conserved region of about 130 amino acid residues that allow them to bind SAM . The substrates that are methylated by these enzymes cover virtually every kind of biomolecules ranging from small molecules, to lipids, proteins and nucleic acids . Methyltransferase are therefore involved in many essential cellular processes including biosynthesis, signal transduction, protein repair, chromatin regulation and gene silencing . More than 230 families of methyltransferases have been described so far, of which more than 220 use SAM as the methyl donor.