SARS and cytoplasmic seryl-tRNA synthetase are a human gene and its encoded enzyme product, respectively. [4] [5] SARS belongs to the class II amino-acyl tRNA family and is found in all humans; its encoded enzyme, seryl-tRNA synthetase, is involved in protein translation and is related to several bacterial and yeast counterparts. [5]
Mutations in SARS have been associated with several conditions, including HUPRA syndrome. [6]
Since the 1960s, seryl-tRNA synthetases have been described in various eukaryotic species, in both biochemical and structural analyses. [7] [8] It was not until 1997 that human SARS and its enzyme product were isolated and expressed in Escherichia coli by a team from The European Molecular Biology Laboratory in France. [4]
The human SARS gene is located on the plus strand of chromosome 1, from base pair 109,213,893 to base pair 109,238,182. [9]
Seryl-tRNA synthetase is made up of 514 amino acid residues as weighs 58,777 Da. [10] It exists as a homodimer of two identical subunits, with the tRNA molecule binding across the dimer by similarity. [11] It has two distinct domains:
"SARS" and it’s enzyme product seryl-tRNA synthetase are involved in protein translation; specifically, seryl-tRNA synthetase catalyses the transfer of L-serine to tRNA (Ser). [12] The cytosolic enzyme recognises its cognate tRNA species and binds with a high level of specificity, allowing the accurate interaction between corresponding codons and anticodons on mRNA and tRNA during protein translation. [4]
As with many mutations that affect protein translation, [13] mutations in the SARS gene set have been shown to cause a collection of diseases, such as hyperuricemia, metabolic alkalosis, pulmonary hypertension, and progressive kidney failure in infancy; together, these conditions are known as HUPRA syndrome. [6]
In these cases, the SARS gene (in particular, "SARS2") undergoes a missense mutation, which results in a complete lack of acetylated seryl-tRNA synthetase and a severely reduced amount of non-acetylated enzyme. [6] This results in the ineffective or complete inability of L-serine to be transferred to its cognate tRNA, resulting in incomplete protein translation and folding. The impacts appear to only reach a phenotypic pathology in certain high energy expenditure cells, such as renal cells and lung tissue. It has been suggested that the residual activity of the SARS2 gene allows most other tissues to avoid cytopathic symptoms, however, is unable to protect high-energy requirement cells from damage. [6]
The prevalence of SARS mutations resulting in HUPRA syndrome are incredibly rare, with less than 1 in 1,000,000 babies born with the condition. [14] A Palestinian community in the Greater Jerusalem region appears to have a much higher incidence of the mutation, potentially due to a common ancestor. [6]
Ribonuclease H is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly all organisms, from bacteria to archaea to eukaryotes.
An aminoacyl-tRNA synthetase, also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its corresponding tRNA. It does so by catalyzing the transesterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.
Chromosome 21 is one of the 23 pairs of chromosomes in humans. Chromosome 21 is both the smallest human autosome and chromosome, with 45 million base pairs representing about 1.5 percent of the total DNA in cells. Most people have two copies of chromosome 21, while those with three copies of chromosome 21 have Down syndrome, also called "trisomy 21".
Argininosuccinate synthase or synthetase is an enzyme that catalyzes the synthesis of argininosuccinate from citrulline and aspartate. In humans, argininosuccinate synthase is encoded by the ASS gene located on chromosome 9.
Cathepsin C (CTSC) also known as dipeptidyl peptidase I (DPP-I) is a lysosomal exo-cysteine protease belonging to the peptidase C1 protein family, a subgroup of the cysteine cathepsins. In humans, it is encoded by the CTSC gene.
Glycine decarboxylase also known as glycine cleavage system P protein or glycine dehydrogenase is an enzyme that in humans is encoded by the GLDC gene.
Glycine—tRNA ligase also known as glycyl–tRNA synthetase is an enzyme that in humans is encoded by the GARS1 gene.
Tyrosine—tRNA ligase, also known as tyrosyl-tRNA synthetase is an enzyme that is encoded by the gene YARS. Tyrosine—tRNA ligase catalyzes the chemical reaction
Serine protease HTRA2, mitochondrial is an enzyme that in humans is encoded by the HTRA2 gene. This protein is involved in caspase-dependent apoptosis and in Parkinson's disease.
Argininosuccinate synthetase is an enzyme that in humans is encoded by the ASS1 gene.
Tyrosyl-tRNA synthetase, cytoplasmic, also known as Tyrosine-tRNA ligase, is an enzyme that in humans is encoded by the YARS gene.
Folylpolyglutamate synthase, mitochondrial is an enzyme that in humans is encoded by the FPGS gene.
Valyl-tRNA synthetase is an enzyme that in humans is encoded by the VARS gene.
Probable leucyl-tRNA synthetase, mitochondrial is an enzyme that in humans is encoded by the LARS2 gene.
Isoleucyl-tRNA synthetase, cytoplasmic is an enzyme that in humans is encoded by the IARS1 gene.
Succinyl-CoA ligase [ADP-forming] subunit beta, mitochondrial (SUCLA2), also known as ADP-forming succinyl-CoA synthetase (SCS-A), is an enzyme that in humans is encoded by the SUCLA2 gene on chromosome 13.
Tryptophanyl-tRNA synthetase, mitochondrial is an enzyme that in humans is encoded by the WARS2 gene.
Phenylalanyl-tRNA synthetase, mitochondrial (FARS2) is an enzyme that in humans is encoded by the FARS2 gene. This protein encoded by FARS2 localizes to the mitochondrion and plays a role in mitochondrial protein translation. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 14, also known as Alpers encephalopathy, as well as spastic paraplegia 77 and infantile-onset epilepsy and cytochrome c oxidase deficiency.
Seryl-tRNA synthetase, mitochondrial is an enzyme that in humans is encoded by the SARS2 gene.
HUPRA syndrome is a rare syndrome that was first described in 2010 in two infants of Palestinian origin from the same village in the Jerusalem area. One of the two infants' parents were related. It was later described in a third infant from the same village, whose parents were not related.
