ID LY6E_HUMAN Reviewed; 131 AA.
AC Q16553; B2R4X5; D3DWJ2; Q0VDE5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JUL-2024, entry version 186.
DE RecName: Full=Lymphocyte antigen 6E {ECO:0000305};
DE Short=Ly-6E;
DE AltName: Full=Retinoic acid-induced gene E protein;
DE Short=RIG-E;
DE AltName: Full=Stem cell antigen 2;
DE Short=SCA-2;
DE AltName: Full=Thymic shared antigen 1;
DE Short=TSA-1;
DE Flags: Precursor;
GN Name=LY6E {ECO:0000312|HGNC:HGNC:6727}; Synonyms=9804, RIGE, SCA2, TSA1;
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].
RC TISSUE=Promyelocytic leukemia;
RX PubMed=8650192; DOI=10.1073/pnas.93.12.5910;
RA Mao M., Yu M., Tong J.-H., Ye J., Zhu J., Huang Q.-H., Fu G., Yu L.,
RA Zhao S.-Y., Waxman S., Lanotte M., Wang Z.-Y., Tan J.-Z., Chan S.-J.,
RA Chen Z.;
RT "RIG-E, a human homolog of the murine Ly-6 family, is induced by retinoic
RT acid during the differentiation of acute promyelocytic leukemia cell.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5910-5914(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain, and Mammary gland;
RX PubMed=8757598;
RA Capone M.C., Gorman D.M., Ching E.P., Zlotnik A.;
RT "Identification through bioinformatics of cDNAs encoding human thymic
RT shared Ag-1/stem cell Ag-2: a new member of the human Ly-6 family.";
RL J. Immunol. 157:969-973(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Monocyte;
RX PubMed=9551972;
RA Shan X., Bourdeau A., Rhoton A., Wells D.E., Cohen E.H., Landgraf B.E.,
RA Palfree R.G.E.;
RT "Characterization and mapping to human chromosome 8q24.3 of Ly-6-related
RT gene 9804 encoding an apparent homologue of mouse TSA-1.";
RL J. Immunol. 160:197-208(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 FUNCTION (MICROBIAL INFECTION).
RX PubMed=28130445; DOI=10.1074/jbc.m116.755819;
RA Yu J., Liang C., Liu S.L.;
RT "Interferon-inducible LY6E Protein Promotes HIV-1 Infection.";
RL J. Biol. Chem. 292:4674-4685(2017).
RN [8]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=29610346; DOI=10.1073/pnas.1720032115;
RA Hackett B.A., Cherry S.;
RT "Flavivirus internalization is regulated by a size-dependent endocytic
RT pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:4246-4251(2018).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), AND MUTAGENESIS OF LEU-36 AND ILE-57.
RX PubMed=30190477; DOI=10.1038/s41467-018-06000-y;
RA Mar K.B., Rinkenberger N.R., Boys I.N., Eitson J.L., McDougal M.B.,
RA Richardson R.B., Schoggins J.W.;
RT "LY6E mediates an evolutionarily conserved enhancement of virus infection
RT by targeting a late entry step.";
RL Nat. Commun. 9:3603-3603(2018).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF LEU-36 AND ASN-99.
RX PubMed=32641482; DOI=10.1128/jvi.00562-20;
RA Zhao X., Zheng S., Chen D., Zheng M., Li X., Li G., Lin H., Chang J.,
RA Zeng H., Guo J.T.;
RT "LY6E Restricts Entry of Human Coronaviruses, Including Currently Pandemic
RT SARS-CoV-2.";
RL J. Virol. 94:0-0(2020).
RN [11]
RP FUNCTION.
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. Regulates
CC the T-cell receptor (TCR) signaling by interacting with component
CC CD3Z/CD247 at the plasma membrane, leading to CD3Z/CD247
CC phosphorylation modulation (By similarity). Restricts the entry of
CC human coronaviruses, including SARS-CoV, MERS-CoV and SARS-CoV-2, by
CC interfering with spike protein-mediated membrane fusion
CC (PubMed:32641482). Also plays an essential role in placenta formation
CC by acting as the main receptor for syncytin-A (SynA). Therefore,
CC participates in the normal fusion of syncytiotrophoblast layer I (SynT-
CC I) and in the proper morphogenesis of both fetal and maternal
CC vasculatures within the placenta. May also act as a modulator of
CC nicotinic acetylcholine receptors (nAChRs) activity (By similarity).
CC {ECO:0000250|UniProtKB:Q64253, ECO:0000269|PubMed:32641482}.
CC -!- FUNCTION: (Microbial infection) Promotes entry, likely through an
CC enhanced virus-cell fusion process, of various viruses including HIV-1,
CC West Nile virus, dengue virus and Zika virus (PubMed:28130445). In
CC contrast, the paramyxovirus PIV5, which enters at the plasma membrane,
CC does not require LY6E (PubMed:28130445, PubMed:29610346).
CC Mechanistically, adopts a microtubule-like organization upon viral
CC infection and enhances viral uncoating after endosomal escape
CC (PubMed:28130445, PubMed:30190477). {ECO:0000269|PubMed:28130445,
CC ECO:0000269|PubMed:29610346, ECO:0000269|PubMed:30190477}.
CC -!- SUBUNIT: Interacts with CHRNA4. {ECO:0000250|UniProtKB:Q64253}.
CC -!- INTERACTION:
CC Q16553; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-18234679, EBI-2858252;
CC Q16553; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-18234679, EBI-2844246;
CC Q16553; Q96HH6: TMEM19; NbExp=3; IntAct=EBI-18234679, EBI-741829;
CC Q16553; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-18234679, EBI-11988865;
CC Q16553; PRO_0000449624 [P0DTD1]: rep; Xeno; NbExp=3; IntAct=EBI-18234679, EBI-25475868;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q64253};
CC Lipid-anchor, GPI-anchor {ECO:0000250|UniProtKB:Q64253}.
CC -!- TISSUE SPECIFICITY: Widely expressed, predominantly in liver, kidney,
CC ovary, spleen and peripheral blood Leukocytes.
CC -!- INDUCTION: By retinoic acid; in promyelocytic leukemia NB4 and in
CC myeloblast HL-60 cell lines. Activated by IFN-alpha in monocytic cell
CC line U-937 and in peripheral blood monocyte cells.
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DR EMBL; Z68179; CAA92321.1; -; mRNA.
DR EMBL; U42376; AAC50519.1; -; mRNA.
DR EMBL; U56145; AAC50616.1; -; mRNA.
DR EMBL; U66711; AAB07513.1; -; Genomic_DNA.
DR EMBL; AK311983; BAG34922.1; -; mRNA.
DR EMBL; CH471162; EAW82287.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82288.1; -; Genomic_DNA.
DR EMBL; CH471162; EAW82290.1; -; Genomic_DNA.
DR EMBL; BC119708; AAI19709.1; -; mRNA.
DR EMBL; BC119709; AAI19710.1; -; mRNA.
DR CCDS; CCDS6394.1; -.
DR RefSeq; NP_001120685.1; NM_001127213.1.
DR RefSeq; NP_002337.1; NM_002346.2.
DR AlphaFoldDB; Q16553; -.
DR BioGRID; 110239; 8.
DR IntAct; Q16553; 5.
DR STRING; 9606.ENSP00000428572; -.
DR ChEMBL; CHEMBL4523584; -.
DR GlyCosmos; Q16553; 1 site, No reported glycans.
DR GlyGen; Q16553; 1 site.
DR iPTMnet; Q16553; -.
DR PhosphoSitePlus; Q16553; -.
DR BioMuta; LY6E; -.
DR DMDM; 10720072; -.
DR MassIVE; Q16553; -.
DR PaxDb; 9606-ENSP00000428572; -.
DR PeptideAtlas; Q16553; -.
DR ProteomicsDB; 60911; -.
DR ABCD; Q16553; 3 sequenced antibodies.
DR Antibodypedia; 14558; 237 antibodies from 27 providers.
DR CPTC; Q16553; 3 antibodies.
DR DNASU; 4061; -.
DR Ensembl; ENST00000292494.11; ENSP00000292494.6; ENSG00000160932.11.
DR Ensembl; ENST00000429120.6; ENSP00000414307.2; ENSG00000160932.11.
DR Ensembl; ENST00000517503.1; ENSP00000428427.3; ENSG00000160932.11.
DR Ensembl; ENST00000520466.5; ENSP00000428572.1; ENSG00000160932.11.
DR Ensembl; ENST00000521003.5; ENSP00000428169.1; ENSG00000160932.11.
DR Ensembl; ENST00000521699.5; ENSP00000427915.1; ENSG00000160932.11.
DR Ensembl; ENST00000522024.1; ENSP00000428442.1; ENSG00000160932.11.
DR Ensembl; ENST00000522971.5; ENSP00000428159.1; ENSG00000160932.11.
DR Ensembl; ENST00000619718.2; ENSP00000482517.1; ENSG00000278032.2.
DR Ensembl; ENST00000631568.1; ENSP00000488891.1; ENSG00000278032.2.
DR Ensembl; ENST00000632424.1; ENSP00000488421.1; ENSG00000278032.2.
DR Ensembl; ENST00000632516.1; ENSP00000487664.1; ENSG00000278032.2.
DR Ensembl; ENST00000632519.1; ENSP00000488443.1; ENSG00000278032.2.
DR Ensembl; ENST00000632812.1; ENSP00000488556.1; ENSG00000278032.2.
DR Ensembl; ENST00000633451.1; ENSP00000488559.1; ENSG00000278032.2.
DR GeneID; 4061; -.
DR KEGG; hsa:4061; -.
DR MANE-Select; ENST00000292494.11; ENSP00000292494.6; NM_002346.3; NP_002337.1.
DR UCSC; uc003yxm.3; human.
DR AGR; HGNC:6727; -.
DR CTD; 4061; -.
DR DisGeNET; 4061; -.
DR GeneCards; LY6E; -.
DR HGNC; HGNC:6727; LY6E.
DR HPA; ENSG00000160932; Tissue enhanced (liver).
DR MIM; 601384; gene.
DR neXtProt; NX_Q16553; -.
DR OpenTargets; ENSG00000160932; -.
DR PharmGKB; PA30491; -.
DR VEuPathDB; HostDB:ENSG00000160932; -.
DR eggNOG; ENOG502SRPS; Eukaryota.
DR GeneTree; ENSGT00940000153378; -.
DR HOGENOM; CLU_141358_0_0_1; -.
DR InParanoid; Q16553; -.
DR OMA; FCSPICG; -.
DR OrthoDB; 4256072at2759; -.
DR PhylomeDB; Q16553; -.
DR TreeFam; TF336080; -.
DR PathwayCommons; Q16553; -.
DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins.
DR SignaLink; Q16553; -.
DR BioGRID-ORCS; 4061; 22 hits in 1164 CRISPR screens.
DR ChiTaRS; LY6E; human.
DR GeneWiki; LY6E; -.
DR GenomeRNAi; 4061; -.
DR Pharos; Q16553; Tbio.
DR PRO; PR:Q16553; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q16553; Protein.
DR Bgee; ENSG00000160932; Expressed in right lobe of liver and 99 other cell types or tissues.
DR ExpressionAtlas; Q16553; baseline and differential.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; IDA:UniProtKB.
DR CDD; cd00117; LU; 1.
DR Gene3D; 2.10.60.10; CD59; 1.
DR InterPro; IPR051110; Ly-6/neurotoxin-like_GPI-ap.
DR InterPro; IPR016054; LY6_UPA_recep-like.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR PANTHER; PTHR16983:SF13; LYMPHOCYTE ANTIGEN 6E; 1.
DR PANTHER; PTHR16983; UPAR/LY6 DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00021; UPAR_LY6; 1.
DR SMART; SM00134; LU; 1.
DR SUPFAM; SSF57302; Snake toxin-like; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW Host-virus interaction; Lipoprotein; Membrane; Reference proteome; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..101
FT /note="Lymphocyte antigen 6E"
FT /id="PRO_0000036138"
FT PROPEP 102..131
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000036139"
FT DOMAIN 21..101
FT /note="UPAR/Ly6"
FT LIPID 101
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..48
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 26..35
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 41..71
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 75..92
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT DISULFID 93..98
FT /evidence="ECO:0000250|UniProtKB:P0DP57,
FT ECO:0000250|UniProtKB:P0DP58"
FT MUTAGEN 36
FT /note="L->A: Complete loss of viral entry enhancement.
FT Abolishes inhibition of human coronaviruses entry."
FT /evidence="ECO:0000269|PubMed:30190477,
FT ECO:0000269|PubMed:32641482"
FT MUTAGEN 57
FT /note="I->A: About 50% loss of viral entry enhancement."
FT /evidence="ECO:0000269|PubMed:30190477"
FT MUTAGEN 99
FT /note="N->A: Abolishes inhibition of human coronaviruses
FT entry."
FT /evidence="ECO:0000269|PubMed:32641482"
SQ SEQUENCE 131 AA; 13507 MW; 0F6D1157741AFC98 CRC64;
MKIFLPVLLA ALLGVERASS LMCFSCLNQK SNLYCLKPTI CSDQDNYCVT VSASAGIGNL
VTFGHSLSKT CSPACPIPEG VNVGVASMGI SCCQSFLCNF SAADGGLRAS VTLLGAGLLL
SLLPALLRFG P
//