Any feedback?
Information on EC 2.1.1.220 - tRNA (adenine58-N1)-methyltransferase and Organism(s) Homo sapiens and UniProt Accession Q96FX7
for references in articles please use BRENDA:EC2.1.1.220Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.1.1.220 tRNA (adenine58-N1)-methyltransferaseIUBMB Comments
The enzyme specifically methylates adenine58 in tRNA. The methylation of A58 is critical for maintaining the stability of initiator tRNAMet in yeast .
Specify your search results
Word Map
- 2.1.1.220
- trnaimet
- 1-methyladenosine
- nucleoside
- mtases
-
two-subunit
-
thermus
-
exosome
-
polyadenylation
- adomet
-
t-loop
- polya
- s-adenosylmethionine
-
n1-methylation
- heterotetramer
-
homotetrameric
- methionyl-trna
-
high-copy-number
- eubacteria
- methyltransferases
- s-adenosyl-l-homocysteine
-
two-component
-
s-adenosyl-l-methionine-dependent
-
l-shaped
-
tpsic
-
trna-binding
-
hypomodified
- drug development
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
+
adenine58 in tRNA
=
+
N1-methyladenine58 in tRNA
Synonyms
gcd14p, gcd10p, rv2118c, trna m(1)a58 methyltransferase, rv2118p, trm61p, trm6p, trm6-trm61 holoenzyme, trna (m1a58) methyltransferase, m1a58 trna methyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
m1A58 MTase
tRNA m1A58 methyltransferase
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:tRNA (adenine58-N1)-methyltransferase
The enzyme specifically methylates adenine58 in tRNA. The methylation of A58 is critical for maintaining the stability of initiator tRNAMet in yeast [3].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA3Lys
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA3Lys
-
-
-
?
2 S-adenosyl-L-methionine + adenine58 in tRNA
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
-
-
?
2 S-adenosyl-L-methionine + adenine58 in tRNALys3
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3
-
-
-
?
S-adenosyl-L-methionine + adenine58 in human tRNA3Lys
S-adenosyl-L-homocysteine + N1-methyladenine58 in human tRNA3Lys
-
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
S-adenosyl-L-methionine + adenine58 in yeast initiator tRNAMet
S-adenosyl-L-homocysteine + N1-methyladenine58 in yeast initiator tRNAMet
no methylation of the A58U mutant of yeast initiator tRNA(Met)
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
-
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
modification at the conserved nucleotide 58 in the TCC loop
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
tRNA m1A58 methyltransferase, TrmI, catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to N1 of adenine 58 in the T-loop of tRNAs
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA3Lys
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA3Lys
-
-
-
?
2 S-adenosyl-L-methionine + adenine58 in tRNA
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
-
-
?
2 S-adenosyl-L-methionine + adenine58 in tRNALys3
2 S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNALys3
-
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
modification at the conserved nucleotide 58 in the TCC loop
-
-
?
S-adenosyl-L-methionine + adenine58 in tRNA
S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
-
tRNA m1A58 methyltransferase, TrmI, catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to N1 of adenine 58 in the T-loop of tRNAs
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
m1A58 modification of tRNA3Lys also has a role in replication of HIV in humans, human tRNA3 Lys is the primer for reverse transcription of HIV, the 3' end is complementary to the primer-binding site on HIV RNA. The complementarity ends at the 18th base, A58, which in tRNA3 Lys is modified to remove Watson-Crick pairing. tRNA m1A58 methyltransferase methylates N1 of A58, which is buried in the TPsiC-loop of tRNA, from cofactor S-adenosyl-L-methionine. This conserved tRNA modification is essential for stability of initiator tRNA
evolution
malfunction
metabolism
in cytosolic (cyt) tRNA, the m1A modification occurs at five different positions (9, 14, 22, 57, and 58), two of which (9 and 58) are also found in mitochondrial (mt) tRNAs. In some cases, these modifications have been shown to increase tRNA structural stability and induce correct tRNA folding. Two enzyme families are responsible for formation of m1A at nucleotide position 9 and 58 in tRNA, tRNA binding, m1A mechanism, protein domain organisation and overall structures
physiological function
additional information
evolution
-
comparative structural analysis of TrmIs from archea, prokaryota, and eukaryota, overview
evolution
the m1A58 modification occurs on (cyt)tRNAs from all three domains of life and further in (mt)tRNAs. The enzyme belongs to the RFM class I methyltransferases. In eukaryotes, the m1A58 MTase located in the cytosol is composed of a catalytic protein unit from the Trm61 subfamily (Trm61A) and an RNA-binding protein unit from the Trm6 subfamily (Trm6). Trm6 and Trm61 share a common ancestor and arose via gene duplication and divergent evolution. The mitochondrial m1A58 MTase consists of a single protein from the Trm61 family (Trmt61B), which is a paralogue to Trm61A from the cytosolic complex. In mitochondria, MTase Trmt61B forms a tetramer, presumed to resemble the homotetramers of TrmI proteins. In support of a similar structural arrangement between Trmt61B and TrmI, a phylogenetic analysis confirmed a bacterial origin of the human protein
malfunction
-
siRNA knockdown of either subunit of the m1A58-methyltransferase results in a slow-growth phenotype, and a marked increase in the amount of m1A58 hypomodified tRNAs. Most m1A58 hypomodified tRNAs can associate with polysomes in varying extents
malfunction
the lack of m1A58 in human tRNALys3 has been shown to be crucial for reverse transcription fidelity and efficiency of retroviruses like HIV-1. The lack of m1A58 results in an abnormal tRNAi structure, guiding it for degradation. This might explain why exclusion of this MTase by siRNA-mediated knockdown gives rise to a slow-growth phenotype in human cells
physiological function
methylation of A58 is critical for maintaining the stability of initiator tRNAMet in yeast
physiological function
-
N1-adenine58 methylation of initiator-tRNAMet is required for stabilizing this tRNA in human cells
physiological function
-
tRNA m1A58 methyltransferase catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to N1 of adenine 58 in the T-loop of tRNAs, a modification, that is essential for cell growth in yeast
physiological function
the m1A58 modifications have both been linked to structural stability and/or correct folding of the tRNA and is related to structural thermostability of tRNA, role of m1A58 in tRNAi structure stability. The initiator tRNA from eukaryotes (tRNAi) has a conserved A-rich T-loop (A54, A58, and A69), a conserved A20 and a shorter-than-average D-loop (seven nucleobases). These features cluster in the corner of the L-shaped tRNA and the structure is maintained by a dense network f hydrogen bonds between the conserved adenines. In this network, A58 forms hydrogen bonds to A54 and A60
additional information
m1A58 MTase is composed of two subunits, a catalytic component, Trm61, and an RNA-binding component, Trm6. tRNAs bind across the dimer interface such that Trm6 from the opposing heterodimer brings A58 into the active site of Trm61. T-loop and D-loop are splayed apart showing how A58, normally buried in tRNA, becomes accessible for modification, mechanisms of modifying internal sites in folded tRNA, overview. 2Fold related tRNAs bind across the tetramer interface, active site structure analysis. m1A58 MTase uses induced fit to access its target base
additional information
-
m1A58 MTase is composed of two subunits, a catalytic component, Trm61, and an RNA-binding component, Trm6. tRNAs bind across the dimer interface such that Trm6 from the opposing heterodimer brings A58 into the active site of Trm61. T-loop and D-loop are splayed apart showing how A58, normally buried in tRNA, becomes accessible for modification, mechanisms of modifying internal sites in folded tRNA, overview. 2Fold related tRNAs bind across the tetramer interface, active site structure analysis. m1A58 MTase uses induced fit to access its target base
additional information
-
microarray method genomic approach to determine the presence of m1A58 hypomodified tRNAs, on the basis of their permissiveness in primer extension, in human cell lines, overview. A58 hypomodification affects stability and involvement of tRNAs in translation. No hypomodification of initiator-tRNAMet. The pattern of the m1A58 hypomodified tRNAs is similar in five human cell lines
additional information
crystal structure of the human m1A58 MTase in complex with tRNALys3 have not provided information on the correct mechanism, as the position of A58 in the active site resembles a methylated nucleobase in a product-complex
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). TRM61_HUMAN
289
0
31382
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
dimer of heterodimers in which each heterodimer comprises a catalytic chain, Trm61, and a homologous but noncatalytic chain, Trm6, repurposed as a tRNA-binding subunit that acts in trans, crystal structure analysis
heterotetramer
additional information
heterotetramer
-
dimers of tightly assembled heterodimers, formed by TrmI-6 and TrmI-61 subunits, interactions and structure analysis, overview
heterotetramer
the eukaryotic complex of Trm6-Trm61 has been reported as a heterotetramer
additional information
Trm6 is less conserved with respect to TrmI than Trm61 and lacks a cofactor-binding pocket, enzyme quaternary structure, overview
additional information
-
Trm6 is less conserved with respect to TrmI than Trm61 and lacks a cofactor-binding pocket, enzyme quaternary structure, overview
additional information
in mitochondria, MTase Trmt61B forms a tetramer, presumed to resemble the homotetramers of TrmI proteins. In support of a similar structural arrangement between Trmt61B and TrmI, a phylogenetic analysis confirmed a bacterial origin of the human protein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
human enzyme tRNA m1A58 MTase in complex with human tRNA3Lys and cofactors S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, hanging drop vapor diffusion method, mixing of 0.001 ml of 4.8 mg/ml protein in 50 mM HEPES, pH 7.5, 0.0664 mM tRNA3Lys, 2 mM S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, and 1 mM MgCl2, with 0.001 ml of reservoir solution containing 0.1 M Na acetate, pH 4.8-5.0, 2% w/v PEG 4000 and 15% v/v methyl-2,4-pentanediol, 16°C, 4-7 days, X-ray diffraction structure determination and analysis at 2.2-4.0 A resolution, molecular replacement
crystal structure of the human m1A58 MTase in complex with tRNALys3 (PDB ID 5CCB), and of human complex Trm6-Trm61 (PDB ID 2B25)
TrmI-61 protein complexed with S-adenosyl-L-methionine, X-ray diffraction structure determination and analysis at 2.5 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
siRNA knockdown of m1A58 methyltransferase subunits TRM6 or TRM61
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the tag by 3C protease, and gel filtration
coexpression of catalytic subunit Trm61p and non-catalytic subunit Trm6p in Saccharomyces cerevisiae, purification of the hTrm6p/hTrm61p complexes
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
coexpression of catalytic subunit Trm61p and non-catalytic subunit Trm6p in Saccharomyces cerevisiae
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme crystal structures serve as templates for design of inhibitors that can be used to test tRNA m1A58 MTase's impact on retroviral priming and transcription
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ozanick, S.; Krecic, A.; Andersland, J.; Anderson, J.T.
The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans
RNA
11
1281-1290
2005
Homo sapiens (Q96FX7 and Q9UJA5), Homo sapiens
Guelorget, A.; Barraud, P.; Tisne, C.; Golinelli-Pimpaneau, B.
Structural comparison of tRNA m(1)A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions
BMC Struct. Biol.
11
48
2011
Aquifex aeolicus, Homo sapiens, Mycobacterium tuberculosis, Pyrococcus abyssi, Saccharomyces cerevisiae, Thermotoga maritima, Thermus thermophilus
Saikia, M.; Fu, Y.; Pavon-Eternod, M.; He, C.; Pan, T.
Genome-wide analysis of N1-methyl-adenosine modification in human tRNAs
RNA
16
1317-1327
2010
Homo sapiens
Finer-Moore, J.; Czudnochowski, N.; OConnell, J.I.; Wang, A.; Stroud, R.
Crystal structure of the human tRNA m1A58 methyltransferase-tRNA3 Lys complex: Refolding of Substrate tRNA Allows Access to the Methylation Target
J. Mol. Biol.
427
3862-3876
2015
Homo sapiens (Q96FX7), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 2.1.1.220)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
