Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis. (updated: April 1, 2015)
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 sequence conservation computed yet.
Total structural coverage: 100%
No model available.
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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 AJ
238617) 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 ...
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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