{{Short description|Protein-coding gene in the species Homo sapiens}} {{italic title}} {{Infobox gene}} '''''SARS''''' and '''cytoplasmic seryl-tRNA synthetase''' are a human gene and its encoded enzyme product, respectively.<ref name="pmid9431993">{{cite journal | vauthors = Vincent C, Tarbouriech N, Härtlein M | title = Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase | journal = European Journal of Biochemistry | volume = 250 | issue = 1 | pages = 77–84 | date = November 1997 | pmid = 9431993 | doi = 10.1111/j.1432-1033.1997.00077.x | doi-access = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SARS seryl-tRNA synthetase| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=6301}}</ref> ''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.<ref name="entrez" />
Mutations in ''SARS'' have been associated with several conditions, including HUPRA syndrome.<ref name="pmid21255763">{{cite journal | vauthors = Belostotsky R, Ben-Shalom E, Rinat C, Becker-Cohen R, Feinstein S, Zeligson S, Segel R, Elpeleg O, Nassar S, Frishberg Y | title = Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome. | journal = American Journal of Human Genetics | volume = 88 | issue = 2 | pages = 193–200 | date = February 2011 | pmid = 21255763 | pmc = 3035710| doi = 10.1016/j.ajhg.2010.12.010 }}</ref>
== Discovery ==
Since the 1960s, seryl-tRNA synthetases have been described in various eukaryotic species, in both biochemical and structural analyses.<ref name="pmid4661528">{{cite journal | vauthors = Le Meur MA, Gerlinger P, Clavert J, Ebel JP | title = Purification and properties of seryl-tRNA synthetase from hen's liver | journal = Biochimie | volume = 54 | issue = 11 | pages = 1391–7 | date = November 1972 | pmid = 4661528 | doi = 10.1016/S0300-9084(72)80080-4 }}</ref><ref name="pmid6565588">{{cite journal | vauthors = Mizutani T, Narihara T, Hashimoto A | title = Purification and properties of bovine liver seryl-tRNA synthetase | journal = European Journal of Biochemistry | volume = 143 | issue = 1 | pages = 9–13 | date = 1984 | pmid = 6565588 | doi = 10.1111/j.1432-1033.1984.tb08331.x | doi-access = free }}</ref> 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.<ref name="pmid9431993" />
== 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.<ref name = "P49591" >UniProt: {{UniProt|P49591}}</ref>
== Protein ==
Seryl-tRNA synthetase is made up of 514 amino acid residues as weighs 58,777 Da.<ref>[https://www.uniprot.org/uniprot/P49591 "UnitProt"]</ref> It exists as a homodimer of two identical subunits, with the tRNA molecule binding across the dimer by similarity.<ref name="pmid7540217">{{cite journal | vauthors = Härtlein M, Cusack S | title = Structure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code. | journal = BMC Nephrology | volume = 40 | issue = 5 | pages = 519–530 | date = May 1995 | pmid = 7540217 | doi = 10.1007/BF00166620 | bibcode = 1995JMolE..40..519H | s2cid = 20176737 }}</ref> It has two distinct domains:
* A catalytic core<ref name = "P49591" /> * A 3 base pair serine binding N-terminal extension<ref name = "P49591" />
== 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).<ref name="pmid5773438">{{cite journal | vauthors = Rouge M | title = Purification and some properties of rat liver seryl-tRNA synthetase. | journal = Biochimica et Biophysica Acta | volume = 171 | issue = 2 | pages = 342–51 | date = February 1969 | pmid = 5773438 | doi=10.1016/0005-2744(69)90167-3}}</ref> 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.<ref name="pmid9431993" />
== Mutations == As with many mutations that affect protein translation,<ref name="pmid 1732728">{{cite journal | vauthors = King MP, Koga Y, Davidson M, Schon EA | title = 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. | journal = Molecular and Cellular Biology | volume = 12 | issue = 2 | pages = 480–90 | date = February 1992 | pmid = 1732728 | pmc = 364194| doi=10.1128/mcb.12.2.480}}</ref> 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.<ref name="pmid21255763" />
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.<ref name="pmid21255763" /> 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.<ref name="pmid21255763" />
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.<ref>[http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=363694 "Orpha"]</ref> A Palestinian community in the Greater Jerusalem region appears to have a much higher incidence of the mutation, potentially due to a common ancestor.<ref name="pmid21255763" />
== References == {{reflist}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Härtlein M, Cusack S | title = Structure, function and evolution of seryl-tRNA synthetases: implications for the evolution of aminoacyl-tRNA synthetases and the genetic code | journal = Journal of Molecular Evolution | volume = 40 | issue = 5 | pages = 519–30 | date = May 1995 | pmid = 7540217 | doi = 10.1007/BF00166620 | bibcode = 1995JMolE..40..519H | s2cid = 20176737 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Heckl M, Busch K, Gross HJ | title = Minimal tRNA(Ser) and tRNA(Sec) substrates for human seryl-tRNA synthetase: contribution of tRNA domains to serylation and tertiary structure | journal = FEBS Letters | volume = 427 | issue = 3 | pages = 315–9 | date = May 1998 | pmid = 9637248 | doi = 10.1016/S0014-5793(98)00435-9 | s2cid = 1897938 | doi-access = free | bibcode = 1998FEBSL.427..315H }} * {{cite journal | vauthors = Shah ZH, Toompuu M, Hakkinen T, Rovio AT, van Ravenswaay C, De Leenheer EM, Smith RJ, Cremers FP, Cremers CW, Jacobs HT | title = Novel coding-region polymorphisms in mitochondrial seryl-tRNA synthetase (SARSM) and mitoribosomal protein S12 (RPMS12) genes in DFNA4 autosomal dominant deafness families | journal = Human Mutation | volume = 17 | issue = 5 | pages = 433–4 | date = May 2001 | pmid = 11317363 | doi = 10.1002/humu.1123 | s2cid = 26793784 | doi-access = free }} * {{cite journal | vauthors = Shimada N, Suzuki T, Watanabe K | title = Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl-tRNA synthetase | journal = The Journal of Biological Chemistry | volume = 276 | issue = 50 | pages = 46770–8 | date = December 2001 | pmid = 11577083 | doi = 10.1074/jbc.M105150200 | doi-access = free }} * {{cite journal | vauthors = Rigler R, Cronvall E, Hirsch R, Pachmann U, Zachau HG | title = Interactions of seryl-tRNA synthetase with serine and phenylalanine specific tRNA | journal = FEBS Letters | volume = 11 | issue = 5 | pages = 320–323 | date = December 1970 | pmid = 11945516 | doi = 10.1016/0014-5793(70)80558-0 | s2cid = 32467286 | doi-access = free | bibcode = 1970FEBSL..11..320R }} * {{cite journal | vauthors = 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 | title = Large-scale mapping of human protein-protein interactions by mass spectrometry | journal = Molecular Systems Biology | volume = 3 | issue = 1 | pages = 89 | year = 2007 | pmid = 17353931 | pmc = 1847948 | doi = 10.1038/msb4100134 }} {{refend}}