Selenocysteine (symbol Sec or U, in older publications also as
Se-Cys) is the 21st proteinogenic amino acid.
Selenocysteine exists naturally in all three domains of life, but not
in every lineage, as a building block of selenoproteins.
Selenocysteine is a cysteine analogue with a selenium-containing
selenol group in place of the sulfur-containing thiol group.
Selenocysteine is present in several enzymes (for example glutathione
peroxidases, tetraiodothyronine 5' deiodinases, thioredoxin
reductases, formate dehydrogenases, glycine reductases,
selenophosphate synthetase 2, methionine-R-sulfoxide reductase B1
(SEPX1), and some hydrogenases).
Selenocysteine was discovered by biochemist Thressa Stadtman at the
National Institutes of Health.
4 See also
6 Further reading
Selenocysteine has a structure similar to that of cysteine, but with
an atom of selenium taking the place of the usual sulfur, forming a
selenol group which is deprotonated at physiological pH. (Like other
natural proteinogenic amino acids, cysteine and selenocysteine have L
chirality in the older D/L notation based on homology to D- and
L-glyceraldehyde. In the newer R/S system of designating chirality,
based on the atomic numbers of atoms near the asymmetric carbon, they
have R chirality, because of the presence sulfur (resp. selenium) as a
second neighbor to the asymmetric carbon. The remaining chiral amino
acids, having only lighter atoms in that position, have S chirality.)
Proteins which contain one or more selenocysteine residues are called
selenoproteins. Most selenoproteins contain a single selenocysteine
residue. Selenoproteins which depend on selenocysteine's catalytic
activity are called selenoenzymes. Selenoenzymes have been found to
employ catalytic triad structures that influence the nucleophilicity
of the active site selenocysteine.
Selenocysteine has both a lower pKa (5.47) and a lower reduction
potential than cysteine. These properties make it very suitable in
proteins that are involved in antioxidant activity.
Although it is found in the three domains of life, it is not universal
in all organisms. Unlike other amino acids present in biological
proteins, selenocysteine is not coded for directly in the genetic
code. Instead, it is encoded in a special way by a UGA codon, which
is normally a stop codon. Such a mechanism is called translational
recoding and its efficiency depends on the selenoprotein being
synthesized and on translation initiation factors. When cells are
grown in the absence of selenium, translation of selenoproteins
terminates at the UGA codon, resulting in a truncated, nonfunctional
enzyme. The UGA codon is made to encode selenocysteine by the presence
of a selenocysteine insertion sequence (SECIS) in the mRNA. The SECIS
element is defined by characteristic nucleotide sequences and
secondary structure base-pairing patterns. In bacteria, the SECIS
element is typically located immediately following the UGA codon
within the reading frame for the selenoprotein. In
Archaea and in
SECIS element is in the 3' untranslated region (3'
UTR) of the mRNA and can direct multiple UGA codons to encode
Again unlike the other amino acids, no free pool of selenocysteine
exists in the cell. Its high reactivity would cause damage to
cells.[original research?] Instead, cells store selenium in the less
reactive selenide form (H2Se).
Selenocysteine synthesis occurs on a
specialized tRNA, which also functions to incorporate it into nascent
The primary and secondary structure of selenocysteine-specific tRNA,
tRNASec, differ from those of standard tRNAs in several respects, most
notably in having an 8-base (bacteria) or 10-base
(eukaryotes)[Archaea?] pair acceptor stem, a long variable region arm,
and substitutions at several well-conserved base positions. The
selenocysteine tRNAs are initially charged with serine by seryl-tRNA
ligase, but the resulting Ser-tRNASec is not used for translation
because it is not recognised by the normal translation elongation
EF-Tu in bacteria, eEF1A in eukaryotes).[Archaea?]
Rather, the tRNA-bound seryl residue is converted to a selenocysteine
residue by the pyridoxal phosphate-containing enzyme selenocysteine
synthase. In eukaryotes and archaea, two enzymes are required to
convert tRNA-bound seryl residue into tRNA selenocysteinyl residue:
PSTK [O-phosphoseryl-tRNA[Ser]Sec kinase]) and selenocysteine
synthase. Finally, the resulting Sec-tRNASec is specifically
bound to an alternative translational elongation factor (SelB or mSelB
(or eEFSec)), which delivers it in a targeted manner to the ribosomes
translating mRNAs for selenoproteins. The specificity of this delivery
mechanism is brought about by the presence of an extra protein domain
(in bacteria, SelB) or an extra subunit (SBP2 for eukaryotic
mSelB/eEFSec)[Archaea?] which bind to the corresponding RNA secondary
structures formed by the SECIS elements in selenoprotein mRNAs.
As of 2016, fifty-four human proteins are known to contain
Selenocysteine derivatives γ-glutamyl-
Se-methylselenocysteine occur naturally in plants of the genera Allium
Biotechnological applications of selenocysteine include use of
73Se-labeled Sec (half-life of 73Se = 7.2 hours) in positron emission
tomography (PET) studies and 75Se-labeled Sec (half-life of 75Se =
118.5 days) in specific radiolabeling, facilitation of phase
determination by multiwavelength anomalous diffraction in X-ray
crystallography of proteins by introducing Sec alone, or Sec together
with selenomethionine (SeMet), and incorporation of the stable 77Se
isotope, which has a nuclear spin of 1/2 and can be used for
high-resolution NMR, among others.
Pyrrolysine, another amino acid not in the basic set of 20.
Selenomethionine, another selenium-containing amino acid, which is
randomly substituted for methionine.
^ Merck Index, 12th Edition, 8584
^ "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB
Joint Commission on Biochemical Nomenclature. 1983. Archived from the
original on 9 October 2008. Retrieved 5 March 2018.
^ "IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and
Nomenclature Committee of IUBMB (NC-IUBMB)" (PDF). European Journal of
Biochemistry. 264 (2): 607–609. 17 August 1999.
^ a b Johansson, L.; Gafvelin, G.; Amér, E. S. J. (30 October 2005).
Selenocysteine in Proteins — Properties and Biotechnological Use".
Biochimica et Biophysica Acta. 1726 (1): 1–13.
doi:10.1016/j.bbagen.2005.05.010. (Subscription required
^ Stadtman, Therese (Mar 8, 1974). "
Selenium Biochemistry". Science.
183 (4128): 915–22. Bibcode:1974Sci...183..915S.
doi:10.1126/science.183.4128.915. PMID 4605100.
^ Roy, G.; Sarma, B. K.; Phadnis, P.P.; Mugesh, G. (2005).
"Selenium-containing enzymes in mammals: chemical perspectives".
Journal of Chemical Sciences. 117 (4): 287–303.
^ Byun, B. J.; Kang, Y. K. (2011). "Conformational Preferences and pKa
Selenocysteine Residue". Biopolymers. 95 (5): 345–353.
doi:10.1002/bip.21581. PMID 21213257.
^ Longtin, R (2004). "A forgotten debate: Is selenocysteine the 21st
amino acid?" (PDF). Journal of the National Cancer Institute. 96 (7):
504–5. doi:10.1093/jnci/96.7.504. PMID 15069108.
^ Böck A.; Forchhammer, K.; Heider, J.; Baron, C. (1991).
Selenoprotein Synthesis: An Expansion of the Genetic Code". Trends in
Biochemical Sciences. 16 (12): 463–467.
doi:10.1016/0968-0004(91)90180-4. PMID 1838215.
^ Baranov P. V.; Gesteland R. F.; Atkins, J. F. (2002). "Recoding:
Translational Bifurcations in Gene Expression". Gene. 286 (5):
^ Donovan, J.; Copeland, P. R. (2010). "The Efficiency of
Selenocysteine Incorporation is Regulated by Translation Initiation
Factors". Journal of Molecular Biology. 400 (4): 659–664.
doi:10.1016/j.jmb.2010.05.026. PMC 3721751 .
^ Atkins, J. F. (2009). Recoding: Expansion of Decoding Rules Enriches
Gene Expression. Springer. p. 31.
^ Berry, M. J.; Banu, L.; Harney, J. W.; Larsen, P. R. (1993).
"Functional Characterization of the Eukaryotic SECIS Elements which
Selenocysteine Insertion at UGA Codons" (PDF). The EMBO
Journal. 12 (8): 3315–3322. PMC 413599 .
^ Xu, Xue-Ming; Carlson, Bradley A; Mix, Heiko; Zhang, Yan; Saira,
Kazima; Glass, Richard S; Berry, Marla J; Gladyshev, Vadim N;
Hatfield, Dolph L. "Biosynthesis of
Selenocysteine on Its tRNA in
Eukaryotes". PLoS Biology. 5 (1): e4.
doi:10.1371/journal.pbio.0050004. PMC 1717018 .
^ Yuan, Jing; Palioura, Sotiria; Salazar, Juan Carlos; Su, Dan;
O'Donoghue, Patrick; Hohn, Michael J.; Cardoso, Alexander Machado;
Whitman, William B.; Söll, Dieter (2006-12-12). "RNA-dependent
conversion of phosphoserine forms selenocysteine in eukaryotes and
archaea". Proceedings of the National Academy of Sciences. 103 (50):
18923–18927. doi:10.1073/pnas.0609703104. ISSN 0027-8424.
PMC 1748153 . PMID 17142313.
^ Romagné, Frédéric; Santesmasses, Didac; White, Louise; Sarangi,
Gaurab K.; Mariotti, Marco; Hübler, Ron; Weihmann, Antje; Parra,
Genís; Gladyshev, Vadim N. (2014-01-01). "SelenoDB 2.0: annotation of
selenoprotein genes in animals and their genetic diversity in humans".
Nucleic Acids Research. 42 (D1): D437–D443. doi:10.1093/nar/gkt1045.
ISSN 0305-1048. PMC 3965025 . PMID 24194593. Archived
from the original on June 5, 2016.
^ Block, E. (2010). Garlic and Other Alliums: The Lore and the
Science. Royal Society of Chemistry. ISBN 0-85404-190-7.
Zinoni, F.; Birkmann, A.; Stadtman, T. C.; Bock, A. (1986).
"Nucleotide Sequence and Expression of the Selenocysteine-Containing
Polypeptide of Formate Dehydrogenase (Formate-Hydrogen-Lyase-Linked)
from Escherichia coli". PNAS. 83 (13): 4650–4654.
PMC 323799 . PMID 2941757.
Zinoni, F.; Birkmann, A.; Leinfelder, W.; Bock, A. (1987).
"Cotranslational Insertion of
Selenocysteine into Formate
Dehydrogenase from Escherichia coli Directed by a UGA Codon". PNAS. 84
(10): 3156–3160. Bibcode:1987PNAS...84.3156Z.
doi:10.1073/pnas.84.10.3156. PMC 304827 .
Cone, B. E.; del Rio, R. M.; Davis, J. N.; Stadtman, T. C. (1976).
"Chemical Characterization of the
Selenoprotein Component of
Clostridial Glycine Reductase: Identification of
Selenocysteine as the
Organoselenium Moiety". PNAS. 73 (8): 2659–2663.
PMC 430707 . PMID 1066676.
Fenyö, D.; Beavis, R.C. (2015). "Selenocysteine: Wherefore Art
Thou?". J Proteome Res. doi:10.1021/acs.jproteome.5b01028.