Any feedback?
No. of entries
Information on EC 5.4.99.27 - tRNA pseudouridine13 synthase
for references in articles please use BRENDA:EC5.4.99.27
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 5 Isomerases
5.4 Intramolecular transferases
5.4.99 Transferring other groups
5.4.99.27 tRNA pseudouridine13 synthase
IUBMB Comments
Pseudouridine synthase TruD from Escherichia coli specifically acts on uridine13 in tRNA [2,3]. The Pus7 protein from Saccharomyces cerevisiae is a multisite-multisubstrate pseudouridine synthase that is able to modify uridine13 in several yeast tRNAs, uridine35 in the pre-tRNATyr, uridine35 in U2 small nuclear RNA, and uridine50 in 5S rRNA .
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
- 5.4.99.27
- archaea
- rrna
- eukarya
-
pseudouridylation
- pre-trnatyr
showSynonyms
pus7p, pus7 protein, more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PUS7
Pus7p
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
tRNA uridine13 = tRNA pseudouridine13
-
-
-
-
tRNA uridine13 = tRNA pseudouridine13
a strictly conserved glutamate near the active site in TruD is likely to act as a general base for the proton abstraction at C5 of the uridine base
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
tRNA-uridine13 uracil mutase
Pseudouridine synthase TruD from Escherichia coli specifically acts on uridine13 in tRNA [2,3]. The Pus7 protein from Saccharomyces cerevisiae is a multisite-multisubstrate pseudouridine synthase that is able to modify uridine13 in several yeast tRNAs, uridine35 in the pre-tRNATyr, uridine35 in U2 small nuclear RNA, and uridine50 in 5S rRNA [5].
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
430429-15-5
-
61506-89-6
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Pyrococcus abyssi tRNAAsp(GUA) uridine13
Pyrococcus abyssi tRNAAsp(GUA) pseudouridine13
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: for tRNA and Pus7, many known sites and their associated modifiers are identified, including Pus7-dependent sites at position 13 of glutamate tRNA. Pseudouridylation in ncRNAs at sites of inter or intra-molecular interactions
Products: -
Products: -
?
Pyrococcus abyssi tRNATyr(GUA) uridine13
Pyrococcus abyssi tRNATyr(GUA) pseudouridine13
-
Substrates: the enzyme modifies tRNAs at position 13 and at other positions as well as intron-less and intron-containing tRNAsTyr(GUA) at position 35
Products: -
Products: -
?
Pyrococcus abyssi tRNATyr(GUA) uridine13
Pyrococcus abyssi tRNATyr(GUA) pseudouridine13
-
Substrates: some activity at high temperature on tRNAs that contain a U residue at position 13. No activity of is detected at position 35 in the Sulfolobus solfataricus pre-tRNATyr(GUA), even at 80°C
Products: -
Products: -
?
Pyrococcus abyssi tRNATyr(GUA) uridine35
Pyrococcus abyssi tRNATyr(GUA) pseudouridine35
-
Substrates: residue 35 reinforces the stability of the anticodon stemloop by interaction with residue U33 (13). This structural stabilization may increase the aminoacylation efficiency of tRNATyr(GUA) by its cognate aminoacyl-tRNA synthetase
Products: -
Products: -
?
Pyrococcus abyssi tRNATyr(GUA) uridine35
Pyrococcus abyssi tRNATyr(GUA) pseudouridine35
-
Substrates: the enzyme modifies tRNAs at position 13 and at other positions as well as intron-less and intron-containing tRNAsTyr(GUA) at position 35
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
Substrates: -
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
Substrates: the multisite-specific enzyme Pus7p is able to modify uridine13 in several yeast tRNAs, uridine35 in the pre-tRNATyr, uridine35 in U2 small nuclear RNA, and uridine50 in 5S rRNA. Using site-directed mutagenesis, a set of RNA variants derived from the yeast tRNAAsp(GUC), pretRNA Tyr(G(pseudouridine)A), and U2 small nuclear RNA is designed and the ability to be modified by Pus7p in vitro is tested. Pseudouridine13 formation in tRNAAsp(GUC). Does not depend on correct tRNA three-dimensional structure but is increased by the presence of RNA helices
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
Substrates: Pus7p is a multisite-multisubstrate RNA:PSI-synthase. Recombinant Pus7p has tRNAAsp:pseudouridine13- and pre-RNATyr:pseudouridine35-synthase activities
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
-
Substrates: Pus7p is required for inducible pseudouridylation at position 35 and 56 during nutrient deprivation or heat shock
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Pyrococcus abyssi tRNATyr(GUA) uridine35
Pyrococcus abyssi tRNATyr(GUA) pseudouridine35
-
Substrates: residue 35 reinforces the stability of the anticodon stemloop by interaction with residue U33 (13). This structural stabilization may increase the aminoacylation efficiency of tRNATyr(GUA) by its cognate aminoacyl-tRNA synthetase
Products: -
Products: -
?
additional information
?
-
Substrates: for tRNA and Pus7, many known sites and their associated modifiers are identified, including Pus7-dependent sites at position 13 of glutamate tRNA. Pseudouridylation in ncRNAs at sites of inter or intra-molecular interactions
Products: -
Products: -
?
tRNA uridine13
tRNA pseudouridine13
Substrates: -
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
TruD folds into a V-shaped molecule with a catalytic domain that is structurally very similar to the catalytic modules of the other known pseudouridine synthases despite its lack of sequence homology and likely arose by divergent evolution
malfunction
metabolism
-
Pus7p that catalyses U2 pseudouridylation at position 35, also catalyses pseudouridylation at position 56 during nutrient deprivation or heat shock
physiological function
additional information
transcriptome-wide quantitative mapping of Psi, method development using Psi-seq, relying on the unique stability of N3-[N-cyclohexyl-N'-beta-(4-methylmorpholinium)ethylcarbodiimide-Psi] (N3-CMC-Psi) to alkaline hydrolysis, and the ability of N3-CMC-Psi to terminate reverse transcription. For rRNA, 24/24 Cbf5-dependent sites are known targets of pseudouridylation, 8/9 associations between snoRNAs and rRNA sites are known, as is the identified Pus5-mediated Psi site in mitochondrial 21S rRNA. One snR3-dependent site at position 2140 on 25S rRNA is not specificated, detailed overview. Cbf5-dependent-Psi sites in mRNAs and snoRNAs are likely snoRNA-guided
malfunction
deletion of the ygbO gene causes the loss of tRNAGlu pseudouridine13 and plasmid-borne restoration of the structural gene restores pseudouridine13. Growth competition does not show any effect of the deletion
malfunction
disruption of the PUS7 gene abolishes pseudouridine13 formation in tRNAs in vivo. Absence of pseudouridine13 formation in tRNAAsp and tRNAGlu extracted from the DELTAPUS7 strain
malfunction
-
using a Pus7p mutant strain it is shown that Pus7p is responsible for inducible U2 pseudouridylation at position 56
malfunction
PUS7 inactivation in embryonic stem cells impairs tRNA-derived small fragments (tRFs)-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes, overview. PUS7 loss impacts early embryogenesis and mesoderm specification
physiological function
pseudouridylation (Psi) is the most abundant and widespread type of RNA epigenetic modification in living organisms. Psi-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenes. Mechanistically, the Psi writer PUS7 modifies and activates a network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. Critical function of Psi in directing translation control in stem cells with important implications for development and disease. PUS7 Psi synthase activity impacts stem cell size and protein biosynthesis. PUS7 binds specific tRNA isoacceptors in human stem cells, hESCs. PUS7-mediated Psi directs tRNA-derived small RNAs to inhibit translation. Psi is critically required for 5'tRF-dependent translational repression in vivo. Pseudouridylated mTOG targets the translation initiation complex. PUS7-mediated Psi critically governs hematopoietic stem cell function
physiological function
the most abundant RNA modification is pseudouridine (Psi), Psi is ubiquitous in diverse RNAs, and dynamic in mRNA. Pseudouridylation profiles and mechanisms. Pus7-dependent induction of pseudouridylation during heat shock
Show AA Sequence and Transmembrane Helices (5125 entries)
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of Escherichia coli TruD at 2.0 A resolution. The structure reveals an overall V-shaped molecule with an RNA binding cleft formed between two domains: a catalytic domain and an insertion domain
crystals of TruD are grown at room temperature by the hanging drop vapor diffusion method. TruD folds into a V-shaped molecule with a catalytic domain that is structurally very similar to the catalytic modules of the other known pseudouridine synthases despite its lack of sequence homology and likely arose by divergent evolution
hanging drop vapor diffusion method, 2.2 A resolution structure. TruD reveals a U-shaped molecule with a catalytic domain that superimposes closely on that of other pseudouridine synthases
sitting-drop vapour-diffusion method, crystals diffract to a minimum Bragg spacing of 2.4 A and belong to space group P212121, with unit-cell parameters a = 63.4, b = 108.6, c = 111.7 A
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K79L
G128R
homozygous PUS7 mutation in a family with intellectual disability, autistic features, and aggressive behaviors
G273R
homozygous PUS7 mutation in a family with intellectual disability, autistic features, and aggressive behaviors
R222K
homozygous PUS7 mutation in a family with intellectual disability, autistic features, and aggressive behaviors
K19I
-
mutation decreases the activity at position 13 in the Pyrococcus abyssi tRNAAsp at 55°C. At 80°C the mutation has almost no negative effect on its activity towards the Pyrococcus abyssi tRNATyr(GUA)
K19I/R78A/H79N
-
mutation completely abolishes the activity at position 13 in the Pyrococcus abyssi tRNAAsp at 55°C. At 80°C the mutation nearly abolishes activity towards the Pyrococcus abyssi tRNATyr(GUA)
R78A/H79N
-
mutation decreases the activity at position 13 in the Pyrococcus abyssi tRNAAsp at 55°C. At 80°C the mutation has almost no negative effect on its activity towards the Pyrococcus abyssitRNATyr(GUA)
A78R/N79H
-
mutation has no positive effect on activity at 80°C on Pyrococcus abyssi tRNAAsp(GUA)
I27K
-
mutation increases activity at 80°C on Pyrococcus abyssi tRNAAsp(GUA) 1.6fold
N79H
-
mutation has no positive effect on activity at 80°C on Pyrococcus abyssi tRNAAsp(GUA)
additional information
generation of PUS7-knockout human stem cells, hESCs, using CRISPR/Cas9 technique. There are no differences in cell proliferation, viability, and expression of multiple pluripotency, and germ layer specific markers between wild-type and PUS7-KO cells maintained in culture over long periods of time without loss of self-renewal, but a significant increase in PUS7-KO cell size compared to controls is observed. Knockout of PUS7 in HEK-293T cells
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type and mutant enzymes produced in Escherichia coli as His6-tagged protein fusions
wild-type and mutant enzymes produced in Escherichia coli as His6-tagged protein fusions
-
wild-type and mutant enzymes produced in Escherichia coli as His6-tagged protein fusions
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
wild-type and mutant enzymes are produced in Escherichia coli as His6-tagged protein fusions
wild-type and mutant enzymes are produced in Escherichia coli as His6-tagged protein fusions
-
wild-type and mutant enzymes are produced in Escherichia coli as His6-tagged protein fusions
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ericsson, U.B.; Andersson, M.E.; Engvall, B.; Nordlund, P.; Hallberg, B.M.
Expression, purification, crystallization and preliminary diffraction studies of the tRNA pseudouridine synthase TruD from Escherichia coli
Acta Crystallogr. Sect. D
60
775-776
2004
Escherichia coli (Q57261)
brenda
Kaya, Y.; Del Campo, M.; Ofengand, J.; Malhotra, A.
Crystal structure of TruD, a novel pseudouridine synthase with a new protein fold
J. Biol. Chem.
279
18107-18110
2004
Escherichia coli (Q57261)
brenda
Ericsson, U.B.; Nordlund, P.; Hallberg, B.M.
X-ray structure of tRNA pseudouridine synthase TruD reveals an inserted domain with a novel fold
FEBS Lett.
565
59-64
2004
Escherichia coli (Q57261)
brenda
Hoang, C.; Ferre-D'Amare, A.R.
Crystal structure of the highly divergent pseudouridine synthase TruD reveals a circular permutation of a conserved fold
RNA
10
1026-1033
2004
Escherichia coli (Q57261), Escherichia coli
brenda
Muller, S.; Urban, A.; Hecker, A.; Leclerc, F.; Branlant, C.; Motorin, Y.
Deficiency of the tRNATyr:Psi35-synthase aPus7 in Archaea of the Sulfolobales order might be rescued by the H/ACA sRNA-guided machinery
Nucleic Acids Res.
37
1308-1322
2009
Saccharolobus solfataricus, Pyrococcus abyssi
brenda
Chan, C.M.; Huang, R.H.
Enzymatic characterization and mutational studies of TruD--the fifth family of pseudouridine synthases
Arch. Biochem. Biophys.
489
15-19
2009
Escherichia coli (Q57261)
brenda
Urban, A.; Behm-Ansmant, I.; Branlant, C.; Motorlin, Y.
RNA sequence and two-dimensional structure features required for efficient substrate modification by the Saccharomyces cerevisiae RNA:PSI-synthase Pus7p
J. Biol. Chem.
284
5845-5858
2009
Saccharomyces cerevisiae (Q08647), Saccharomyces cerevisiae
brenda
Behm-Ansmant, I.; Urban, A.; Ma, X.; Yu, Y.T.; Motorin, Y.; Branlant, C.
The Saccharomyces cerevisiae U2 snRNA:pseudouridine-synthase Pus7p is a novel multisite-multisubstrate RNA:PSI-synthase also acting on tRNAs
RNA
9
1371-1382
2003
Saccharomyces cerevisiae (Q08647), Saccharomyces cerevisiae
brenda
Kaya, Y.; Ofengand, J.
A novel unanticipated type of pseudouridine synthase with homologs in bacteria, archaea, and eukarya
RNA
9
711-721
2003
Escherichia coli (Q57261)
brenda
Wu, G.; Xiao, M.; Yang, C.; Yu, Y.
U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP
EMBO J.
30
79-89
2011
Saccharomyces cerevisiae
brenda
Schwartz, S.; Bernstein, D.A.; Mumbach, M.R.; Jovanovic, M.; Herbst, R.H.; Leon-Ricardo, B.X.; Engreitz, J.M.; Guttman, M.; Satija, R.; Lander, E.S.; Fink, G.; Regev, A.
Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA
Cell
159
148-162
2014
Saccharomyces cerevisiae (Q08647)
brenda
Guzzi, N.; Ciesla, M.; Ngoc, P.C.T.; Lang, S.; Arora, S.; Dimitriou, M.; Pimkova, K.; Sommarin, M.N.E.; Munita, R.; Lubas, M.; Lim, Y.; Okuyama, K.; Soneji, S.; Karlsson, G.; Hansson, J.; Joensson, G.; Lund, A.H.; Sigvardsson, M.; Hellstroem-Lindberg, E.; Hsieh, A.C.; Bellodi, C.
Pseudouridylation of tRNA-derived fragments steers translational control in stem cells
Cell
173
1204-1216
2018
Homo sapiens (Q96PZ0)
brenda
Darvish, H.; Azcona, L.; Alehabib, E.; Jamali, F.; Tafakhori, A.; Ranji-Burachaloo, S.; Jen, J.; Paisn-Ruiz, C.
A novel PUS7 mutation causes intellectual disability with autistic and aggressive behaviors
Neurol. Genet.
5
e356
2019
Homo sapiens (Q96PZ0)
-
brenda
EXTERNAL LINKS (specific for EC-Number 5.4.99.27)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
