2.9.1.2	evolution	search in all genomic and metagenomic protein sequence data in the Integrated Microbial Genomes (IMG) system and at the NCBI to reveal new clades of SepRS and SepCysS proteins belonging to diverse archaea in the four major groups (DPANN, Euryarchaeota, TACK, and Asgard) and two groups of bacteria (Candidatus Parcubacteria and Chloroflexi), phylogenetic analysis and tree, overview. The archaea carrying full-length SepCysE employ Sec and SepRS is often found in Pyl-utilizing archaea and Chloroflexi bacteria. SepRS-SepCysS-SepCysE- and the selenocysteine-encoding systems are shared by the Euryarchaeota class I methanogens, the Crenarchaeota AK8/W8A-19 group, and an Asgard archaeon. Ancient archaea may have used both systems. In contrast, bacteria may have obtained the SepRS-SepCysS system from archaea. The SepRS-SepCysS system sometimes coexists with a pyrrolysine-encoding system in both archaea and bacteria	
2.9.1.2	malfunction	enzyme silencing clearly inhibits proliferation of JEG-3 cells, significantly induces cell apoptosis and reduces the production of progesterone and human chorionic gonadotropin	
2.9.1.2	malfunction	four distinct mutations (A239T, Y334C, T325S and nonsense Y429*) in human gene SEPSECS cause congenital cerebellar atrophy termed pontocerebellar hypoplasia type 2D (PCH2D). Pontocerebellar hypoplasia (PCH) is a group of autosomal recessive disorders affecting different cerebral structures, particularly the brainstem and cerebellum. Most PCH types result from mutations in genes important for tRNA splicing and aminoacylation and RNA transport. The PCH2D patients similarly suffer from progressive cerebellar and cerebral atrophy, neonatal irritability, and debilitating spasticity. Neuropathological analysis reveals severe atrophy of the brainstem and cerebellar cortex with loss of both white and gray matter. This subset of patients also exhibits a slight reduction in selenoprotein levels, suggesting that SepSecS catalysis is impaired. Pathogenic variants are less soluble than wild-type SepSecS. Mutations Thr325Ser and Tyr334Cys do not affect the binding affinity of the SepSecS-tRNA complex	
2.9.1.2	metabolism	in mammalian cells, the incorporation of the 21st amino acid, selenocysteine, into proteins is guided by the Sec machinery. The function of this protein complex requires several protein?protein and protein?RNA interactions, leading to the incorporation of selenocysteine at UGA codons. It is guided by stem?loop structures localized in the 3? untranslated regions of the selenoprotein-encoding genes	
2.9.1.2	metabolism	possible contributions of the SepRS-SepCysS system for sulfur assimilation, methanogenesis, and other metabolic processes requiring large amounts of iron-sulfur enzymes or Pyl-containing enzymes	
2.9.1.2	physiological function	Methanococcus maripaludis Mm900 is facultatively selenium-dependent with a single pathway of Sec-tRNASec formation. Seelenocysteine formation is abolished upon individually deleting the genes encoding selenophosphate synthetase, phosphoseryl-tRNASec kinase, or SepSecS. The resulting mutant strains can no longer grow on formate while growth with H2 + CO2 remains unaffected. Deletion of the phosphoseryl-tRNASec kinase and SepSecS genes is not possible unless the selenium-free [NiFe]-hydrogenases Frc and Vhc are expressed	
2.9.1.2	physiological function	the enzyme is dispensable for the parasite survival	
2.9.1.2	physiological function	the enzyme significantly affects proliferation, apoptosis and hormone secretion of human trophoblast cells	
2.9.1.2	physiological function	the enzyme is responsible for the formation of only 25 human proteins, but the human selenoproteome is pivotal for the maintenance of the cellular redox potential (e.g. thioredoxin reductases), regulation of the overall metabolic rate (e.g. iodothyronine deiodinases), removal of reactive oxygen species and prevention of oxidative damage (e.g. glutathione peroxidases, and methionine sulfoxide reductases), and selenium homeostasis (e.g. selenoprotein P)