SARS (gene)

SARS and cytoplasmic seryl-tRNA synthetase are a human gene and its encoded enzyme product, respectively.[5][6] 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.[6]

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 (Human) Chr. Chromosome 1 (human)[1] Band 1p13.3 Start 109,213,918 bp[1] End 109,238,182 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 F3|3 47.08 cM Start 108,424,865 bp[2] End 108,445,209 bp[2]
RNA expression pattern 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 • GO:0001948 protein binding • protein homodimerization activity • DNA binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component • extracellular exosome • cytosol • cytoplasm • cell nucleus Biological process • tRNA processing • tRNA aminoacylation for protein translation • protein biosynthesis • selenocysteine metabolic process • selenocysteinyl-tRNA(Sec) biosynthetic process • negative regulation of transcription from RNA polymerase II promoter • 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	ENSG00000031698	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)	Chr 1: 109.21 – 109.24 Mb	Chr 3: 108.42 – 108.45 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Mutations in SARS have been associated with several conditions, including HUPRA syndrome.[7]

Discovery

Since the 1960s, seryl-tRNA synthetases have been described in various eukaryotic species, in both biochemical and structural analyses.[8][9] 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.[5]

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.[10]

Protein

Seryl-tRNA synthetase is made up of 514 amino acid residues as weighs 58,777 Da.[11] It exists as a homodimer of two identical subunits, with the tRNA molecule binding across the dimer by similarity.[12] It has two distinct domains:

• A catalytic core[10]
• A 3 base pair serine binding N-terminal extension[10]

Function and mechanism

"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).[13] 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.[5]

Mutations

As with many mutations that affect protein translation,[14] 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.[7]

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.[7] 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.[7]

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.[15] A Palestinian community in the Greater Jerusalem region appears to have a much higher incidence of the mutation, potentially due to a common ancestor.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000031698 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000068739 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Vincent C, Tarbouriech N, Härtlein M (November 1997). "Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase". European Journal of Biochemistry / FEBS. 250 (1): 77–84. doi:10.1111/j.1432-1033.1997.00077.x. PMID 9431993.
6. "Entrez Gene: SARS seryl-tRNA synthetase".
7. Belostotsky R, Ben-Shalom E, Rinat C, Becker-Cohen R, Feinstein S, Zeligson S, Segel R, Elpeleg O, Nassar S, Frishberg Y (February 2011). "Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome". American Journal of Human Genetics. 88 (2): 193–200. doi:10.1016/j.ajhg.2010.12.010. PMC 3035710. PMID 21255763.
8. Le Meur MA, Gerlinger P, Clavert J, Ebel JP (November 1972). "Purification and properties of seryl-tRNA synthetase from hen's liver". Biochimie. 54 (11): 1391–7. doi:10.1016/S0300-9084(72)80080-4. PMID 4661528.
9. Mizutani T, Narihara T, Hashimoto A (1984). "Purification and properties of bovine liver seryl‐tRNA synthetase". European Journal of Biochemistry. 143 (1): 9–13. doi:10.1111/j.1432-1033.1984.tb08331.x. PMID 6565588.
10. UniProt: P49591
11. "UnitProt"
12. 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". BMC Nephrology. 40 (5): 519–530. Bibcode:1995JMolE..40..519H. doi:10.1007/BF00166620. PMID 7540217. S2CID 20176737.
13. Rouge M (February 1969). "Purification and some properties of rat liver seryl-tRNA synthetase". Biochimica et Biophysica Acta. 171 (2): 342–51. doi:10.1016/0005-2744(69)90167-3. PMID 5773438.
14. King MP, Koga Y, Davidson M, Schon EA (February 1992). "Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNA(Leu(UUR)) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes". Molecular and Cellular Biology. 12 (2): 480–90. doi:10.1128/mcb.12.2.480. PMC 364194. PMID 1732728.
15. "Orpha"

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.