SELT_HUMAN
ID SELT_HUMAN Reviewed; 195 AA.
AC P62341; O95904; Q8IY80; Q9CZ45; Q9NZJ3;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Thioredoxin reductase-like selenoprotein T {ECO:0000305};
DE Short=SelT {ECO:0000303|PubMed:27645994};
DE EC=1.8.1.9 {ECO:0000250|UniProtKB:Q1H5H1};
DE Flags: Precursor;
GN Name=SELENOT {ECO:0000303|PubMed:27645994, ECO:0000312|HGNC:HGNC:18136};
GN Synonyms=SELT {ECO:0000303|PubMed:27645994};
GN ORFNames=UNQ150/PRO176 {ECO:0000312|EMBL:AAQ88462.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10567350; DOI=10.1074/jbc.274.48.33888;
RA Kryukov G.V., Kryukov V.M., Gladyshev V.N.;
RT "New mammalian selenocysteine-containing proteins identified with an
RT algorithm that searches for selenocysteine insertion sequence elements.";
RL J. Biol. Chem. 274:33888-33897(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Mei G., Yu W., Gibbs R.A.;
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Brain, Pancreas, Skin, and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=23913443; DOI=10.1210/en.2013-1167;
RA Prevost G., Arabo A., Jian L., Quelennec E., Cartier D., Hassan S.,
RA Falluel-Morel A., Tanguy Y., Gargani S., Lihrmann I., Kerr-Conte J.,
RA Lefebvre H., Pattou F., Anouar Y.;
RT "The PACAP-regulated gene selenoprotein T is abundantly expressed in mouse
RT and human beta-cells and its targeted inactivation impairs glucose
RT tolerance.";
RL Endocrinology 154:3796-3806(2013).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION, INDUCTION BY NEUROTOXINS, MUTAGENESIS OF SEC-49, AND INVOLVEMENT
RP IN DISEASE.
RX PubMed=26866473; DOI=10.1089/ars.2015.6478;
RA Boukhzar L., Hamieh A., Cartier D., Tanguy Y., Alsharif I., Castex M.,
RA Arabo A., El Hajji S., Bonnet J.J., Errami M., Falluel-Morel A.,
RA Chagraoui A., Lihrmann I., Anouar Y.;
RT "Selenoprotein T exerts an essential oxidoreductase activity that protects
RT dopaminergic neurons in mouse models of Parkinson's Disease.";
RL Antioxid. Redox Signal. 24:557-574(2016).
RN [8]
RP NOMENCLATURE.
RX PubMed=27645994; DOI=10.1074/jbc.m116.756155;
RA Gladyshev V.N., Arner E.S., Berry M.J., Brigelius-Flohe R., Bruford E.A.,
RA Burk R.F., Carlson B.A., Castellano S., Chavatte L., Conrad M.,
RA Copeland P.R., Diamond A.M., Driscoll D.M., Ferreiro A., Flohe L.,
RA Green F.R., Guigo R., Handy D.E., Hatfield D.L., Hesketh J., Hoffmann P.R.,
RA Holmgren A., Hondal R.J., Howard M.T., Huang K., Kim H.Y., Kim I.Y.,
RA Koehrle J., Krol A., Kryukov G.V., Lee B.J., Lee B.C., Lei X.G., Liu Q.,
RA Lescure A., Lobanov A.V., Loscalzo J., Maiorino M., Mariotti M.,
RA Sandeep Prabhu K., Rayman M.P., Rozovsky S., Salinas G., Schmidt E.E.,
RA Schomburg L., Schweizer U., Simonovic M., Sunde R.A., Tsuji P.A.,
RA Tweedie S., Ursini F., Whanger P.D., Zhang Y.;
RT "Selenoprotein gene nomenclature.";
RL J. Biol. Chem. 291:24036-24040(2016).
CC -!- FUNCTION: Selenoprotein with thioredoxin reductase-like oxidoreductase
CC activity (By similarity). Protects dopaminergic neurons against
CC oxidative stress and cell death (PubMed:26866473). Involved in
CC ADCYAP1/PACAP-induced calcium mobilization and neuroendocrine secretion
CC (By similarity). Plays a role in fibroblast anchorage and redox
CC regulation (By similarity). In gastric smooth muscle, modulates the
CC contraction processes through the regulation of calcium release and
CC MYLK activation (By similarity). In pancreatic islets, involved in the
CC control of glucose homeostasis, contributes to prolonged ADCYAP1/PACAP-
CC induced insulin secretion (By similarity).
CC {ECO:0000250|UniProtKB:P62342, ECO:0000250|UniProtKB:Q1H5H1,
CC ECO:0000269|PubMed:26866473}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + NADP(+) = [thioredoxin]-disulfide +
CC H(+) + NADPH; Xref=Rhea:RHEA:20345, Rhea:RHEA-COMP:10698, Rhea:RHEA-
CC COMP:10700, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.8.1.9;
CC Evidence={ECO:0000250|UniProtKB:Q1H5H1};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q1H5H1}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in the endocrine
CC pancreas. {ECO:0000269|PubMed:23913443}.
CC -!- INDUCTION: Induced by Parkinson disease-inducing neurotoxins such as 1-
CC methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
CC {ECO:0000269|PubMed:26866473}.
CC -!- PTM: May contain a selenide-sulfide bond between Cys-46 and Sec-49.
CC This bond is speculated to serve as redox-active pair (By similarity).
CC {ECO:0000250}.
CC -!- DISEASE: Note=mRNA levels are increased more than 200-folds in the
CC caudate putamen from Parkinson disease (PD) patients compared to
CC control subjects. In conditional brain knockout mice, treatment with
CC PD-inducing neurotoxins provoke rapid and severe parkinsonian-like
CC motor defects. {ECO:0000269|PubMed:26866473}.
CC -!- SIMILARITY: Belongs to the SelWTH family. Selenoprotein T subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD20063.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAF13696.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAQ88462.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAQ88463.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF195141; AAF13696.1; ALT_FRAME; mRNA.
DR EMBL; AF131856; AAD20063.1; ALT_SEQ; mRNA.
DR EMBL; AY358095; AAQ88462.1; ALT_SEQ; mRNA.
DR EMBL; AY358096; AAQ88463.1; ALT_SEQ; mRNA.
DR EMBL; BC006012; AAH06012.2; -; mRNA.
DR EMBL; BC008411; AAH08411.2; -; mRNA.
DR EMBL; BC009556; AAH09556.2; -; mRNA.
DR EMBL; BC009611; AAH09611.2; -; mRNA.
DR EMBL; BC026350; AAH26350.2; -; mRNA.
DR EMBL; BC036738; AAH36738.3; -; mRNA.
DR EMBL; BC071699; AAH71699.1; -; mRNA.
DR CCDS; CCDS46936.1; -.
DR RefSeq; NP_057359.2; NM_016275.3.
DR BioGRID; 119693; 42.
DR IntAct; P62341; 12.
DR MINT; P62341; -.
DR STRING; 9606.ENSP00000418910; -.
DR iPTMnet; P62341; -.
DR PhosphoSitePlus; P62341; -.
DR SwissPalm; P62341; -.
DR BioMuta; SELENOT; -.
DR DMDM; 190358765; -.
DR EPD; P62341; -.
DR jPOST; P62341; -.
DR MassIVE; P62341; -.
DR MaxQB; P62341; -.
DR PaxDb; P62341; -.
DR PeptideAtlas; P62341; -.
DR PRIDE; P62341; -.
DR ProteomicsDB; 57398; -.
DR Antibodypedia; 48150; 67 antibodies from 15 providers.
DR DNASU; 51714; -.
DR Ensembl; ENST00000471696.6; ENSP00000418910.1; ENSG00000198843.14.
DR GeneID; 51714; -.
DR KEGG; hsa:51714; -.
DR MANE-Select; ENST00000471696.6; ENSP00000418910.1; NM_016275.5; NP_057359.2.
DR CTD; 51714; -.
DR DisGeNET; 51714; -.
DR GeneCards; SELENOT; -.
DR HGNC; HGNC:18136; SELENOT.
DR HPA; ENSG00000198843; Low tissue specificity.
DR MIM; 607912; gene.
DR neXtProt; NX_P62341; -.
DR OpenTargets; ENSG00000198843; -.
DR VEuPathDB; HostDB:ENSG00000198843; -.
DR eggNOG; KOG3286; Eukaryota.
DR GeneTree; ENSGT00390000011725; -.
DR InParanoid; P62341; -.
DR OMA; CISXGYR; -.
DR OrthoDB; 1542197at2759; -.
DR PhylomeDB; P62341; -.
DR PathwayCommons; P62341; -.
DR SignaLink; P62341; -.
DR BioGRID-ORCS; 51714; 15 hits in 1035 CRISPR screens.
DR ChiTaRS; SELENOT; human.
DR GeneWiki; SELT; -.
DR GenomeRNAi; 51714; -.
DR Pharos; P62341; Tbio.
DR PRO; PR:P62341; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P62341; protein.
DR Bgee; ENSG00000198843; Expressed in islet of Langerhans and 200 other tissues.
DR ExpressionAtlas; P62341; baseline and differential.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008430; F:selenium binding; NAS:UniProtKB.
DR GO; GO:0004791; F:thioredoxin-disulfide reductase activity; ISS:UniProtKB.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:UniProtKB.
DR GO; GO:0098869; P:cellular oxidant detoxification; ISS:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0031016; P:pancreas development; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0060124; P:positive regulation of growth hormone secretion; ISS:UniProtKB.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR GO; GO:0001514; P:selenocysteine incorporation; NAS:UniProtKB.
DR InterPro; IPR011893; Selenoprotein_Rdx-typ.
DR InterPro; IPR019389; Selenoprotein_T.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR13544; PTHR13544; 1.
DR Pfam; PF10262; Rdx; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR TIGRFAMs; TIGR02174; CXXU_selWTH; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Membrane; NADP; Oxidoreductase; Redox-active center;
KW Reference proteome; Selenocysteine; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..195
FT /note="Thioredoxin reductase-like selenoprotein T"
FT /id="PRO_0000032290"
FT TRANSMEM 85..103
FT /note="Helical"
FT /evidence="ECO:0000255"
FT NON_STD 49
FT /note="Selenocysteine"
FT CROSSLNK 46..49
FT /note="Cysteinyl-selenocysteine (Cys-Sec)"
FT /evidence="ECO:0000255"
FT MUTAGEN 49
FT /note="U->S: Increases ROS levels induced by neurotoxins."
FT /evidence="ECO:0000269|PubMed:26866473"
FT CONFLICT 16..18
FT /note="RSE -> WSD (in Ref. 4; AAH09611)"
FT /evidence="ECO:0000305"
FT CONFLICT 26
FT /note="V -> M (in Ref. 4; AAH09611)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 195 AA; 22324 MW; 5B7949FA7711AE9D CRC64;
MRLLLLLLVA ASAMVRSEAS ANLGGVPSKR LKMQYATGPL LKFQICVSUG YRRVFEEYMR
VISQRYPDIR IEGENYLPQP IYRHIASFLS VFKLVLIGLI IVGKDPFAFF GMQAPSIWQW
GQENKVYACM MVFFLSNMIE NQCMSTGAFE ITLNDVPVWS KLESGHLPSM QQLVQILDNE
MKLNVHMDSI PHHRS
