SARS (gene)

SARS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3VBB, 4L87, 4RQE, 4RQF
Identifiers
Aliases	SARS1, SERRS, SERS, seryl-tRNA synthetase, NEDMAS, SARS, seryl-tRNA synthetase 1
External IDs	OMIM: 607529 MGI: 102809 HomoloGene: 4751 GeneCards: SARS1
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 F3|3 47.08 cM Start 108,332,181 bp End 108,352,525 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in islet of Langerhans body of pancreas frontal pole parotid gland Brodmann area 10 upper lobe of left lung gastric mucosa skin of abdomen body of stomach ganglionic eminence Top expressed in seminal vesicula facial motor nucleus lacrimal gland calvaria yolk sac anterior horn of spinal cord superior frontal gyrus supraoptic nucleus lip salivary gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function aminoacyl-tRNA ligase activity nucleotide binding ligase activity selenocysteine-tRNA ligase activity ATP binding RNA binding core promoter sequence-specific DNA binding serine-tRNA ligase activity protein binding protein homodimerization activity DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component extracellular exosome cytosol cytoplasm nucleus Biological process tRNA processing tRNA aminoacylation for protein translation protein biosynthesis selenocysteine metabolic process selenocysteinyl-tRNA(Sec) biosynthetic process negative regulation of transcription by RNA polymerase II seryl-tRNA aminoacylation negative regulation of angiogenesis negative regulation of vascular endothelial growth factor production transcription, DNA-templated regulation of transcription, DNA-templated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6301 20226 Ensembl n/a ENSMUSG00000068739 UniProt P49591 P26638 RefSeq (mRNA) NM_006513 NM_001330669 NM_001204979 NM_011319 RefSeq (protein) NP_001317598 NP_006504 NP_001191908 NP_035449 Location (UCSC) n/a Chr 3: 108.33 – 108.35 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

SARS and cytoplasmic seryl-tRNA synthetase are a human gene and its encoded enzyme product, respectively. 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.

Mutations in SARS have been associated with several conditions, including HUPRA syndrome.

Discovery

Since the 1960s, seryl-tRNA synthetases have been described in various eukaryotic species, in both biochemical and structural analyses. 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.

Gene location

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.

Protein

Seryl-tRNA synthetase is made up of 514 amino acid residues as weighs 58,777 Da. It exists as a homodimer of two identical subunits, with the tRNA molecule binding across the dimer by similarity. It has two distinct domains:

• A catalytic core
• A 3 base pair serine binding N-terminal extension

Function and mechanism

"SARS" and its enzyme product seryl-tRNA synthetase are involved in protein translation; specifically, seryl-tRNA synthetase catalyses the transfer of L-serine to tRNA (Ser). 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.

Mutations

As with many mutations that affect protein translation, 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.

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. 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.

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. A Palestinian community in the Greater Jerusalem region appears to have a much higher incidence of the mutation, potentially due to a common ancestor.

Further reading

• Härtlein M, Cusack S (May 1995). "Structure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code". Journal of Molecular Evolution. 40 (5): 519–30. Bibcode:1995JMolE..40..519H. doi:10.1007/BF00166620. PMID 7540217. S2CID 20176737.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Heckl M, Busch K, Gross HJ (May 1998). "Minimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase: contribution of tRNA domains to serylation and tertiary structure". FEBS Letters. 427 (3): 315–9. doi:10.1016/S0014-5793(98)00435-9. PMID 9637248. S2CID 1897938.
• Shah ZH, Toompuu M, Hakkinen T, Rovio AT, van Ravenswaay C, De Leenheer EM, Smith RJ, Cremers FP, Cremers CW, Jacobs HT (May 2001). "Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families". Human Mutation. 17 (5): 433–4. doi:10.1002/humu.1123. PMID 11317363. S2CID 26793784.
• Shimada N, Suzuki T, Watanabe K (December 2001). "Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase". The Journal of Biological Chemistry. 276 (50): 46770–8. doi:10.1074/jbc.M105150200. PMID 11577083.
• Rigler R, Cronvall E, Hirsch R, Pachmann U, Zachau HG (December 1970). "Interactions of seryl-tRNA synthetase with serine and phenylalanine specific tRNA". FEBS Letters. 11 (5): 320–323. doi:10.1016/0014-5793(70)80558-0. PMID 11945516. S2CID 32467286.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.