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Information on EC 6.1.1.5 - isoleucine-tRNA ligase and Organism(s) Homo sapiens and UniProt Accession Q9NSE4
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6.1.1.5 isoleucine-tRNA ligaseSpecify your search results
Word Map
- 6.1.1.5
- synthetases
- aminoacyl-trna
- aminoacylation
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isoleucylation
- valyl-trna
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misactivated
- methionyl-trna
- leurs
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mischarged
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pseudomonic
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post-transfer
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noncognate
- valrs
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mupirocin-resistant
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misacylated
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anticodons
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aarss
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kmsks
- glnrs
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trna-dependent
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pretransfer
- lysyl-trna
- molecular biology
- medicine
- drug development
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
Synonyms
isoleucyl-trna synthetase, ilers, iars2, isoleucyl trna synthetase, iles2, ile-trna synthetase, mitochondrial isoleucyl-trna synthetase, isoleucine-trna synthetase, iles1, isoleucyl-transfer rna synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IleRS
IRS
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Isoleucine translase
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Isoleucine--tRNA ligase
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Isoleucine-transfer RNA ligase
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Isoleucine-tRNA synthetase
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Isoleucyl-transfer ribonucleate synthetase
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Isoleucyl-transfer RNA synthetase
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Isoleucyl-tRNA synthetase
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Mupirocin resistance protein
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Synthetase, isoleucyl-transfer ribonucleate
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IleRS
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
esterification
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aminacylation
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deacylation
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SYSTEMATIC NAME
IUBMB Comments
L-isoleucine:tRNAIle ligase (AMP-forming)
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CAS REGISTRY NUMBER
COMMENTARY
9030-96-0
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E,4E)-5-[(2S,3R,6S,8R,9S)-3-butyl-3-[(3-carboxypropanoyl)oxy]-8-(2-hydroxyethyl)-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-3-methylpenta-2,4-dienoic acid
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): not determined
(2E,4E)-5-[(2S,3R,6S,8R,9S)-3-butyl-3-[(3-carboxypropanoyl)oxy]-8-[(2E)-4-hydroxy-3-methylbut-2-en-1-yl]-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-3-methylpenta-2,4-dienoic acid
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): not determined
(2E,4E)-5-[(2S,3R,6S,8R,9S)-3-butyl-3-[(3-carboxypropanoyl)oxy]-8-[(2E)-4-[(3-carboxypropanoyl)oxy]-3-methylbut-2-en-1-yl]-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-3-methylpenta-2,4-dienoic acid
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): above 15
(2E,4E)-5-[(2S,3R,6S,8R,9S)-3-butyl-3-[(3-carboxypropanoyl)oxy]-8-[(2E,4E)-6-hydroxy-3-methylhexa-2,4-dien-1-yl]-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-3-methylpenta-2,4-dienoic acid
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IC50 (ng/ml): 560.3. Cell death inducibility of osteoclasts (microgram/ml): not determined
(2E,4E)-5-[(2S,3R,6S,8R,9S)-3-butyl-3-[(3-carboxypropanoyl)oxy]-8-[(2E,4E,6S,7S)-6,8-dihydroxy-3,7-dimethylocta-2,4-dien-1-yl]-9-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-3-methylpenta-2,4-dienoic acid
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IC50 (ng/ml): 22.9. Cell death inducibility of osteoclasts (microgram/ml): 6.31
(2E,4E)-6-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-9-[(3-carboxypropanoyl)oxy]-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-4-methylhexa-2,4-dienoic acid
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): not determined
(2E,4S,5S,6E,8E)-10-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-3-methyl-9-[(methylsulfanyl)methoxy]-1,7-dioxaspiro[5.5]undec-2-yl]-5-hydroxy-4,8-dimethyldeca-2,6,8-trienoic acid
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IC50 (ng/ml): 497.4. Cell death inducibility of osteoclasts (microgram/ml): 9.6
(2E,4S,5S,6E,8E)-10-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-9-hydroxy-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-5-hydroxy-4,8-dimethyldeca-2,6,8-trienoic acid
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IC50 (ng/ml): 94.6. Cell death inducibility of osteoclasts (microgram/ml): 11.5
(2E,4S,5S,6E,8E)-10-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-9-methoxy-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-5-hydroxy-4,8-dimethyldeca-2,6,8-trienoic acid
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IC50 (ng/ml): 57.9. Cell death inducibility of osteoclasts (microgram/ml): not determined
(2E,4S,5S,6E,8E)-10-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-9-[(3-carboxypropanoyl)oxy]-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-4,5-dihydroxy-8-methyldeca-2,6,8-trienoic acid
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IC50 (ng/ml): 14.4. Cell death inducibility of osteoclasts (microgram/ml): 1.01
(2E,4S,5S,6E,8E)-10-[(2R,3S,6S,8S,9R)-9-butyl-8-[(1E,3E)-4-carboxy-3-methylbuta-1,3-dien-1-yl]-9-[(4-methoxy-4-oxobutanoyl)oxy]-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]-5-hydroxy-4,8-dimethyldeca-2,6,8-trienoic acid
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IC50 (ng/ml): 292.8. Cell death inducibility of osteoclasts (microgram/ml): 2.5
2,3-Dihydro-5-epireveromycin A
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IC50 (ng/ml): 58.3. Cell death inducibility of osteoclasts (microgram/ml): 0.82
2,3-Dihydroreveromycin A
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IC50 (ng/ml): 11.6. Cell death inducibility of osteoclasts (microgram/ml): 0.22
5-acetyl-Reveromycin A
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): 0.46
5-Epireveromycin A
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IC50 (ng/ml): 378.3. Cell death inducibility of osteoclasts (microgram/ml): 21.5
5-methoxy-Reveromycin A
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IC50 (ng/ml): 374. Cell death inducibility of osteoclasts (microgram/ml): above 15
5-O-succinyl-Spirofungin A
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): 12.4
5-tert-butyl-dimethylsilyl-Reveromycin A
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): 5.9
Reveromycin A
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IC50 (ng/ml): 2.95. Cell death inducibility of osteoclasts (microgram/ml): 0.06
Reveromycin A 1-methyl ester
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IC50 (ng/ml): 211. Cell death inducibility of osteoclasts (microgram/ml): 2
Reveromycin A 24-methyl ester
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): 3.1
Reveromycin B
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): above 15
Spirofungin A
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IC50 (ng/ml): 564.5. Cell death inducibility of osteoclasts (microgram/ml): above 30
Spirofungin B
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IC50 (ng/ml): value above 1000. Cell death inducibility of osteoclasts (microgram/ml): above 30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
additional information
malfunction
constitutive high levels of mt isoleucyl-tRNA synthetase (mt-IleRS) are associated with reduced penetrance of the homoplasmic m.4277T>C mt-tRNAIle mutation, causing hypertrophic cardiomyopathy, which is paralleled by results in mutant transmitochondrial cybrids following overexpression of mt-IleRS. Interchangeable ability of three human mt-aaRS, namely mt-ValRS, mt-LeuRS and mt-IleRS, to suppress the mitochondrial functional defects associated with pathogenic homoplasmic mutations in mt-tRNAIle gene (MTTI). Transient overexpression of cognate mt-IleRS causes a 1.5fold increase in the viability of m.4277T>C MTTI mutant cybrids grown in galactose medium. The carboxy-terminal domain of human mt-leucyl-tRNA synthetase is both necessary and sufficient to improve the pathologic phenotype associated either with the mild mutations or with the severe m.3243A>G mutation in the mt-tRNALeu(UUR) gene. This small, non-catalytic domain is able to directly and specifically interact in vitro with human mt-tRNALeu(UUR) with high affinity and stability and, with lower affinity, with mt-tRNAIle
malfunction
mutations in the nuclear-encoded mitochondrial aminoacyltRNA synthetases are associated with a range of clinical phenotypes. A recessive disorder CAGSSS in three adult French-Canadian patients with a phenotype including cataracts, short-stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy, and skeletal dysplasia is caused by a single missense mutation P909L in a conserved residue of the nuclear gene IARS2, encoding mitochondrial isoleucyl-tRNA synthetase. The mutation is homozygous in the affected patients, heterozygous in carriers, and absent in control chromosomes. IARS2 protein level is reduced in skin cells cultured from one of the patients, consistent with a pathogenic effect of the mutation. Compound heterozygous mutations in IARS2 are independently identified in a patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome. Phenotypes, overview
additional information
three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
additional information
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three human mitochondrial aminoacyl-tRNA syntethases, namely leucyl-, valyl-, and isoleucyl-tRNA synthetase are able to improve both viability and bioenergetic proficiency of human transmitochondrial cybrid cells carrying pathogenic mutations in the mt-tRNAIle gene
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). SYIM_HUMAN
1012
0
113792
Swiss-Prot
Mitochondrion (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E708K
naturally occuring mutation found in a heterozygous patient, the mutation is at the junction of the catalytic core domain and the anticodon-binding domain, and is predicted to be disease-causing
P909L
naturally occuring mutation causing the recessive disorder CAGSSS, phenotype, overview
W607X
naturally occuring mutation found in a heterozygous patient, the mutation truncates the protein removing 405 amino acids and is expected to be severely pathogenic
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shimizu, T.; Usui, T.; Fujikura, M.; Kawatani, M.; Satoh, T.; Machida, K.; Kanoh, N.; Woo, J.T.; Osada, H.; Sodeoka, M.
Synthesis and biological activities of reveromycin A and spirofungin A derivatives
Bioorg. Med. Chem. Lett.
18
3756-3760
2008
Homo sapiens
Perli, E.; Giordano, C.; Pisano, A.; Montanari, A.; Campese, A.F.; Reyes, A.; Ghezzi, D.; Nasca, A.; Tuppen, H.A.; Orlandi, M.; Di Micco, P.; Poser, E.; Taylor, R.W.; Colotti, G.; Francisci, S.; Morea, V.; Frontali, L.; Zeviani, M.; dAmati, G.
The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells
EMBO Mol. Med.
6
169-182
2014
Homo sapiens (Q9NSE4), Homo sapiens
Schwartzentruber, J.; Buhas, D.; Majewski, J.; Sasarman, F.; Papillon-Cavanagh, S.; Thiffault, I.; Sheldon, K.; Massicotte, C.; Patry, L.; Simon, M.; Zare, A.; Mckernan, K.; Consortium, F.; Michaud, J.; Boles, R.; Deal, C.; Desilets, V.; Shoubridge, E.; Samuels, M.E.
Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA synthetase IARS2 in patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness, and peripheral neuropathy or with Leigh syndrome
Hum. Mutat.
36
281-281
2015
Homo sapiens (Q9NSE4), Homo sapiens
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