Serine--tRNA ligase, cytoplasmic (SARS)
The protein contains 514 amino acids for an estimated molecular weight of 58777 Da.
Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| NEDMAS |
Biological Process
Gene expression
Negative regulation of angiogenesis
Negative regulation of transcription by RNA polymerase II
Negative regulation of vascular endothelial growth factor production
Selenocysteine metabolic process
Selenocysteinyl-tRNA(Sec) biosynthetic process
Seryl-tRNA aminoacylation
Transcription, DNA-templated
Translation
TRNA aminoacylation for protein translation
TRNA processing
The reference OMIM entry for this protein is 607529
Seryl-trna synthetase; sars
Sers
Serrs
CLONING
Vincent et al. (1997) assembled 2 overlapping clones of SARS, which they called SERS, isolated from human fetal and infant brain cDNA libraries. They obtained the full-length cDNA by 5-prime RACE of a brain cDNA library. The deduced 514-amino acid protein has a calculated molecular mass of about 59 kD. SARS has a 2-domain structure consisting of a tRNA-binding domain and a catalytic domain, which contains the 3 motifs shared by class II aminoacyl-tRNA synthetases. Motifs 2 and 3 share sequence conservation between prokaryotic and eukaryotic seryl-tRNA synthetases. SARS has no mitochondrial import signal sequence. Partial Sars protein sequences from mouse and Chinese hamster share 94% and 92% identity with human SARS. 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 1 catalytic-null splice variant for SerRS.GENE FUNCTION
Vincent et al. (1997) assayed bacterially expressed human SARS against calf liver and E. coli tRNAs and found similar seryl-tRNA synthetase activity against both substrates. Using small interfering RNA, Herzog et al. (2009) found that depletion of SARS from human umbilical vein endothelial cells (HUVECs) increased cell death, presumably due to loss of the function of SARS in protein synthesis. However, prior to cell death, SARS depletion caused abnormal tube formation and increased branching behavior of HUVECs in a rapid network formation assay. Herzog et al. (2009) concluded that SARS functions in angiogenesis, in addition to its role in protein synthesis.GENE STRUCTURE
Vincent et al. (1997) determined that the SARS gene contains 11 exons and spans more than 15 kb.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SARS gene to chromosome 1 (TMAP stSG9565).ANIMAL MODEL
Independently, Fukui et al. (2009) and Herzog et al. (2009) identified mutations in the zebrafish Sars gene that caused abnormal vascular development. The function of Sars in vascular development was independent of its canonical seryl-tRNA synthetase activity. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607529 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed