tRNA modification in the nucleus and cytosol (Homo sapiens)

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1. Maas S, Gerber AP, Rich A.; ''Identification and characterization of a human tRNA-specific adenosine deaminase related to the ADAR family of pre-mRNA editing enzymes.''; PubMed Europe PMC Scholia
2. Chen YC, Brooks AF, Goodenough-Lashua DM, Kittendorf JD, Showalter HD, Garcia GA.; ''Evolution of eukaryal tRNA-guanine transglycosylase: insight gained from the heterocyclic substrate recognition by the wild-type and mutant human and Escherichia coli tRNA-guanine transglycosylases.''; PubMed Europe PMC Scholia
3. Songe-Møller L, van den Born E, Leihne V, Vågbø CB, Kristoffersen T, Krokan HE, Kirpekar F, Falnes PØ, Klungland A.; ''Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding.''; PubMed Europe PMC Scholia
4. Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW.; ''Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.''; PubMed Europe PMC Scholia
5. Begley U, Sosa MS, Avivar-Valderas A, Patil A, Endres L, Estrada Y, Chan CT, Su D, Dedon PC, Aguirre-Ghiso JA, Begley T.; ''A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α.''; PubMed Europe PMC Scholia
6. Khoddami V, Cairns BR.; ''Identification of direct targets and modified bases of RNA cytosine methyltransferases.''; PubMed Europe PMC Scholia
7. Lecointe F, Simos G, Sauer A, Hurt EC, Motorin Y, Grosjean H.; ''Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of psi 38 and psi 39 in tRNA anticodon loop.''; PubMed Europe PMC Scholia
8. Fernandez-Vizarra E, Berardinelli A, Valente L, Tiranti V, Zeviani M.; ''Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA).''; PubMed Europe PMC Scholia
9. Liu J, Strâby KB.; ''The human tRNA(m(2)(2)G(26))dimethyltransferase: functional expression and characterization of a cloned hTRM1 gene.''; PubMed Europe PMC Scholia
10. Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, Miyamoto M, Kondo S, Nakamura Y.; ''A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis.''; PubMed Europe PMC Scholia
11. Auxilien S, Guérineau V, Szweykowska-Kulińska Z, Golinelli-Pimpaneau B.; ''The human tRNA m (5) C methyltransferase Misu is multisite-specific.''; PubMed Europe PMC Scholia
12. Schlieker CD, Van der Veen AG, Damon JR, Spooner E, Ploegh HL.; ''A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway.''; PubMed Europe PMC Scholia
13. Smaldino PJ, Read DF, Pratt-Hyatt M, Hopper AK, Engelke DR.; ''The cytoplasmic and nuclear populations of the eukaryote tRNA-isopentenyl transferase have distinct functions with implications in human cancer.''; PubMed Europe PMC Scholia
14. Golovko A, Hjälm G, Sitbon F, Nicander B.; ''Cloning of a human tRNA isopentenyl transferase.''; PubMed Europe PMC Scholia
15. Hou YM, Gamper H, Yang W.; ''Post-transcriptional modifications to tRNA--a response to the genetic code degeneracy.''; PubMed Europe PMC Scholia
16. Brambillasca S, Altkrueger A, Colombo SF, Friederich A, Eickelmann P, Mark M, Borgese N, Solimena M.; ''CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is a tail-anchored protein in the endoplasmic reticulum (ER) of insulinoma cells.''; PubMed Europe PMC Scholia
17. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, Golic KG, Jacobsen SE, Bestor TH.; ''Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2.''; PubMed Europe PMC Scholia
18. Guo D, Hu K, Lei Y, Wang Y, Ma T, He D.; ''Identification and characterization of a novel cytoplasm protein ICF45 that is involved in cell cycle regulation.''; PubMed Europe PMC Scholia
19. Igoillo-Esteve M, Genin A, Lambert N, Désir J, Pirson I, Abdulkarim B, Simonis N, Drielsma A, Marselli L, Marchetti P, Vanderhaeghen P, Eizirik DL, Wuyts W, Julier C, Chakera AJ, Ellard S, Hattersley AT, Abramowicz M, Cnop M.; ''tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans.''; PubMed Europe PMC Scholia
20. Hyde SJ, Eckenroth BE, Smith BA, Eberley WA, Heintz NH, Jackman JE, Doublié S.; ''tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl transferase, shares unexpected structural homology with canonical 5'-3' DNA polymerases.''; PubMed Europe PMC Scholia
21. Chen J, Patton JR.; ''Pseudouridine synthase 3 from mouse modifies the anticodon loop of tRNA.''; PubMed Europe PMC Scholia
22. Pastore C, Topalidou I, Forouhar F, Yan AC, Levy M, Hunt JF.; ''Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification.''; PubMed Europe PMC Scholia
23. Anderson J, Phan L, Cuesta R, Carlson BA, Pak M, Asano K, Björk GR, Tamame M, Hinnebusch AG.; ''The essential Gcd10p-Gcd14p nuclear complex is required for 1-methyladenosine modification and maturation of initiator methionyl-tRNA.''; PubMed Europe PMC Scholia
24. Gu C, Begley TJ, Dedon PC.; ''tRNA modifications regulate translation during cellular stress.''; PubMed Europe PMC Scholia
25. Jackman JE, Alfonzo JD.; ''Transfer RNA modifications: nature's combinatorial chemistry playground.''; PubMed Europe PMC Scholia
26. Li S, Mason CE.; ''The pivotal regulatory landscape of RNA modifications.''; PubMed Europe PMC Scholia
27. Lamichhane TN, Mattijssen S, Maraia RJ.; ''Human cells have a limited set of tRNA anticodon loop substrates of the tRNA isopentenyltransferase TRIT1 tumor suppressor.''; PubMed Europe PMC Scholia
28. Ozanick S, Krecic A, Andersland J, Anderson JT.; ''The bipartite structure of the tRNA m1A58 methyltransferase from S. cerevisiae is conserved in humans.''; PubMed Europe PMC Scholia
29. Chen YC, Kelly VP, Stachura SV, Garcia GA.; ''Characterization of the human tRNA-guanine transglycosylase: confirmation of the heterodimeric subunit structure.''; PubMed Europe PMC Scholia
30. Guy MP, Phizicky EM.; ''Conservation of an intricate circuit for crucial modifications of the tRNAPhe anticodon loop in eukaryotes.''; PubMed Europe PMC Scholia
31. Waas WF, Druzina Z, Hanan M, Schimmel P.; ''Role of a tRNA base modification and its precursors in frameshifting in eukaryotes.''; PubMed Europe PMC Scholia
32. Boland C, Hayes P, Santa-Maria I, Nishimura S, Kelly VP.; ''Queuosine formation in eukaryotic tRNA occurs via a mitochondria-localized heteromeric transglycosylase.''; PubMed Europe PMC Scholia
33. Young AP, Bandarian V.; ''Radical mediated ring formation in the biosynthesis of the hypermodified tRNA base wybutosine.''; PubMed Europe PMC Scholia
34. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T.; ''Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA.''; PubMed Europe PMC Scholia
35. Torres AG, Piñeyro D, Rodríguez-Escribà M, Camacho N, Reina O, Saint-Léger A, Filonava L, Batlle E, Ribas de Pouplana L.; ''Inosine modifications in human tRNAs are incorporated at the precursor tRNA level.''; PubMed Europe PMC Scholia
36. Sarin LP, Leidel SA.; ''Modify or die?--RNA modification defects in metazoans.''; PubMed Europe PMC Scholia
37. Boschi-Muller S, Motorin Y.; ''Chemistry enters nucleic acids biology: enzymatic mechanisms of RNA modification.''; PubMed Europe PMC Scholia
38. Costessi A, Mahrour N, Sharma V, Stunnenberg R, Stoel MA, Tijchon E, Conaway JW, Conaway RC, Stunnenberg HG.; ''The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME.''; PubMed Europe PMC Scholia
39. Sibert BS, Fischel-Ghodsian N, Patton JR.; ''Partial activity is seen with many substitutions of highly conserved active site residues in human Pseudouridine synthase 1.''; PubMed Europe PMC Scholia
40. Haag S, Warda AS, Kretschmer J, Günnigmann MA, Höbartner C, Bohnsack MT.; ''NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs.''; PubMed Europe PMC Scholia
41. Konevega AL, Soboleva NG, Makhno VI, Semenkov YP, Wintermeyer W, Rodnina MV, Katunin VI.; ''Purine bases at position 37 of tRNA stabilize codon-anticodon interaction in the ribosomal A site by stacking and Mg2+-dependent interactions.''; PubMed Europe PMC Scholia
42. Jurkowski TP, Shanmugam R, Helm M, Jeltsch A.; ''Mapping the tRNA binding site on the surface of human DNMT2 methyltransferase.''; PubMed Europe PMC Scholia
43. Guy MP, Shaw M, Weiner CL, Hobson L, Stark Z, Rose K, Kalscheuer VM, Gecz J, Phizicky EM.; ''Defects in tRNA Anticodon Loop 2'-O-Methylation Are Implicated in Nonsyndromic X-Linked Intellectual Disability due to Mutations in FTSJ1.''; PubMed Europe PMC Scholia
44. Helm M, Alfonzo JD.; ''Posttranscriptional RNA Modifications: playing metabolic games in a cell's chemical Legoland.''; PubMed Europe PMC Scholia
45. Cartlidge RA, Knebel A, Peggie M, Alexandrov A, Phizicky EM, Cohen P.; ''The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells.''; PubMed Europe PMC Scholia
46. Jurkowski TP, Meusburger M, Phalke S, Helm M, Nellen W, Reuter G, Jeltsch A.; ''Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism.''; PubMed Europe PMC Scholia
47. Torres AG, Batlle E, Ribas de Pouplana L.; ''Role of tRNA modifications in human diseases.''; PubMed Europe PMC Scholia
48. Spinola M, Galvan A, Pignatiello C, Conti B, Pastorino U, Nicander B, Paroni R, Dragani TA.; ''Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer.''; PubMed Europe PMC Scholia
49. Alexandrov A, Martzen MR, Phizicky EM.; ''Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA.''; PubMed Europe PMC Scholia
50. Brzezicha B, Schmidt M, Makalowska I, Jarmolowski A, Pienkowska J, Szweykowska-Kulinska Z.; ''Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA).''; PubMed Europe PMC Scholia
51. Vilardo E, Nachbagauer C, Buzet A, Taschner A, Holzmann J, Rossmanith W.; ''A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive moonlighting in mitochondrial tRNA biogenesis.''; PubMed Europe PMC Scholia
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
53. Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, Phizicky EM, Alkuraya FS.; ''A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition.''; PubMed Europe PMC Scholia
54. Arragain S, Handelman SK, Forouhar F, Wei FY, Tomizawa K, Hunt JF, Douki T, Fontecave M, Mulliez E, Atta M.; ''Identification of eukaryotic and prokaryotic methylthiotransferase for biosynthesis of 2-methylthio-N6-threonylcarbamoyladenosine in tRNA.''; PubMed Europe PMC Scholia
55. Perche-Letuvée P, Molle T, Forouhar F, Mulliez E, Atta M.; ''Wybutosine biosynthesis: structural and mechanistic overview.''; PubMed Europe PMC Scholia
56. Fu D, Brophy JA, Chan CT, Atmore KA, Begley U, Paules RS, Dedon PC, Begley TJ, Samson LD.; ''Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
4Fe-4S cluster	Metabolite	CHEBI:49883 (ChEBI)
5'-pppG-p-tRNA(His)		R-HSA-6782455 (Reactome)
ADAT1	Protein	Q9BUB4 (Uniprot-TrEMBL)
ADAT2	Protein	Q7Z6V5 (Uniprot-TrEMBL)
ADAT2:ADAT3	Complex	R-HSA-6782302 (Reactome)
ADAT3	Protein	Q96EY9 (Uniprot-TrEMBL)
ALKBH8	Protein	Q96BT7 (Uniprot-TrEMBL)
ALKBH8:Fe2+	Complex	R-HSA-6786518 (Reactome)
AMP	Metabolite	CHEBI:16027 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
AdoHcy	Metabolite	CHEBI:16680 (ChEBI)
AdoMet	Metabolite	CHEBI:15414 (ChEBI)
CDKAL1	Protein	Q5VV42 (Uniprot-TrEMBL)
CDKAL1:4Fe-4S	Complex	R-HSA-6786606 (Reactome)
CTU1	Protein	Q7Z7A3 (Uniprot-TrEMBL)
CTU1:CTU2:URM1	Complex	R-HSA-6782330 (Reactome)
CTU1:CTU2:thio-URM1	Complex	R-HSA-6782334 (Reactome)
CTU2	Protein	Q2VPK5 (Uniprot-TrEMBL)
DUS2	Protein	Q9NX74 (Uniprot-TrEMBL)
DUS2:EPRS	Complex	R-HSA-6782346 (Reactome)
EKC complex	Complex	R-HSA-6784495 (Reactome)
EPRS	Protein	P07814 (Uniprot-TrEMBL)
Fe2+	Metabolite	CHEBI:18248 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
Gua	Metabolite	CHEBI:16235 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
KIAA1456	Protein	Q9P272 (Uniprot-TrEMBL)
L-threonylcarbamoyladenylate	Metabolite	CHEBI:73687 (ChEBI)
LAGE3	Protein	Q14657 (Uniprot-TrEMBL)
METTL1	Protein	Q9UBP6 (Uniprot-TrEMBL)
METTL1:WDR4	Complex	R-HSA-6782313 (Reactome)
NAD(P)+	Complex	R-HSA-R-ALL-428218 (Reactome)
NAD(P)H	Complex	R-HSA-R-ALL-428206 (Reactome)
NAD+	Metabolite	CHEBI:15846 (ChEBI)
NADH	Metabolite	CHEBI:16908 (ChEBI)
NADP+	Metabolite	CHEBI:18009 (ChEBI)
NADPH	Metabolite	CHEBI:16474 (ChEBI)
NH3	Metabolite	CHEBI:16134 (ChEBI)
NSUN2	Protein	Q08J23 (Uniprot-TrEMBL)
OSGEP	Protein	Q9NPF4 (Uniprot-TrEMBL)
PPi	Metabolite	CHEBI:29888 (ChEBI)
PUS1-2	Protein	Q9Y606-2 (Uniprot-TrEMBL)
PUS7	Protein	Q96PZ0 (Uniprot-TrEMBL)
QTRT1	Protein	Q9BXR0 (Uniprot-TrEMBL)
QTRT1:QTRTD1	Complex	R-HSA-6782406 (Reactome)
QTRTD1	Protein	Q9H974 (Uniprot-TrEMBL)
Synthesis of wybutosine at G37 of tRNA(Phe)	Pathway	R-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).
THG1L	Protein	Q9NWX6 (Uniprot-TrEMBL)
TP53RK	Protein	Q96S44 (Uniprot-TrEMBL)
TPRKB	Protein	Q9Y3C4 (Uniprot-TrEMBL)
TRDMT1	Protein	O14717 (Uniprot-TrEMBL)
TRIT1	Protein	Q9H3H1 (Uniprot-TrEMBL)
TRMT10A	Protein	Q8TBZ6 (Uniprot-TrEMBL)
TRMT11	Protein	Q7Z4G4 (Uniprot-TrEMBL)
TRMT112	Protein	Q9UI30 (Uniprot-TrEMBL)
TRMT11:TRMT112	Complex	R-HSA-6786618 (Reactome)
TRMT13	Protein	Q9NUP7 (Uniprot-TrEMBL)
TRMT1	Protein	Q9NXH9 (Uniprot-TrEMBL)	Location in nucleus inferred from yeast homolog
TRMT44	Protein	Q8IYL2 (Uniprot-TrEMBL)
TRMT6	Protein	Q9UJA5 (Uniprot-TrEMBL)
TRMT61A	Protein	Q96FX7 (Uniprot-TrEMBL)
TRMT6:TRMT61A	Complex	R-HSA-6783454 (Reactome)
URM1	Protein	Q9BTM9 (Uniprot-TrEMBL)
WDR4	Protein	P57081 (Uniprot-TrEMBL)
dimethylallyl-PP	Metabolite	CHEBI:16057 (ChEBI)
pre-tRNAs containing A-34	Complex	R-HSA-6782314 (Reactome)
pre-tRNAs containing I-34	Complex	R-HSA-6782325 (Reactome)
queuine	Metabolite	CHEBI: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-9		R-HSA-6786591 (Reactome)
tRNA containing 2-methylG-10		R-HSA-6786548 (Reactome)
tRNA containing 5-carboxymethylU-34		R-HSA-6786496 (Reactome)
tRNA containing U-13, pre-tRNA(Tyr) containing U-35	Complex	R-HSA-6790218 (Reactome)
tRNA containing dihydroU		R-HSA-6782353 (Reactome)
tRNA containing pseudoU-13, pre-tRNA(Tyr) containing pseudoU-35	Complex	R-HSA-6790181 (Reactome)
tRNA containing A-37		R-HSA-6784474 (Reactome)
tRNA containing G-10		R-HSA-6786524 (Reactome)
tRNA containing G-9		R-HSA-6786513 (Reactome)
tRNA containing U-13		R-HSA-6786581 (Reactome)
tRNA containing U		R-HSA-6782279 (Reactome)
tRNA containing pseudoU-13		R-HSA-6786494 (Reactome)
tRNA(Ala) containing A-37		R-HSA-6782349 (Reactome)
tRNA(Ala) containing I-37		R-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	Complex	R-HSA-6786556 (Reactome)
tRNA(Arg,Glu) containing 5-methoxycarbonylmethylU-34	Complex	R-HSA-6786617 (Reactome)
tRNA(Asp) containing 5-mC-38		R-HSA-6782430 (Reactome)
tRNA(Asp) containing C-38		R-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(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	Complex	R-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	Complex	R-HSA-6788678 (Reactome)
tRNA(Gly,Pro) containing C-4	Complex	R-HSA-6788700 (Reactome)
tRNA(His) containing 2'-O-methylA-4		R-HSA-6788686 (Reactome)
tRNA(His) containing A-4		R-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 U	Complex	R-HSA-6787570 (Reactome)
tRNA(Ile,Met,Ser) containing pseudoU	Complex	R-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-58		R-HSA-6783466 (Reactome)
tRNA(Met) containing A-58		R-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 7-methylG-46		R-HSA-6782293 (Reactome)
tRNA(Phe) containing G-46		R-HSA-6782309 (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-44		R-HSA-6788717 (Reactome)
tRNA(Ser) containing A-37		R-HSA-6784467 (Reactome)
tRNA(Ser) containing U-44		R-HSA-6788714 (Reactome)
tRNA(Ser) containing isopentenylA-37		R-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) containing A-34		R-HSA-6782273 (Reactome)
tRNA(Thr) containing I-34		R-HSA-6782332 (Reactome)
tRNA(Tyr) containing 2,2-dimethylG-26		R-HSA-6782408 (Reactome)
tRNA(Tyr) containing G-26		R-HSA-6782418 (Reactome)
tRNA(Tyr) containing G-34		R-HSA-6782425 (Reactome)
tRNA(Tyr) containing Q-34		R-HSA-6782458 (Reactome)
tRNA(Val) containing A-34		R-HSA-6782268 (Reactome)
tRNA(Val) containing I-34		R-HSA-6782252 (Reactome)
tRNAs containing U-34	Complex	R-HSA-6782242 (Reactome)
thioG101-URM1	Protein	Q9BTM9 (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

Source	Target	Type	Database reference	Comment
	5'-pppG-p-tRNA(His)	Arrow	R-HSA-6782434 (Reactome)
ADAT1		mim-catalysis	R-HSA-6782336 (Reactome)
ADAT2:ADAT3		mim-catalysis	R-HSA-6782311 (Reactome)
ALKBH8:Fe2+		mim-catalysis	R-HSA-6786500 (Reactome)
	AMP	Arrow	R-HSA-6784494 (Reactome)
ATP			R-HSA-6782434 (Reactome)
	AdoHcy	Arrow	R-HSA-6782286 (Reactome)
	AdoHcy	Arrow	R-HSA-6782388 (Reactome)
	AdoHcy	Arrow	R-HSA-6782416 (Reactome)
	AdoHcy	Arrow	R-HSA-6782419 (Reactome)
	AdoHcy	Arrow	R-HSA-6783492 (Reactome)
	AdoHcy	Arrow	R-HSA-6785409 (Reactome)
	AdoHcy	Arrow	R-HSA-6785438 (Reactome)
	AdoHcy	Arrow	R-HSA-6786500 (Reactome)
	AdoHcy	Arrow	R-HSA-6786501 (Reactome)
	AdoHcy	Arrow	R-HSA-6786567 (Reactome)
	AdoHcy	Arrow	R-HSA-6786571 (Reactome)
	AdoHcy	Arrow	R-HSA-6786621 (Reactome)
	AdoHcy	Arrow	R-HSA-6788668 (Reactome)
	AdoHcy	Arrow	R-HSA-6788684 (Reactome)
	AdoHcy	Arrow	R-HSA-6788707 (Reactome)
AdoMet			R-HSA-6782286 (Reactome)
AdoMet			R-HSA-6782388 (Reactome)
AdoMet			R-HSA-6782416 (Reactome)
AdoMet			R-HSA-6782419 (Reactome)
AdoMet			R-HSA-6783492 (Reactome)
AdoMet			R-HSA-6785409 (Reactome)
AdoMet			R-HSA-6785438 (Reactome)
AdoMet			R-HSA-6786500 (Reactome)
AdoMet			R-HSA-6786501 (Reactome)
AdoMet			R-HSA-6786567 (Reactome)
AdoMet			R-HSA-6786571 (Reactome)
AdoMet			R-HSA-6786621 (Reactome)
AdoMet			R-HSA-6788668 (Reactome)
AdoMet			R-HSA-6788684 (Reactome)
AdoMet			R-HSA-6788707 (Reactome)
CDKAL1:4Fe-4S		mim-catalysis	R-HSA-6786571 (Reactome)
	CTU1:CTU2:URM1	Arrow	R-HSA-6782264 (Reactome)
CTU1:CTU2:thio-URM1			R-HSA-6782264 (Reactome)
CTU1:CTU2:thio-URM1		mim-catalysis	R-HSA-6782264 (Reactome)
DUS2:EPRS		mim-catalysis	R-HSA-6782296 (Reactome)
EKC complex		mim-catalysis	R-HSA-6784494 (Reactome)
GTP			R-HSA-6782434 (Reactome)
	Gua	Arrow	R-HSA-6782443 (Reactome)
H2O			R-HSA-6782311 (Reactome)
H2O			R-HSA-6782336 (Reactome)
KIAA1456		mim-catalysis	R-HSA-6786567 (Reactome)
L-threonylcarbamoyladenylate			R-HSA-6784494 (Reactome)
METTL1:WDR4		mim-catalysis	R-HSA-6782286 (Reactome)
	NAD(P)+	Arrow	R-HSA-6782296 (Reactome)
NAD(P)H			R-HSA-6782296 (Reactome)
	NH3	Arrow	R-HSA-6782311 (Reactome)
	NH3	Arrow	R-HSA-6782336 (Reactome)
NSUN2		mim-catalysis	R-HSA-6782388 (Reactome)
NSUN2		mim-catalysis	R-HSA-6785409 (Reactome)
NSUN2		mim-catalysis	R-HSA-6785438 (Reactome)
	PPi	Arrow	R-HSA-6782434 (Reactome)
	PPi	Arrow	R-HSA-6784462 (Reactome)
PUS1-2		mim-catalysis	R-HSA-6782381 (Reactome)
PUS7		mim-catalysis	R-HSA-6786583 (Reactome)
QTRT1:QTRTD1		mim-catalysis	R-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).
THG1L		mim-catalysis	R-HSA-6782434 (Reactome)
TRDMT1		mim-catalysis	R-HSA-6782419 (Reactome)
TRIT1		mim-catalysis	R-HSA-6784462 (Reactome)
TRMT10A		mim-catalysis	R-HSA-6786621 (Reactome)
TRMT11:TRMT112		mim-catalysis	R-HSA-6786501 (Reactome)
TRMT13		mim-catalysis	R-HSA-6788668 (Reactome)
TRMT13		mim-catalysis	R-HSA-6788684 (Reactome)
TRMT1		mim-catalysis	R-HSA-6782416 (Reactome)
TRMT44		mim-catalysis	R-HSA-6788707 (Reactome)
TRMT6:TRMT61A		mim-catalysis	R-HSA-6783492 (Reactome)
dimethylallyl-PP			R-HSA-6784462 (Reactome)
pre-tRNAs containing A-34			R-HSA-6782311 (Reactome)
	pre-tRNAs containing I-34	Arrow	R-HSA-6782311 (Reactome)
queuine			R-HSA-6782443 (Reactome)
	tRNA containing 2-methylthio-N6-threonylcarbamoylA-37	Arrow	R-HSA-6786571 (Reactome)
	tRNA containing 5-methoxycarbonylmethylU-34	Arrow	R-HSA-6786567 (Reactome)
	tRNA containing threonylcarbamoylA-37	Arrow	R-HSA-6784494 (Reactome)
tRNA containing threonylcarbamoylA-37			R-HSA-6786571 (Reactome)
	tRNA containing 1-methylG-9	Arrow	R-HSA-6786621 (Reactome)
	tRNA containing 2-methylG-10	Arrow	R-HSA-6786501 (Reactome)
tRNA containing 5-carboxymethylU-34			R-HSA-6786567 (Reactome)
tRNA containing U-13, pre-tRNA(Tyr) containing U-35			R-HSA-6786583 (Reactome)
	tRNA containing dihydroU	Arrow	R-HSA-6782296 (Reactome)
	tRNA containing pseudoU-13, pre-tRNA(Tyr) containing pseudoU-35	Arrow	R-HSA-6786583 (Reactome)
tRNA containing A-37			R-HSA-6784494 (Reactome)
tRNA containing G-10			R-HSA-6786501 (Reactome)
tRNA containing G-9			R-HSA-6786621 (Reactome)
tRNA containing U			R-HSA-6782296 (Reactome)
tRNA(Ala) containing A-37			R-HSA-6782336 (Reactome)
	tRNA(Ala) containing I-37	Arrow	R-HSA-6782336 (Reactome)
tRNA(Arg,Glu) containing 5-carboxymethylU-34			R-HSA-6786500 (Reactome)
	tRNA(Arg,Glu) containing 5-methoxycarbonylmethylU-34	Arrow	R-HSA-6786500 (Reactome)
	tRNA(Asp) containing 5-mC-38	Arrow	R-HSA-6782419 (Reactome)
tRNA(Asp) containing C-38			R-HSA-6782419 (Reactome)
	tRNA(Asp)(GUC) containing 5-mC-48,49	Arrow	R-HSA-6785409 (Reactome)
tRNA(Asp)(GUC) containing C-48,C-49			R-HSA-6785409 (Reactome)
	tRNA(Gln,Glu,Lys) containing 2-thioU-34	Arrow	R-HSA-6782264 (Reactome)
	tRNA(Gly)(GCC) containing 5mC-40,48,49,50	Arrow	R-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	Arrow	R-HSA-6788684 (Reactome)
tRNA(Gly,Pro) containing C-4			R-HSA-6788684 (Reactome)
	tRNA(His) containing 2'-O-methylA-4	Arrow	R-HSA-6788668 (Reactome)
tRNA(His) containing A-4			R-HSA-6788668 (Reactome)
tRNA(His)			R-HSA-6782434 (Reactome)
tRNA(Ile,Met,Ser) containing U			R-HSA-6782381 (Reactome)
	tRNA(Ile,Met,Ser) containing pseudoU	Arrow	R-HSA-6782381 (Reactome)
	tRNA(Met) containing 1-methylA-58	Arrow	R-HSA-6783492 (Reactome)
tRNA(Met) containing A-58			R-HSA-6783492 (Reactome)
	tRNA(Phe) containing 7-methylG-46	Arrow	R-HSA-6782286 (Reactome)
tRNA(Phe) containing G-46			R-HSA-6782286 (Reactome)
	tRNA(Ser) containing 2'-O-methylU-44	Arrow	R-HSA-6788707 (Reactome)
tRNA(Ser) containing A-37			R-HSA-6784462 (Reactome)
tRNA(Ser) containing U-44			R-HSA-6788707 (Reactome)
	tRNA(Ser) containing isopentenylA-37	Arrow	R-HSA-6784462 (Reactome)
	tRNA(Tyr) containing 2,2-dimethylG-26	Arrow	R-HSA-6782416 (Reactome)
tRNA(Tyr) containing G-26			R-HSA-6782416 (Reactome)
tRNA(Tyr) containing G-34			R-HSA-6782443 (Reactome)
	tRNA(Tyr) containing Q-34	Arrow	R-HSA-6782443 (Reactome)
tRNAs containing U-34			R-HSA-6782264 (Reactome)
	unspliced tRNA(Leu)(CAA) containing 5mC-34,48	Arrow	R-HSA-6782388 (Reactome)
unspliced tRNA(Leu)(CAA) containing C-34,48			R-HSA-6782388 (Reactome)