O-phosphoseryl-tRNA(Sec) selenium transferase (SEPSECS)
The protein contains 501 amino acids for an estimated molecular weight of 55726 Da.
Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis. (updated: April 1, 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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.
No binding partner found
The reference OMIM entry for this protein is 613009
O-phosphoserine trna-selenocysteine trna synthase; sepsecs
Soluble liver antigen; sla
Liver pancreas antigen; lp
DESCRIPTION
The 21st amino acid, selenocysteine (sec), is distinct from other amino acids because it lacks its own tRNA synthetase and is the only amino acid synthesized on its cognate tRNA. Synthesis of sec begins with acylation of tRNA(sec) (TRSP; 165060) by seryl-tRNA synthetase (SARS; 607529) to give ser-tRNA(sec), which is subsequently phosphorylated by O-phosphoseryl-tRNA kinase (PSTK; 611310) to give O-phosphoseryl-tRNA(sec). SEPSECS catalyzes the final step of sec synthesis by converting O-phosphoseryl-tRNA(sec) to selenocysteinyl-tRNA(sec) using selenophosphate as the selenium donor (Palioura et al., 2009).CLONING
Using sera from patients with autoimmune chronic active hepatitis, Gelpi et al. (1992) identified an antigenic ribonucleoprotein containing SEPSECS. Western blot analysis of HeLa cell extracts detected SEPSECS at an apparent molecular mass of 48 kD. Autoantibodies to soluble liver antigen (SLA) and to liver and pancreas antigen (LP) occur in about 30% of all patients with autoimmune hepatitis. Using ELISA, Wies et al. (2000) confirmed that the SLA and LP autoantibodies are identical. By screening Jurkat and human liver cDNA expression libraries with SLA/LP autoantibodies, Wies et al. (2000) cloned SEPSECS, which they designated SLA/LP. The deduced 422-amino acid protein has a possible peroxidase proximal heme-ligand signature near its N terminus and a number of possible phosphorylation sites, but it lacks typical transmembrane features. Wies et al. (2000) also cloned a splice variant of SEPSECS that includes a 156-bp insertion within the coding region that leads to an altered N terminus in the protein. Western blot analysis detected a major protein of about 50 kD in human liver cytosol and in lung, kidney, and pancreas. Expression was weak in normal human lymphocytes, but it was elevated in activated lymphocytes.MAPPING
By genomic sequence analysis, Wies et al. (2000) mapped the SEPSECS gene to chromosome 4. Hartz (2009) mapped the SEPSECS gene to chromosome 4p15.2 based on an alignment of the SEPSECS sequence (GenBank GENBANK AJ238617) with the genomic sequence (GRCh37).GENE FUNCTION
Using mutation analysis, Wies et al. (2000) found that amino acids 371 to 409 of SLA/LP were critical for immune recognition by SLA/LP autoantibodies. Using mutation analysis, Palioura et al. (2009) showed that arg75, gln105, and arg313 were required for conversion of O-phosphoseryl-tRNA(sec) to sec-tRNA(sec) by SEPSECS. The reaction also required pyridoxal phosphate as cofactor.BIOCHEMICAL FEATURES
Palioura et al. (2009) noted that SEPSECS forms a stable tetramer and acts on phosphoserine that is linked to tRNA(sec), but not on free phosphoserine or ser-tRNA(sec). They determined the crystal structure of the quaternary complex between human SEPSECS, unacylated tRNA(sec), and a mixture of O-phosphoserine and thiophosphate to 2.8-angstrom resolution. SEPSECS formed a tetramer that was bound to 2 tRNA(sec) molecules. SEPSECS tetramers were made up of 2 SEPSECS homodimers that interacted via their N-terminal alpha(1)-loop-alpha(2) motifs. The CCA ends of both tRNA(sec) molecules pointed to the active sites of the same homodimer, which the authors called the catalytic dimer. The noncatalytic homodimer served as a binding platform to orient tRNA(sec) for catalysis.MOLECULAR GENETICS
In 2 unrelated patients of Jewish Iraqi ancestry with progressive cerebellocerebral atrophy ... 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 613009 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed