SepSecS

SEPSECS
Identifiers
AliasesSEPSECS, LP, PCH2D, SLA, SLA/LP, Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase, soluble liver antigen, SecS
External IDsOMIM: 613009; MGI: 1098791; GeneCards: SEPSECS
Available structures
PDBOrtholog search: PDBe RCSB
Enzyme activity
EC #BRENDAExPASyKEGGMetaCyc
2.9.1.2↗↗↗↗
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

51091

211006

Ensembl

ENSG00000109618

ENSMUSG00000029173

UniProt

Q9HD40

Q6P6M7

RefSeq (mRNA)

NM_001159728
NM_016955

NM_172490
NM_001363463

RefSeq (protein)

NP_058651

NP_766078
NP_001350392

Location (UCSC)Chr 4: 25.12 – 25.16 MbChr 5: 52.8 – 52.83 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse
O-phospho-L-seryl-tRNASec:L-selenocysteinyl-tRNA synthase
Selenocysteine synthase tetramer, Mus musculus
Identifiers
EC no.2.9.1.2
Databases
BRENDAenzyme data
ExPASyNiceZyme view
KEGGenzyme entry
MetaCycmetabolic pathway
Rheareactions
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins
Selenocysteine synthesis pathway

O-phosphoseryl-tRNA(Sec) selenium transferase (or SepSecS) is an enzyme that in humans is encoded by the SEPSECS gene. This enzyme is part of the multi-step process of producing selenocysteinyl-tRNASec which is needed for the synthesis of selenoproteins.

Also called O-phospho-L-seryl-tRNASec:L-selenocysteinyl-tRNA synthase (EC 2.9.1.2), this enzyme catalyses the following chemical reaction:

O-phospho-L-seryl-tRNASec + selenophosphate ⇌ L-selenocysteinyl-tRNASec + phosphate

using pyridoxal phosphate (PLP) as a cofactor.

Other names

Other names for this enzyme include MMPSepSecS, SLA/LP, O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase, and O-phospho-L-seryl-tRNA:L-selenocysteinyl-tRNA synthase. The enzyme's systematic name is selenophosphate:O-phospho-L-seryl-tRNASec selenium transferase.

Medical significance

Pathogenic mutations in SEPSECS have been associated with a small brain and skull size (microcephaly) and progressive brain atrophy, designated type 2D pontocerebellar hypoplasia (PCH2D). This is inherited in an autosomal recessive manner. Affected individuals were found to have reduced expression of selenoproteins in brain tissue, but not in other types of cells. In particular, it did not appear to consistently share the biochemical hallmark symptoms of low circulating selenoproteins and abnormal thyroid hormone levels found in selenoprotein deficiency caused by mutations in SECISBP2 or selenocysteine tRNA (TRU-TCA1-1).

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000109618 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029173 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Xu XM, Mix H, Carlson BA, Grabowski PJ, Gladyshev VN, Berry MJ, Hatfield DL (Dec 2005). "Evidence for direct roles of two additional factors, SECp43 and soluble liver antigen, in the selenoprotein synthesis machinery". J. Biol. Chem. 280 (50): 41568–75. doi:10.1074/jbc.M506696200. PMID 16230358.
  6. ↑ Costa M, Rodríguez-Sánchez JL, Czaja AJ, Gelpí C (Aug 2000). "Isolation and characterization of cDNA encoding the antigenic protein of the human tRNP(Ser)Sec complex recognized by autoantibodies from patients with type-1 autoimmune hepatitis". Clin. Exp. Immunol. 121 (2): 364–74. doi:10.1046/j.1365-2249.2000.01280.x. PMC 1905695. PMID 10931155.
  7. ↑ Yuan J, Palioura S, Salazar JC, Su D, O'Donoghue P, Hohn MJ, Cardoso AM, Whitman WB, Söll D (Dec 2006). "RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea". Proc. Natl. Acad. Sci. U.S.A. 103 (50): 18923–7. Bibcode:2006PNAS..10318923Y. doi:10.1073/pnas.0609703104. PMC 1748153. PMID 17142313.
  8. ↑ "Entrez Gene: SLA/LP soluble liver antigen/liver pancreas antigen".
  9. ↑ Xu XM, Carlson BA, Mix H, Zhang Y, Saira K, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL (Apr 2007). "Biosynthesis of selenocysteine on its tRNA in eukaryotes". PLOS Biol. 5 (1) e4. doi:10.1371/journal.pbio.0050004. PMC 1717018. PMID 17194211.
  10. ↑ Palioura S, Sherrer RL, Steitz TA, Söll D, Simonovic M (July 2009). "The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation". Science. 325 (5938): 321–5. Bibcode:2009Sci...325..321P. doi:10.1126/science.1173755. PMC 2857584. PMID 19608919.
  11. ↑ Araiso Y, Palioura S, Ishitani R, Sherrer RL, O'Donoghue P, Yuan J, Oshikane H, Domae N, Defranco J, Söll D, Nureki O (March 2008). "Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation". Nucleic Acids Research. 36 (4): 1187–99. doi:10.1093/nar/gkm1122. PMC 2275076. PMID 18158303.
  12. ↑ Aeby E, Palioura S, Pusnik M, Marazzi J, Lieberman A, Ullu E, Söll D, Schneider A (March 2009). "The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes". Proceedings of the National Academy of Sciences of the United States of America. 106 (13): 5088–92. Bibcode:2009PNAS..106.5088A. doi:10.1073/pnas.0901575106. PMC 2664009. PMID 19279205.
  13. ↑ Yuan J, Palioura S, Salazar JC, Su D, O'Donoghue P, Hohn MJ, Cardoso AM, Whitman WB, Söll D (December 2006). "RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea". Proceedings of the National Academy of Sciences of the United States of America. 103 (50): 18923–7. Bibcode:2006PNAS..10318923Y. doi:10.1073/pnas.0609703104. PMC 1748153. PMID 17142313.
  14. 1 2 3 Schoenmakers E, Chatterjee K (2021-11-29). "Human genetic disorders resulting in systemic selenoprotein deficiency". International Journal of Molecular Sciences. 22 (23) 12927. doi:10.3390/ijms222312927. PMC 8658020. PMID 34884733.
  15. 1 2 "PONTOCEREBELLAR HYPOPLASIA, TYPE 2D; PCH2D". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2026-10-09.

Further reading