Phenylalanine--tRNA ligase alpha subunit (FARSA)
The protein contains 508 amino acids for an estimated molecular weight of 57564 Da.
No function (updated: March 4, 2015)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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 |
|---|---|
| dbSNP:rs35087277 |
Biological Process
Gene expression
Phenylalanyl-tRNA aminoacylation
Protein heterotetramerization
TRNA aminoacylation for protein translation
Molecular Function
ATP binding
Phenylalanine-tRNA ligase activity
Poly(A) RNA binding
RNA binding
TRNA binding
The reference OMIM entry for this protein is 602918
Phenylalanine-trna synthetase, alpha subunit; farsa
Phenylalanine-trna synthetase, cytoplasmic, alpha subunit; frsa
Phenylalanine-trna synthetase-like, alpha subunit; farsla
Phersa
Cml33
DESCRIPTION
Aminoacyl-tRNA synthetases are enzymes that charge tRNAs with specific amino acids. Cytoplasmic phenylalanine-tRNA synthetase is a heterodimer consisting of a catalytic alpha subunit, FARSA, and a regulatory beta subunit, FARSB (609690) (Rodova et al., 1999).CLONING
Using subtractive hybridization, Sen et al. (1997) identified a gene that is differentially expressed between a tumorigenic human acute-phase chronic myeloid leukemia (CML; 608232) cell line and its nontumorigenic variant. Sequence analysis of the predicted 508-amino acid protein, called CML33, revealed that it has homology to the catalytic subunit of prokaryotic and S. cerevisiae phenylalanyl-tRNA synthetases (PheRS). Recombinant CML33 reacted with antibodies against sheep liver PheRS on Western blots. Since CML33 does not have the leader sequence characteristic of mitochondrial proteins and does not resemble yeast mitochondrial PheRS, Sen et al. (1997) suggested that it is a subunit of human cytoplasmic PheRS. Using Northern blot analysis, the authors determined that CML33 expression is sensitive to the stage of the cell cycle and to induction of differentiation. Expression of the 1.8-kb transcript is also substantially enhanced in tumorigenic cells. Sen et al. (1997) noted that CML33 is the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression. By database analysis, RT-PCR using embryonic kidney cell RNA, and screening a fetal kidney cDNA library, Rodova et al. (1999) cloned FARSA. The 508-amino acid protein has a calculated molecular mass of 57 kD. Sequence alignment of FARSA orthologs from multiple species showed conservation of active site regions and suggested that the heterodimer of FARSA and FARSB forms a 4-helix bundle interface similar to that in Thermus thermophilus. Northern blot analysis detected a 2.4-kb transcript in heart, brain, placenta, skeletal muscle, kidney, and pancreas. Expression was stronger in malignant cell lines compared with normal tissue. 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 2 catalytic-null and 1 catalytic domain-retained splice variants for PheRSa.GENE FUNCTION
Rodova et al. (1999) showed that COS-7 cells transfected with FARSA and FARSB increase phenylalanine charging of tRNA.MAPPING
By analysis of a somatic cell hybrid panel, Sen et al. (1997) mapped the CML33 gene to chromosome 19. Rasooly (1998) noted that the CML33 gene was contained within genomic clones from chromosomal region 19p13.2 (Genbank GENBANK AD000092). ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602918 was added.