The AtlasAmino acidsWritten in a stop codon

SelenocysteineSec · U

The twenty-first amino acid: cysteine with one atom changed, written in a codon that means stop, and built on its own private machinery.

Status Investigation 008Sources 42Reviewed October 2026

Investigation 008 Open in the Atlas Find it on the map

Skeletal formula — every corner and every line end is a carbon, and the hydrogens on carbon are left implied.

Molecule · Sec · 7 heavy atoms

Selenocysteine

C₃H₇NO₂Se168.05 g/mol

The twenty-first amino acid: cysteine with one atom changed, written in a codon that means stop, and built on its own private machinery.

Built fromthe charted ones open their own entry

C3CarbonH7Hydrogen N Nitrogen O2Oxygen Se Selenium

Codes: Sec · U
Formula: C₃H₇NO₂Se
Molar mass: 168.05 g/mol
Systematic name: (2R)-2-amino-3-selanylpropanoic acid
Side chain: Selenomethyl: one carbon and a selenol (–SeH); ionised at the pH of a cell.
Class: Written in a stop codon
In the diet: Made on its own tRNA
Carbon skeleton: Not applicable
pKa: side chain 5.2
Codons: UGA
Main transporters: SELENOP (selenoprotein P), LRP8 (ApoER2), LRP2 (megalin)

Side-chain pKa: Huber and Criddle, Arch Biochem Biophys 1967; later estimates run nearer 5.7. Formula and mass computed from the structure.

In brief

What it is

Cysteine with selenium in place of sulfur: the same skeleton, with a selenol (–SeH) where cysteine has a thiol ¹. It is written in the genetic code as UGA, a codon that otherwise tells the ribosome to stop ².

Why it matters

Most of what selenium does in the body, it does as selenocysteine ³. The 25 human selenoproteins include the glutathione peroxidases, the thioredoxin reductases and the deiodinases that turn thyroid T4 into T3 ^4,5,6.

Where it runs short

When selenium runs short the body rations it: the liver keeps exporting selenoprotein P, the brain and testis hold on to theirs, and inside cells the most vital selenoproteins are made first ^7,8.

Where it turns

The amino acid has a ceiling: once selenoproteins are fully made, more selenium makes no more of them ^9,10. The excess goes elsewhere, selenomethionine into ordinary protein in place of methionine, and enough of it causes selenosis: hair loss, brittle nails, diarrhoea and fatigue ^11,12.

The amino acid has a ceiling. The element does not.

The molecule

Selenocysteine is cysteine with one atom changed. Selenium, the element directly below sulfur in the periodic table, sits where cysteine’s sulfur would, so the side chain is a selenol, –SeH, rather than a thiol ¹.

The selenol gives up its hydrogen far more easily. Its pKa was measured at about 5.2 in 1967 ¹³, and later estimates put it near 5.7, against 8.2 to 8.5 for cysteine’s thiol ¹⁴. At the pH inside a cell a selenol is almost entirely ionised into the reactive selenolate; a thiol mostly is not ¹⁴.

The bigger difference is what happens after it reacts. Selenium forms only weak double bonds to oxygen, so an oxidised selenium is readily reduced back, and a selenium enzyme resists the permanent overoxidation that would end a sulfur one ¹. When mice were given a GPX4 with cysteine in place of selenocysteine, the enzyme was irreversibly overoxidised and the cells became highly sensitive to ferroptosis ¹⁵.

StereochemistryLike cysteine, L-selenocysteine is R rather than S. Nothing about its shape differs from the other L-amino acids: selenium outranks the oxygens of the carboxyl group under the Cahn–Ingold–Prelog rules, which flips the letter.

Ionisation · pHAt the pH of a cell, selenocysteine’s side chain is already ionised. Cysteine’s mostly is not.

Selenocysteine, selenol pKa 5.2Cysteine, thiol pKa 8.18

Fraction of side chains ionised (Se− or S−), from each pKa by the Henderson–Hasselbalch equation, for the free amino acid. An ionised selenol or thiol is the reactive form.

The genetic codeSelenocysteine is written as UGA, which in every other message means stop. It is read as selenocysteine only when the messenger RNA carries a SECIS hairpin further along it.

The 64 codons of the standard genetic code. Codons for selenocysteine are marked.
1st ↓ 2nd →	U	C	A	G	3rd
U	UUUPhe	UCUSer	UAUTyr	UGUCys	U
	UUCPhe	UCCSer	UACTyr	UGCCys	C
	UUALeu	UCASer	UAAStop	UGASec	A
	UUGLeu	UCGSer	UAGStop	UGGTrp	G
C	CUULeu	CCUPro	CAUHis	CGUArg	U
	CUCLeu	CCCPro	CACHis	CGCArg	C
	CUALeu	CCAPro	CAAGln	CGAArg	A
	CUGLeu	CCGPro	CAGGln	CGGArg	G
A	AUUIle	ACUThr	AAUAsn	AGUSer	U
	AUCIle	ACCThr	AACAsn	AGCSer	C
	AUAIle	ACAThr	AAALys	AGAArg	A
	AUGMet	ACGThr	AAGLys	AGGArg	G
G	GUUVal	GCUAla	GAUAsp	GGUGly	U
	GUCVal	GCCAla	GACAsp	GGCGly	C
	GUAVal	GCAAla	GAAGlu	GGAGly	A
	GUGVal	GCGAla	GAGGlu	GGGGly	G

Two stop codons, two solutionsSelenocysteine and pyrrolysine both took over a stop codon. They did it in opposite ways.

	Selenocysteine	Pyrrolysine
Codon	UGA	UAG
How it is made	On its tRNA: serine is loaded first and converted in place ¹⁶	As a free amino acid, from two lysines, then loaded onto its tRNA ^17,18
What the message needs	A SECIS hairpin; without it UGA is read as stop ^19,20	A nearby signal helps but is not required ^20,21
Who uses it	All three domains of life, humans included ²	Some methane-making archaea and a few bacteria; not humans ^22,23
How many proteins	25 in humans ⁴	More than 1,800 known in archaea ²⁴
What it does there	Redox chemistry: peroxides, thioredoxin, thyroid hormone ²	Takes the methyl group off methylamines, the first step in making methane from them ¹⁷

Only one organism is known to use both ²².

Where it comes from

Selenocysteine is the only amino acid in humans that is made on its own transfer RNA ²⁵. Seryl-tRNA synthetase loads serine onto tRNA[Ser]Sec; a kinase, PSTK, phosphorylates it; and selenocysteine synthase, SEPSECS, a vitamin B6 enzyme, replaces the phosphate with selenium, delivered as selenophosphate that selenophosphate synthetase 2 makes from selenide ¹⁶.

The selenium comes from food in several forms and is pooled. The liver is the central organ: it secretes selenoprotein P, which carries one selenocysteine in its larger domain and nine in its smaller one, and the rest of the body takes its selenium from that ^7,26.

Free selenocysteine released when selenoproteins are broken down is not reused as such. Selenocysteine lyase splits it into alanine and selenide, and the selenide goes back to be made into selenophosphate ²⁷.

Made on its own tRNANot taken from the diet as an amino acid: the body builds it from serine on its own tRNA, with selenium supplied as selenophosphate ¹⁶. What the diet must supply is selenium, for which the US recommended allowance for adults is 55 µg a day ¹².

How much

The requirement is for selenium, not selenocysteine: the US recommended allowance for adults is 55 µg a day ¹², and selenoprotein P was fully expressed at a total intake of about 49 µg a day in a repletion trial ⁹.

Where it is in food

Selenium in food varies widely with the soil it grew in, so intakes differ greatly between countries and regions ²⁸.

In the bottle · not sold as itselfSupplements labelled selenium contain selenomethionine, selenite or Se-methylselenocysteine, which is a different molecule despite the name ^11,29. The body makes its own selenocysteine from whatever selenium arrives ¹⁶.

What the body does with it

In 2003 Kryukov and colleagues counted 25 selenoprotein genes in the human genome, many of them misannotated until then because their UGA had been read as a stop ⁴. Most are oxidoreductases, enzymes that move electrons, and in most the selenocysteine sits at the active site ².

The glutathione peroxidases dismantle peroxides, and one of them, GPX4, repairs oxidised fats in membranes and is the main brake on ferroptosis ¹⁵. The thioredoxin reductases reduce thioredoxin through a selenocysteine near their tail, and are targeted by drugs including auranofin, the old gold-based arthritis treatment ^5,30. The three deiodinases are the selenoproteins of thyroid hormone metabolism, converting T4, the main circulating form, into active T3 ⁶.

Selenoprotein P is the courier. Made mostly in the liver, it delivers selenium to the testis and brain through the receptor ApoER2 and is reclaimed by the kidney through megalin ²⁶. In rats about a quarter of the body’s selenium passes through it each day, and mice without it have very little selenium in the brain, the testis and the fetus ³¹.

Under shortage the body ranks its selenoproteins. Cells make the ones most important to them first, and tissues are supplied in order of their selenoprotein P receptors ⁷. In rats fed graded selenium, testis GPX4 activity held at the lowest intakes while GPX1 fell to 28% of normal ⁸.

In three sentences each

Encoded by a stop codon

UGA normally ends a protein. In a selenoprotein message, a hairpin in the 3′ untranslated region, the SECIS element, recruits SECISBP2, the selenocysteine tRNA and its own elongation factor, EEFSEC, and the ribosome inserts selenocysteine instead of stopping ¹⁹.

Built on its own tRNA

Serine is loaded onto a dedicated tRNA, phosphorylated, and then converted to selenocysteine by SEPSECS using selenophosphate, so the amino acid is made in place, already attached, rather than picked up free ¹⁶.

Why selenium and not sulfur

Selenium holds its outer electrons more loosely, so it reacts faster with oxidants, and its oxidised forms are far easier to reduce back; a selenium enzyme survives the oxidation that would permanently disable a sulfur one ^1,15.

How it is made, moved and broken down

Its lifecycle is a loop. Serine goes onto the tRNA, the finished selenocysteine goes into a selenoprotein, and when that protein is broken down selenocysteine lyase returns the selenium to the start ^16,27.

Carbon skeleton · not applicableThe point of breaking it down is the selenium, not the carbon: selenocysteine lyase splits free selenocysteine into alanine and selenide, and the selenide is reused to make new selenoproteins ²⁷.

Building it on the tRNAThe amino acid is assembled while attached to its own transfer RNA ¹⁶.

Serine + tRNA[Ser]Sec
Seryl-tRNA synthetaseSARS1 · ATP
Seryl-tRNA[Ser]Sec
Phosphoseryl-tRNA kinasePSTK · ATP
Phosphoseryl-tRNA[Ser]Sec
Selenocysteine synthaseSEPSECS · vitamin B6
Selenocysteinyl-tRNA[Ser]Sec

Reading UGA as selenocysteineThe message carries its own instruction, the SECIS hairpin, in its 3′ untranslated region ¹⁹.

UGA in a selenoprotein message
SECIS-binding protein 2SECISBP2 · SECIS element
Ribosome paused, SECIS bound
Selenocysteine elongation factorEEFSEC
Selenocysteine in the protein

Recovering the seleniumFree selenocysteine from broken-down proteins is split, and the selenium goes round again ^16,27.

Free selenocysteine
Selenocysteine lyaseSCLY
Alanine + selenide
Selenophosphate synthetase 2SEPHS2 · ATP
Selenophosphate

How it crosses membranes

SELENOP · selenoprotein Pmade in the liver, carried in plasma — ten selenocysteines per molecule; the body’s selenium courier ²⁶
LRP8 · ApoER2testis and brain — the receptor that takes up selenoprotein P, which is how those tissues hold their selenium in deficiency ^7,26
LRP2 · megalinkidney proximal tubule — reclaims selenoprotein P filtered by the kidney ⁷

Where it matters most

Thyroid and the tissues that use its hormone: The deiodinases are selenoproteins, and the thyroid’s own antioxidant defence depends on glutathione peroxidases ⁶.
Liver: The central organ of selenium regulation: it makes most plasma selenoprotein P and, in deficiency, cuts excretion and keeps exporting it at the expense of its own selenoproteins ⁷.
Brain: Holds its selenium in deficiency through ApoER2; GPX4 with selenocysteine is required for the survival of a class of interneurons in mice ^15,26.
Testis and sperm: Protected first in deficiency; loss of testis selenoproteins causes azoospermia in people with SECISBP2 defects ^8,32.
Muscle: Selenoprotein N defects cause a myopathy, and people with SECISBP2 defects develop a similar axial muscular dystrophy ³².

When it goes wrong

Inherited

SECISBP2 deficiency

SECISBP2 · autosomal recessive

The first human defect of selenocysteine insertion, described in 2005 in children with abnormal thyroid hormone metabolism caused by low deiodinase activity ³³. More severe defects reduce most of the 25 selenoproteins and cause a multisystem disorder: azoospermia, an axial muscular dystrophy, photosensitivity, impaired T-cell function and, paradoxically, increased insulin sensitivity ³².

How it is foundThyroid hormone measurements with selenium and selenoprotein levels; confirmed by sequencing SECISBP2 ^32,33.

Inherited

Selenocysteine tRNA mutation

TRU-TCA1-1 · homozygous

One person with a mutation in the selenocysteine tRNA itself had abdominal pain, fatigue, muscle weakness and low plasma selenium; the stress-related selenoproteins fell while the housekeeping ones were kept, through a defect in a single modification of the tRNA ^19,34.

How it is foundSelenoprotein expression in the person’s cells, and sequencing ³⁴.

Inherited

SEPSECS-related neurodevelopmental disorder

SEPSECS · autosomal recessive

Defects in the last enzyme of selenocysteine synthesis cause progressive atrophy of the cerebellum and cerebrum, first found in families of Iraqi and Moroccan Jewish ancestry ²⁵. A 2026 cohort of 27 people described three courses, from severe early onset to mild disease in adulthood, and proposed renaming the condition from pontocerebellar hypoplasia type 2D, since the pons was involved in fewer than half ³⁵.

How it is foundBrain imaging and SEPSECS sequencing; plasma selenium, glutathione, GPX activity and selenoprotein P for monitoring ³⁵.

Inherited

Sedaghatian-type spondylometaphyseal dysplasia

GPX4 · autosomal recessive

Truncating mutations in GPX4 cause a skeletal dysplasia that is lethal in newborns, with heart rhythm and brain abnormalities, showing what the loss of this one selenoprotein does to development ³⁶.

How it is foundExome or targeted sequencing ³⁶.

Too little

Selenium deficiency

Fewer selenoproteins are made, in a fixed order of priority ⁷. In severely selenium-poor regions it is linked to Keshan disease, an endemic cardiomyopathy, and in children to Kashin–Beck disease, a disorder of bone and cartilage ^6,37,38.

How it is foundSelenoprotein P and plasma selenium ^9,10.

Biomarker

Anti-SLA antibodies in autoimmune hepatitis

SEPSECS

The enzyme that makes selenocysteine is the soluble liver antigen of autoimmune hepatitis: some patients make antibodies against SEPSECS, and their disease tends to be more severe ^16,39.

How it is foundAnti-SLA antibody testing, alongside the other autoantibodies of autoimmune hepatitis ³⁹.

Too much

Selenosis

In 2008 a liquid supplement containing 200 times its labelled selenium poisoned 201 people in ten US states, at a median dose of about 41,700 µg a day: diarrhoea, fatigue, hair loss, joint pain and nail damage, with nail changes and fatigue lasting beyond 90 days in many ¹².

How it is foundSerum and urine selenium ¹².

How it is measured

Nobody measures selenocysteine itself in clinical practice. Selenium status is judged by what the selenoproteins do, selenoprotein P concentration and glutathione peroxidase activity, within the range of intake where their synthesis is regulated, and by total selenium, which reflects intake over a wider range but not function ¹⁰.

Selenoprotein PThe selenium transport protein, made by the liver; in a repletion trial it was the last plasma marker to plateau, so it is the best single readout of whether all selenoproteins are being made ⁹.Informative within the range where selenoprotein synthesis is regulated, roughly intakes below 55 µg a day ¹⁰.Once selenoproteins are full it stops rising, so it cannot show excess; with selenomethionine supplements, part of the measured rise is selenomethionine built nonspecifically into the protein ¹¹.
Plasma or serum seleniumTotal selenium, in selenoproteins and in selenomethionine-containing proteins such as albumin ^10,11.Tracks intake over a wide range, including from food, and confirms poisoning: serum averaged 751 µg/L in a supplement outbreak, against a reference limit of 125 ^10,12.Says nothing directly about function; in the Chinese repletion trial it kept rising with dose and never plateaued ⁹.
Glutathione peroxidase activityThe activity of a selenoenzyme, in plasma, platelets or red cells ^9,29.A direct functional measure in deficiency ¹⁰.It plateaus at a lower intake than selenoprotein P, so it calls marginal intakes adequate; platelet activity did not change at all with supplementation in UK adults ^9,29.

Food, supplements and the evidence

Establishedreplicated in people, for a named outcome

Correcting deficiency restores selenoprotein expression, measured as selenoprotein P, until it plateaus ^9,29.
Selenium is toxic in excess, and a mislabelled supplement is enough to do it ¹².

Uncertainsmall, short, mixed, surrogate or preclinical

Selenium for autoimmune thyroid disease: thyroid antibodies fall in several trials, but the effect on hypothyroidism itself is inconsistent ⁴⁰.
Cancer prevention: prospective studies suggested benefit where status was low, but trials have been mixed ⁴¹.

Sold asthe claim on the label, against the evidence

“Selenium for antioxidant protection,” sold to people already replete. Once selenoproteins have plateaued extra selenium makes no more of them, and in people with adequate status supplementation may raise the risk of type 2 diabetes ^9,38,41.

What is strange about it

UGA means stop in almost every human gene. In twenty-five of them, a fold of RNA further down the same message turns it into an instruction to insert selenium ^4,19.

The enzyme that makes selenocysteine was known to medicine before anyone knew what it did: it is the soluble liver antigen, a target of autoantibodies in autoimmune hepatitis ^16,39.

Land plants and fungi have lost selenoproteins entirely, and several groups of land animals, insects and nematodes among them, have replaced most of theirs with cysteine; aquatic organisms keep the largest selenoproteomes ^3,42.

Mice whose GPX4 has cysteine instead of selenocysteine develop normally as embryos, then lose a specific class of interneurons and die of seizures. It took two hundred years after selenium’s discovery to find a role in mammals that sulfur could not fill ¹⁵.

Where it connects

In the Atlas

SeSeleniumElement CysCysteinePolar, uncharged SerSerinePolar, uncharged MetMethionineNonpolar, aliphatic AlaAlanineNonpolar, aliphatic PylPyrrolysineWritten in a stop codon

Topics on the map

On the map

A star in The rest of the amino acids, one of 6. The twenty-first amino acid, written with a stop codon. The cell reads UGA as selenocysteine only when the message carries a hairpin that says so.

Find it on the map

Sources

42 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1
Reich HJ, Hondal RJ. Why nature chose selenium.ACS Chem Biol · 2016 · 11(4):821–841doi:10.1021/acschembio.6b00031 · PMID 26949981
Review: selenium against sulfur, and why selenium enzymes resist permanent oxidation.
2
Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins: molecular pathways and physiological roles.Physiol Rev · 2014 · 94(3):739–777doi:10.1152/physrev.00039.2013 · PMID 24987004
Review of selenoprotein function and the SECIS insertion machinery.
3
Lobanov AV, Hatfield DL, Gladyshev VN. Eukaryotic selenoproteins and selenoproteomes.Biochim Biophys Acta · 2009 · 1790(11):1424–1428doi:10.1016/j.bbagen.2009.05.014 · PMID 19477234
Selenium’s dietary importance is mainly as selenocysteine; plants and fungi lost selenoproteins.
4
Kryukov GV, Castellano S, Novoselov SV, et al. Characterization of mammalian selenoproteomes.Science · 2003 · 300(5624):1439–1443doi:10.1126/science.1083516 · PMID 12775843
The human selenoproteome: 25 selenoproteins, many previously misannotated.
5
Arnér ES. Focus on mammalian thioredoxin reductases: important selenoproteins with versatile functions.Biochim Biophys Acta · 2009 · 1790(6):495–526doi:10.1016/j.bbagen.2009.01.014 · PMID 19364476
Review: TXNRD1–3, their selenocysteine, and the drugs that target them.
6
Souza LSL, Campos RO, Braga JS, et al. Selenium nutritional status and thyroid dysfunction.Arch Endocrinol Metab · 2025 · 69(1):e230348doi:10.20945/2359-4292-2023-0348 · PMID 39992731
Narrative review: deiodinases, glutathione peroxidases, Keshan and Kashin–Beck disease.
7
Burk RF, Hill KE. Regulation of selenium metabolism and transport.Annu Rev Nutr · 2015 · 35:109–134doi:10.1146/annurev-nutr-071714-034250 · PMID 25974694
The selenoprotein hierarchy, the liver’s role, and the ApoER2 and megalin receptors.
8
Schriever SC, Barnes KM, Evenson JK, et al. Selenium requirements are higher for glutathione peroxidase-1 mRNA than gpx1 activity in rat testis.Exp Biol Med (Maywood) · 2009 · 234(5):513–521doi:10.3181/0812-RM-369 · PMID 19234057
Rats: GPX4 held at the lowest selenium intakes, GPX1 fell to 28%. Animal study.
9
Xia Y, Hill KE, Li P, et al. Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects.Am J Clin Nutr · 2010 · 92(3):525–531doi:10.3945/ajcn.2010.29642 · PMID 20573787
98 selenium-deficient adults, 40 weeks: selenoprotein P optimised near 49 µg/day, GPX earlier; plasma selenium never plateaued.
10
Combs GF. Biomarkers of selenium status.Nutrients · 2015 · 7(4):2209–2236doi:10.3390/nu7042209 · PMID 25835046
Review: functional markers below about 55 µg/day; total selenium over wider ranges.
11
Del Castillo Busto ME, Ward-Deitrich C, Evans SO, et al. Selenium speciation studies in cancer patients to evaluate the responses of biomarkers of selenium status to different selenium compounds.Anal Bioanal Chem · 2024 · 416(11):2835–2848doi:10.1007/s00216-024-05141-y · PMID 38286852
Selenite, selenomethionine or Se-methylselenocysteine at 400 µg/day: about 45% of the selenoprotein P rise with selenomethionine was nonspecific incorporation.
12
MacFarquhar JK, Broussard DL, Melstrom P, et al. Acute selenium toxicity associated with a dietary supplement.Arch Intern Med · 2010 · 170(3):256–261doi:10.1001/archinternmed.2009.495 · PMID 20142570
201 cases in ten states from a supplement with 200 times its labelled selenium.
13
Huber RE, Criddle RS. Comparison of the chemical properties of selenocysteine and selenocystine with their sulfur analogs.Arch Biochem Biophys · 1967 · 122(1):164–173doi:10.1016/0003-9861(67)90136-1 · PMID 6076213
The original measurement of selenocysteine’s chemistry against cysteine’s, including the selenol pKa.
14
McGrath NA, Raines RT. Chemoselectivity in chemical biology: acyl transfer reactions with sulfur and selenium.Acc Chem Res · 2011 · 44(9):752–761doi:10.1021/ar200081s · PMID 21639109
Gives pKa 8.5 for the cysteine thiol and 5.7 for the selenocysteine selenol.
15
Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis.Cell · 2018 · 172(3):409–422.e21doi:10.1016/j.cell.2017.11.048 · PMID 29290465
Mice: cysteine-GPX4 is overoxidised; interneurons die and seizures follow. Animal and cell study.
16
Xu XM, Carlson BA, Mix H, et al. Biosynthesis of selenocysteine on its tRNA in eukaryotes.PLoS Biol · 2007 · 5(1):e4doi:10.1371/journal.pbio.0050004 · PMID 17194211
Identified mammalian selenocysteine synthase and the full pathway from serine and selenide.
17
Gaston MA, Zhang L, Green-Church KB, Krzycki JA. The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine.Nature · 2011 · 471(7340):647–650doi:10.1038/nature09918 · PMID 21455182
PylB, PylC and PylD make pyrrolysine from two lysines; required for methane from methylamines.
18
Blight SK, Larue RC, Mahapatra A, et al. Direct charging of tRNA(CUA) with pyrrolysine in vitro and in vivo.Nature · 2004 · 431(7006):333–335doi:10.1038/nature02895 · PMID 15329732
Synthetic pyrrolysine attached as a free molecule by PylS, with ATP.
19
Chavatte L, Lange L, Schweizer U, et al. Understanding the role of tRNA modifications in UGA recoding as selenocysteine in eukaryotes.J Mol Biol · 2025 · 437(16):169017doi:10.1016/j.jmb.2025.169017 · PMID 39988117
Review of SECIS, SECISBP2, EEFSEC and the tRNA modifications that tune recoding.
20
Peiter N, Rother M, Krzycki JA. Recent developments in (archaeal) pyrrolysine and selenocysteine specification and metabolism.Cold Spring Harb Perspect Biol · 2026doi:10.1101/cshperspect.a041979 · PMID 41997725
Review contrasting how the two recoded amino acids are made and read.
21
Longstaff DG, Blight SK, Zhang L, et al. In vivo contextual requirements for UAG translation as pyrrolysine.Mol Microbiol · 2007 · 63(1):229–241doi:10.1111/j.1365-2958.2006.05500.x · PMID 17140411
A downstream PYLIS enhances UAG translation; a UAG with no evolved context was still read at 20%.
22
Zhang Y, Baranov PV, Atkins JF, Gladyshev VN. Pyrrolysine and selenocysteine use dissimilar decoding strategies.J Biol Chem · 2005 · 280(21):20740–20751doi:10.1074/jbc.M501458200 · PMID 15788401
The pyrrolysine trait in a few microbes; one organism with both; four protein families.
23
Srinivasan G, James CM, Krzycki JA. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA.Science · 2002 · 296(5572):1459–1462doi:10.1126/science.1069588 · PMID 12029131
The pylT tRNA with a CUA anticodon and the pylS synthetase; homologs in a Gram-positive bacterium.
24
Kivenson V, Peters SL, Borrel G, et al. An archaeal genetic code with all TAG codons as pyrrolysine.Science · 2025 · 390(6775):eadu2404doi:10.1126/science.adu2404 · PMID 41264687
The Pyl code: 62 sense codons, 21 amino acids; more than 1,800 pyrrolysine proteins.
25
Agamy O, Ben Zeev B, Lev D, et al. Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy.Am J Hum Genet · 2010 · 87(4):538–544doi:10.1016/j.ajhg.2010.09.007 · PMID 20920667
SEPSECS founder mutations in families of Iraqi and Moroccan Jewish ancestry.
26
Burk RF, Hill KE. Selenoprotein P: expression, functions, and roles in mammals.Biochim Biophys Acta · 2009 · 1790(11):1441–1447doi:10.1016/j.bbagen.2009.03.026 · PMID 19345254
Ten selenocysteines; ApoER2 uptake in testis and brain, megalin in kidney.
27
Seale LA, Khadka VS, Menor M, et al. Combined omics reveals that disruption of the selenocysteine lyase gene affects amino acid pathways in mice.Nutrients · 2019 · 11(11):2584doi:10.3390/nu11112584 · PMID 31717805
Selenocysteine lyase splits selenocysteine into selenide and alanine for reuse. Mouse study.
28
Rayman MP. Food-chain selenium and human health: emphasis on intake.Br J Nutr · 2008 · 100(2):254–268doi:10.1017/S0007114508939830 · PMID 18346308
Review: how selenium enters the food chain and how much intakes vary.
29
Hurst R, Armah CN, Dainty JR, et al. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial.Am J Clin Nutr · 2010 · 91(4):923–931doi:10.3945/ajcn.2009.28169 · PMID 20181815
119 UK adults, 12 weeks of selenium yeast or selenium-enriched onion: selenoprotein P rose, platelet GPx did not.
30
Bak DW, Gao J, Wang C, Weerapana E. A quantitative chemoproteomic platform to monitor selenocysteine reactivity within a complex proteome.Cell Chem Biol · 2018 · 25(9):1157–1167.e4doi:10.1016/j.chembiol.2018.05.017 · PMID 29983274
Uses selenocysteine’s low pKa to profile selenoproteins; auranofin as a thioredoxin reductase inhibitor.
31
Burk RF, Hill KE. Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis.Annu Rev Nutr · 2005 · 25:215–235doi:10.1146/annurev.nutr.24.012003.132120 · PMID 16011466
About a quarter of whole-body selenium passes through it daily in rats; knockout mice lose brain and testis selenium.
32
Schoenmakers E, Agostini M, Mitchell C, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.J Clin Invest · 2010 · 120(12):4220–4235doi:10.1172/JCI43653 · PMID 21084748
Multisystem disorder from reduced synthesis of most selenoproteins.
33
Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism.Nat Genet · 2005 · 37(11):1247–1252doi:10.1038/ng1654 · PMID 16228000
The first inherited selenocysteine incorporation defect in humans.
34
Schoenmakers E, Carlson B, Agostini M, et al. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis.J Clin Invest · 2016 · 126(3):992–996doi:10.1172/JCI84747 · PMID 26854926
One proband; stress-related selenoproteins fall, housekeeping ones are kept.
35
Killam BY, Knol MJ, Fradejas-Villar N, et al. Disease characteristics of SEPSECS deficiency: an international, retrospective, multicenter cohort study.Genet Med · 2026 · 28(11):102684doi:10.1016/j.gim.2026.102684 · PMID 42603098
27 people; three clinical courses; proposes renaming from PCH2D.
36
Smith AC, Mears AJ, Bunker R, et al. Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia.J Med Genet · 2014 · 51(7):470–474doi:10.1136/jmedgenet-2013-102218 · PMID 24706940
Truncating GPX4 mutations in two families with this neonatal-lethal dysplasia.
37
Pierce WG, Mackrill JJ. Selenium in aging and longevity.Biochimie · 2026doi:10.1016/j.biochi.2026.09.002 · PMID 42710827
Review: deficiency and excess, including Keshan disease and selenosis.
38
Wang P, Chen B, Huang Y, et al. Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses.Front Nutr · 2023 · 10:1263853doi:10.3389/fnut.2023.1263853 · PMID 37781125
Umbrella review: mostly low-quality evidence; possible higher type 2 diabetes risk; no general supplementation.
39
Kramer M, Mele F, Jovic S, et al. Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.J Clin Invest · 2025 · 135(2):e183776doi:10.1172/JCI183776 · PMID 39817450
SEPSECS is the soluble liver antigen; anti-SepSecS antibodies go with a more severe phenotype.
40
Linn YH, Aziz S, Mok SL. Selenium status and supplementation in thyroid disorders: a narrative review of current evidence.J Trace Elem Med Biol · 2025 · 92:127799doi:10.1016/j.jtemb.2025.127799 · PMID 41206976
Antibodies fall in autoimmune thyroiditis; effects on hypothyroidism inconsistent.
41
Rayman MP. Selenium and human health.Lancet · 2012 · 379(9822):1256–1268doi:10.1016/S0140-6736(11)61452-9 · PMID 22381456
Review: the U-shaped relationship with status; supplementation may harm the replete.
42
Lobanov AV, Fomenko DE, Zhang Y, et al. Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life.Genome Biol · 2007 · 8(9):R198doi:10.1186/gb-2007-8-9-r198 · PMID 17880704
Independent selenoprotein losses on land; replacement of selenocysteine by cysteine.

This is education, not medical advice. Nothing on this page is written with knowledge of your history, your medications or your risks, and nothing here is a dose. Do not start or stop any treatment on the basis of it — talk to your own physician. Read the full medical disclaimer.

In brief

The molecule

Where it comes from

What the body does with it

Encoded by a stop codon

Built on its own tRNA

Why selenium and not sulfur

How it is made, moved and broken down

Where it matters most

When it goes wrong

SECISBP2 deficiency

Selenocysteine tRNA mutation

SEPSECS-related neurodevelopmental disorder

Sedaghatian-type spondylometaphyseal dysplasia

Selenium deficiency

Anti-SLA antibodies in autoimmune hepatitis

Selenosis

How it is measured

Food, supplements and the evidence

What is strange about it

Where it connects

Sources

Every source, in your inbox.