tRNA modification in the nucleus and cytosol (Homo sapiens)

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15, 24-26, 36...945, 4923, 288, 39, 52156, 11206, 11, 34, 5030, 432, 29, 321019, 5130, 43123, 567, 21, 534, 13, 14, 27, 4817, 42, 466, 344016, 5435cytosolnucleoplasmmitochondrionMETTL1 tRNA containingpseudoU-39tRNA(Met) containing1-methylA-58CTU1 TRMT11 AdoMetTP53RK ATPCTU1:CTU2:thio-URM1unspliced tRNA(Tyr) containing pseudoU-35 tRNA containingpseudoU-13,pre-tRNA(Tyr)containingpseudoU-35KIAA1456tRNA(Leu) containing I-34 tRNA(Pro) containing A-34 tRNA(Arg) containing A-34 QTRT1 WDR4 AdoHcypre-tRNAs containingI-34DUS2:EPRSAdoHcytRNA(Ile,Met,Ser)containing UtRNA(Pro) containing C-4 tRNA(Gln) containing U-34 tRNAs containingU-34ALKBH8 tRNA(Gln) containing 2-thioU-34 tRNA(Arg)(UCU) containing 5-methoxycarbonylmethylU-34 AdoMetNADH AdoMettRNA(Tyr) containingQ-34tRNA(Cys) CTU1 tRNA(Ile)(AAU) containing pseudoU-27,30 FTSJ1tRNA(Ile) containing I-34 tRNA(Cys,Thr)containing 5mC72tRNA(Asp) containing5-mC-38TRMT44tRNA(Arg,Glu)containing5-carboxymethylU-34QTRTD1 AdoMettRNA(Lys) containing U-34 tRNA(Thr) containing 5mC72 tRNA(Arg)(UCU) containing 5-carboxymethylU-34 tRNA containing A-37CTU1:CTU2:URM1tRNA(Ser) containing2'-O-methylU-44tRNA containing pseudoU-13 TRMT10AADAT1tRNA(Glu)(UUC) containing 5-methoxycarbonylmethylU-34 AdoHcytRNA(Phe) containingG-46tRNA containingU-13, pre-tRNA(Tyr)containing U-35tRNA(Gly)(GCC)containing5mC-40,48,49,50ADAT2 unsplicedtRNA(Leu)(CAA)containing5mC-34,48tRNA(Ala) containingA-37queuinetRNA containingdihydroUTRMT6 NAD(P)+AdoMetAdoMetDMAPPAdoHcytRNA(Asp)(GUC)containing5-mC-48,49TRMT13tRNA(Val) containing I-34 tRNA containing2-methylG-10tRNA(Met) containingA-58tRNA containing U-13 THG1LtRNAcontaining5-methoxycarbonylmethylU-34QTRT1:QTRTD1tRNA(Thr) containing I-34 AdoHcytRNA(Tyr) containingG-26tRNAcontainingthreonylcarbamoylA-37EKC complextRNA containing G-10tRNA containing U-39unspliced tRNA(Tyr) containing U-35 tRNA(Gly,Pro)containing C-4ALKBH8:Fe2+tRNA(Gly,Pro)containing2'-O-methylC-4NSUN2AdoHcytRNA(Phe) containing2'-O-methylC-32LAGE3 tRNA(Ser) containingisopentenylA-37TRIT1TRMT61A NAD+ tRNA(Cys) containing 5mC72 CDKAL1:4Fe-4SNH3AdoHcytRNAcontaining2-methylthio-N6-threonylcarbamoylA-37NADPH AdoHcytRNA(Asp) containingC-38PUS3tRNA(Met)(CAU) containing U-27 tRNA(Ala) containingI-37tRNA(Lys) containing 2-thioU-34 CDKAL1 tRNA containing1-methylG-9TRDMT1PPitRNA containing UtRNA(Ala) containing A-34 NAD(P)HtRNA(Ala) containing I-34 tRNA(Gly)(GCC)containingC-40,C-48,C-49,C-50AdoMettRNA(Ile,Met,Ser)containing pseudoUGTPAdoMettRNAcontainingthreonylcarbamoylA-37ADAT3 tRNA(Ser) containing A-34 AdoHcytRNA containing G-9tRNA(Gly)(GCC) containing 2'-O-methylC-4 unsplicedtRNA(Leu)(CAA)containing C-34,48CTU2 NSUN6tRNA(Asp)(GUC)containingC-48,C-49Fe2+ tRNA(Arg) containing I-34 tRNA(Leu) containing A-34 tRNA(Ser)(UGA) containing U-28 THADAAdoHcytRNA(Val) containing A-34 tRNA containing5-carboxymethylU-34DUS2 AdoHcyTRMT112 tRNA(Ile)(AAU) containing U-27,30 ADAT2:ADAT3tRNA(Ser) containingA-37tRNA(Cys,Thr)URM1 tRNA(Gly)(GCC) containing C-4 tRNA(His) containing2'-O-methylA-4METTL1:WDR4pre-tRNAs containingA-34PUS1-24Fe-4S cluster tRNA(Phe)AdoMettRNA(Phe) containing2'-O-methylG-34NADP+ AdoMettRNA(Ser)(UGA) containing pseudoU-28 L-threonylcarbamoyladenylateH2OTPRKB AdoHcySynthesis ofwybutosine at G37of tRNA(Phe)AdoMettRNA(Thr) tRNA(Glu)(UUC) containing 5-carboxymethylU-34 tRNA(Ser) containing I-34 AMPGuatRNA(Gln,Glu,Lys)containing2-thioU-34tRNA(Arg,Glu)containing5-methoxycarbonylmethylU-34PUS7tRNA(His)TRMT6:TRMT61AtRNA(Glu) containing U-34 tRNA(His) containingA-4tRNA(Thr) containing A-34 AdoMetH2ONH3tRNA(Pro) containing I-34 5'-pppG-p-tRNA(His)tRNA(Met)(CAU) containing pseudoU-27 OSGEP tRNA(Tyr) containing2,2-dimethylG-26EPRS PPiAdoHcytRNA(Ser) containingU-44AdoMettRNA(Ile) containing A-34 thioG101-URM1 tRNA(Phe) containing7-methylG-46tRNA(Glu) containing 2-thioU-34 tRNA(Pro) containing 2'-O-methylC-4 AdoMetCTU2 TRMT11:TRMT112AdoHcytRNA(Tyr) containingG-34TRMT138184010564540282054822121231, 33, 41, 551329


Description

At least 92 distinct tRNA nucleotide base modifications have been found. The modifications are made post-transcriptionally by a large group of disparate enzymes located in the nucleus, cytosol, and mitochondria (reviewed in Boschi-Muller and Motorin 2013, Jackman and Alfonzo 2013, Gu et al. 2014, Helm and Alfonzo 2014, Li and Mason 2014). Modifications near the anticodon and near the 3' end affect interaction of the tRNA with ribosomes and tRNA synthetases, respectively, while modifications in other regions of the tRNA affect folding and stability of the tRNA (reviewed in Hou et al. 2015). Mutations in tRNA modification enzymes are associated with human diseases (reviewed in Sarin and Leidel 2014, Torres et al. 2014). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 6782315
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: May, Bruce

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Bibliography

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  52. Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N.; ''Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA).''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
115064view17:01, 25 January 2021ReactomeTeamReactome version 75
113508view11:58, 2 November 2020ReactomeTeamReactome version 74
112708view16:10, 9 October 2020ReactomeTeamReactome version 73
101623view11:49, 1 November 2018ReactomeTeamreactome version 66
101159view21:35, 31 October 2018ReactomeTeamreactome version 65
100685view20:08, 31 October 2018ReactomeTeamreactome version 64
100235view16:53, 31 October 2018ReactomeTeamreactome version 63
99787view15:18, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
94054view13:54, 16 August 2017ReactomeTeamreactome version 61
93682view11:31, 9 August 2017ReactomeTeamreactome version 61
88356view16:27, 1 August 2016FehrhartOntology Term : 'tRNA maturation pathway' added !
86806view09:26, 11 July 2016ReactomeTeamreactome version 56
83451view12:26, 18 November 2015ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
4Fe-4S cluster MetaboliteCHEBI:49883 (ChEBI)
5'-pppG-p-tRNA(His)R-HSA-6782455 (Reactome)
ADAT1ProteinQ9BUB4 (Uniprot-TrEMBL)
ADAT2 ProteinQ7Z6V5 (Uniprot-TrEMBL)
ADAT2:ADAT3ComplexR-HSA-6782302 (Reactome)
ADAT3 ProteinQ96EY9 (Uniprot-TrEMBL)
ALKBH8 ProteinQ96BT7 (Uniprot-TrEMBL)
ALKBH8:Fe2+ComplexR-HSA-6786518 (Reactome)
AMPMetaboliteCHEBI:16027 (ChEBI)
ATPMetaboliteCHEBI:30616 (ChEBI)
AdoHcyMetaboliteCHEBI:16680 (ChEBI)
AdoMetMetaboliteCHEBI:15414 (ChEBI)
CDKAL1 ProteinQ5VV42 (Uniprot-TrEMBL)
CDKAL1:4Fe-4SComplexR-HSA-6786606 (Reactome)
CTU1 ProteinQ7Z7A3 (Uniprot-TrEMBL)
CTU1:CTU2:URM1ComplexR-HSA-6782330 (Reactome)
CTU1:CTU2:thio-URM1ComplexR-HSA-6782334 (Reactome)
CTU2 ProteinQ2VPK5 (Uniprot-TrEMBL)
DMAPPMetaboliteCHEBI:16057 (ChEBI)
DUS2 ProteinQ9NX74 (Uniprot-TrEMBL)
DUS2:EPRSComplexR-HSA-6782346 (Reactome)
EKC complexComplexR-HSA-6784495 (Reactome)
EPRS ProteinP07814 (Uniprot-TrEMBL)
FTSJ1ProteinQ9UET6 (Uniprot-TrEMBL)
Fe2+ MetaboliteCHEBI:29033 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
GuaMetaboliteCHEBI:16235 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
KIAA1456ProteinQ9P272 (Uniprot-TrEMBL)
L-threonylcarbamoyladenylateMetaboliteCHEBI:73687 (ChEBI)
LAGE3 ProteinQ14657 (Uniprot-TrEMBL)
METTL1 ProteinQ9UBP6 (Uniprot-TrEMBL)
METTL1:WDR4ComplexR-HSA-6782313 (Reactome)
NAD(P)+ComplexR-ALL-428218 (Reactome)
NAD(P)HComplexR-ALL-428206 (Reactome)
NAD+ MetaboliteCHEBI:57540 (ChEBI)
NADH MetaboliteCHEBI:57945 (ChEBI)
NADP+ MetaboliteCHEBI:18009 (ChEBI)
NADPH MetaboliteCHEBI:16474 (ChEBI)
NH3MetaboliteCHEBI:16134 (ChEBI)
NSUN2ProteinQ08J23 (Uniprot-TrEMBL)
NSUN6ProteinQ8TEA1 (Uniprot-TrEMBL)
OSGEP ProteinQ9NPF4 (Uniprot-TrEMBL)
PPiMetaboliteCHEBI:29888 (ChEBI)
PUS1-2ProteinQ9Y606-2 (Uniprot-TrEMBL)
PUS3ProteinQ9BZE2 (Uniprot-TrEMBL)
PUS7ProteinQ96PZ0 (Uniprot-TrEMBL)
QTRT1 ProteinQ9BXR0 (Uniprot-TrEMBL)
QTRT1:QTRTD1ComplexR-HSA-6782406 (Reactome)
QTRTD1 ProteinQ9H974 (Uniprot-TrEMBL)
Synthesis of

wybutosine at G37

of tRNA(Phe)
PathwayR-HSA-6782861 (Reactome) Derivatives of wyosine are tricyclic bases found at nucleotide 37 of tRNA(Phe) in eukaryotes. The pathway of wybutosine synthesis begins with a templated guanosine residue and proceeds through 6 steps catalyzed by 5 enzymes: N1 methylation of guanosine, condensation of 1-methylguanosine with pyruvate to yield 4-demethylwyosine, addition of an aminocarboxypropyl group to yield yW-86, methylation of yW-86 to yield yW-72, methylation of yW-72 to yield yW-58, and methoxycarbonylation of yW-58 to yield wybutosine (reviewed in Young and Bandarian 2013, Perche-Letuvée et al. 2014). Wybutosine may further be modified by hydroxylation and methylation. Wyosine derivatives at position 37 of tRNAs participate in translational fidelity by stabilizing codon-anticodon pairing (Konevega et al. 2004) and preventing frameshifting (Waas et al. 2007).
THADAProteinQ6YHU6 (Uniprot-TrEMBL)
THG1LProteinQ9NWX6 (Uniprot-TrEMBL)
TP53RK ProteinQ96S44 (Uniprot-TrEMBL)
TPRKB ProteinQ9Y3C4 (Uniprot-TrEMBL)
TRDMT1ProteinO14717 (Uniprot-TrEMBL)
TRIT1ProteinQ9H3H1 (Uniprot-TrEMBL)
TRMT10AProteinQ8TBZ6 (Uniprot-TrEMBL)
TRMT11 ProteinQ7Z4G4 (Uniprot-TrEMBL)
TRMT112 ProteinQ9UI30 (Uniprot-TrEMBL)
TRMT11:TRMT112ComplexR-HSA-6786618 (Reactome)
TRMT13ProteinQ9NUP7 (Uniprot-TrEMBL)
TRMT1ProteinQ9NXH9 (Uniprot-TrEMBL) Location in nucleus inferred from yeast homolog
TRMT44ProteinQ8IYL2 (Uniprot-TrEMBL)
TRMT6 ProteinQ9UJA5 (Uniprot-TrEMBL)
TRMT61A ProteinQ96FX7 (Uniprot-TrEMBL)
TRMT6:TRMT61AComplexR-HSA-6783454 (Reactome)
URM1 ProteinQ9BTM9 (Uniprot-TrEMBL)
WDR4 ProteinP57081 (Uniprot-TrEMBL)
pre-tRNAs containing A-34ComplexR-HSA-6782314 (Reactome)
pre-tRNAs containing I-34ComplexR-HSA-6782325 (Reactome)
queuineMetaboliteCHEBI:17433 (ChEBI)
tRNA

containing

2-methylthio-N6-threonylcarbamoylA-37
R-HSA-6786533 (Reactome)
tRNA

containing

5-methoxycarbonylmethylU-34
R-HSA-6786605 (Reactome)
tRNA

containing

threonylcarbamoylA-37
R-HSA-6784468 (Reactome)
tRNA

containing

threonylcarbamoylA-37
R-HSA-6786554 (Reactome)
tRNA containing 1-methylG-9R-HSA-6786591 (Reactome)
tRNA containing 2-methylG-10R-HSA-6786548 (Reactome)
tRNA containing 5-carboxymethylU-34R-HSA-6786496 (Reactome)
tRNA containing

U-13, pre-tRNA(Tyr)

containing U-35
ComplexR-HSA-6790218 (Reactome)
tRNA containing dihydroUR-HSA-6782353 (Reactome)
tRNA containing

pseudoU-13, pre-tRNA(Tyr) containing

pseudoU-35
ComplexR-HSA-6790181 (Reactome)
tRNA containing pseudoU-39R-HSA-8870285 (Reactome)
tRNA containing A-37R-HSA-6784474 (Reactome)
tRNA containing G-10R-HSA-6786524 (Reactome)
tRNA containing G-9R-HSA-6786513 (Reactome)
tRNA containing U-13 R-HSA-6786581 (Reactome)
tRNA containing U-39R-HSA-8870284 (Reactome)
tRNA containing UR-HSA-6782279 (Reactome)
tRNA containing pseudoU-13 R-HSA-6786494 (Reactome)
tRNA(Ala) containing A-37R-HSA-6782349 (Reactome)
tRNA(Ala) containing I-37R-HSA-6782283 (Reactome)
tRNA(Ala) containing A-34 R-HSA-6782342 (Reactome)
tRNA(Ala) containing I-34 R-HSA-6782343 (Reactome)
tRNA(Arg) containing A-34 R-HSA-6782265 (Reactome)
tRNA(Arg) containing I-34 R-HSA-6782282 (Reactome)
tRNA(Arg)(UCU) containing 5-carboxymethylU-34 R-HSA-6786613 (Reactome)
tRNA(Arg)(UCU) containing 5-methoxycarbonylmethylU-34 R-HSA-6786590 (Reactome)
tRNA(Arg,Glu)

containing

5-carboxymethylU-34
ComplexR-HSA-6786556 (Reactome)
tRNA(Arg,Glu)

containing

5-methoxycarbonylmethylU-34
ComplexR-HSA-6786617 (Reactome)
tRNA(Asp) containing 5-mC-38R-HSA-6782430 (Reactome)
tRNA(Asp) containing C-38R-HSA-6782393 (Reactome)
tRNA(Asp)(GUC)

containing

5-mC-48,49
R-HSA-6785430 (Reactome)
tRNA(Asp)(GUC)

containing

C-48,C-49
R-HSA-6785426 (Reactome)
tRNA(Cys) R-HSA-379725 (Reactome)
tRNA(Cys) containing 5mC72 R-HSA-8932758 (Reactome)
tRNA(Cys,Thr) containing 5mC72ComplexR-HSA-8932759 (Reactome)
tRNA(Cys,Thr)ComplexR-HSA-8932763 (Reactome)
tRNA(Gln) containing 2-thioU-34 R-HSA-6782271 (Reactome)
tRNA(Gln) containing U-34 R-HSA-6782280 (Reactome)
tRNA(Gln,Glu,Lys)

containing

2-thioU-34
ComplexR-HSA-6782249 (Reactome)
tRNA(Glu) containing 2-thioU-34 R-HSA-6782351 (Reactome)
tRNA(Glu) containing U-34 R-HSA-6782277 (Reactome)
tRNA(Glu)(UUC) containing 5-carboxymethylU-34 R-HSA-6786510 (Reactome)
tRNA(Glu)(UUC) containing 5-methoxycarbonylmethylU-34 R-HSA-6786498 (Reactome)
tRNA(Gly)(GCC)

containing

5mC-40,48,49,50
R-HSA-6785415 (Reactome)
tRNA(Gly)(GCC)

containing

C-40,C-48,C-49,C-50
R-HSA-6785425 (Reactome)
tRNA(Gly)(GCC) containing 2'-O-methylC-4 R-HSA-6788688 (Reactome)
tRNA(Gly)(GCC) containing C-4 R-HSA-6788690 (Reactome)
tRNA(Gly,Pro)

containing

2'-O-methylC-4
ComplexR-HSA-6788678 (Reactome)
tRNA(Gly,Pro) containing C-4ComplexR-HSA-6788700 (Reactome)
tRNA(His) containing 2'-O-methylA-4R-HSA-6788686 (Reactome)
tRNA(His) containing A-4R-HSA-6788711 (Reactome)
tRNA(His)R-HSA-379758 (Reactome)
tRNA(Ile) containing A-34 R-HSA-6782347 (Reactome)
tRNA(Ile) containing I-34 R-HSA-6782305 (Reactome)
tRNA(Ile)(AAU) containing U-27,30 R-HSA-6782364 (Reactome)
tRNA(Ile)(AAU) containing pseudoU-27,30 R-HSA-6782356 (Reactome)
tRNA(Ile,Met,Ser) containing UComplexR-HSA-6787570 (Reactome)
tRNA(Ile,Met,Ser) containing pseudoUComplexR-HSA-6787569 (Reactome)
tRNA(Leu) containing A-34 R-HSA-6782269 (Reactome)
tRNA(Leu) containing I-34 R-HSA-6782270 (Reactome)
tRNA(Lys) containing 2-thioU-34 R-HSA-6782348 (Reactome)
tRNA(Lys) containing U-34 R-HSA-6782243 (Reactome)
tRNA(Met) containing 1-methylA-58R-HSA-6783466 (Reactome)
tRNA(Met) containing A-58R-HSA-6783486 (Reactome)
tRNA(Met)(CAU) containing U-27 R-HSA-6787574 (Reactome)
tRNA(Met)(CAU) containing pseudoU-27 R-HSA-6787565 (Reactome)
tRNA(Phe) containing 2'-O-methylC-32R-HSA-9024158 (Reactome)
tRNA(Phe) containing 2'-O-methylG-34R-HSA-9024162 (Reactome)
tRNA(Phe) containing 7-methylG-46R-HSA-6782293 (Reactome)
tRNA(Phe) containing G-46R-HSA-6782309 (Reactome)
tRNA(Phe)R-HSA-379767 (Reactome)
tRNA(Pro) containing 2'-O-methylC-4 R-HSA-6788708 (Reactome)
tRNA(Pro) containing A-34 R-HSA-6782316 (Reactome)
tRNA(Pro) containing C-4 R-HSA-6788709 (Reactome)
tRNA(Pro) containing I-34 R-HSA-6782327 (Reactome)
tRNA(Ser) containing 2'-O-methylU-44R-HSA-6788717 (Reactome)
tRNA(Ser) containing A-37R-HSA-6784467 (Reactome)
tRNA(Ser) containing U-44R-HSA-6788714 (Reactome)
tRNA(Ser) containing isopentenylA-37R-HSA-6784451 (Reactome)
tRNA(Ser) containing A-34 R-HSA-6782246 (Reactome)
tRNA(Ser) containing I-34 R-HSA-6782308 (Reactome)
tRNA(Ser)(UGA) containing U-28 R-HSA-6787576 (Reactome)
tRNA(Ser)(UGA) containing pseudoU-28 R-HSA-6787585 (Reactome)
tRNA(Thr) R-HSA-379749 (Reactome)
tRNA(Thr) containing 5mC72 R-HSA-8932760 (Reactome)
tRNA(Thr) containing A-34 R-HSA-6782273 (Reactome)
tRNA(Thr) containing I-34 R-HSA-6782332 (Reactome)
tRNA(Tyr) containing 2,2-dimethylG-26R-HSA-6782408 (Reactome)
tRNA(Tyr) containing G-26R-HSA-6782418 (Reactome)
tRNA(Tyr) containing G-34R-HSA-6782425 (Reactome)
tRNA(Tyr) containing Q-34R-HSA-6782458 (Reactome)
tRNA(Val) containing A-34 R-HSA-6782268 (Reactome)
tRNA(Val) containing I-34 R-HSA-6782252 (Reactome)
tRNAs containing U-34ComplexR-HSA-6782242 (Reactome)
thioG101-URM1 ProteinQ9BTM9 (Uniprot-TrEMBL)
unspliced

tRNA(Leu)(CAA) containing

5mC-34,48
R-HSA-6782369 (Reactome)
unspliced

tRNA(Leu)(CAA)

containing C-34,48
R-HSA-6782371 (Reactome)
unspliced tRNA(Tyr) containing U-35 R-HSA-6790174 (Reactome)
unspliced tRNA(Tyr) containing pseudoU-35 R-HSA-6790176 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
5'-pppG-p-tRNA(His)ArrowR-HSA-6782434 (Reactome)
ADAT1mim-catalysisR-HSA-6782336 (Reactome)
ADAT2:ADAT3mim-catalysisR-HSA-6782311 (Reactome)
ALKBH8:Fe2+mim-catalysisR-HSA-6786500 (Reactome)
AMPArrowR-HSA-6784494 (Reactome)
ATPR-HSA-6782434 (Reactome)
AdoHcyArrowR-HSA-6782286 (Reactome)
AdoHcyArrowR-HSA-6782388 (Reactome)
AdoHcyArrowR-HSA-6782416 (Reactome)
AdoHcyArrowR-HSA-6782419 (Reactome)
AdoHcyArrowR-HSA-6783492 (Reactome)
AdoHcyArrowR-HSA-6785409 (Reactome)
AdoHcyArrowR-HSA-6785438 (Reactome)
AdoHcyArrowR-HSA-6786500 (Reactome)
AdoHcyArrowR-HSA-6786501 (Reactome)
AdoHcyArrowR-HSA-6786567 (Reactome)
AdoHcyArrowR-HSA-6786571 (Reactome)
AdoHcyArrowR-HSA-6786621 (Reactome)
AdoHcyArrowR-HSA-6788668 (Reactome)
AdoHcyArrowR-HSA-6788684 (Reactome)
AdoHcyArrowR-HSA-6788707 (Reactome)
AdoHcyArrowR-HSA-8932765 (Reactome)
AdoHcyArrowR-HSA-9024159 (Reactome)
AdoHcyArrowR-HSA-9024161 (Reactome)
AdoMetR-HSA-6782286 (Reactome)
AdoMetR-HSA-6782388 (Reactome)
AdoMetR-HSA-6782416 (Reactome)
AdoMetR-HSA-6782419 (Reactome)
AdoMetR-HSA-6783492 (Reactome)
AdoMetR-HSA-6785409 (Reactome)
AdoMetR-HSA-6785438 (Reactome)
AdoMetR-HSA-6786500 (Reactome)
AdoMetR-HSA-6786501 (Reactome)
AdoMetR-HSA-6786567 (Reactome)
AdoMetR-HSA-6786571 (Reactome)
AdoMetR-HSA-6786621 (Reactome)
AdoMetR-HSA-6788668 (Reactome)
AdoMetR-HSA-6788684 (Reactome)
AdoMetR-HSA-6788707 (Reactome)
AdoMetR-HSA-8932765 (Reactome)
AdoMetR-HSA-9024159 (Reactome)
AdoMetR-HSA-9024161 (Reactome)
CDKAL1:4Fe-4Smim-catalysisR-HSA-6786571 (Reactome)
CTU1:CTU2:URM1ArrowR-HSA-6782264 (Reactome)
CTU1:CTU2:thio-URM1R-HSA-6782264 (Reactome)
CTU1:CTU2:thio-URM1mim-catalysisR-HSA-6782264 (Reactome)
DMAPPR-HSA-6784462 (Reactome)
DUS2:EPRSmim-catalysisR-HSA-6782296 (Reactome)
EKC complexmim-catalysisR-HSA-6784494 (Reactome)
FTSJ1mim-catalysisR-HSA-9024159 (Reactome)
FTSJ1mim-catalysisR-HSA-9024161 (Reactome)
GTPR-HSA-6782434 (Reactome)
GuaArrowR-HSA-6782443 (Reactome)
H2OR-HSA-6782311 (Reactome)
H2OR-HSA-6782336 (Reactome)
KIAA1456mim-catalysisR-HSA-6786567 (Reactome)
L-threonylcarbamoyladenylateR-HSA-6784494 (Reactome)
METTL1:WDR4mim-catalysisR-HSA-6782286 (Reactome)
NAD(P)+ArrowR-HSA-6782296 (Reactome)
NAD(P)HR-HSA-6782296 (Reactome)
NH3ArrowR-HSA-6782311 (Reactome)
NH3ArrowR-HSA-6782336 (Reactome)
NSUN2mim-catalysisR-HSA-6782388 (Reactome)
NSUN2mim-catalysisR-HSA-6785409 (Reactome)
NSUN2mim-catalysisR-HSA-6785438 (Reactome)
NSUN6mim-catalysisR-HSA-8932765 (Reactome)
PPiArrowR-HSA-6782434 (Reactome)
PPiArrowR-HSA-6784462 (Reactome)
PUS1-2mim-catalysisR-HSA-6782381 (Reactome)
PUS3mim-catalysisR-HSA-8870289 (Reactome)
PUS7mim-catalysisR-HSA-6786583 (Reactome)
QTRT1:QTRTD1mim-catalysisR-HSA-6782443 (Reactome)
R-HSA-6782264 (Reactome) The CTU1:CTU2:URM1 complex transfers a thiol group from the thiolcarboxylated C-terminus of URM1 to uridine-34 residues of tRNAs, yielding 2-thiouridine-34 (Schlieker et al. 2008). The same reaction is catalyzed by TRMU (MTU1) in mitochondria.
R-HSA-6782286 (Reactome) The METTL1:WDR4 complex transfers a methyl group from S-adenosylmethionine to guanosine-46 of tRNA(Phe), yielding 7-methylguanosine-46 (Alexandrov et al. 2002, Cartlidge et al. 2005). A homologous complex, Trm8p:Trm82p, exists in Saccharomyces cerevisiae and catalyzes the same reaction.
R-HSA-6782296 (Reactome) DUS2 catalyzes the reduction of the 5,6 double bond in uridine residues in the D-loop of tRNAs, yielding 5,6-dihydrouridine (Kato et al. 2005). By inference with the homolog from Saccharomyces cerevisiae, Smm1p (Dus2p), NADH or NADPH is the reducing agent.
R-HSA-6782311 (Reactome) The ADAT2:ADAT3 heterodimer (hetADAT) deaminates adenosine-34 in 8 human tRNAs: tRNA(Ala-AGC), tRNA(Arg-ACG), tRNA(Ile-AAT), tRNA(leu-AAG), tRNA(Pro-AGG), tRNA(Ser-AGA), tRNA(Thr-AGT), tRNA(Val-AAC) (Torres et al. 2015). The deamination occurs in the nucleus on precursor tRNAs from which the 5' leaders and 3' trailers have not yet been cleaved. The corresponding homologues in Saccharomyces cerevisiae are Tad2p and Tad3p.
R-HSA-6782336 (Reactome) ADAT1 deaminates adenosine-37 of tRNA(Ala) yielding inosine-37, which may then be methylated to N1-methylinosine-37 (Maas et al. 1999). The homologue in Saccharomyces, Tad1p, catalyzes the same reaction, indicating the deamination of adenosine-37 is highly conserved in eukaryotes.
R-HSA-6782381 (Reactome) The shorter isoform of PUS1, PUS1-2, converts uridine to pseudouridine in the anticodon stem of tRNAs in the nucleus (Fernandez-Vizarra et al. 2007, Sibert et al. 2008). The longer isoform of PUS1 (PUS1-1) is present in mitochondria; a shorter isoform of PUS1 (PUS1-2) possessing a different N-terminus is present in the nucleus (Fernandez-Vizarra et al. 2007). In contrast, the yeast Saccharomyces cerevisiae has 2 genes: PUS1 which encodes the nuclear enzyme and PUS2 which encodes the mitochodrial enzyme. PUS1 and its substrates are conserved from yeast to humans. Like the yeast homologue, Pus1p, human PUS1 may also act on additional tRNAs, pre-tRNAs, and U2 snRNA. Mutations in PUS1 cause mitochondrial myopathy and sideroblastic anemia (MLASA) (Bykhovskaya et al. 2004, Fernandez-Vizarra et al. 2007).
R-HSA-6782388 (Reactome) NSUN2 transfers a methyl group from S-adenosylmethionine to the 5 positions of cytidine-34 and cytidine-48 in tRNA(Leu)(CAA) (Brzezicha et al. 2006, Auxilien et al. 2012, Squires et al. 2012, Khoddami and Cairns 2013). Methylation of cytidine-34 occurs on the uspliced precursor tRNA(Leu)(CAA) (Brzezicha et al. 2006, Auxilien et al. 2012); methylation of cytidine-48 occurs on either the spliced or unspliced tRNA(Leu)(CAA) (Auxilien et al. 2012).
R-HSA-6782416 (Reactome) TRMT1 (hTRM1) transfers two methyl groups from two molecules of S-adenosylmethionine to the 2 position of guanosine-26 of tRNA(Tyr), yielding 2-dimethylguanosine (Liu and Straby 2000). TRMT1 can dimethylate both spliced and unspliced tRNA (Liu and Straby 2000).
R-HSA-6782419 (Reactome) TRDMT1 (DNMT2) transfers a methyl group from S-adenosylmethionine to the 5 position of cytidine-38 of tRNA(Asp) (Goll et al. 2006, Jurkowski et al. 2008, Jurkowski et al. 2012). TRDMT1 uses a similar mechanism to DNA methyltransferases (DNMT1, DNMT3A, DNMT3B) (Jurkowski et al. 2008).
R-HSA-6782434 (Reactome) THG1L (THG1) adds a guanosine triphosphate residue to the 5' end of tRNA(His), a 3'-5' addition that contrasts with the usual 5'-3' directionality of nucleotide polymerases (Hyde et al. 2010).
R-HSA-6782443 (Reactome) The transglycosylase complex QTRT1:QTRTD1 exchanges guanine for queuine at nucleotide 34 of tRNA(Tyr) (Chen et al. 2010, Chen et al. 2011). The QTRT1 subunit is responsible for the transglycosylase activity. Eukaryotes are unable to synthesize queuine and must obtain it from dietary sources or symbiotic gut flora. As inferred from the mouse homologs, QTRT1:QTRTD1 associates with the outer mitochondrial membrane (Boland et al. 2009). The homologous enzyme in Escherichia coli is tgt.
R-HSA-6783492 (Reactome) The TRMT6:TRMT61A complex transfers a methyl group from S-adenosylmethionine to the 1 position of adenosine-58 of tRNA(Met) (Ozanick et al. 2005). Based on the location of the homologous complex (GCD10:GCD14) in yeast (Anderson et al. 1998), methylation by the TRMT6:TRMT61A complex is inferred to occur in the nucleus.
R-HSA-6784462 (Reactome) TRIT1 transfers a dimethylallyl group (isopentenyl group) from dimethylallyl diphosphate to the N6 position of adenosine-37 in tRNA(Ser), yielding N6-dimethylallyladenosine-37 (N6-isopentenyladenosine-37) (Golovko et al. 2000, Spinola et al. 2005, Lamichhane et al. 2013, Yarham et al. 2014, Smaldino et al. 2015). TRIT1 modifies both cytosolic and mitochondrial tRNAs and a mutation in TRIT1 causes mitochondrial respiratory defects (Yarham et al. 2014). Expression of TRIT1 is down-regulated in lung adenocarcinomas compared with normal tissue (Spinola et al. 2005). The homologue in Saccharomyces cerevisiae, MOD5, catalyzes the same reaction.
R-HSA-6784494 (Reactome) As inferred from the yeast homologs (EKC complex, KEOPS complex, BUD32:CGI121:KAE1:PCC1), the EKC complex (LAGE3:OSGEP:TP53RK:TPRKB) transfers a threonylcarbamoyl group from L-threonylcarbamoyladenylate to adenosine-37 of tRNAs, yielding threonylcarbamoyladenosine-37.
R-HSA-6785409 (Reactome) NSUN2 transfers methyl groups from S-adenosylmethionine to the 5 positions of cytidine-48 and cytidine-49 of tRNA(Asp)(GUC) (Squires et al. 2012, Khoddami et al. 2013).
R-HSA-6785438 (Reactome) NSUN2 transfers methyl groups from S-adenosylmethionine to the 5 positions of cytidine-40, cytidine-48, cytidine-49, and cytidine-50 of tRNA(Gly)(GCC) (Auxilien et al. 2012, Khoddami and Cairns 2013).
R-HSA-6786500 (Reactome) ALKBH8:Fe2+ transfers a methyl group from S-adenosylmethionine (AdoMet) to 5-carboxymethyluridine-34 of tRNA, yielding 5-methoxycarbonylmethyluridine-34 (5-(2-methoxy-2-oxoethyl)uridine-34) (Fu et al. 2010, Songe-Møller et al. 2010). The corresponding homologue in Saccharomyces, Trm9p, catalyzes the same reaction.
R-HSA-6786501 (Reactome) As inferred from homologues in Saccharomyces cerevisiae, TRMT11 (catalytic subunit) and TRMT112 (zinc-binding subunit) form a complex which methylates the 2 position of guanosine-10 in tRNA (Purushothaman et al. 2005).
R-HSA-6786567 (Reactome) KIAA1456 (TRM9L, hTRM9L) transfers a methyl group from S-adenosylmethionine (AdoMet) to 5-carboxymethyluridine in tRNA, yielding 5-methoxycarbonylmethyluridine (5-(2-methoxy-2-oxoethyl)uridine) (Begley et al. 2013). The subcellular location of the reaction is unknown.
R-HSA-6786571 (Reactome) The CDKAL1:4Fe-4S complex methylthiolates N6-threonylcarbamoyladenosine-37 in several tRNAs (Arragain et al. 2010). The source of the methyl group is S-adenosylmethionine (AdoMet). The source of the sulfur is unknown. The homologue in Bacillus subtilis, mtaB, catalyzes the same reaction (Arragain et al. 2010).
CDKAL1 is located on the cytosolic face of the endoplasmic reticulum therefore the reaction is presumed to occur in the cytosol (Brambillasca et al. 2012).
R-HSA-6786583 (Reactome) As inferred from the homologue in Saccharmyces cerivisiae, PUS7 converts uridine to pseudouridine at nucleotide 13 of cytoplasmic tRNA and at nucleotide 35 of unspliced tRNA(Tyr). PUS7 also synthesizes pseudouridine in U2 snRNA and in pre-tRNA(Tyr). Pus7p is a nuclear protein according to global analysis of protein locations in yeast.
R-HSA-6786621 (Reactome) As inferred from the homologue in Saccharomyces cerevisiae, TRMT10A methylates the 1 position of guanosine at nucleotide 9 of tRNAs. TRMT10A is located in the nucleus (Igoillo-Esteve et al. 2013). A nonsense mutation in TRMT10A causes diabetes and microcephaly (Igoillo-Esteve et al. 2013).
R-HSA-6788668 (Reactome) As inferred from the yeast homolog, TRMT13 methylates the 2' hydroxyl group of adenosine-4 in the acceptor stems of tRNA(His). The subcellular location of the reaction is unknown. Yeast lacking TRM13 do not have an obvious growth defect.
R-HSA-6788684 (Reactome) As inferred from the yeast homolog, TRMT13 methylates the 2' hydroxyl group of cytidine-4 in the acceptor stems of tRNA(Gly) and tRNA(Pro). The subcellular location of the reaction is unknown. Yeast lacking TRM13 do not have an obvious growth defect.
R-HSA-6788707 (Reactome) As inferred from the yeast homolog, TRMT44 methylates the 2' hydroxyl group of uridine-44 in tRNA(Ser). In yeast 2'-O-methyluridine-44 together with N(4)-acetylcytidine appears to be required to maintain abundance of tRNA(Ser).
R-HSA-8870289 (Reactome) PUS3 catalyzes the modification (isomerization) of uridine to pseudouridine at nucleotides 38 and 39 in the anticodon loops of tRNAs (Shaheen et al. 2016). Homologues of PUS3 in mouse (Chen and Patton 2000) and yeast (Lecointe et al. 1998) catalyze the same reaction, and both the PUS3 gene family and the modification are highly conserved. Deletion of DEG1 encoding Pus3p in budding yeast (Saccharomyces cerevisiae) causes slow growth (Lecointe et al. 1998) while a truncating mutation in human PUS3 causes a reduction in pseudouridines 38 and 39 with consequent intellectual disability (Shaheen et al. 2016).
R-HSA-8932765 (Reactome) NSUN6 methylates position 5 of the cytosine ring of cytidine-72 in the acceptor stem of tRNA(Cys) and tRNA(Thr) (Haag et al. 2015). As the reaction occurs in the cytoplasm and requires the 3' CCA on the tRNA substrates, it is believed to occur late in tRNA biogenesis
R-HSA-9024159 (Reactome) FTSJ1 methylates the 2'‑hydroxyl group of cytidine‑32 and guanosine‑34 in the anticodon loop of tRNA(Phe), as well as C32 and N34 of other substrate tRNAs (Guy and Phizicky 2015a, Guy et al. 2015b). Based on the functional and sequence homology between human FTSJ1 and yeast Trm7 the reaction is inferred to occur in the cytosol. THADA is required together with FTSJ1 for the methylation reaction at C32, based on its complementation of trm732 mutants in yeast, but the function of THADA has not been directly demonstrated in human cells (Guy and Phizicky 2015a).
R-HSA-9024161 (Reactome) FTSJ1 methylates the 2'‑hydroxyl group of cytidine‑32 and guanosine‑34 in the anticodon loop of tRNA(Phe), as well as C32 and N34 of other substrate tRNAs (Guy and Phizicky 2015a, Guy et al. 2015b). Based on the functional and sequence homology between human FTSJ1 and yeast Trm7 the reaction is inferred to occur in the cytosol. THADA is required together with FTSJ1 for the methylation reaction at C32, based on its complementation of trm732 mutants in yeast, but the function of THADA has not been directly demonstrated in human cells (Guy and Phizicky 2015a).
THADAArrowR-HSA-9024159 (Reactome)
THADAArrowR-HSA-9024161 (Reactome)
THG1Lmim-catalysisR-HSA-6782434 (Reactome)
TRDMT1mim-catalysisR-HSA-6782419 (Reactome)
TRIT1mim-catalysisR-HSA-6784462 (Reactome)
TRMT10Amim-catalysisR-HSA-6786621 (Reactome)
TRMT11:TRMT112mim-catalysisR-HSA-6786501 (Reactome)
TRMT13mim-catalysisR-HSA-6788668 (Reactome)
TRMT13mim-catalysisR-HSA-6788684 (Reactome)
TRMT1mim-catalysisR-HSA-6782416 (Reactome)
TRMT44mim-catalysisR-HSA-6788707 (Reactome)
TRMT6:TRMT61Amim-catalysisR-HSA-6783492 (Reactome)
pre-tRNAs containing A-34R-HSA-6782311 (Reactome)
pre-tRNAs containing I-34ArrowR-HSA-6782311 (Reactome)
queuineR-HSA-6782443 (Reactome)
tRNA

containing

2-methylthio-N6-threonylcarbamoylA-37
ArrowR-HSA-6786571 (Reactome)
tRNA

containing

5-methoxycarbonylmethylU-34
ArrowR-HSA-6786567 (Reactome)
tRNA

containing

threonylcarbamoylA-37
ArrowR-HSA-6784494 (Reactome)
tRNA

containing

threonylcarbamoylA-37
R-HSA-6786571 (Reactome)
tRNA containing 1-methylG-9ArrowR-HSA-6786621 (Reactome)
tRNA containing 2-methylG-10ArrowR-HSA-6786501 (Reactome)
tRNA containing 5-carboxymethylU-34R-HSA-6786567 (Reactome)
tRNA containing

U-13, pre-tRNA(Tyr)

containing U-35
R-HSA-6786583 (Reactome)
tRNA containing dihydroUArrowR-HSA-6782296 (Reactome)
tRNA containing

pseudoU-13, pre-tRNA(Tyr) containing

pseudoU-35
ArrowR-HSA-6786583 (Reactome)
tRNA containing pseudoU-39ArrowR-HSA-8870289 (Reactome)
tRNA containing A-37R-HSA-6784494 (Reactome)
tRNA containing G-10R-HSA-6786501 (Reactome)
tRNA containing G-9R-HSA-6786621 (Reactome)
tRNA containing U-39R-HSA-8870289 (Reactome)
tRNA containing UR-HSA-6782296 (Reactome)
tRNA(Ala) containing A-37R-HSA-6782336 (Reactome)
tRNA(Ala) containing I-37ArrowR-HSA-6782336 (Reactome)
tRNA(Arg,Glu)

containing

5-carboxymethylU-34
R-HSA-6786500 (Reactome)
tRNA(Arg,Glu)

containing

5-methoxycarbonylmethylU-34
ArrowR-HSA-6786500 (Reactome)
tRNA(Asp) containing 5-mC-38ArrowR-HSA-6782419 (Reactome)
tRNA(Asp) containing C-38R-HSA-6782419 (Reactome)
tRNA(Asp)(GUC)

containing

5-mC-48,49
ArrowR-HSA-6785409 (Reactome)
tRNA(Asp)(GUC)

containing

C-48,C-49
R-HSA-6785409 (Reactome)
tRNA(Cys,Thr) containing 5mC72ArrowR-HSA-8932765 (Reactome)
tRNA(Cys,Thr)R-HSA-8932765 (Reactome)
tRNA(Gln,Glu,Lys)

containing

2-thioU-34
ArrowR-HSA-6782264 (Reactome)
tRNA(Gly)(GCC)

containing

5mC-40,48,49,50
ArrowR-HSA-6785438 (Reactome)
tRNA(Gly)(GCC)

containing

C-40,C-48,C-49,C-50
R-HSA-6785438 (Reactome)
tRNA(Gly,Pro)

containing

2'-O-methylC-4
ArrowR-HSA-6788684 (Reactome)
tRNA(Gly,Pro) containing C-4R-HSA-6788684 (Reactome)
tRNA(His) containing 2'-O-methylA-4ArrowR-HSA-6788668 (Reactome)
tRNA(His) containing A-4R-HSA-6788668 (Reactome)
tRNA(His)R-HSA-6782434 (Reactome)
tRNA(Ile,Met,Ser) containing UR-HSA-6782381 (Reactome)
tRNA(Ile,Met,Ser) containing pseudoUArrowR-HSA-6782381 (Reactome)
tRNA(Met) containing 1-methylA-58ArrowR-HSA-6783492 (Reactome)
tRNA(Met) containing A-58R-HSA-6783492 (Reactome)
tRNA(Phe) containing 2'-O-methylC-32ArrowR-HSA-9024159 (Reactome)
tRNA(Phe) containing 2'-O-methylG-34ArrowR-HSA-9024161 (Reactome)
tRNA(Phe) containing 7-methylG-46ArrowR-HSA-6782286 (Reactome)
tRNA(Phe) containing G-46R-HSA-6782286 (Reactome)
tRNA(Phe)R-HSA-9024159 (Reactome)
tRNA(Phe)R-HSA-9024161 (Reactome)
tRNA(Ser) containing 2'-O-methylU-44ArrowR-HSA-6788707 (Reactome)
tRNA(Ser) containing A-37R-HSA-6784462 (Reactome)
tRNA(Ser) containing U-44R-HSA-6788707 (Reactome)
tRNA(Ser) containing isopentenylA-37ArrowR-HSA-6784462 (Reactome)
tRNA(Tyr) containing 2,2-dimethylG-26ArrowR-HSA-6782416 (Reactome)
tRNA(Tyr) containing G-26R-HSA-6782416 (Reactome)
tRNA(Tyr) containing G-34R-HSA-6782443 (Reactome)
tRNA(Tyr) containing Q-34ArrowR-HSA-6782443 (Reactome)
tRNAs containing U-34R-HSA-6782264 (Reactome)
unspliced

tRNA(Leu)(CAA) containing

5mC-34,48
ArrowR-HSA-6782388 (Reactome)
unspliced

tRNA(Leu)(CAA)

containing C-34,48
R-HSA-6782388 (Reactome)
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