SELS_HUMAN
ID SELS_HUMAN Reviewed; 189 AA.
AC Q9BQE4; Q3B771; Q9P0I6;
DT 04-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Selenoprotein S {ECO:0000303|PubMed:27645994};
DE Short=SelS {ECO:0000303|PubMed:12775843};
DE AltName: Full=VCP-interacting membrane protein {ECO:0000303|PubMed:15215856};
GN Name=SELENOS {ECO:0000303|PubMed:27645994, ECO:0000312|HGNC:HGNC:30396};
GN Synonyms=SELS {ECO:0000303|PubMed:12775843},
GN VIMP {ECO:0000303|PubMed:15215856, ECO:0000312|HGNC:HGNC:30396};
GN ORFNames=AD-015, SBBI8;
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], AND SUBCELLULAR LOCATION.
RX PubMed=12775843; DOI=10.1126/science.1083516;
RA Kryukov G.V., Castellano S., Novoselov S.V., Lobanov A.V., Zehtab O.,
RA Guigo R., Gladyshev V.N.;
RT "Characterization of mammalian selenoproteomes.";
RL Science 300:1439-1443(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Li N., Wan T., Zhang W., Cao X.;
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH VCP AND DERL1.
RX PubMed=15215856; DOI=10.1038/nature02656;
RA Ye Y., Shibata Y., Yun C., Ron D., Rapoport T.A.;
RT "A membrane protein complex mediates retro-translocation from the ER lumen
RT into the cytosol.";
RL Nature 429:841-847(2004).
RN [7]
RP INTERACTION WITH DERL1.
RX PubMed=16186510; DOI=10.1073/pnas.0505006102;
RA Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.;
RT "Recruitment of the p97 ATPase and ubiquitin ligases to the site of
RT retrotranslocation at the endoplasmic reticulum membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005).
RN [8]
RP INTERACTION WITH DERL1.
RX PubMed=16186509; DOI=10.1073/pnas.0505014102;
RA Lilley B.N., Ploegh H.L.;
RT "Multiprotein complexes that link dislocation, ubiquitination, and
RT extraction of misfolded proteins from the endoplasmic reticulum membrane.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:14296-14301(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH VCP, AND VIM MOTIF.
RX PubMed=21896481; DOI=10.1074/jbc.m111.274472;
RA Stapf C., Cartwright E., Bycroft M., Hofmann K., Buchberger A.;
RT "The general definition of the p97/valosin-containing protein (VCP)-
RT interacting motif (VIM) delineates a new family of p97 cofactors.";
RL J. Biol. Chem. 286:38670-38678(2011).
RN [12]
RP INTERACTION WITH SELENOK; DERL1; DERL2 AND DERL3.
RX PubMed=22016385; DOI=10.1074/jbc.m111.310920;
RA Shchedrina V.A., Everley R.A., Zhang Y., Gygi S.P., Hatfield D.L.,
RA Gladyshev V.N.;
RT "Selenoprotein K binds multiprotein complexes and is involved in the
RT regulation of endoplasmic reticulum homeostasis.";
RL J. Biol. Chem. 286:42937-42948(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP UBIQUITINATION.
RX PubMed=26138980; DOI=10.1126/science.aab0515;
RA Lin H.C., Ho S.C., Chen Y.Y., Khoo K.H., Hsu P.H., Yen H.C.;
RT "SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced
RT by failed UGA/Sec decoding.";
RL Science 349:91-95(2015).
RN [16]
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).
RN [17]
RP UBIQUITINATION.
RX PubMed=32200094; DOI=10.1016/j.isci.2020.100970;
RA Okumura F., Fujiki Y., Oki N., Osaki K., Nishikimi A., Fukui Y.,
RA Nakatsukasa K., Kamura T.;
RT "Cul5-type ubiquitin ligase KLHDC1 contributes to the elimination of
RT truncated SELENOS produced by failed UGA/Sec decoding.";
RL IScience 23:100970-100970(2020).
RN [18] {ECO:0007744|PDB:6DO4}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 182-187 IN COMPLEX WITH KLHDC2,
RP AND UBIQUITINATION.
RX PubMed=30526872; DOI=10.1016/j.molcel.2018.10.021;
RA Rusnac D.V., Lin H.C., Canzani D., Tien K.X., Hinds T.R., Tsue A.F.,
RA Bush M.F., Yen H.S., Zheng N.;
RT "Recognition of the diglycine C-end degron by CRL2(KLHDC2) ubiquitin
RT ligase.";
RL Mol. Cell 72:813-822(2018).
CC -!- FUNCTION: Involved in the degradation process of misfolded endoplasmic
CC reticulum (ER) luminal proteins. Participates in the transfer of
CC misfolded proteins from the ER to the cytosol, where they are destroyed
CC by the proteasome in a ubiquitin-dependent manner. Probably acts by
CC serving as a linker between DERL1, which mediates the
CC retrotranslocation of misfolded proteins into the cytosol, and the
CC ATPase complex VCP, which mediates the translocation and
CC ubiquitination. {ECO:0000269|PubMed:15215856}.
CC -!- SUBUNIT: Interacts with DERL1 and (via VIM motif) with VCP, suggesting
CC that it forms a membrane complex with DERL1 that serves as a receptor
CC for VCP. Also interacts with DERL2, DERL3 and SELENOK. The SELENOK-
CC SELENOS complex interacts with VCP. Interacts with CCDC47 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BCZ4,
CC ECO:0000269|PubMed:15215856, ECO:0000269|PubMed:16186509,
CC ECO:0000269|PubMed:16186510, ECO:0000269|PubMed:21896481,
CC ECO:0000269|PubMed:22016385}.
CC -!- INTERACTION:
CC Q9BQE4; Q6Q788: APOA5; NbExp=3; IntAct=EBI-398970, EBI-3936819;
CC Q9BQE4; Q01853: Vcp; Xeno; NbExp=4; IntAct=EBI-398970, EBI-80597;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein. Cytoplasm {ECO:0000250}.
CC -!- PTM: Truncated SELENOS proteins produced by failed UGA/Sec decoding are
CC ubiquitinated by the CRL2(KLHDC2) and CRL2(KLHDC3) complexes, which
CC recognizes the glycine (Gly) at the C-terminus of truncated SELENOS
CC proteins (PubMed:26138980, PubMed:30526872). Truncated SELENOS proteins
CC produced by failed UGA/Sec decoding are also ubiquitinated by the
CC CRL5(KLHDC1) complex (PubMed:32200094). {ECO:0000269|PubMed:26138980,
CC ECO:0000269|PubMed:30526872, ECO:0000269|PubMed:32200094}.
CC -!- SIMILARITY: Belongs to the selenoprotein S family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF67483.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAK15708.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY324824; AAP85541.1; -; mRNA.
DR EMBL; AF157317; AAF67483.1; ALT_FRAME; mRNA.
DR EMBL; AF328864; AAK15708.1; ALT_SEQ; mRNA.
DR EMBL; AC023024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005840; AAH05840.2; -; mRNA.
DR EMBL; BC107774; AAI07775.1; -; mRNA.
DR CCDS; CCDS53979.1; -.
DR RefSeq; NP_060915.2; NM_018445.5.
DR RefSeq; NP_982298.2; NM_203472.2.
DR PDB; 2Q2F; X-ray; 1.50 A; A=52-122.
DR PDB; 5KIU; X-ray; 2.20 A; A=49-122.
DR PDB; 5KIY; X-ray; 2.79 A; B=49-122.
DR PDB; 6DO4; X-ray; 2.20 A; C/D=182-187.
DR PDBsum; 2Q2F; -.
DR PDBsum; 5KIU; -.
DR PDBsum; 5KIY; -.
DR PDBsum; 6DO4; -.
DR BMRB; Q9BQE4; -.
DR SMR; Q9BQE4; -.
DR BioGRID; 120934; 60.
DR CORUM; Q9BQE4; -.
DR IntAct; Q9BQE4; 21.
DR MINT; Q9BQE4; -.
DR STRING; 9606.ENSP00000381282; -.
DR iPTMnet; Q9BQE4; -.
DR PhosphoSitePlus; Q9BQE4; -.
DR BioMuta; SELENOS; -.
DR DMDM; 172045769; -.
DR EPD; Q9BQE4; -.
DR jPOST; Q9BQE4; -.
DR MassIVE; Q9BQE4; -.
DR MaxQB; Q9BQE4; -.
DR PaxDb; Q9BQE4; -.
DR PeptideAtlas; Q9BQE4; -.
DR PRIDE; Q9BQE4; -.
DR ProteomicsDB; 78662; -.
DR Antibodypedia; 2437; 148 antibodies from 25 providers.
DR DNASU; 55829; -.
DR Ensembl; ENST00000398226.7; ENSP00000381282.3; ENSG00000131871.15.
DR Ensembl; ENST00000526049.6; ENSP00000433541.1; ENSG00000131871.15.
DR GeneID; 55829; -.
DR KEGG; hsa:55829; -.
DR MANE-Select; ENST00000526049.6; ENSP00000433541.1; NM_018445.6; NP_060915.2.
DR UCSC; uc021sxv.3; human.
DR CTD; 55829; -.
DR DisGeNET; 55829; -.
DR GeneCards; SELENOS; -.
DR HGNC; HGNC:30396; SELENOS.
DR HPA; ENSG00000131871; Low tissue specificity.
DR MIM; 607918; gene.
DR neXtProt; NX_Q9BQE4; -.
DR OpenTargets; ENSG00000131871; -.
DR VEuPathDB; HostDB:ENSG00000131871; -.
DR eggNOG; ENOG502RXYU; Eukaryota.
DR GeneTree; ENSGT00390000015688; -.
DR InParanoid; Q9BQE4; -.
DR OMA; LSLYGWY; -.
DR OrthoDB; 1489479at2759; -.
DR PhylomeDB; Q9BQE4; -.
DR TreeFam; TF329454; -.
DR PathwayCommons; Q9BQE4; -.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; Q9BQE4; -.
DR SIGNOR; Q9BQE4; -.
DR BioGRID-ORCS; 55829; 14 hits in 1088 CRISPR screens.
DR ChiTaRS; SELENOS; human.
DR EvolutionaryTrace; Q9BQE4; -.
DR GeneWiki; SELS_(gene); -.
DR GenomeRNAi; 55829; -.
DR Pharos; Q9BQE4; Tbio.
DR PRO; PR:Q9BQE4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9BQE4; protein.
DR Bgee; ENSG00000131871; Expressed in ileal mucosa and 180 other tissues.
DR ExpressionAtlas; Q9BQE4; baseline and differential.
DR Genevisible; Q9BQE4; HS.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0036513; C:Derlin-1 retrotranslocation complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0036502; C:Derlin-1-VIMP complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0034362; C:low-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:BHF-UCL.
DR GO; GO:0034361; C:very-low-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0016209; F:antioxidant activity; IDA:UniProtKB.
DR GO; GO:0051117; F:ATPase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; TAS:BHF-UCL.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:BHF-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:BHF-UCL.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IDA:BHF-UCL.
DR GO; GO:0045184; P:establishment of protein localization; TAS:UniProtKB.
DR GO; GO:0002865; P:negative regulation of acute inflammatory response to antigenic stimulus; IMP:BHF-UCL.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0046325; P:negative regulation of glucose import; TAS:BHF-UCL.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:BHF-UCL.
DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; IMP:BHF-UCL.
DR GO; GO:0051771; P:negative regulation of nitric-oxide synthase biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0006111; P:regulation of gluconeogenesis; TAS:BHF-UCL.
DR GO; GO:0080164; P:regulation of nitric oxide metabolic process; IMP:BHF-UCL.
DR GO; GO:0009749; P:response to glucose; IEP:UniProtKB.
DR GO; GO:0051775; P:response to redox state; IDA:UniProtKB.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IDA:UniProtKB.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IDA:UniProtKB.
DR InterPro; IPR009703; Selenoprotein_S.
DR PANTHER; PTHR28621; PTHR28621; 1.
DR Pfam; PF06936; Selenoprotein_S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Membrane; Phosphoprotein;
KW Reference proteome; Selenocysteine; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..189
FT /note="Selenoprotein S"
FT /id="PRO_0000097672"
FT TRANSMEM 28..48
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 78..90
FT /note="VCP/p97-interacting motif (VIM)"
FT /evidence="ECO:0000269|PubMed:21896481"
FT REGION 115..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT NON_STD 188
FT /note="Selenocysteine"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT HELIX 53..68
FT /evidence="ECO:0007829|PDB:2Q2F"
FT HELIX 72..121
FT /evidence="ECO:0007829|PDB:2Q2F"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:6DO4"
SQ SEQUENCE 189 AA; 21163 MW; 720DDCC597A7135A CRC64;
MERQEESLSA RPALETEGLR FLHTTVGSLL ATYGWYIVFS CILLYVVFQK LSARLRALRQ
RQLDRAAAAV EPDVVVKRQE ALAAARLKMQ EELNAQVEKH KEKLKQLEEE KRRQKIEMWD
SMQEGKSYKG NAKKPQEEDS PGPSTSSVLK RKSDRKPLRG GGYNPLSGEG GGACSWRPGR
RGPSSGGUG
