The reference OMIM entry for this protein is 603727

Glutaminyl-trna synthetase; qars
Glnrs

DESCRIPTION

GLnRS is a class I aminoacyl-tRNA synthetase (Lamour et al., 1994). Aminoacyl-tRNA synthetases are enzymes that charge tRNAs with their cognate amino acids. The specificity of this reaction determines the fidelity of mRNA translation. At least 1 synthetase exists in the cytoplasm for each amino acid.

CLONING

Lamour et al. (1994) isolated cDNAs encoding human GlnRS. Northern blot analysis detected GlnRS expression as an approximately 2.5-kb mRNA in a variety of tumor cell lines. The predicted 775-amino acid protein contains the HIGH and KMSKS sequence motifs characteristic of class I aminoacyl-tRNA synthetases. Human and S. cerevisiae GlnRS are 41% identical. Both eukaryotic enzymes have a large N-terminal extension compared to prokaryotic GlnRS. By immunostaining, Zhang et al. (2014) detected the QARS protein in normal human fetal brain at 15 weeks' gestation. High levels were found in the ventricular zone, inner and outer subventricular zones, and cortical plate. QARS was mainly distributed in the cytoplasm and showed localization to the endoplasmic reticulum, but not the Golgi. Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 6 catalytic-null and 4 catalytic domain-retained splice variants for GlnRS.

EVOLUTION

Lamour et al. (1994) noted that GlnRS is present in eukaryotes but is absent from many prokaryotes, mitochondria, and chloroplasts, in which Gln-tRNA(Gln) is formed by transamidation of the misacylated Glu-tRNA(Gln). Sequence comparisons revealed that the eukaryotic glutamyl-tRNA synthetase (GluRS; 612799) has more extensive sequence similarities with prokaryotic and eukaryotic GlnRS than with the functionally homologous prokaryotic GluRS. Lamour et al. (1994) presented evidence that bacterial GlnRS has a eukaryotic origin and was acquired by a mechanism of horizontal gene transfer.

MAPPING

By analysis of a somatic cell hybrid panel, Lamour et al. (1994) mapped the GlnRS gene to chromosome 3.

MOLECULAR GENETICS

In 4 patients from 2 unrelated families with progressive microcephaly, seizures, and cerebral and cerebellar atrophy (MSCCA; 615760), Zhang et al. (2014) identified compound heterozygous mutations in the QARS gene (603727.0001-603727.0004). The mutations were found by whole-exome sequencing. The patients had onset of microcephaly at birth and intractable seizures in the first days or months of life. All had profoundly delayed development and hypotonia. Studies in patient cells and expression of recombinant variants in E. coli showed that all 4 mutations caused a severe loss of QARS catalytic activity, consistent with a loss-of-function effect. Homozygous loss of qar ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 603727 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).