ID SYCY1_HUMAN Reviewed; 538 AA. AC Q9UQF0; B2RPD4; O95244; O95245; Q8NHY7; Q9NRZ2; Q9NZG3; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 171. DE RecName: Full=Syncytin-1; DE AltName: Full=Endogenous retrovirus group W member 1; DE AltName: Full=Env-W; DE AltName: Full=Envelope polyprotein gPr73; DE AltName: Full=Enverin; DE AltName: Full=HERV-7q Envelope protein; DE AltName: Full=HERV-W envelope protein; DE AltName: Full=HERV-W_7q21.2 provirus ancestral Env polyprotein; DE AltName: Full=Syncytin; DE Contains: DE RecName: Full=Surface protein; DE Short=SU; DE AltName: Full=gp50; DE Contains: DE RecName: Full=Transmembrane protein; DE Short=TM; DE AltName: Full=gp24; DE Flags: Precursor; GN Name=ERVW-1; Synonyms=ERVWE1; 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=Placenta; RX PubMed=9882319; DOI=10.1128/jvi.73.2.1175-1185.1999; RA Blond J.-L., Beseme F., Duret L., Bouton O., Bedin F., Perron H., RA Mandrand B., Mallet F.; RT "Molecular characterization and placental expression of HERV-W, a new human RT endogenous retrovirus family."; RL J. Virol. 73:1175-1185(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, AND VARIANT RP ASN-307. RC TISSUE=Testis; RX PubMed=10693809; DOI=10.1038/35001608; RA Sha M., Lee X., Li X.-P., Veldman G.M., Finnerty H., Racie L., LaVallie E., RA Tang X.-Y., Edouard P., Howes S., Keith J.C. Jr., McCoy J.M.; RT "Syncytin is captive retroviral envelope protein involved in human RT placental morphogenesis."; RL Nature 403:785-789(2000). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10826480; DOI=10.1089/088922200308738; RA Voisset C., Bouton O., Bedin F., Duret L., Mandrand B., Mallet F., RA Paranhos-Baccala G.; RT "Chromosomal distribution and coding capacity of the human endogenous RT retrovirus HERV-W family."; RL AIDS Res. Hum. Retroviruses 16:731-740(2000). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-129; GLN-138; ASN-307 RP AND PHE-477. RX PubMed=14757826; DOI=10.1073/pnas.0305763101; RA Mallet F., Bouton O., Prudhomme S., Cheynet V., Oriol G., Bonnaud B., RA Lucotte G., Duret L., Mandrand B.; RT "The endogenous retroviral locus ERVWE1 is a bona fide gene involved in RT hominoid placental physiology."; RL Proc. Natl. Acad. Sci. U.S.A. 101:1731-1736(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). 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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-533, AND VARIANT ASN-307. RC TISSUE=Placenta; RX PubMed=11990458; RA Alliel P.M., Perin J.-P., Goudou D., Bitoun M., Robert B., Rieger F.; RT "The HERV-W/7q family in the human genome. Potential for protein expression RT and gene regulation."; RL Cell. Mol. Biol. 48:213-217(2002). RN [8] RP IDENTIFICATION. RX PubMed=9835022; DOI=10.1016/s0764-4469(99)80026-2; RA Alliel P.M., Perin J.-P., Pierig R., Nussbaum J.-L., Menard A., Rieger F.; RT "Endogenous retroviruses and multiple sclerosis. II. HERV-7q."; RL C. R. Acad. Sci. III, Sci. Vie 321:857-863(1998). RN [9] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=10708449; DOI=10.1128/jvi.74.7.3321-3329.2000; RA Blond J.-L., Lavillette D., Cheynet V., Bouton O., Oriol G., RA Chapel-Fernandes S., Mandrand B., Mallet F., Cosset F.-L.; RT "An envelope glycoprotein of the human endogenous retrovirus HERV-W is RT expressed in the human placenta and fuses cells expressing the type D RT mammalian retrovirus receptor."; RL J. Virol. 74:3321-3329(2000). RN [10] RP FUNCTION. RX PubMed=11238877; DOI=10.1128/jvi.75.7.3488-3489.2001; RA An D.S., Xie Y.-M., Chen I.S.Y.; RT "Envelope gene of the human endogenous retrovirus HERV-W encodes a RT functional retrovirus envelope."; RL J. Virol. 75:3488-3489(2001). RN [11] RP FUNCTION. RX PubMed=11531410; DOI=10.1006/viro.2001.1045; RA Perron H., Jouvin-Marche E., Michel M., Ounanian-Paraz A., Camelo S., RA Dumon A., Jolivet-Reynaud C., Marcel F., Souillet Y., Borel E., RA Gebuhrer L., Santoro L., Marcel S., Seigneurin J.M., Marche P.N., Lafon M.; RT "Multiple sclerosis retrovirus particles and recombinant envelope trigger RT an abnormal immune response in vitro, by inducing polyclonal Vbeta16 T- RT lymphocyte activation."; RL Virology 287:321-332(2001). RN [12] RP FUNCTION. RX PubMed=12050356; DOI=10.1128/jvi.76.13.6442-6452.2002; RA Lavillette D., Marin M., Ruggieri A., Mallet F., Cosset F.-L., Kabat D.; RT "The envelope glycoprotein of human endogenous retrovirus type W uses a RT divergent family of amino acid transporters/cell surface receptors."; RL J. Virol. 76:6442-6452(2002). RN [13] RP FUNCTION. RX PubMed=14557543; DOI=10.1073/pnas.2132646100; RA Blaise S., de Parseval N., Benit L., Heidmann T.; RT "Genomewide screening for fusogenic human endogenous retrovirus envelopes RT identifies syncytin 2, a gene conserved on primate evolution."; RL Proc. Natl. Acad. Sci. U.S.A. 100:13013-13018(2003). RN [14] RP FUNCTION. RX PubMed=12664292; DOI=10.1007/s00705-002-0960-x; RA Ponferrada V.G., Mauck B.S., Wooley D.P.; RT "The envelope glycoprotein of human endogenous retrovirus HERV-W induces RT cellular resistance to spleen necrosis virus."; RL Arch. Virol. 148:659-675(2003). RN [15] RP TISSUE SPECIFICITY. RX PubMed=12970426; DOI=10.1128/jvi.77.19.10414-10422.2003; RA de Parseval N., Lazar V., Casella J.-F., Benit L., Heidmann T.; RT "Survey of human genes of retroviral origin: identification and RT transcriptome of the genes with coding capacity for complete envelope RT proteins."; RL J. Virol. 77:10414-10422(2003). RN [16] RP DEVELOPMENTAL STAGE. RX PubMed=12620933; DOI=10.1095/biolreprod.102.013078; RA Smallwood A., Papageorghiou A., Nicolaides K., Alley M.K.R., Jim A., RA Nargund G., Ojha K., Campbell S., Banerjee S.; RT "Temporal regulation of the expression of syncytin (HERV-W), maternally RT imprinted PEG10, and SGCE in human placenta."; RL Biol. Reprod. 69:286-293(2003). RN [17] RP FUNCTION. RX PubMed=15254254; DOI=10.1093/molbev/msh206; RA Bonnaud B., Bouton O., Oriol G., Cheynet V., Duret L., Mallet F.; RT "Evidence of selection on the domesticated ERVWE1 env retroviral element RT involved in placentation."; RL Mol. Biol. Evol. 21:1895-1901(2004). RN [18] RP INVOLVEMENT IN MULTIPLE SCLEROSIS, AND TISSUE SPECIFICITY. RX PubMed=15452578; DOI=10.1038/nn1319; RA Antony J.M., Van Marle G., Opii W., Butterfield D.A., Mallet F., Yong V.W., RA Wallace J.L., Deacon R.M., Warren K., Power C.; RT "Human endogenous retrovirus glycoprotein-mediated induction of redox RT reactants causes oligodendrocyte death and demyelination."; RL Nat. Neurosci. 7:1088-1095(2004). RN [19] RP PROTEOLYTIC PROCESSING OF POLYPROTEIN, SUBUNIT, INTERACTION WITH RP CD209/DC-SIGN, AND MUTAGENESIS OF 314-ARG--LYS-316; ARG-317 AND CYS-405. RX PubMed=15827173; DOI=10.1128/jvi.79.9.5585-5593.2005; RA Cheynet V., Ruggieri A., Oriol G., Blond J.-L., Boson B., Vachot L., RA Verrier B., Cosset F.-L., Mallet F.; RT "Synthesis, assembly, and processing of the Env ERVWE1/syncytin human RT endogenous retroviral envelope."; RL J. Virol. 79:5585-5593(2005). RN [20] RP FUNCTION. RX PubMed=23492904; DOI=10.1038/srep01462; RA Sugimoto J., Sugimoto M., Bernstein H., Jinno Y., Schust D.; RT "A novel human endogenous retroviral protein inhibits cell-cell fusion."; RL Sci. Rep. 3:1462-1462(2013). CC -!- FUNCTION: This endogenous retroviral envelope protein has retained its CC original fusogenic properties and participates in trophoblast fusion CC and the formation of a syncytium during placenta morphogenesis. May CC induce fusion through binding of SLC1A4 and SLC1A5 (PubMed:10708449, CC PubMed:12050356, PubMed:23492904). {ECO:0000269|PubMed:10708449, CC ECO:0000269|PubMed:12050356, ECO:0000269|PubMed:23492904}. CC -!- FUNCTION: Endogenous envelope proteins may have kept, lost or modified CC their original function during evolution. Retroviral envelope proteins CC mediate receptor recognition and membrane fusion during early CC infection. The surface protein (SU) mediates receptor recognition, CC while the transmembrane protein (TM) acts as a class I viral fusion CC protein. The protein may have at least 3 conformational states: pre- CC fusion native state, pre-hairpin intermediate state, and post-fusion CC hairpin state. During viral and target cell membrane fusion, the coiled CC coil regions (heptad repeats) assume a trimer-of-hairpins structure, CC positioning the fusion peptide in close proximity to the C-terminal CC region of the ectodomain. The formation of this structure appears to CC drive apposition and subsequent fusion of membranes. CC -!- SUBUNIT: The mature envelope protein (Env) consists of a trimer of SU- CC TM heterodimers attached probably by a labile interchain disulfide CC bond. Interacts with the C-type lectin CD209/DC-SIGN. CC {ECO:0000269|PubMed:15827173}. CC -!- SUBCELLULAR LOCATION: [Surface protein]: Cell membrane CC {ECO:0000305|PubMed:15827173}; Peripheral membrane protein CC {ECO:0000305|PubMed:15827173}. Note=The surface protein is not anchored CC to the membrane, but localizes to the extracellular surface through its CC binding to TM. {ECO:0000305|PubMed:15827173}. CC -!- SUBCELLULAR LOCATION: [Transmembrane protein]: Cell membrane CC {ECO:0000305}; Single-pass type I membrane protein {ECO:0000255}. CC -!- SUBCELLULAR LOCATION: [Syncytin-1]: Virion {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed at higher level in placental CC syncytiotrophoblast. Expressed at intermediate level in testis. Seems CC also to be found at low level in adrenal tissue, bone marrow, breast, CC colon, kidney, ovary, prostate, skin, spleen, thymus, thyroid, brain CC and trachea. Both mRNA and protein levels are significantly increased CC in the brain of individuals with multiple sclerosis, particularly in CC astrocytes and microglia. {ECO:0000269|PubMed:10693809, CC ECO:0000269|PubMed:10708449, ECO:0000269|PubMed:12970426, CC ECO:0000269|PubMed:15452578}. CC -!- DEVELOPMENTAL STAGE: In placenta, detected at higher level during early CC pregnancy and at lower level during late pregnancy. CC {ECO:0000269|PubMed:12620933}. CC -!- DOMAIN: The cytoplasmic region is essential for the fusiogenic CC function. CC -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in CC many retroviral envelope proteins. Synthetic peptides derived from this CC relatively conserved sequence inhibit immune function in vitro and in CC vivo (By similarity). {ECO:0000250}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. CC Envelope glycoproteins are synthesized as an inactive precursor that is CC heavily N-glycosylated and processed likely by furin in the Golgi to CC yield the mature SU and TM proteins. The cleavage site between SU and CC TM requires the minimal sequence [KR]-X-[KR]-R. The intracytoplasmic CC tail cleavage by the viral protease that is required for the fusiogenic CC activity of some retroviruses envelope proteins seems to have been lost CC during evolution. {ECO:0000269|PubMed:15827173}. CC -!- PTM: The CXXC motif is highly conserved across a broad range of CC retroviral envelope proteins. It is thought to participate in the CC formation of a labile disulfide bond possibly with the CX6CC motif CC present in the transmembrane protein. Isomerization of the intersubunit CC disulfide bond to an SU intrachain disulfide bond is thought to occur CC upon receptor recognition in order to allow membrane fusion. CC {ECO:0000305|PubMed:15827173}. CC -!- POLYMORPHISM: All variants have fusogenic properties. CC -!- MISCELLANEOUS: Probably involved in the development of multiple CC sclerosis (MS). MS is a neurodegenerative disease characterized by the CC gradual accumulation of focal plaques of demyelination particularly in CC the periventricular areas of the brain. It leads to physical and CC cognitive disabilities. Viral particles or intracellular RNA of HERV-W CC family members have been detected in tissue from patients with multiple CC sclerosis or schizophrenia. CC -!- MISCELLANEOUS: Orthologs in P.troglodytes, G.gorilla, P.pygmaeus and CC H.moloch. CC -!- MISCELLANEOUS: It can make pseudotypes with HIV-1 virions and confer CC infectivity. Can also induce cellular resistance to spleen necrosis CC virus in vitro. CC -!- MISCELLANEOUS: HERV-W family subgenomic RNAs have been observed. CC -!- MISCELLANEOUS: This provirus is intergenic, the closest flanking genes CC being ODAG and PEX1. CC -!- MISCELLANEOUS: The human genome contains a high percentage of proviral- CC like elements, also called endogenous retroviruses (ERVs) that are the CC genomic traces of ancient infections of the germline by exogenous CC retroviruses. Although most of these elements are defective, some have CC conserved a functional envelope (env) gene, most probably diverted by CC the host for its benefit. CC -!- SIMILARITY: Belongs to the gamma type-C retroviral envelope protein CC family. HERV class-I W env subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40497/ERVWE1"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A virus for life - Issue 50 CC of September 2004; CC URL="https://web.expasy.org/spotlight/back_issues/050"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF072503; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF072505; AAD14545.1; -; mRNA. DR EMBL; AF072506; AAD14546.2; -; mRNA. DR EMBL; AF072508; AAD14548.1; -; mRNA. DR EMBL; AF208161; AAF28334.1; -; mRNA. DR EMBL; AF513360; AAM47599.1; -; mRNA. DR EMBL; AF156963; AAF74215.1; -; Genomic_DNA. DR EMBL; AC007566; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY101582; AAM68161.1; -; Genomic_DNA. DR EMBL; AY101583; AAM68162.1; -; Genomic_DNA. DR EMBL; AY101584; AAM68163.1; -; Genomic_DNA. DR EMBL; AY101585; AAM68164.1; -; Genomic_DNA. DR EMBL; AF520478; AAQ17561.1; -; Genomic_DNA. DR EMBL; AF520480; AAQ17562.1; -; Genomic_DNA. DR EMBL; AF520482; AAQ17563.1; -; Genomic_DNA. DR EMBL; AF520484; AAQ17564.1; -; Genomic_DNA. DR EMBL; AF520486; AAQ17565.1; -; Genomic_DNA. DR EMBL; AF520488; AAQ17566.1; -; Genomic_DNA. DR EMBL; AF520490; AAQ17567.1; -; Genomic_DNA. DR EMBL; AF520492; AAQ17568.1; -; Genomic_DNA. DR EMBL; AF520494; AAQ17569.1; -; Genomic_DNA. DR EMBL; AF520496; AAQ17570.1; -; Genomic_DNA. DR EMBL; AF520498; AAQ17571.1; -; Genomic_DNA. DR EMBL; AF520500; AAQ17572.1; -; Genomic_DNA. DR EMBL; AF520502; AAQ17573.1; -; Genomic_DNA. DR EMBL; AF520504; AAQ17574.1; -; Genomic_DNA. DR EMBL; AF520506; AAQ17575.1; -; Genomic_DNA. DR EMBL; AF520508; AAQ17576.1; -; Genomic_DNA. DR EMBL; AF520510; AAQ17577.1; -; Genomic_DNA. DR EMBL; AF520512; AAQ17578.1; -; Genomic_DNA. DR EMBL; AF520514; AAQ17579.1; -; Genomic_DNA. DR EMBL; AF520516; AAQ17580.1; -; Genomic_DNA. DR EMBL; AF520518; AAQ17581.1; -; Genomic_DNA. DR EMBL; AF520520; AAQ17582.1; -; Genomic_DNA. DR EMBL; AF520522; AAQ17583.1; -; Genomic_DNA. DR EMBL; AF520524; AAQ17584.1; -; Genomic_DNA. DR EMBL; AF520526; AAQ17585.1; -; Genomic_DNA. DR EMBL; AF520528; AAQ17586.1; -; Genomic_DNA. DR EMBL; AF520530; AAQ17587.1; -; Genomic_DNA. DR EMBL; AF520532; AAQ17588.1; -; Genomic_DNA. DR EMBL; AF520534; AAQ17589.1; -; Genomic_DNA. DR EMBL; AF520536; AAQ17590.1; -; Genomic_DNA. DR EMBL; AF520538; AAQ17591.1; -; Genomic_DNA. DR EMBL; AF520540; AAQ17592.1; -; Genomic_DNA. DR EMBL; AF520542; AAQ17593.1; -; Genomic_DNA. DR EMBL; AF520544; AAQ17594.1; -; Genomic_DNA. DR EMBL; AF520546; AAQ17595.1; -; Genomic_DNA. DR EMBL; AF520548; AAQ17596.1; -; Genomic_DNA. DR EMBL; AF520550; AAQ17597.1; -; Genomic_DNA. DR EMBL; AF520552; AAQ17598.1; -; Genomic_DNA. DR EMBL; AF520554; AAQ17599.1; -; Genomic_DNA. DR EMBL; AF520556; AAQ17600.1; -; Genomic_DNA. DR EMBL; AF520558; AAQ17601.1; -; Genomic_DNA. DR EMBL; AF520560; AAQ17602.1; -; Genomic_DNA. DR EMBL; AF520562; AAQ17603.1; -; Genomic_DNA. DR EMBL; AF520564; AAQ17604.1; -; Genomic_DNA. DR EMBL; BC137381; AAI37382.1; -; mRNA. DR EMBL; AF506835; AAM33413.1; -; mRNA. DR CCDS; CCDS5626.1; -. DR RefSeq; NP_001124397.1; NM_001130925.1. DR RefSeq; NP_055405.3; NM_014590.3. DR PDB; 5HA6; X-ray; 2.00 A; A/B=343-435. DR PDB; 6RX1; X-ray; 2.10 A; A=342-435. DR PDBsum; 5HA6; -. DR PDBsum; 6RX1; -. DR AlphaFoldDB; Q9UQF0; -. DR SMR; Q9UQF0; -. DR BioGRID; 119040; 2. DR IntAct; Q9UQF0; 2. DR STRING; 9606.ENSP00000419945; -. DR ChEMBL; CHEMBL4662944; -. DR GuidetoPHARMACOLOGY; 3182; -. DR TCDB; 1.G.9.1.1; the syncytin (syncytin) family. DR GlyCosmos; Q9UQF0; 7 sites, No reported glycans. DR GlyGen; Q9UQF0; 7 sites. DR iPTMnet; Q9UQF0; -. DR PhosphoSitePlus; Q9UQF0; -. DR BioMuta; ERVW-1; -. DR DMDM; 47605755; -. DR MassIVE; Q9UQF0; -. DR PaxDb; 9606-ENSP00000419945; -. DR PeptideAtlas; Q9UQF0; -. DR ProteomicsDB; 85550; -. DR Antibodypedia; 29999; 278 antibodies from 24 providers. DR DNASU; 30816; -. DR Ensembl; ENST00000493463.2; ENSP00000419945.1; ENSG00000242950.7. DR Ensembl; ENST00000603053.2; ENSP00000474984.1; ENSG00000242950.7. DR GeneID; 30816; -. DR KEGG; hsa:30816; -. DR MANE-Select; ENST00000603053.2; ENSP00000474984.1; NM_001130925.2; NP_001124397.1. DR UCSC; uc022ahe.2; human. DR AGR; HGNC:13525; -. DR DisGeNET; 30816; -. DR GeneCards; ERVW-1; -. DR HGNC; HGNC:13525; ERVW-1. DR HPA; ENSG00000242950; Tissue enriched (placenta). DR MIM; 604659; gene. DR neXtProt; NX_Q9UQF0; -. DR OpenTargets; ENSG00000242950; -. DR PharmGKB; PA27878; -. DR VEuPathDB; HostDB:ENSG00000242950; -. DR eggNOG; ENOG502SD08; Eukaryota. DR GeneTree; ENSGT00690000102286; -. DR HOGENOM; CLU_037857_0_0_1; -. DR InParanoid; Q9UQF0; -. DR OMA; NLTCINY; -. DR OrthoDB; 4765182at2759; -. DR PhylomeDB; Q9UQF0; -. DR TreeFam; TF332233; -. DR PathwayCommons; Q9UQF0; -. DR SignaLink; Q9UQF0; -. DR BioGRID-ORCS; 30816; 348 hits in 1032 CRISPR screens. DR ChiTaRS; ERVW-1; human. DR GeneWiki; ERVWE1; -. DR GenomeRNAi; 30816; -. DR Pharos; Q9UQF0; Tbio. DR PRO; PR:Q9UQF0; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9UQF0; Protein. DR Bgee; ENSG00000242950; Expressed in placenta and 103 other cell types or tissues. DR ExpressionAtlas; Q9UQF0; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0007520; P:myoblast fusion; IMP:MGI. DR GO; GO:0006949; P:syncytium formation; IDA:UniProtKB. DR GO; GO:0000768; P:syncytium formation by plasma membrane fusion; IDA:UniProtKB. DR CDD; cd09851; HTLV-1-like_HR1-HR2; 1. DR Gene3D; 1.10.287.210; -; 1. DR InterPro; IPR018154; TLV/ENV_coat_polyprotein. DR PANTHER; PTHR10424:SF48; SYNCYTIN-1; 1. DR PANTHER; PTHR10424; VIRAL ENVELOPE PROTEIN; 1. DR Pfam; PF00429; TLV_coat; 1. DR SUPFAM; SSF58069; Virus ectodomain; 1. DR Genevisible; Q9UQF0; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cleavage on pair of basic residues; KW Disulfide bond; ERV; Glycoprotein; Membrane; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Transposable element; KW Viral envelope protein; Virion. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..538 FT /note="Syncytin-1" FT /id="PRO_0000008485" FT CHAIN 21..317 FT /note="Surface protein" FT /id="PRO_0000008486" FT CHAIN 318..538 FT /note="Transmembrane protein" FT /id="PRO_0000008487" FT TOPO_DOM 21..443 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 444..464 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 465..538 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 320..340 FT /note="Fusion peptide" FT /evidence="ECO:0000255" FT REGION 380..396 FT /note="Immunosuppression" FT /evidence="ECO:0000250" FT REGION 465..484 FT /note="Essential for the fusiogenic function" FT REGION 496..538 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 186..189 FT /note="CXXC" FT /evidence="ECO:0000305" FT MOTIF 397..406 FT /note="CX6CC" FT /evidence="ECO:0000305" FT COMPBIAS 496..510 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 317..318 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:15827173" FT CARBOHYD 169 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 234 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 242 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 281 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 409 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 186..405 FT /note="Interchain (between SU and TM chains, or C-189 with FT C-405); in linked form" FT /evidence="ECO:0000305|PubMed:15827173" FT DISULFID 186..189 FT /evidence="ECO:0000250|UniProtKB:P23064" FT DISULFID 397..404 FT /evidence="ECO:0000250|UniProtKB:P60508" FT VARIANT 129 FT /note="V -> A (in dbSNP:rs142852059)" FT /evidence="ECO:0000269|PubMed:14757826" FT /id="VAR_018638" FT VARIANT 138 FT /note="R -> Q (in dbSNP:rs55903518)" FT /evidence="ECO:0000269|PubMed:14757826" FT /id="VAR_018639" FT VARIANT 307 FT /note="S -> N (in dbSNP:rs10266695)" FT /evidence="ECO:0000269|PubMed:10693809, FT ECO:0000269|PubMed:11990458, ECO:0000269|PubMed:14757826" FT /id="VAR_018640" FT VARIANT 477 FT /note="S -> F (in dbSNP:rs141340741)" FT /evidence="ECO:0000269|PubMed:14757826" FT /id="VAR_018641" FT MUTAGEN 314..316 FT /note="RNK->AAA: Complete loss of cleavage between SU and FT TM. Loss of fusiogenic function." FT /evidence="ECO:0000269|PubMed:15827173" FT MUTAGEN 317 FT /note="R->T: Complete loss of cleavage between SU and TM. FT Loss of fusiogenic function." FT /evidence="ECO:0000269|PubMed:15827173" FT MUTAGEN 405 FT /note="C->A: Loss of fusiogenic function. No effect on FT cleavage between SU and TM." FT /evidence="ECO:0000269|PubMed:15827173" FT CONFLICT 13..14 FT /note="LL -> VS (in Ref. 1; AAD14545)" FT /evidence="ECO:0000305" FT CONFLICT 56 FT /note="S -> C (in Ref. 1; AAD14545)" FT /evidence="ECO:0000305" FT CONFLICT 298 FT /note="T -> A (in Ref. 1; AAD14545/AAD14548)" FT /evidence="ECO:0000305" FT CONFLICT 381 FT /note="Q -> R (in Ref. 3; AAF74215)" FT /evidence="ECO:0000305" FT CONFLICT 388 FT /note="L -> S (in Ref. 1; AAD14548)" FT /evidence="ECO:0000305" FT HELIX 343..389 FT /evidence="ECO:0007829|PDB:5HA6" FT HELIX 391..393 FT /evidence="ECO:0007829|PDB:5HA6" FT HELIX 396..400 FT /evidence="ECO:0007829|PDB:5HA6" FT HELIX 411..433 FT /evidence="ECO:0007829|PDB:5HA6" SQ SEQUENCE 538 AA; 59866 MW; C54648A3C7043870 CRC64; MALPYHIFLF TVLLPSFTLT APPPCRCMTS SSPYQEFLWR MQRPGNIDAP SYRSLSKGTP TFTAHTHMPR NCYHSATLCM HANTHYWTGK MINPSCPGGL GVTVCWTYFT QTGMSDGGGV QDQAREKHVK EVISQLTRVH GTSSPYKGLD LSKLHETLRT HTRLVSLFNT TLTGLHEVSA QNPTNCWICL PLNFRPYVSI PVPEQWNNFS TEINTTSVLV GPLVSNLEIT HTSNLTCVKF SNTTYTTNSQ CIRWVTPPTQ IVCLPSGIFF VCGTSAYRCL NGSSESMCFL SFLVPPMTIY TEQDLYSYVI SKPRNKRVPI LPFVIGAGVL GALGTGIGGI TTSTQFYYKL SQELNGDMER VADSLVTLQD QLNSLAAVVL QNRRALDLLT AERGGTCLFL GEECCYYVNQ SGIVTEKVKE IRDRIQRRAE ELRNTGPWGL LSQWMPWILP FLGPLAAIIL LLLFGPCIFN LLVNFVSSRI EAVKLQMEPK MQSKTKIYRR PLDRPASPRS DVNDIKGTPP EEISAAQPLL RPNSAGSS //