LY6E_MOUSE
ID LY6E_MOUSE Reviewed; 136 AA.
AC Q64253; Q61128; Q99JA5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Lymphocyte antigen 6E {ECO:0000305};
DE Short=Ly-6E;
DE AltName: Full=Stem cell antigen 2;
DE AltName: Full=Thymic shared antigen 1;
DE Short=TSA-1;
DE Flags: Precursor;
GN Name=Ly6e {ECO:0000312|MGI:MGI:106651}; Synonyms=Ly67, Sca-2, Tsa-1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=8258699;
RA Macneil I., Kennedy J., Godfrey D.I., Jenkins N.A., Masciantonio M.,
RA Mineo C., Gilbert D.J., Copeland N.G., Boyd R.L., Zlotnik A.;
RT "Isolation of a cDNA encoding thymic shared antigen-1. A new member of the
RT Ly6 family with a possible role in T cell development.";
RL J. Immunol. 151:6913-6923(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=8202484; DOI=10.1073/pnas.91.12.5296;
RA Classon B.J., Coverdale L.;
RT "Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell
RT surface proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:5296-5300(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=8662090; DOI=10.1007/bf02602589;
RA Classon B.J., Coverdale L.;
RT "Genomic organization and expression of mouse thymic shared antigen-1 (TSA-
RT 1): evidence for a processed pseudogene.";
RL Immunogenetics 44:222-226(1996).
RN [4] {ECO:0000312|Ensembl:ENSMUSP00000056703, ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000056703,
RC ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5] {ECO:0000312|EMBL:CAJ18428.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000312|EMBL:AAH05684.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=2987354;
RA Flood P.M., Murphy D.B., Horowitz M., LeClair K.P., Smith F.R.,
RA Stockert E., Palladino M.A. Jr., DeLeo A.B.;
RT "A monoclonal antibody that recognizes an Ly-6-linked antigen inhibits the
RT generation of functionally active T cell subsets.";
RL J. Immunol. 135:63-72(1985).
RN [8]
RP INDUCTION BY INTERFERON GAMMA.
RX PubMed=3040423; DOI=10.1002/eji.1830170816;
RA Dumont F.J., Dijkmans R., Palfree R.G., Boltz R.D., Coker L.;
RT "Selective up-regulation by interferon-gamma of surface molecules of the
RT Ly-6 complex in resting T cells: the Ly-6A/E and TAP antigens are
RT preferentially enhanced.";
RL Eur. J. Immunol. 17:1183-1191(1987).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=1531995;
RA Godfrey D.I., Masciantonio M., Tucek C.L., Malin M.A., Boyd R.L., Hugo P.;
RT "Thymic shared antigen-1. A novel thymocyte marker discriminating immature
RT from mature thymocyte subsets.";
RL J. Immunol. 148:2006-2011(1992).
RN [10]
RP FUNCTION.
RX PubMed=7499840;
RA Saitoh S., Kosugi A., Noda S., Yamamoto N., Ogata M., Minami Y., Miyake K.,
RA Hamaoka T.;
RT "Modulation of TCR-mediated signaling pathway by thymic shared antigen-1
RT (TSA-1)/stem cell antigen-2 (Sca-2).";
RL J. Immunol. 155:5574-5581(1995).
RN [11]
RP FUNCTION IN T-CELL DEVELOPMENT.
RX PubMed=8642345; DOI=10.1084/jem.183.5.2355;
RA Noda S., Kosugi A., Saitoh S., Narumiya S., Hamaoka T.;
RT "Protection from anti-TCR/CD3-induced apoptosis in immature thymocytes by a
RT signal through thymic shared antigen-1/stem cell antigen-2.";
RL J. Exp. Med. 183:2355-2360(1996).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CD247.
RX PubMed=9575182; DOI=10.1074/jbc.273.20.12301;
RA Kosugi A., Saitoh S., Noda S., Miyake K., Yamashita Y., Kimoto M.,
RA Ogata M., Hamaoka T.;
RT "Physical and functional association between thymic shared antigen-1/stem
RT cell antigen-2 and the T cell receptor complex.";
RL J. Biol. Chem. 273:12301-12306(1998).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=11784869; DOI=10.1128/mcb.22.3.946-952.2002;
RA Zammit D.J., Berzins S.P., Gill J.W., Randle-Barrett E.S., Barnett L.,
RA Koentgen F., Lambert G.W., Harvey R.P., Boyd R.L., Classon B.J.;
RT "Essential role for the lymphostromal plasma membrane Ly-6 superfamily
RT molecule thymic shared antigen 1 in development of the embryonic adrenal
RT gland.";
RL Mol. Cell. Biol. 22:946-952(2002).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [15]
RP FUNCTION, AND INTERACTION WITH CHRNA4.
RX PubMed=26276394; DOI=10.1074/jbc.m115.647248;
RA Wu M., Puddifoot C.A., Taylor P., Joiner W.J.;
RT "Mechanisms of inhibition and potentiation of alpha4beta2 nicotinic
RT acetylcholine receptors by members of the Ly6 protein family.";
RL J. Biol. Chem. 290:24509-24518(2015).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28679758; DOI=10.1128/jvi.00832-17;
RA Bacquin A., Bireau C., Tanguy M., Romanet C., Vernochet C., Dupressoir A.,
RA Heidmann T.;
RT "A Cell Fusion-Based Screening Method Identifies
RT Glycosylphosphatidylinositol-Anchored Protein Ly6e as the Receptor for
RT Mouse Endogenous Retroviral Envelope Syncytin-A.";
RL J. Virol. 91:0-0(2017).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29500366; DOI=10.1038/s41598-018-22040-2;
RA Langford M.B., Outhwaite J.E., Hughes M., Natale D.R.C., Simmons D.G.;
RT "Deletion of the Syncytin A receptor Ly6e impairs syncytiotrophoblast
RT fusion and placental morphogenesis causing embryonic lethality in mice.";
RL Sci. Rep. 8:3961-3961(2018).
RN [18]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32704094; DOI=10.1038/s41564-020-0769-y;
RA Pfaender S., Mar K.B., Michailidis E., Kratzel A., Boys I.N., V'kovski P.,
RA Fan W., Kelly J.N., Hirt D., Ebert N., Stalder H., Kleine-Weber H.,
RA Hoffmann M., Hoffmann H.H., Saeed M., Dijkman R., Steinmann E.,
RA Wight-Carter M., McDougal M.B., Hanners N.W., Poehlmann S., Gallagher T.,
RA Todt D., Zimmer G., Rice C.M., Schoggins J.W., Thiel V.;
RT "LY6E impairs coronavirus fusion and confers immune control of viral
RT disease.";
RL Nat. Microbiol. 5:1330-1339(2020).
CC -!- FUNCTION: GPI-anchored cell surface protein that regulates T-
CC lymphocytes proliferation, differentiation, and activation
CC (PubMed:9575182, PubMed:8642345). Regulates the T-cell receptor (TCR)
CC signaling by interacting with component CD3Z/CD247 at the plasma
CC membrane, leading to CD3Z/CD247 phosphorylation modulation
CC (PubMed:9575182). Restricts the entry of murine coronavirus, mouse
CC hepatitis virus, by interfering with spike protein-mediated membrane
CC fusion (PubMed:32704094). Also plays an essential role in placenta
CC formation by acting as the main receptor for syncytin-A (SynA)
CC (PubMed:28679758). Therefore, participates in the normal fusion of
CC syncytiotrophoblast layer I (SynT-I) and in the proper morphogenesis of
CC both fetal and maternal vasculatures within the placenta
CC (PubMed:29500366). May also act as a modulator of nicotinic
CC acetylcholine receptors (nAChRs) activity. In vitro inhibits alpha-
CC 3:beta-4-containing nAChRs maximum response (PubMed:26276394).
CC {ECO:0000269|PubMed:26276394, ECO:0000269|PubMed:28679758,
CC ECO:0000269|PubMed:29500366, ECO:0000269|PubMed:32704094,
CC ECO:0000269|PubMed:8642345, ECO:0000269|PubMed:9575182}.
CC -!- SUBUNIT: Interacts with CHRNA4 (PubMed:26276394). Interacts with
CC CD3Z/CD247 (PubMed:9575182). {ECO:0000269|PubMed:26276394,
CC ECO:0000269|PubMed:9575182}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9575182};
CC Lipid-anchor, GPI-anchor {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in mouse adult tissues with
CC maximal expression in the lung and the salivary gland. Expression is
CC strikingly lower in the fetal tissues except for the placenta
CC (PubMed:28679758). Present in thymus where its expression is observed
CC in immature thymocytes and thymic stromal cells (PubMed:1531995). Also
CC found on functionally active T-cells as well as B-cells and thymic
CC dendritic cells (PubMed:2987354). {ECO:0000269|PubMed:1531995,
CC ECO:0000269|PubMed:28679758, ECO:0000269|PubMed:2987354}.
CC -!- INDUCTION: By interferon gamma/IFN-gamma on resting T-cells.
CC {ECO:0000269|PubMed:3040423}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show embryonic lethality at 14.5
CC dpc (PubMed:11784869). Lethality is due to a critical role in the
CC trophoblast stem cells which form the outer layer of fetal part of the
CC placenta. Alters syncytiotropoblast-I layer I (SynT-I) fusion while
CC SynT-II cell fusion does not seem to be affected, indicating a cell
CC autonomous role in SynT-I fusion (PubMed:29500366). Konckout mice
CC specific to immune cells are highly susceptible to the murine
CC coronavirus, mouse hepatitis virus (PubMed:32704094).
CC {ECO:0000269|PubMed:11784869, ECO:0000269|PubMed:29500366,
CC ECO:0000269|PubMed:32704094}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB17698.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U09192; AAB03366.1; -; mRNA.
DR EMBL; U04268; AAA19121.1; -; mRNA.
DR EMBL; U47737; AAB17698.1; ALT_INIT; Genomic_DNA.
DR EMBL; AC124637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CT010244; CAJ18452.1; -; mRNA.
DR EMBL; CT010220; CAJ18428.1; -; mRNA.
DR EMBL; BC002116; AAH02116.1; -; mRNA.
DR EMBL; BC003926; AAH03926.1; -; mRNA.
DR EMBL; BC005684; AAH05684.1; -; mRNA.
DR EMBL; BC040691; AAH40691.1; -; mRNA.
DR EMBL; BC019113; AAH19113.1; -; mRNA.
DR EMBL; BC080711; AAH80711.1; -; mRNA.
DR EMBL; BC053523; AAH53523.1; -; mRNA.
DR PIR; I49013; I49013.
DR RefSeq; NP_001157508.1; NM_001164036.1.
DR RefSeq; NP_001157509.1; NM_001164037.1.
DR RefSeq; NP_001157510.1; NM_001164038.1.
DR RefSeq; NP_001157511.1; NM_001164039.1.
DR RefSeq; NP_001157512.1; NM_001164040.1.
DR RefSeq; NP_032555.1; NM_008529.3.
DR AlphaFoldDB; Q64253; -.
DR SMR; Q64253; -.
DR BioGRID; 201242; 1.
DR IntAct; Q64253; 1.
DR STRING; 10090.ENSMUSP00000056703; -.
DR GlyGen; Q64253; 1 site.
DR PhosphoSitePlus; Q64253; -.
DR SwissPalm; Q64253; -.
DR EPD; Q64253; -.
DR jPOST; Q64253; -.
DR MaxQB; Q64253; -.
DR PaxDb; Q64253; -.
DR PeptideAtlas; Q64253; -.
DR PRIDE; Q64253; -.
DR ProteomicsDB; 291973; -.
DR ProteomicsDB; 330273; -.
DR ABCD; Q64253; 3 sequenced antibodies.
DR DNASU; 17069; -.
DR Ensembl; ENSMUST00000051698; ENSMUSP00000056703; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000169343; ENSMUSP00000132081; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000185861; ENSMUSP00000141145; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000187284; ENSMUSP00000140553; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000187606; ENSMUSP00000139471; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000188042; ENSMUSP00000141059; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000188866; ENSMUSP00000140145; ENSMUSG00000022587.
DR Ensembl; ENSMUST00000191436; ENSMUSP00000139549; ENSMUSG00000022587.
DR GeneID; 17069; -.
DR KEGG; mmu:17069; -.
DR UCSC; uc007wgh.2; mouse.
DR CTD; 4061; -.
DR MGI; MGI:106651; Ly6e.
DR VEuPathDB; HostDB:ENSMUSG00000022587; -.
DR eggNOG; ENOG502SRPS; Eukaryota.
DR GeneTree; ENSGT00940000153378; -.
DR HOGENOM; CLU_141358_0_0_1; -.
DR InParanoid; Q64253; -.
DR OMA; TTCADHE; -.
DR OrthoDB; 1493078at2759; -.
DR PhylomeDB; Q64253; -.
DR TreeFam; TF336080; -.
DR Reactome; R-MMU-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR BioGRID-ORCS; 17069; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Ly6e; mouse.
DR PRO; PR:Q64253; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q64253; protein.
DR Bgee; ENSMUSG00000022587; Expressed in thoracic mammary gland and 164 other tissues.
DR ExpressionAtlas; Q64253; baseline and differential.
DR GO; GO:0031225; C:anchored component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0033130; F:acetylcholine receptor binding; IDA:MGI.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IDA:MGI.
DR GO; GO:0095500; P:acetylcholine receptor signaling pathway; IDA:MGI.
DR GO; GO:0030325; P:adrenal gland development; IMP:MGI.
DR GO; GO:0048242; P:epinephrine secretion; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IMP:UniProtKB.
DR GO; GO:0042415; P:norepinephrine metabolic process; IMP:MGI.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:MGI.
DR CDD; cd00117; LU; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR016054; LY6_UPA_recep-like.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR Pfam; PF00021; UPAR_LY6; 1.
DR SMART; SM00134; LU; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor; Lipoprotein;
KW Membrane; Reference proteome; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..108
FT /note="Lymphocyte antigen 6E"
FT /id="PRO_0000036140"
FT PROPEP 109..136
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000036141"
FT DOMAIN 27..118
FT /note="UPAR/Ly6"
FT /evidence="ECO:0000255"
FT LIPID 108
FT /note="GPI-anchor amidated alanine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 29..54
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 32..41
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 47..76
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 80..98
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 99..104
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
SQ SEQUENCE 136 AA; 14392 MW; 5A1CBBE1464DC029 CRC64;
MSATSNMRVF LPVLLAALLG MEQVHSLMCF SCTDQKNNIN CLWPVSCQEK DHYCITLSAA
AGFGNVNLGY TLNKGCSPIC PSENVNLNLG VASVNSYCCQ SSFCNFSAAG LGLRASIPLL
GLGLLLSLLA LLQLSP
