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Information on EC 2.7.7.72 - CCA tRNA nucleotidyltransferase and Organism(s) Homo sapiens and UniProt Accession Q96Q11
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2.7.7.72 CCA tRNA nucleotidyltransferaseIUBMB Comments
The acylation of all tRNAs with an amino acid occurs at the terminal ribose of a 3' CCA sequence. The CCA sequence is added to the tRNA precursor by stepwise nucleotide addition performed by a single enzyme that is ubiquitous in all living organisms. Although the enzyme has the option of releasing the product after each addition, it prefers to stay bound to the product and proceed with the next addition .
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide(3 overall reactions are displayed. Show all (4)>>)
a tRNA precursor
+
=
a tRNA with a 3' cytidine end
+
a tRNA with a 3' cytidine
+
=
a tRNA with a 3' CC end
+
a tRNA with a 3' CC end
+
=
a tRNA with a 3' CCA end
+
Synonyms
cca-adding enzyme, trnt1, cca enzyme, cca1p, atp(ctp):trna nucleotidyltransferase, trna-nt, class i cca-adding enzyme, ccase, afcca, ctp(atp):trna nucleotidyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
-C-C-A pyrophosphorylase
-
-
-
-
ATP(CTP)-tRNA nucleotidyltransferase
-
-
-
-
ATP:tRNA adenylyltransferase
-
-
-
-
ATP:tRNA nucleotidyltransferase (CTP)
-
-
-
-
CTP(ATP):tRNA nucleotidyltransferase
-
-
-
-
CTP:tRNA cytidylyltransferase
-
-
-
-
ribonucleic cytidylic cytidylic adenylic pyrophosphorylase
-
-
-
-
ribonucleic cytidylyltransferase
-
-
-
-
transfer ribonucleate adenyltransferase
-
-
-
-
transfer ribonucleate adenylyltransferase
-
-
-
-
transfer ribonucleate adenylyltransferase,
-
-
-
-
transfer ribonucleate cytidylyltransferase
-
-
-
-
transfer ribonucleate nucleotidyltransferase
-
-
-
-
transfer ribonucleic acid nucleotidyl transferase
-
-
-
-
transfer ribonucleic adenylyl (cytidylyl) transferase
-
-
-
-
transfer ribonucleic-terminal trinucleotide nucleotidyltransferase
-
-
-
-
transfer RNA adenylyltransferase
-
-
-
-
transfer-RNA nucleotidyltransferase
-
-
-
-
tRNA adenylyl(cytidylyl)transferase
-
-
-
-
tRNA adenylyltransferase
-
-
-
-
tRNA CCA-pyrophosphorylase
-
-
-
-
tRNA cytidylyltransferase
-
-
-
-
tRNA-nucleotidyltransferase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate
catalytic core and reaction mechanism of class II CCA-adding enzymes, overview
-
SYSTEMATIC NAME
IUBMB Comments
CTP,CTP,ATP:tRNA cytidylyl,cytidylyl,adenylyltransferase
The acylation of all tRNAs with an amino acid occurs at the terminal ribose of a 3' CCA sequence. The CCA sequence is added to the tRNA precursor by stepwise nucleotide addition performed by a single enzyme that is ubiquitous in all living organisms. Although the enzyme has the option of releasing the product after each addition, it prefers to stay bound to the product and proceed with the next addition [5].
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
a tRNA precursor + 2 CTP + ATP
a tRNA with a 3' CCA end + 3 diphosphate
-
-
-
?
armless tRNA(Arg) precursor + 2 CTP
armless tRNA(Arg) with a 3' CC end + 2 diphosphate
poor substrate for wild-type
-
-
?
armless tRNA(Arg) precursor + 2 CTP + ATP
armless tRNA(Arg) with a 3' CCA end + 3 diphosphate
poor substrate for wild-type
-
-
?
armless tRNA(Ile) precursor + 2 CTP
armless tRNA(Ile) with a 3' CC end + 2 diphosphate
poor substrate for wild-type
-
-
?
armless tRNA(Ile) precursor + 2 CTP + ATP
armless tRNA(Ile) with a 3' CCA end + 3 diphosphate
poor substrate for wild-type
-
-
?
tRNA(Phe) precursor + 2 CTP
tRNA(Phe) with a 3' CC end + 2 diphosphate
-
-
-
?
tRNA(Phe) precursor + 2 CTP + ATP
tRNA(Phe) with a 3' CCA end + 3 diphosphate
-
-
-
?
yeast tRNAPhe + 2 CTP + ATP
yeast tRNAPhe with 3'-CCA end + 3 diphosphate
preparation of substrate lacking the CCA-terminus or ending with a partial CCA-end
-
-
?
a tRNA precursor + 2 CTP + ATP
a tRNA with a 3' CCA end + 3 diphosphate
-
-
-
-
r
a tRNA precursor + 2 CTP + ATP
a tRNA with a 3' CCA end + 3 diphosphate
-
substrate is synthetic DNA templates based on the sequence of Escherichia coli tRNAVal. Overall reaction, class II CCA-adding enzymes also perform the reverse reaction, mechanism, overview. The enzyme catalyzes diphosphorolysis slowly relative to the forward nucleotide addition and that it exhibits weak binding affinity to diphosphate relative to NTP
-
-
r
a tRNA with a 3' CCA end + 3 diphosphate
a tRNA precursor + 2 CTP + ATP
-
-
-
-
r
a tRNA with a 3' CCA end + 3 diphosphate
a tRNA precursor + 2 CTP + ATP
-
substrate is synthetic DNA templates based on the sequence of Escherichia coli tRNAVal. Overall reaction, class II CCA-adding enzymes also perform the reverse reaction, mechanism, overview. The enzyme catalyzes diphosphorolysis slowly relative to the forward nucleotide addition and that it exhibits weak binding affinity to diphosphate relative to NTP
-
-
r
additional information
?
-
the enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction, active site structure and molecular mechanism, overview. Construction of a corkscrew model for CCA addition that includes a fixed active site and a traveling tRNA-binding region formed by flexible parts of the protein
-
-
?
additional information
?
-
-
the enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction, active site structure and molecular mechanism, overview. Construction of a corkscrew model for CCA addition that includes a fixed active site and a traveling tRNA-binding region formed by flexible parts of the protein
-
-
?
additional information
?
-
-
CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview
-
-
?
additional information
?
-
-
the specific enzyme incorporates only a highly restricted number of nucleotides in a tRNA primer and then stops polymerization at a high efficiency and accuracy. It selects exclusively CTP and ATP for incorporation and discriminates strongly against the other two nucleotide triphosphates. It does not require a nucleic acid template for directing order and nature of nucleotides to be inserted and is highly selective for tRNA-like structures as a polymerization substrate. The enzyme fulfills both functions in maintenance/repair as well as de novo polymerization
-
-
?
additional information
?
-
-
class 2 enzymes select the nucleotides to be incorporated by a true amino acid template that consists of the three highly conserved residues glutamic acid, aspartic acid and arginine (EDxxR). The arginine residue forms hydrogen bonds with ATP (1 bond) and CTP (2 bonds), assisted by aspartate that contributes one hydrogen bond
-
-
?
additional information
?
-
-
only class II CCA enzymes catalyze diphosphorolysis, the reaction can initiate from all three CCA positions and proceed processively until the removal of nucleotide C74. Diphosphorolysis enables class II enzymes to efficiently remove an incorrect A75 nucleotide from the 3' end, at a rate much faster than the rate of A75 incorporation, suggesting the ability to perform a previously unexpected quality control mechanism for CCA synthesis. No activity with non-tRNA substrate BMVTLSTyr or U2 snRNA. The enzyme shows a robust activity with tRNA-A75, degrading it down to tRNA-A73 (by 50%) while showing a minor activity with tRNA-C76 (less than 5% substrate conversion) and no activity with tRNA-A74. The incorrect A75 is more readily removed than it is synthesized, suggesting a quality control mechanism that can improve the overall accuracy of CCA synthesis
-
-
?
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
a tRNA precursor + 2 CTP + ATP
a tRNA with a 3' CCA end + 3 diphosphate
-
-
-
-
r
a tRNA with a 3' CCA end + 3 diphosphate
a tRNA precursor + 2 CTP + ATP
-
-
-
-
r
additional information
?
-
the enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction, active site structure and molecular mechanism, overview. Construction of a corkscrew model for CCA addition that includes a fixed active site and a traveling tRNA-binding region formed by flexible parts of the protein
-
-
?
additional information
?
-
-
the enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction, active site structure and molecular mechanism, overview. Construction of a corkscrew model for CCA addition that includes a fixed active site and a traveling tRNA-binding region formed by flexible parts of the protein
-
-
?
additional information
?
-
-
CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview
-
-
?
additional information
?
-
-
the specific enzyme incorporates only a highly restricted number of nucleotides in a tRNA primer and then stops polymerization at a high efficiency and accuracy. It selects exclusively CTP and ATP for incorporation and discriminates strongly against the other two nucleotide triphosphates. It does not require a nucleic acid template for directing order and nature of nucleotides to be inserted and is highly selective for tRNA-like structures as a polymerization substrate. The enzyme fulfills both functions in maintenance/repair as well as de novo polymerization
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
additional information
Mg2+
-
essentially required, two metal ions are coordinated by highly conserved carboxylates and fulfill specific roles in catalyzing the reaction. Metal ion A activates the 3'-hydroxyl group of the primer for a nucleophilic in-line attack on the alpha-phosphate of the incoming NTP, while metal ion B promotes the leaving of the diphosphate group that is released during this reaction
Mg2+
-
essentially required, two metal ions are coordinated by highly conserved carboxylates and fulfill specific roles in catalyzing the reaction. Metal ion A activates the 3'-hydroxyl group of the primer for a nucleophilic in-line attack on the alpha-phosphate of the incoming NTP, while metal ion B promotes the leaving of the diphosphate group that is released during this reaction. The Mg2+ ions are also required for the diposphorolysis reaction, overview
additional information
-
the nature of the divalent metal ions can influence the positioning of diphosphate in the active site
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
protein Hfq
-
the multifunctional protein Hfq, originally discovered as a host factor for phage Qb, can stimulate the CCA-adding activity, Hfq facilitates the release of the reaction product, after CCA addition has taken place
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.008
a tRNA precursor
mutant D139A, pH not specified in the publication, temperature not specified in the publication
-
0.119
a tRNA precursor
wild-type, pH not specified in the publication, temperature not specified in the publication
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.09
a tRNA precursor
wild-type, pH not specified in the publication, temperature not specified in the publication
-
0.11
a tRNA precursor
mutant D139A, pH not specified in the publication, temperature not specified in the publication
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.07
a tRNA precursor
mutant D139A, pH not specified in the publication, temperature not specified in the publication
-
1.23
a tRNA precursor
wild-type, pH not specified in the publication, temperature not specified in the publication
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
TRNT1 protein levels are 10fold lower in muscle than in fibroblasts
TRNT1 protein levels are 10fold lower in muscle than in fibroblasts
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
evolution
malfunction
physiological function
additional information
physiological function
all tRNA molecules carry the invariant sequence CCA at their 3'-terminus for amino acid attachment. The post-transcriptional addition of CCA is carried out by ATP(CTP):tRNA nucleotidyltransferase, also called CCase. This enzyme catalyses a unique template-independent but sequence-specific nucleotide polymerization reaction
physiological function
conserved motif C in CCA-adding enzyme forms a flexible spring element modulating the relative orientation of the enzyme's head and body domains to accommodate the growing 3'-end of the tRNA. These conformational transitions initiate the rearranging of the templating amino acids to switch the specificity of the nucleotide binding pocket from CTP to ATP during CCA-synthesis
physiological function
introduction of a beta-turn element of the catalytic core into the human enzyme confers full CCA-adding activity on armless tRNAs. This region, identified to position the 3'-end of the tRNA primer in the catalytic core, dramatically increases the enzyme's substrate affinity. Conventional tRNA substrates bind to the enzyme by interactions with the T-arm, this is not possible in the case of armless tRNAs of the Romanomermis culicivorax mitochondrion
evolution
-
a class II CCA-adding enzyme. Compared to class I, class II CCA-adding enzymes show a much higher evolutionary conservation of individual catalytic core motifs. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview
evolution
-
diphosphorolysis of class II enzymes establishes a fundamental difference from class I enzymes, and it is achieved only with the tRNA structure and with specific divalent metal ions
evolution
-
with a possible origin of ancient telomerase-like activity, the CCA-adding enzymes obviously emerged twice during evolution, leading to structurally different, but functionally identical enzymes. While the enzyme class 1 is exclusively found in archaea, class 2 tRNA-nucleotidyltransferases are present in eukaryotes and bacteria. In class 2 enzymes, only the head domain carries a beta sheet and forms the nucleotidyltransferase core, while neck, body and tail consist exclusively of alpha helices, giving the enzyme a hook- or seahorse-like overall structure. The chemical mechanism underlying the polymerization appears conserved in all polymerases across the three kingdoms of life
malfunction
-
CCA ends with misincorporated nucleotides are only rarely detected. Only under rather artificial in vitro conditions, e.g. in the presence of Mn2+ ions instead of Mg2+ or deviating NTP concentrations, incorporation of CCC as well as poly(C) tails can be observed
malfunction
-
mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding
physiological function
-
CCA enzymes catalyze stepwise CCA addition to the tRNA 3' end at positions 74-76 as an obligatory sequence for tRNA activity in the cell. Only class II CCA enzymes catalyze pyrophosphorolysis, the reaction can initiate from all three CCA positions and proceed processively until the removal of nucleotide C74. Diphosphorolysis enables class II enzymes to efficiently remove an incorrect A75 nucleotide from the 3' end, at a rate much faster than the rate of A75 incorporation, suggesting the ability to perform a previously unexpected quality control mechanism for CCA synthesis
physiological function
-
CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms
physiological function
-
tRNA-nucleotidyltransferases are RNA polymerases responsible for the synthesis of the nucleotide triplet CCA at the 3'-terminus of tRNAs. As this CCA end represents an essential functional element for aminoacylation and translation, the CCA-adding enzymes are of vital importance in all organisms. The enzyme fulfills both functions in maintenance/repair as well as de novo polymerization
physiological function
-
identification of candidate non-tRNA substrates of CCA-adding enzyme, i.e. fourteen CCA-RNAs that only contain CCA as non-genomic sequences, and eleven NCCA-RNAs that contain CCA and other nucleotides as non-genomic sequences. All (N)CCA-RNAs are derived from the mitochondrial genome and are localized in mitochondria. Knockdown of CCA-adding enzyme severely reduces the expression levels of (N)CCA-RNAs
additional information
-
in class 2 enzymes, only the head domain carries a beta-sheet and forms the nucleotidyltransferase core, while neck, body and tail consist exclusively of alpha helices, giving the enzyme a hook- or seahorse-like overall structure, structure-function relationship, overview
additional information
-
structure-function relationship, overview. The active site is located in the N-terminal part of the enzyme and consists of five elements that are involved in metal ion binding, catalysis, ribose recognition, nucleotide selection, and templating. Motif A is located in the head domain and includes the general signature motif of all nucleotidyltransferases with the two metal-binding carboxylates DxD that are involved in catalysis and binding of the triphosphate moiety of the incoming nucleotides. The head domain carries motif B, where highly conserved residues play a critical role in discriminating between NTPs and dNTPs. The neck domain contains motif D, a single nucleotide-binding pocket that is specific for binding of CTP and ATP. Head and neck domain form a cleft that binds the incoming nucleotide as well as the 3'-end of the tRNA primer. The body and tail domains at the enzyme's C-terminus recognize the top-half region of the tRNA primer. The CCA-enzyme does not move along the tRNA during synthesis but remains at a fixed position
additional information
-
the CCA enzymes are unusual RNA polymerases, which catalyze CCA addition to positions 74-76 at the tRNA 3' end without using a nucleic acid template, reaction mechanism of CCA addition and reverse phosphorolysis reaction, overview
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). TRNT1_HUMAN
434
0
50128
Swiss-Prot
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
class II enzymes found in bacteria and eukaryotes carry a flexible loop in their catalytic core required for switching the specificity of the nucleotide binding pocket from CTP- to ATP-recognition, with the existence of conserved loop families. Loop replacements within families do not interfere with enzymatic activity. Modeling experiments suggest specific interactions of loop positions with important elements of the protein, forming a lever-like structure
additional information
four domain architecture with a cluster of conserved residues forming a positively charged cleft between the first two domains, modeling of human mitochondrial tRNA-nucleotidyltransferase monomer
additional information
-
four domain architecture with a cluster of conserved residues forming a positively charged cleft between the first two domains, modeling of human mitochondrial tRNA-nucleotidyltransferase monomer
additional information
-
in class 2 enzymes, only the head domain carries a beta-sheet and forms the nucleotidyltransferase core, while neck, body and tail consist exclusively of alpha helices, giving the enzyme a hook- or seahorse-like overall structure, structure-function relationship, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
modeling of a loop sequence inserted into the structure of human CCA-adding enzyme based on pdb-entry 1OU5. The conserved loop residue R105 forms a salt bridge to the first residue E164 of the amino acid template EDxxR in motif D
purified recombinant monomeric native enzyme or enzyme in complex with thimerosal, sitting drop vapor diffusion method, mixing of 0.003-0.005 ml of protein solution with 0.001 ml of reservoir solution containing 100 mM sodium citrate, pH 5.6, 2.2 M ammonium sulfate, and equilibration against 0.4 ml of reservoir solution, 3 days to 3 weeks, for ligand bound enzyme crystals soaking in reservoir solution containing 0.5 mM thimerosal for 45 min, 18°C, X-ray diffraction structure determination and analysis at 3.4-3.7 A resolution, single isomorphous replacement
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D139A
mutant shows a strong reduction in the addition of the terminal A position
G143A
similar to wild-type, mutant catalyzes the addition of the complete CCA sequence
L166S
and T154I, compound heterozygous mutation identified in a patient with sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay
R153A
similar to wild-type, mutant catalyzes the addition of the complete CCA sequence
R190I
homozygous mutation identified in a patient with sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay
T154I
and L166S, compound heterozygous mutation identified in a patient with sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay
additional information
additional information
replacement of residues 100117 in the human enzyme by the corresponding part of the Escherichia coli enzyme, positions 6687, leading to the chimera HEH with human enzyme N-terminus, Escherichia coli flexible loop, human enzyme C-terminus. Replacement of the region in the Escherichia coli enzyme by the human loop element, representing the reciprocal experiment, chimera EHE. Whereas the wild-type enzymes incorporate the complete CCA sequence, the chimeric enzymes EHE, HEH show a reduced activity and add only 2 C residues to the tRNA substrate. The chimeras EHE, HEH show a 45- to 145fold reduced kcat for A-incorporation. The corresponding KM values are consistent with the KM values of the loop donor enzymes
additional information
-
replacement of the highly conserved residues glutamic acid, aspartic acid and arginine o f the EDxxR motif aabolishes nucleotide specificity of the enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally His-tagged mitochondrial CCase from Escherichia coli strain BL21 CodonPlus (DE3)-RP by nickel affinity chromatography and gel filtration to over 95% purity
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mitochondrial CCase, expression as N-terminally His-tagged enzyme in Escherichia coli strain BL21 CodonPlus (DE3)-RP
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
congenital sideroblastic anemia causing mutations in patient-derived fibroblasts do not affect subcellular localization of TRNT1 and show no gross morphological differences when compared to control cells. Both basal and maximal respiration rates are decreased in patient cells
medicine
the clinical phenotypes associated with TRNT1 mutations are largely due to impaired mitochondrial translation, resulting from defective CCA addition to mitochondrial tRNASer(AGY), and the severity of this biochemical phenotype determines the severity and tissue distribution of clinical features. TRNT1 mutations A148V and.D128G/Y173F are identified in two unrelated subjects with different clinical features. The first presented with acute lactic acidosis at 3 weeks of age and developed severe developmental delay, hypotonia, microcephaly, seizures, progressive cortical atrophy, neurosensorial deafness, sideroblastic anemia and renal Fanconi syndrome, dying at 21 months. The second presented at 3.5 years with gait ataxia, dysarthria, gross motor regression, hypotonia, ptosis and ophthalmoplegia and had abnormal signals in brainstem and dentate nucleus. In subject 1, muscle biopsy showed combined oxidative phosphorylation defects, but there was no oxidative phosphorylation deficiency in fibroblasts from either subject, despite a 10fold reduction in TRNT1 protein levels in fibroblasts of the first subject. In normal controls, TRNT1 protein levels are 10fold lower in muscle than in fibroblasts
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Augustin, M.A.; Reichert, A.S.; Betat, H.; Huber, R.; Morl, M.; Steegborn, C.
Crystal structure of the human CCA-adding enzyme: insights into template-independent polymerization
J. Mol. Biol.
328
985-994
2003
Homo sapiens (Q96Q11), Homo sapiens
Hoffmeier, A.; Betat, H.; Bluschke, A.; Gunther, R.; Junghanns, S.; Hofmann, H.J.; Morl, M.
Unusual evolution of a catalytic core element in CCA-adding enzymes
Nucleic Acids Res.
38
4436-4447
2010
Geobacillus stearothermophilus, Escherichia coli, Homo sapiens (Q96Q11)
Mrl, M.; Betat, H.; Rammelt, C.
TRNA nucleotidyltransferases: ancient catalysts with an unusual mechanism of polymerization
Cell. Mol. Life Sci.
67
1447-1463
2010
Archaeoglobus fulgidus, Escherichia coli, Geobacillus stearothermophilus, Homo sapiens, Saccharolobus shibatae, Thermotoga maritima, Thermus thermophilus
Vrtler, S.; Mrl, M.
tRNA-nucleotidyltransferases: Highly unusual RNA polymerases with vital functions
FEBS Lett.
584
297-302
2010
Aquifex aeolicus, Archaea, Caldanaerobacter subterraneus subsp. tengcongensis, Deinococcus radiodurans, Escherichia coli, Halalkalibacterium halodurans, Homo sapiens, Thermus thermophilus
Igarashi, T.; Liu, C.; Morinaga, H.; Kim, S.; Hou, Y.
Pyrophosphorolysis of CCA addition: implication for fidelity
J. Mol. Biol.
414
28-43
2011
Archaeoglobus fulgidus, Escherichia coli, Homo sapiens
Sasarman, F.; Thiffault, I.; Weraarpachai, W.; Salomon, S.; Maftei, C.; Gauthier, J.; Ellazam, B.; Webb, N.; Antonicka, H.; Janer, A.; Brunel-Guitton, C.; Elpeleg, O.; Mitchell, G.; Shoubridge, E.A.
The 3 addition of CCA to mitochondrial tRNASer(AGY) is specifically impaired in patients with mutations in the tRNA nucleotidyl transferase TRNT1
Hum. Mol. Genet.
24
2841-2847
2015
Homo sapiens (Q96Q11), Homo sapiens
Liwak-Muir, U.; Mamady, H.; Naas, T.; Wylie, Q.; McBride, S.; Lines, M.; Michaud, J.; Baird, S.D.; Chakraborty, P.K.; Holcik, M.
Impaired activity of CCA-adding enzyme TRNT1 impacts OXPHOS complexes and cellular respiration in SIFD patient-derived fibroblasts
Orphanet J. Rare Dis.
11
79
2016
Homo sapiens (Q96Q11)
Ernst, F.G.; Rickert, C.; Bluschke, A.; Betat, H.; Steinhoff, H.J.; Moerl, M.
Domain movements during CCA-addition: a new function for motif C in the catalytic core of the human tRNA nucleotidyltransferases
RNA Biol.
12
435-446
2015
Homo sapiens (Q96Q11)
Hennig, O.; Philipp, S.; Bonin, S.; Rollet, K.; Kolberg, T.; Juehling, T.; Betat, H.; Sauter, C.; Moerl, M.
Adaptation of the Romanomermis culicivorax CCA-adding enzyme to miniaturized armless tRNA substrates
Int. j. Mol. Sci.
21
9047
2020
Homo sapiens (Q96Q11), Homo sapiens, Romanomermis culicivorax
EXTERNAL LINKS (specific for EC-Number 2.7.7.72)
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Release 2023.1 (January 2023)
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