Literature summary for 6.1.1.18 extracted from

Zhang, X.; Ling, J.; Barcia, G.; Jing, L.; Wu, J.; Barry, B.J.; Mochida, G.H.; Hill, R.S.; Weimer, J.M.; Stein, Q.; Poduri, A.; Partlow, J.N.; Ville, D.; Dulac, O.; Yu, T.W.; Lam, A.T.; Servattalab, S.; Rodriguez, J.; Boddaert, N.; Munnich, A.; Colleaux, L.; Zon, L.I.; Soell, D.; Walsh, C.A.; Nabbout, R.
Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures (2014), Am. J. Hum. Genet., 94, 547-558 .

Cloned(Commentary)

Cloned (Comment)	Organism
gene QARS, genotyping, recombinant expression of codon-optimized His-tagged wild-type and mutant enzymes in Escherichia coli	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
G45V	naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation is located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, the mutant shows an over 10fold reduction in aminoacylation activity, heterozygous mutation	Homo sapiens
G45V/R403W	naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutant shows a highly reduced aminoacylation activity, heterozygous mutations	Homo sapiens
additional information	microcephaly and neurodegeneration in two nonconsanguineous families and the identification of QARS mutations, phenotypes, overview	Homo sapiens
R403W	naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation renders QARS less soluble and disrupts the domain structure and overall folding of QARS, the mutant shows no aminoacylation activity in vitro, heterozygous mutation	Homo sapiens
R515W	naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation renders QARS less soluble, the mutation disrupts QARS-RARS (arginyl-tRNA synthetase 1) interaction and disrupts the domain structure and overall folding of QARS, the mutant shows no aminoacylation activity in vitro, heterozygous mutation	Homo sapiens
Y57H	naturally occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutation is located in the N-terminal domain required for QARS interaction with proteins in the multisynthetase complex and potentially with glutamine tRNA, the mutant shows an over 10fold reduction in aminoacylation activity, heterozygous mutation	Homo sapiens
Y57H/R515W	occuring mutation involved in progressive microcephaly, severe seizures in infancy, atrophy of the cerebral cortex and cerebellar vermis, and mild atrophy of the cerebellar hemispheres, the mutant shows a highly reduced aminoacylation activity, heterozygous mutations	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytoplasm	mainly	Homo sapiens	5737	-
endoplasmic reticulum	-	Homo sapiens	5783	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + L-glutamine + tRNAGln	Homo sapiens	-	AMP + diphosphate + L-glutaminyl-tRNAGln	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P47897	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography and dialysis	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	QARS is widely expressed in fetal human brain during early development	Homo sapiens	-
cerebral cortex	-	Homo sapiens	-
additional information	QARS is highly expressed in the developing fetal human cerebral cortex in many cell types	Homo sapiens	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
0.00024	0.00033	recombinant mutant Y57H/R515W enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens
0.00028	-	recombinant mutant G45V/R403W enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens
0.00041	-	recombinant mutant G45V enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens
0.00051	-	recombinant mutant R515W enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens
0.00058	-	recombinant mutant Y57H enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens
0.00079	0.00083	recombinant wild-type enzyme in crude cell extract, pH 7.5, 37°C	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + L-glutamine + tRNAGln	-	Homo sapiens	AMP + diphosphate + L-glutaminyl-tRNAGln	-	?

Synonyms

Synonyms	Comment	Organism
Glutaminyl-tRNA synthetase	-	Homo sapiens
QARS	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.5	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures	Homo sapiens