ID VGP_EBOZM Reviewed; 676 AA. AC Q05320; Q66818; Q77LU5; Q8B9S1; Q8JS62; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 27-MAR-2024, entry version 164. DE RecName: Full=Envelope glycoprotein; DE AltName: Full=GP1,2; DE Short=GP; DE Contains: DE RecName: Full=Shed GP; DE AltName: Full=GP1,2-delta; DE Contains: DE RecName: Full=GP1; DE Contains: DE RecName: Full=GP2; DE Flags: Precursor; GN Name=GP; OS Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus; OC Orthoebolavirus zairense; Zaire ebolavirus. OX NCBI_TaxID=128952; OH NCBI_TaxID=77231; Epomops franqueti (Franquet's epauletted fruit bat) (Epomophorus franqueti). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=8237108; DOI=10.1016/0168-1702(93)90063-s; RA Sanchez A., Kiley M.P., Holloway B.P., Auperin D.D.; RT "Sequence analysis of the Ebola virus genome: organization, genetic RT elements, and comparison with the genome of Marburg virus."; RL Virus Res. 29:215-240(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA], AND RNA EDITING. RX PubMed=8553543; DOI=10.1006/viro.1995.0052; RA Volchkov V.E., Becker S., Volchkova V.A., Ternovoj V.A., Kotov A.N., RA Netesov S.V., Klenk H.-D.; RT "GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 RT and vaccinia virus polymerases."; RL Virology 214:421-430(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND RNA EDITING. RX PubMed=8622982; DOI=10.1073/pnas.93.8.3602; RA Sanchez A., Trappier S.G., Mahy B.W.J., Peters C.J., Nichol S.T.; RT "The virion glycoproteins of Ebola viruses are encoded in two reading RT frames and are expressed through transcriptional editing."; RL Proc. Natl. Acad. Sci. U.S.A. 93:3602-3607(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate guinea pig-adapted; RX PubMed=11062045; DOI=10.1006/viro.2000.0572; RA Volchkov V.E., Chepurnov A.A., Volchkova V.A., Ternovoj V.A., Klenk H.D.; RT "Molecular characterization of guinea pig-adapted variants of Ebola RT virus."; RL Virology 277:147-155(2000). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Volchkov V.E.; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate mouse-adapted; RA Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 359-676. RX PubMed=1299611; DOI=10.1016/0014-5793(92)80662-z; RA Volchkov V.E., Blinov V.M., Netesov S.V.; RT "The envelope glycoprotein of Ebola virus contains an immunosuppressive- RT like domain similar to oncogenic retroviruses."; RL FEBS Lett. 305:181-184(1992). RN [8] RP PROTEOLYTIC PROCESSING (ENVELOPE GLYCOPROTEIN), AND TOPOLOGY. RX PubMed=9576958; DOI=10.1073/pnas.95.10.5762; RA Volchkov V.E., Feldmann H., Volchkova V.A., Klenk H.-D.; RT "Processing of the Ebola virus glycoprotein by the proprotein convertase RT furin."; RL Proc. Natl. Acad. Sci. U.S.A. 95:5762-5767(1998). RN [9] RP PROTEOLYTIC PROCESSING (ENVELOPE GLYCOPROTEIN). RX PubMed=9614872; DOI=10.1006/viro.1998.9143; RA Volchkov V.E., Volchkova V.A., Slenczka W., Klenk H.-D., Feldmann H.; RT "Release of viral glycoproteins during Ebola virus infection."; RL Virology 245:110-119(1998). RN [10] RP DOMAIN. RX PubMed=9499027; DOI=10.1128/jvi.72.3.1775-1781.1998; RA Ruiz-Arguello M.B., Goni F.M., Pereira F.B., Nieva J.L.; RT "Phosphatidylinositol-dependent membrane fusion induced by a putative RT fusogenic sequence of Ebola virus."; RL J. Virol. 72:1775-1781(1998). RN [11] RP DOMAIN, AND MUTAGENESIS OF GLY-528; LEU-529; ILE-532; PHE-535; GLY-536 AND RP PRO-537. RX PubMed=10482652; DOI=10.1128/jvi.73.10.8907-8912.1999; RA Ito H., Watanabe S., Sanchez A., Whitt M.A., Kawaoka Y.; RT "Mutational analysis of the putative fusion domain of Ebola virus RT glycoprotein."; RL J. Virol. 73:8907-8912(1999). RN [12] RP PROTEOLYTIC PROCESSING (ENVELOPE GLYCOPROTEIN), AND MUTAGENESIS OF RP 498-ARG--ARG-501. RX PubMed=9882347; DOI=10.1128/jvi.73.2.1419-1426.1999; RA Wool-Lewis R.J., Bates P.; RT "Endoproteolytic processing of the ebola virus envelope glycoprotein: RT cleavage is not required for function."; RL J. Virol. 73:1419-1426(1999). RN [13] RP FUNCTION, AND DOMAIN MUCIN/LIKE REGION. RX PubMed=10932225; DOI=10.1038/78645; RA Yang Z.-Y., Duckers H.J., Sullivan N.J., Sanchez A., Nabel E.G., RA Nabel G.J.; RT "Identification of the Ebola virus glycoprotein as the main viral RT determinant of vascular cell cytotoxicity and injury."; RL Nat. Med. 6:886-889(2000). RN [14] RP FUNCTION (ENVELOPE GLYCOPROTEIN). RX PubMed=11112476; DOI=10.1006/viro.2000.0601; RA Takada A., Watanabe S., Ito H., Okazaki K., Kida H., Kawaoka Y.; RT "Downregulation of beta1 integrins by Ebola virus glycoprotein: implication RT for virus entry."; RL Virology 278:20-26(2000). RN [15] RP PROTEOLYTIC PROCESSING (ENVELOPE GLYCOPROTEIN), PALMITOYLATION AT CYS-670 RP AND CYS-672, AND MUTAGENESIS OF 497-ARG--ARG-501; CYS-670 AND CYS-672. RX PubMed=11152533; DOI=10.1128/jvi.75.3.1576-1580.2001; RA Ito H., Watanabe S., Takada A., Kawaoka Y.; RT "Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, RT and detection of neutralizing antibodies."; RL J. Virol. 75:1576-1580(2001). RN [16] RP COILED-COIL. RX PubMed=11024148; DOI=10.1128/jvi.74.21.10194-10201.2000; RA Watanabe S., Takada A., Watanabe T., Ito H., Kida H., Kawaoka Y.; RT "Functional importance of the coiled-coil of the Ebola virus RT glycoprotein."; RL J. Virol. 74:10194-10201(2000). RN [17] RP INTERACTION WITH HUMAN FOLR1 (ENVELOPE GLYCOPROTEIN). RX PubMed=11461707; DOI=10.1016/s0092-8674(01)00418-4; RA Chan S.Y., Empig C.J., Welte F.J., Speck R.F., Schmaljohn A., RA Kreisberg J.F., Goldsmith M.A.; RT "Folate receptor-alpha is a cofactor for cellular entry by Marburg and RT Ebola viruses."; RL Cell 106:117-126(2001). RN [18] RP DISULFIDE BONDS, GLYCOSYLATION, AND MUTAGENESIS OF ASN-40; CYS-53; CYS-108; RP CYS-121; CYS-135; CYS-147; ASN-204; ASN-238; ASN-257; ASN-296; CYS-511; RP CYS-556; ASN-563; CYS-601; CYS-608; CYS-609; ASN-618; CYS-670 AND CYS-672. RX PubMed=12438572; DOI=10.1128/jvi.76.24.12463-12472.2002; RA Jeffers S.A., Sanders D.A., Sanchez A.; RT "Covalent modifications of the ebola virus glycoprotein."; RL J. Virol. 76:12463-12472(2002). RN [19] RP FUNCTION (ENVELOPE GLYCOPROTEIN). RX PubMed=11836430; DOI=10.1128/jvi.76.5.2518-2528.2002; RA Simmons G., Wool-Lewis R.J., Baribaud F., Netter R.C., Bates P.; RT "Ebola virus glycoproteins induce global surface protein down-modulation RT and loss of cell adherence."; RL J. Virol. 76:2518-2528(2002). RN [20] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-670 AND CYS-672. RX PubMed=11877482; DOI=10.1084/jem.20011500; RA Bavari S., Bosio C.M., Wiegand E., Ruthel G., Will A.B., Geisbert T.W., RA Hevey M., Schmaljohn C., Schmaljohn A., Aman M.J.; RT "Lipid raft microdomains: a gateway for compartmentalized trafficking of RT Ebola and Marburg viruses."; RL J. Exp. Med. 195:593-602(2002). RN [21] RP INTERACTION WITH HUMAN CD209 (ENVELOPE GLYCOPROTEIN), INTERACTION WITH HOST RP CLEC4M (ENVELOPE GLYCOPROTEIN), AND ROLE IN TRANS INFECTION. RX PubMed=12050398; DOI=10.1128/jvi.76.13.6841-6844.2002; RA Alvarez C.P., Lasala F., Carrillo J., Muniz O., Corbi A.L., Delgado R.; RT "C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in RT cis and in trans."; RL J. Virol. 76:6841-6844(2002). RN [22] RP PUTATIVE ROLE OF FOLR1 IN VIRUS ENTRY INTO THE CELL. RX PubMed=14645601; DOI=10.1128/jvi.77.24.13433-13438.2003; RA Simmons G., Rennekamp A.J., Chai N., Vandenberghe L.H., Riley J.L., RA Bates P.; RT "Folate receptor alpha and caveolae are not required for Ebola virus RT glycoprotein-mediated viral infection."; RL J. Virol. 77:13433-13438(2003). RN [23] RP INTERACTION WITH HUMAN CD209 (ENVELOPE GLYCOPROTEIN), AND INTERACTION WITH RP HOST CLEC4M (ENVELOPE GLYCOPROTEIN). RX PubMed=12504546; DOI=10.1006/viro.2002.1730; RA Simmons G., Reeves J.D., Grogan C.C., Vandenberghe L.H., Baribaud F., RA Whitbeck J.C., Burke E., Buchmeier M.J., Soilleux E.J., Riley J.L., RA Doms R.W., Bates P., Poehlmann S.; RT "DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of RT macrophages and endothelial cells."; RL Virology 305:115-123(2003). RN [24] RP CLEAVAGE BY HOST ADAM17, MUTAGENESIS OF ASP-632; LYS-633; THR-634; LEU-635; RP ASP-637; GLN-638; GLY-639; ASP-640; ASN-641; ASP-642 AND ASN-643, AND RP SUBCELLULAR LOCATION. RX PubMed=15103332; DOI=10.1038/sj.emboj.7600219; RA Dolnik O., Volchkova V., Garten W., Carbonnelle C., Becker S., Kahnt J., RA Stroeher U., Klenk H.-D., Volchkov V.; RT "Ectodomain shedding of the glycoprotein GP of Ebola virus."; RL EMBO J. 23:2175-2184(2004). RN [25] RP INTERACTION WITH HUMAN CLEC10A (ENVELOPE GLYCOPROTEIN). RX PubMed=14990712; DOI=10.1128/jvi.78.6.2943-2947.2004; RA Takada A., Fujioka K., Tsuiji M., Morikawa A., Higashi N., Ebihara H., RA Kobasa D., Feldmann H., Irimura T., Kawaoka Y.; RT "Human macrophage C-type lectin specific for galactose and N- RT acetylgalactosamine promotes filovirus entry."; RL J. Virol. 78:2943-2947(2004). RN [26] RP FUNCTION (GP1). RX PubMed=16051836; DOI=10.1128/jvi.79.16.10442-10450.2005; RA Wahl-Jensen V.M., Afanasieva T.A., Seebach J., Stroeher U., Feldmann H., RA Schnittler H.J.; RT "Effects of Ebola virus glycoproteins on endothelial cell activation and RT barrier function."; RL J. Virol. 79:10442-10450(2005). RN [27] RP PROTEOLYSIS (GP1). RX PubMed=15831716; DOI=10.1126/science.1110656; RA Chandran K., Sullivan N.J., Felbor U., Whelan S.P., Cunningham J.M.; RT "Endosomal proteolysis of the Ebola virus glycoprotein is necessary for RT infection."; RL Science 308:1643-1645(2005). RN [28] RP FUNCTION (GP1,2DELTA), AND SUBUNIT (GP1,2DELTA). RX PubMed=15681442; DOI=10.1128/jvi.79.4.2413-2419.2005; RA Wahl-Jensen V., Kurz S.K., Hazelton P.R., Schnittler H.J., Stroeher U., RA Burton D.R., Feldmann H.; RT "Role of Ebola virus secreted glycoproteins and virus-like particles in RT activation of human macrophages."; RL J. Virol. 79:2413-2419(2005). RN [29] RP DOWN-MODULATION OF HOST INTEGRIN DIMER ALPHA-V/BETA-3, AND INTERACTION WITH RP HUMAN INTEGRIN ITGAV (ENVELOPE GLYCOPROTEIN). RX PubMed=15596847; DOI=10.1128/jvi.79.1.547-553.2005; RA Sullivan N.J., Peterson M., Yang Z.-Y., Kong W.-P., Duckers H., Nabel E., RA Nabel G.J.; RT "Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent RT protein-trafficking pathway."; RL J. Virol. 79:547-553(2005). RN [30] RP PROTEOLYSIS (GP1). RX PubMed=16571833; DOI=10.1128/jvi.80.8.4174-4178.2006; RA Schornberg K., Matsuyama S., Kabsch K., Delos S., Bouton A., White J.; RT "Role of endosomal cathepsins in entry mediated by the Ebola virus RT glycoprotein."; RL J. Virol. 80:4174-4178(2006). RN [31] RP FUNCTION. RX PubMed=16603527; DOI=10.1099/vir.0.81361-0; RA Alazard-Dany N., Volchkova V., Reynard O., Carbonnelle C., Dolnik O., RA Ottmann M., Khromykh A., Volchkov V.E.; RT "Ebola virus glycoprotein GP is not cytotoxic when expressed constitutively RT at a moderate level."; RL J. Gen. Virol. 87:1247-1257(2006). RN [32] RP FUNCTION OF SIGNAL PEPTIDE. RX PubMed=16775318; DOI=10.1128/jvi.02545-05; RA Marzi A., Akhavan A., Simmons G., Gramberg T., Hofmann H., Bates P., RA Lingappa V.R., Poehlmann S.; RT "The signal peptide of the ebolavirus glycoprotein influences interaction RT with the cellular lectins DC-SIGN and DC-SIGNR."; RL J. Virol. 80:6305-6317(2006). RN [33] RP RECEPTOR-BINDING REGION. RX PubMed=16595665; DOI=10.1074/jbc.m601796200; RA Kuhn J.H., Radoshitzky S.R., Guth A.C., Warfield K.L., Li W., Vincent M.J., RA Towner J.S., Nichol S.T., Bavari S., Choe H., Aman M.J., Farzan M.; RT "Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire RT ebolavirus bind a common receptor."; RL J. Biol. Chem. 281:15951-15958(2006). RN [34] RP FUNCTION. RX PubMed=20862315; DOI=10.1371/journal.ppat.1001110; RA Saeed M.F., Kolokoltsov A.A., Albrecht T., Davey R.A.; RT "Cellular entry of ebola virus involves uptake by a macropinocytosis-like RT mechanism and subsequent trafficking through early and late endosomes."; RL PLoS Pathog. 6:0-0(2010). RN [35] RP INTERACTION WITH HOST TLR4 (ENVELOPE GLYCOPROTEIN). RX PubMed=19846529; DOI=10.1128/jvi.01462-09; RA Okumura A., Pitha P.M., Yoshimura A., Harty R.N.; RT "Interaction between Ebola virus glycoprotein and host toll-like receptor 4 RT leads to induction of proinflammatory cytokines and SOCS1."; RL J. Virol. 84:27-33(2010). RN [36] RP FUNCTION. RX PubMed=20202662; DOI=10.1016/j.virol.2010.02.015; RA Bhattacharyya S., Warfield K.L., Ruthel G., Bavari S., Aman M.J., RA Hope T.J.; RT "Ebola virus uses clathrin-mediated endocytosis as an entry pathway."; RL Virology 401:18-28(2010). RN [37] RP INTERACTION WITH HOST NPC1 (ENVELOPE GLYCOPROTEIN), AND FUNCTION (GP1). RX PubMed=21866103; DOI=10.1038/nature10348; RA Carette J.E., Raaben M., Wong A.C., Herbert A.S., Obernosterer G., RA Mulherkar N., Kuehne A.I., Kranzusch P.J., Griffin A.M., Ruthel G., RA Dal Cin P., Dye J.M., Whelan S.P., Chandran K., Brummelkamp T.R.; RT "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1."; RL Nature 477:340-343(2011). RN [38] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE (GP1). RX PubMed=22031933; DOI=10.1128/jvi.05708-11; RA Brecher M., Schornberg K.L., Delos S.E., Fusco M.L., Saphire E.O., RA White J.M.; RT "Cathepsin cleavage potentiates the Ebola virus glycoprotein to undergo a RT subsequent fusion-relevant conformational change."; RL J. Virol. 86:364-372(2012). RN [39] RP FUNCTION (SHED GP), SUBCELLULAR LOCATION (SHED GP), AND GLYCOSYLATION (SHED RP GP). RX PubMed=25412102; DOI=10.1371/journal.ppat.1004509; RA Escudero-Perez B., Volchkova V.A., Dolnik O., Lawrence P., Volchkov V.E.; RT "Shed GP of Ebola virus triggers immune activation and increased vascular RT permeability."; RL PLoS Pathog. 10:E1004509-E1004509(2014). RN [40] RP FUNCTION (ENVELOPE GLYCOPROTEIN). RX PubMed=26516900; DOI=10.3390/v7102888; RA Vande Burgt N.H., Kaletsky R.L., Bates P.; RT "Requirements within the Ebola viral glycoprotein for tetherin RT antagonism."; RL Viruses 7:5587-5602(2015). RN [41] RP FUNCTION (SHED GP), AND MUTAGENESIS OF LEU-635 AND ASP-637. RX PubMed=26092855; DOI=10.1093/infdis/jiv268; RA Dolnik O., Volchkova V.A., Escudero-Perez B., Lawrence P., Klenk H.D., RA Volchkov V.E.; RT "Shedding of Ebola Virus Surface Glycoprotein Is a Mechanism of Self- RT regulation of Cellular Cytotoxicity and Has a Direct Effect on Virus RT Infectivity."; RL J. Infect. Dis. 212:S322-S328(2015). RN [42] RP FUNCTION (ENVELOPE GLYCOPROTEIN), INTERACTION WITH HOST BST2 (ENVELOPE RP GLYCOPROTEIN), AND MUTAGENESIS OF PHE-88; LEU-111 AND LEU-122. RX PubMed=27707924; DOI=10.1128/jvi.01563-16; RA Brinkmann C., Nehlmeier I., Walendy-Gnirss K., Nehls J., RA Gonzalez Hernandez M., Hoffmann M., Qiu X., Takada A., Schindler M., RA Poehlmann S.; RT "The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact RT Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies."; RL J. Virol. 90:11075-11086(2016). RN [43] RP INTERACTION WITH HOST FCN1 (ENVELOPE GLYCOPROTEIN). RX PubMed=26984723; DOI=10.1128/jvi.00232-16; RA Favier A.L., Gout E., Reynard O., Ferraris O., Kleman J.P., Volchkov V., RA Peyrefitte C., Thielens N.M.; RT "Enhancement of Ebola Virus Infection via Ficolin-1 Interaction with the RT Mucin Domain of GP Glycoprotein."; RL J. Virol. 90:5256-5269(2016). RN [44] RP FUNCTION (ENVELOPE GLYCOPROTEIN), AND INTERACTION WITH HOST TLR4 (ENVELOPE RP GLYCOPROTEIN). RX PubMed=28542576; DOI=10.1371/journal.ppat.1006397; RA Iampietro M., Younan P., Nishida A., Dutta M., Lubaki N.M., Santos R.I., RA Koup R.A., Katze M.G., Bukreyev A.; RT "Ebola virus glycoprotein directly triggers T lymphocyte death despite of RT the lack of infection."; RL PLoS Pathog. 13:E1006397-E1006397(2017). RN [45] RP FUNCTION (ENVELOPE GLYCOPROTEIN). RX PubMed=28878074; DOI=10.1128/jvi.01308-17; RA Rizk M.G., Basler C.F., Guatelli J.; RT "Cooperation of the Ebola Virus Proteins VP40 and GP1,2 with BST2 To RT Activate NF-kappaB Independently of Virus-Like Particle Trapping."; RL J. Virol. 91:0-0(2017). RN [46] RP FUNCTION (ENVELOPE GLYCOPROTEIN), MOTIF, AND MUTAGENESIS OF GLY-660 AND RP ALA-664. RX PubMed=29669839; DOI=10.1128/jvi.00403-18; RA Gonzalez-Hernandez M., Hoffmann M., Brinkmann C., Nehls J., Winkler M., RA Schindler M., Poehlmann S.; RT "A GXXXA Motif in the Transmembrane Domain of the Ebola Virus Glycoprotein RT Is Required for Tetherin Antagonism."; RL J. Virol. 92:0-0(2018). RN [47] RP FUNCTION (ENVELOPE GLYCOPROTEIN). RX PubMed=30013549; DOI=10.3389/fimmu.2018.01428; RA Edri A., Shemesh A., Iraqi M., Matalon O., Brusilovsky M., Hadad U., RA Radinsky O., Gershoni-Yahalom O., Dye J.M., Mandelboim O., Barda-Saad M., RA Lobel L., Porgador A.; RT "The Ebola-Glycoprotein Modulates the Function of Natural Killer Cells."; RL Front. Immunol. 9:1428-1428(2018). RN [48] RP FUNCTION (SHED GP), AND SUBCELLULAR LOCATION (SHED GP). RX PubMed=30085081; DOI=10.1093/infdis/jiy406; RA Iampietro M., Santos R.I., Lubaki N.M., Bukreyev A.; RT "Ebola Virus Shed Glycoprotein Triggers Differentiation, Infection, and RT Death of Monocytes Through Toll-Like Receptor 4 Activation."; RL J. Infect. Dis. 218:S327-S334(2018). RN [49] RP INTERACTION WITH HOST NPC1, AND FUNCTION. RX PubMed=32040508; DOI=10.1371/journal.pbio.3000626; RA Das D.K., Bulow U., Diehl W.E., Durham N.D., Senjobe F., Chandran K., RA Luban J., Munro J.B.; RT "Conformational changes in the Ebola virus membrane fusion machine induced RT by pH, Ca2+, and receptor binding."; RL PLoS Biol. 18:e3000626-e3000626(2020). RN [50] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 557-630. RX PubMed=10077567; DOI=10.1073/pnas.96.6.2662; RA Malashkevich V.N., Schneider B.J., McNally M.L., Milhollen M.A., Pang J.X., RA Kim P.S.; RT "Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A RT resolution."; RL Proc. Natl. Acad. Sci. U.S.A. 96:2662-2667(1999). RN [51] {ECO:0007744|PDB:7SWD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.59 ANGSTROMS) OF 33-188 AND 504-599 IN RP COMPLEX WITH ANTIBODIES 1C3 AND 1C11, AND SUBUNIT (ENVELOPE GLYCOPROTEIN). RX PubMed=35303429; DOI=10.1016/j.cell.2022.02.023; RA Milligan J.C., Davis C.W., Yu X., Ilinykh P.A., Huang K., Halfmann P.J., RA Cross R.W., Borisevich V., Agans K.N., Geisbert J.B., Chennareddy C., RA Goff A.J., Piper A.E., Hui S., Shaffer K.C.L., Buck T., Heinrich M.L., RA Branco L.M., Crozier I., Holbrook M.R., Kuhn J.H., Kawaoka Y., Glass P.J., RA Bukreyev A., Geisbert T.W., Worwa G., Ahmed R., Saphire E.O.; RT "Asymmetric and non-stoichiometric glycoprotein recognition by two distinct RT antibodies results in broad protection against ebolaviruses."; RL Cell 185:995-1007.e18(2022). CC -!- FUNCTION: [Envelope glycoprotein]: Trimeric GP1,2 complexes form the CC virion surface spikes and mediate the viral entry processes, with GP1 CC acting as the receptor-binding subunit and GP2 as the membrane fusion CC subunit. At later times of infection, down-regulates the expression of CC various host cell surface molecules that are essential for immune CC surveillance and cell adhesion (PubMed:11836430). Down-modulates CC several integrins including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, CC ITGAV and ITGB1 (PubMed:11112476). This decrease in cell adhesion CC molecules may lead to cell detachment, contributing to the disruption CC of blood vessel integrity and hemorrhages developed during infection CC (cytotoxicity) (Probable). Interacts with host TLR4 and thereby CC stimulates the differentiation and activation of monocytes leading to CC bystander death of T-lymphocytes (PubMed:28542576). Down-regulates as CC well the function of host natural killer cells (PubMed:30013549). CC Counteracts the antiviral effect of host BST2/tetherin that restricts CC release of progeny virions from infected cells (PubMed:26516900, CC PubMed:27707924, PubMed:29669839). However, cooperates with VP40 and CC host BST2 to activate canonical NF-kappa-B pathway in a manner CC dependent on neddylation (PubMed:28878074). CC {ECO:0000269|PubMed:11112476, ECO:0000269|PubMed:11836430, CC ECO:0000269|PubMed:26516900, ECO:0000269|PubMed:27707924, CC ECO:0000269|PubMed:28542576, ECO:0000269|PubMed:28878074, CC ECO:0000269|PubMed:29669839, ECO:0000269|PubMed:30013549, CC ECO:0000305|PubMed:11112476}. CC -!- FUNCTION: [Shed GP]: Functions as a decoy for anti-GP1,2 antibodies CC thereby contributing to viral immune evasion. Interacts and activates CC host macrophages and dendritic cells inducing up-regulation of cytokine CC transcription. This effect is mediated throught activation of host CC TLR4. {ECO:0000269|PubMed:25412102, ECO:0000269|PubMed:26092855, CC ECO:0000269|PubMed:30085081}. CC -!- FUNCTION: [GP1]: Responsible for binding to the receptor(s) on target CC cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as CC cofactors for virus entry into dendritic cells (DCs) and endothelial CC cells (PubMed:16051836). Binding to the macrophage specific lectin CC CLEC10A also seems to enhance virus infectivity (By similarity). CC Interaction with FOLR1/folate receptor alpha may be a cofactor for CC virus entry in some cell types, although results are contradictory. CC Members of the Tyro3 receptor tyrosine kinase family also seem to be CC cell entry factors in filovirus infection (By similarity). Once CC attached, the virions are internalized through clathrin-dependent CC endocytosis and/or macropinocytosis. After internalization of the virus CC into the endosomes of the host cell, proteolysis of GP1 by two cysteine CC proteases, CTSB/cathepsin B and CTSL/cathepsin L removes the glycan cap CC and allows GP1 binding to the host entry receptor NPC1 CC (PubMed:21866103, PubMed:32040508). NPC1-binding, Ca(2+) and acidic pH CC induce a conformational change of GP2, which unmasks its fusion peptide CC and permit membranes fusion (PubMed:21866103, PubMed:22031933, CC PubMed:32040508). {ECO:0000250|UniProtKB:O11457, CC ECO:0000250|UniProtKB:Q66814, ECO:0000269|PubMed:16051836, CC ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:22031933, CC ECO:0000269|PubMed:32040508}. CC -!- FUNCTION: [GP2]: Acts as a class I viral fusion protein. Under the CC current model, the protein has 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 viral and target cell CC membranes. Responsible for penetration of the virus into the cell CC cytoplasm by mediating the fusion of the membrane of the endocytosed CC virus particle with the endosomal membrane. Low pH in endosomes induces CC an irreversible conformational change in GP2, releasing the fusion CC hydrophobic peptide. CC -!- SUBUNIT: [Envelope glycoprotein]: Homotrimer; each monomer consists of CC a GP1 and a GP2 subunit linked by disulfide bonds (PubMed:35303429). CC The resulting peplomers (GP1,2) protrude from the virus surface as CC spikes. Interacts with host integrin alpha-V/ITGAV (PubMed:15596847). CC Interacts with host CLEC10A (PubMed:14990712). Binds also to host CD209 CC and CLEC4M/DC-SIGN(R) (PubMed:12050398, PubMed:12504546). Interacts CC with host FOLR1 (PubMed:11461707). Interacts with BST2; this CC interaction inhibits the antiviral effect of BST2 and this allows viral CC release from infected cells (PubMed:27707924). Interacts with host CC FCN1; this interaction enhances viral entry (PubMed:26984723). CC Interacts with host TLR4; this interaction induces cell death in T- CC lymphocytes or proinflammatory cytokines and SOCS1 production in CC monocytes (PubMed:28542576, PubMed:19846529). CC {ECO:0000269|PubMed:11461707, ECO:0000269|PubMed:12050398, CC ECO:0000269|PubMed:12504546, ECO:0000269|PubMed:14990712, CC ECO:0000269|PubMed:15596847, ECO:0000269|PubMed:19846529, CC ECO:0000269|PubMed:26984723, ECO:0000269|PubMed:27707924, CC ECO:0000269|PubMed:28542576, ECO:0000269|PubMed:35303429}. CC -!- SUBUNIT: [GP1]: Interacts with host entry receptor NPC1. CC {ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:32040508}. CC -!- SUBUNIT: [Shed GP]: GP1 and GP2delta are part of GP1,2delta soluble CC complexes released by ectodomain shedding. CC {ECO:0000269|PubMed:15681442}. CC -!- INTERACTION: CC Q05320; Q05320: GP; NbExp=3; IntAct=EBI-16200230, EBI-16200230; CC -!- SUBCELLULAR LOCATION: [GP2]: Virion membrane CC {ECO:0000305|PubMed:11877482}; Single-pass type I membrane protein CC {ECO:0000255}. Host cell membrane {ECO:0000305|PubMed:11877482}; CC Single-pass type I membrane protein {ECO:0000255}. Note=In the cell, CC localizes to the plasma membrane lipid rafts, which probably represent CC the assembly and budding site. {ECO:0000305|PubMed:11877482}. CC -!- SUBCELLULAR LOCATION: [GP1]: Virion membrane CC {ECO:0000305|PubMed:11877482}; Peripheral membrane protein. Host cell CC membrane {ECO:0000305|PubMed:11877482}; Peripheral membrane protein CC {ECO:0000269|PubMed:9576958}. Note=GP1 is not anchored to the viral CC envelope, but forms a disulfid-linked complex with the extravirion CC surface GP2 (PubMed:9576958). In the cell, both GP1 and GP2 localize to CC the plasma membrane lipid rafts, which probably represent the assembly CC and budding site (PubMed:11877482). GP1 can also be shed after CC proteolytic processing. {ECO:0000269|PubMed:11877482, CC ECO:0000269|PubMed:9576958}. CC -!- SUBCELLULAR LOCATION: [Shed GP]: Secreted {ECO:0000269|PubMed:15103332, CC ECO:0000269|PubMed:25412102, ECO:0000269|PubMed:30085081}. Note=GP2- CC delta bound to GP1 (GP1,2-delta) is produced by proteolytic cleavage of CC GP1,2 by host ADAM17 and shed by the virus. CC {ECO:0000269|PubMed:15103332}. CC -!- DOMAIN: [GP1]: The mucin-like region seems to be involved in the CC cytotoxic function. This region is also involved in binding to human CC CLEC10A. CC -!- DOMAIN: The coiled coil regions play a role in oligomerization and CC fusion activity. CC -!- PTM: The signal peptide region modulates GP's high mannose CC glycosylation, thereby determining the efficiency of the interactions CC with DC-SIGN(R). {ECO:0000269|PubMed:12438572}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12438572}. CC -!- PTM: [Shed GP]: Glycosylated; glycosylation is essential for the CC activation of dendritic cells and macrophages. CC {ECO:0000269|PubMed:25412102}. CC -!- PTM: [GP1]: O-glycosylated in the mucin-like region. CC {ECO:0000269|PubMed:12438572}. CC -!- PTM: [GP2]: Palmitoylation is not required for its function. CC {ECO:0000269|PubMed:11152533}. CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The CC precursor is processed into GP1 and GP2 by host cell furin in the trans CC Golgi, and maybe by other host proteases, to yield the mature GP1 and CC GP2 proteins (PubMed:9576958, PubMed:9614872) (PubMed:9882347). The CC cleavage site corresponds to the furin optimal cleavage sequence [KR]- CC X-[KR]-R (PubMed:9576958). This cleavage does not seem to be required CC for function (PubMed:9576958). After the internalization of the virus CC into cell endosomes, GP1 C-terminus is removed by the endosomal CC proteases cathepsin B, cathepsin L, or both, leaving a 19-kDa N- CC terminal fragment which is further digested by cathepsin B CC (PubMed:16571833). This cleaved 19-kDa GP1 can then bind to the host CC entry receptor NPC1 (PubMed:21866103). Proteolytic processing of GP1,2 CC by host ADAM17 can remove the transmembrane anchor of GP2 and leads to CC shedding of complexes consisting in GP1 and truncated GP2 (GP1,2delta) CC (PubMed:15103332). {ECO:0000269|PubMed:11152533, CC ECO:0000269|PubMed:15103332, ECO:0000269|PubMed:16571833, CC ECO:0000269|PubMed:21866103, ECO:0000269|PubMed:9576958, CC ECO:0000269|PubMed:9614872, ECO:0000269|PubMed:9882347}. CC -!- RNA EDITING: Modified_positions=295 {ECO:0000269|PubMed:8553543, CC ECO:0000269|PubMed:8622982}; Note=Partially edited. RNA editing at this CC position consists of an insertion of one or two adenine nucleotides. CC The sequence displayed here is the full-length transmembrane CC glycoprotein GP, derived from the +1A edited RNA. The unedited RNA CC gives rise to the small secreted glycoprotein sGP (AC P60170), the +2A CC edited RNA gives rise to the super small secreted glycoprotein ssGP (AC CC Q9YMG2).; CC -!- MISCELLANEOUS: Filoviruses entry requires functional lipid rafts at the CC host cell surface. CC -!- MISCELLANEOUS: Essential for infectivity, as it is the sole viral CC protein expressed at the virion surface. CC -!- SIMILARITY: Belongs to the filoviruses glycoprotein family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA96744.1; Type=Frameshift; Evidence={ECO:0000305}; 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; L11365; AAB81004.1; -; Genomic_RNA. DR EMBL; U31033; AAA96744.1; ALT_FRAME; Genomic_RNA. DR EMBL; U23187; AAC54887.1; -; Genomic_RNA. DR EMBL; AF272001; AAG40168.1; -; Genomic_RNA. DR EMBL; AY142960; AAN37507.1; -; Genomic_RNA. DR EMBL; AF086833; AAD14585.1; -; Genomic_RNA. DR EMBL; AF499101; AAM76034.1; -; Genomic_RNA. DR PIR; S23155; S23155. DR RefSeq; NP_066246.1; NC_002549.1. DR PDB; 2EBO; X-ray; 1.90 A; A/B/C=557-630. DR PDB; 2RLJ; NMR; -; A=524-539. DR PDB; 3CSY; X-ray; 3.40 A; I/K/M/O=32-311, J/L/N/P=464-501. DR PDB; 5FHC; X-ray; 6.70 A; J=502-599, K=1-308, K=490-501. DR PDB; 5HJ3; X-ray; 3.30 A; C/G/K/O=32-194. DR PDB; 5JQ3; X-ray; 2.23 A; A=32-501, B=502-632. DR PDB; 5JQ7; X-ray; 2.69 A; A=32-501, B=502-632. DR PDB; 5JQB; X-ray; 2.68 A; A=32-501, B=502-632. DR PDB; 5KEL; EM; 4.30 A; A/E/F=33-501, B/G/I=502-637. DR PDB; 5KEM; EM; 5.50 A; A/F=53-284. DR PDB; 5KEN; EM; 4.30 A; A/E/K=33-308, B/F/M=503-615. DR PDB; 6EA7; X-ray; 4.25 A; A/C/E=32-194, B/D/F=502-612. DR PDB; 6EAY; X-ray; 3.72 A; A=502-637, B=32-336. DR PDB; 6F5U; X-ray; 2.07 A; A=32-312, B=502-632. DR PDB; 6F6I; X-ray; 2.40 A; A=32-336, B=502-632. DR PDB; 6F6N; X-ray; 2.15 A; A=32-336. DR PDB; 6F6S; X-ray; 2.29 A; A=32-336. DR PDB; 6G95; X-ray; 2.31 A; A=32-311, B=502-632. DR PDB; 6G9B; X-ray; 2.26 A; A=32-311, B=502-632. DR PDB; 6G9I; X-ray; 2.19 A; A=32-311, B=502-632. DR PDB; 6HRO; X-ray; 2.30 A; A=32-312, B=502-632. DR PDB; 6HS4; X-ray; 2.05 A; A=32-311, B=502-632. DR PDB; 6MAM; X-ray; 4.10 A; G/I/K=32-226, H/J/L=502-611. DR PDB; 6NAE; X-ray; 2.75 A; A=32-336, B=502-632. DR PDB; 6OZ9; X-ray; 3.46 A; A=32-188, B=503-615. DR PDB; 6QD7; EM; 3.10 A; A/C/E=32-311, B/D/F=502-632. DR PDB; 6QD8; EM; 3.30 A; A/C/E=32-311, B/D/F=502-632. DR PDB; 6S8D; EM; 3.49 A; A/C/E=32-334, B/D/F=502-632. DR PDB; 6S8I; EM; 2.99 A; A/C/E=32-336, B/D/F=502-632. DR PDB; 6S8J; EM; 2.91 A; A/C/E=32-336, B/D/F=502-632. DR PDB; 6VKM; X-ray; 3.50 A; A=1-647. DR PDB; 7JPH; X-ray; 3.19 A; B=502-637. DR PDB; 7JPI; X-ray; 2.28 A; B=502-637. DR PDB; 7KEJ; EM; 3.80 A; A/B/C=32-309, D/E/F=461-633. DR PDB; 7KEX; EM; 4.25 A; A/B/C=32-309, D/E/F=461-629. DR PDB; 7KF9; EM; 4.40 A; A/B/C=32-309, D/E/F=461-629. DR PDB; 7KFB; EM; 3.90 A; A/B/C=32-309, D/E/F=461-629. DR PDB; 7KFH; EM; 3.80 A; A/B/C=32-309, D/E/F=461-629. DR PDB; 7LYD; X-ray; 2.35 A; A=32-318, B=502-632. DR PDB; 7LYY; X-ray; 2.75 A; A=32-317, B=502-632. DR PDB; 7M2D; X-ray; 2.70 A; A=32-317, B=502-632. DR PDB; 7M8L; EM; 3.90 A; A/B/C=32-309, D/E/F=461-629. DR PDB; 7SSQ; X-ray; 2.25 A; A=32-336, B=502-632. DR PDB; 7SSR; X-ray; 2.50 A; A=32-336, B=502-632. DR PDB; 7SWD; EM; 3.59 A; A/C/E=33-188, B/D/F=504-599. DR PDB; 7TN9; EM; 3.10 A; S/T/U=32-311, V/W/X=503-637. DR PDB; 8DPL; EM; 2.53 A; D/I/M=33-312. DR PDB; 8DPM; EM; 3.00 A; A/F/K=33-312. DR PDB; 8F87; X-ray; 2.60 A; A=32-318, B=502-632. DR PDBsum; 2EBO; -. DR PDBsum; 2RLJ; -. DR PDBsum; 3CSY; -. DR PDBsum; 5FHC; -. DR PDBsum; 5HJ3; -. DR PDBsum; 5JQ3; -. DR PDBsum; 5JQ7; -. DR PDBsum; 5JQB; -. DR PDBsum; 5KEL; -. DR PDBsum; 5KEM; -. DR PDBsum; 5KEN; -. DR PDBsum; 6EA7; -. DR PDBsum; 6EAY; -. DR PDBsum; 6F5U; -. DR PDBsum; 6F6I; -. DR PDBsum; 6F6N; -. DR PDBsum; 6F6S; -. DR PDBsum; 6G95; -. DR PDBsum; 6G9B; -. DR PDBsum; 6G9I; -. DR PDBsum; 6HRO; -. DR PDBsum; 6HS4; -. DR PDBsum; 6MAM; -. DR PDBsum; 6NAE; -. DR PDBsum; 6OZ9; -. DR PDBsum; 6QD7; -. DR PDBsum; 6QD8; -. DR PDBsum; 6S8D; -. DR PDBsum; 6S8I; -. DR PDBsum; 6S8J; -. DR PDBsum; 6VKM; -. DR PDBsum; 7JPH; -. DR PDBsum; 7JPI; -. DR PDBsum; 7KEJ; -. DR PDBsum; 7KEX; -. DR PDBsum; 7KF9; -. DR PDBsum; 7KFB; -. DR PDBsum; 7KFH; -. DR PDBsum; 7LYD; -. DR PDBsum; 7LYY; -. DR PDBsum; 7M2D; -. DR PDBsum; 7M8L; -. DR PDBsum; 7SSQ; -. DR PDBsum; 7SSR; -. DR PDBsum; 7SWD; -. DR PDBsum; 7TN9; -. DR PDBsum; 8DPL; -. DR PDBsum; 8DPM; -. DR PDBsum; 8F87; -. DR BMRB; Q05320; -. DR EMDB; EMD-10118; -. DR EMDB; EMD-10123; -. DR EMDB; EMD-10124; -. DR EMDB; EMD-11665; -. DR EMDB; EMD-26005; -. DR EMDB; EMD-27637; -. DR EMDB; EMD-27638; -. DR EMDB; EMD-3310; -. DR EMDB; EMD-3311; -. DR EMDB; EMD-4520; -. DR EMDB; EMD-4521; -. DR EMDB; EMD-8240; -. DR EMDB; EMD-8242; -. DR SMR; Q05320; -. DR DIP; DIP-62002N; -. DR ELM; Q05320; -. DR IntAct; Q05320; 1. DR BindingDB; Q05320; -. DR ChEMBL; CHEMBL4105829; -. DR DrugBank; DB16385; Ansuvimab. DR DrugBank; DB15898; Atoltivimab. DR DrugBank; DB15899; Maftivimab. DR DrugBank; DB15900; Odesivimab. DR TCDB; 1.G.12.2.2; the avian leukosis virus gp95 fusion protein (alv-gp95) family. DR GlyCosmos; Q05320; 17 sites, No reported glycans. DR ABCD; Q05320; 59 sequenced antibodies. DR DNASU; 911829; -. DR GeneID; 911829; -. DR KEGG; vg:911829; -. DR EvolutionaryTrace; Q05320; -. DR Proteomes; UP000007209; Genome. DR Proteomes; UP000109874; Genome. DR Proteomes; UP000149419; Genome. DR Proteomes; UP000150973; Genome. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0030430; C:host cell cytoplasm; IDA:CACAO. DR GO; GO:0044165; C:host cell endoplasmic reticulum; IMP:CACAO. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045121; C:membrane raft; IDA:CACAO. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008289; F:lipid binding; IDA:DisProt. DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW. DR GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0039587; P:suppression by virus of host tetherin activity; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0046761; P:viral budding from plasma membrane; IDA:CACAO. DR GO; GO:0046718; P:viral entry into host cell; IDA:DisProt. DR CDD; cd09850; Ebola-like_HR1-HR2; 1. DR Gene3D; 1.10.287.210; -; 1. DR InterPro; IPR014625; GPC_FiloV. DR InterPro; IPR002561; GPC_filovir-type_extra_dom. DR Pfam; PF01611; Filo_glycop; 1. DR PIRSF; PIRSF036874; GPC_FiloV; 1. DR SUPFAM; SSF58069; Virus ectodomain; 1. PE 1: Evidence at protein level; KW 3D-structure; Clathrin-mediated endocytosis of virus by host; KW Cleavage on pair of basic residues; Coiled coil; Disulfide bond; KW Fusion of virus membrane with host endosomal membrane; KW Fusion of virus membrane with host membrane; Glycoprotein; KW Host cell membrane; Host membrane; Host-virus interaction; KW Inhibition of host innate immune response by virus; KW Inhibition of host tetherin by virus; Lipoprotein; Membrane; Palmitate; KW Reference proteome; RNA editing; Secreted; Signal; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; KW Viral attachment to host entry receptor; Viral envelope protein; KW Viral immunoevasion; Viral penetration into host cytoplasm; Virion; KW Virus endocytosis by host; Virus entry into host cell. FT SIGNAL 1..32 FT /evidence="ECO:0000255" FT CHAIN 33..676 FT /note="Envelope glycoprotein" FT /id="PRO_0000037485" FT CHAIN 33..637 FT /note="Shed GP" FT /id="PRO_0000445686" FT CHAIN 33..501 FT /note="GP1" FT /id="PRO_0000037486" FT CHAIN 502..676 FT /note="GP2" FT /id="PRO_0000037487" FT TOPO_DOM 33..650 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 651..671 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 672..676 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 54..201 FT /note="Receptor-binding" FT /evidence="ECO:0000255" FT REGION 305..485 FT /note="Mucin-like region" FT REGION 315..337 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 373..392 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 402..479 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 524..539 FT /note="Fusion peptide" FT /evidence="ECO:0000305" FT COILED 554..595 FT /evidence="ECO:0000255" FT COILED 615..634 FT /evidence="ECO:0000255" FT MOTIF 660..664 FT /note="Important role for host BST2/tetherin antagonism" FT /evidence="ECO:0000269|PubMed:27707924" FT COMPBIAS 416..479 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 57 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 63 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 64 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 88 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 95 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 170 FT /note="Involved in receptor recognition and/or post-binding FT events" FT /evidence="ECO:0000255" FT SITE 501..502 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000269|PubMed:9576958" FT SITE 637..638 FT /note="Cleavage; by host ADAM17" FT /evidence="ECO:0000269|PubMed:15103332" FT LIPID 670 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000269|PubMed:11152533" FT LIPID 672 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000269|PubMed:11152533" FT CARBOHYD 40 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 204 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 228 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 238 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 257 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 268 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 317 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 333 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 346 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 386 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 413 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 436 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 454 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 462 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 563 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 618 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT DISULFID 53..609 FT /note="Interchain (between GP1 and GP2 chains)" FT /evidence="ECO:0000269|PubMed:12438572" FT DISULFID 108..135 FT /evidence="ECO:0000255" FT DISULFID 121..147 FT /evidence="ECO:0000255" FT DISULFID 511..556 FT /evidence="ECO:0000255" FT DISULFID 601..608 FT /evidence="ECO:0000269|PubMed:12438572" FT VARIANT 65 FT /note="S -> P (in strain: Isolate mouse-adapted)" FT VARIANT 246 FT /note="S -> P (in strain: Isolate mouse-adapted)" FT VARIANT 544 FT /note="I -> T" FT MUTAGEN 40 FT /note="N->D: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 53 FT /note="C->G: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 55 FT /note="D->A: 80% loss of virus capability to enter into FT host cell." FT MUTAGEN 55 FT /note="D->E,K: No effect on viral entry." FT MUTAGEN 57 FT /note="L->A: Complete loss of virus capability to enter FT into host cell." FT MUTAGEN 57 FT /note="L->F,I,K: 90% loss of virus capability to enter into FT host cell." FT MUTAGEN 63 FT /note="L->A: 90% loss of virus capability to enter into FT host cell." FT MUTAGEN 63 FT /note="L->F: Almost complete loss of virus capability to FT enter into host cell." FT MUTAGEN 63 FT /note="L->K: Complete loss of virus capability to enter FT into host cell." FT MUTAGEN 64 FT /note="R->A,E: Complete loss of virus capability to enter FT into host cell." FT MUTAGEN 64 FT /note="R->K: No loss of virus capability to enter into host FT cell." FT MUTAGEN 88 FT /note="F->A,E: Complete loss of virus capability to enter FT into host cell." FT MUTAGEN 88 FT /note="F->A: About 50% loss of ability to counteract host FT BST2." FT /evidence="ECO:0000269|PubMed:27707924" FT MUTAGEN 88 FT /note="F->I: No loss of virus capability to enter into host FT cell." FT MUTAGEN 95 FT /note="K->A,E: 80% loss of virus capability to enter into FT host cell." FT MUTAGEN 95 FT /note="K->R: 20% loss of virus capability to enter into FT host cell." FT MUTAGEN 108 FT /note="C->G: Almost complete loss of expression of GP1 and FT GP2. Almost complete loss of virus capability to enter into FT host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 111 FT /note="L->A: About 60% loss of ability to counteract host FT BST2." FT /evidence="ECO:0000269|PubMed:27707924" FT MUTAGEN 121 FT /note="C->G: Reduced levels of expression of GP1 and GP2. FT 50% loss of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 122 FT /note="L->A: About 60% loss of ability to counteract host FT BST2." FT /evidence="ECO:0000269|PubMed:27707924" FT MUTAGEN 135 FT /note="C->S: Almost complete loss of expression of GP1 and FT GP2. Complete loss of virus capability to enter into host FT cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 147 FT /note="C->S: Reduced levels of expression of GP1 and GP2. FT Almost complete loss of virus capability to enter into host FT cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 170 FT /note="I->A: 90% loss of virus capability to enter into FT host cell." FT MUTAGEN 170 FT /note="I->E: Complete loss of virus capability to enter FT into host cell." FT MUTAGEN 170 FT /note="I->F: 50% loss of virus capability to enter into FT host cell." FT MUTAGEN 204 FT /note="N->D: No effect on GP1 and GP2 expression. No loss FT of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 238 FT /note="N->Y: No effect on GP1 and GP2 expression. 12% loss FT of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 257 FT /note="N->D: No effect on GP1 and GP2 expression. 12% loss FT of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 296 FT /note="N->D: No effect on GP1 and GP2 expression. 18% loss FT of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 497..501 FT /note="RRTRR->AGTAA: Almost complete loss of cleavage FT between GP1 and GP2. No loss of infectivity." FT /evidence="ECO:0000269|PubMed:11152533" FT MUTAGEN 498..501 FT /note="RTRR->ATAA: No effect on cleavage between GP1 and FT GP2." FT /evidence="ECO:0000269|PubMed:9882347" FT MUTAGEN 511 FT /note="C->G: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 528 FT /note="G->R: Reduced infectivity." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 529 FT /note="L->A,R: Reduced infectivity." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 532 FT /note="I->A: Reduced infectivity." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 532 FT /note="I->R: Almost complete loss of infectivity. No effect FT on transport of GP to the cell surface and incorporation FT onto virions." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 535 FT /note="F->A: Reduced infectivity." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 535 FT /note="F->R: Almost complete loss of infectivity. No effect FT on transport of GP to the cell surface and incorporation FT onto virions." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 536 FT /note="G->A: Almost complete loss of infectivity. No effect FT on transport of GP to the cell surface and incorporation FT onto virions." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 537 FT /note="P->R: Almost complete loss of infectivity. No effect FT on transport of GP to the cell surface and incorporation FT onto virions." FT /evidence="ECO:0000269|PubMed:10482652" FT MUTAGEN 556 FT /note="C->S: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 563 FT /note="N->D: Reduced levels of expression of GP, GP1 and FT GP2. 20% loss of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 601 FT /note="C->S: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 608 FT /note="C->G: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 609 FT /note="C->G: Induces GP1 secretion. Complete loss of virus FT capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 618 FT /note="N->D: Slightly reduced levels of expression of GP1 FT and GP2. No loss of virus capability to enter into host FT cell." FT /evidence="ECO:0000269|PubMed:12438572" FT MUTAGEN 632 FT /note="D->V: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 633 FT /note="K->R,V: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 634 FT /note="T->I: 50% loss of release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 635 FT /note="L->V: 60% loss of release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 635 FT /note="L->V: Increased GP shedding." FT /evidence="ECO:0000269|PubMed:26092855" FT MUTAGEN 636 FT /note="P->A: 60% loss of release of soluble GP1,2delta." FT MUTAGEN 637 FT /note="D->E: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 637 FT /note="D->L,V: Increased release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 637 FT /note="D->V: Decreased GP shedding." FT /evidence="ECO:0000269|PubMed:26092855" FT MUTAGEN 638 FT /note="Q->V: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 639 FT /note="G->V: 40% loss of release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 640 FT /note="D->V: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 641 FT /note="N->A: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 642 FT /note="D->V: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 643 FT /note="N->A: No effect on release of soluble GP1,2delta." FT /evidence="ECO:0000269|PubMed:15103332" FT MUTAGEN 660 FT /note="G->L: About 60% loss of viral release; when FT associated with L-664." FT /evidence="ECO:0000269|PubMed:29669839" FT MUTAGEN 664 FT /note="A->L: About 60% loss of viral release; when FT associated with L-660." FT /evidence="ECO:0000269|PubMed:29669839" FT MUTAGEN 670 FT /note="C->A: Reduced palmitoylation. No effect on GP FT processing and association with retrovirus particle. No FT loss of virus capability to enter into host cell. Loss of FT localization to the rafts; when associated with A-670." FT /evidence="ECO:0000269|PubMed:11152533, FT ECO:0000269|PubMed:11877482, ECO:0000269|PubMed:12438572" FT MUTAGEN 670 FT /note="C->F: Slightly reduced levels of expression of GP1 FT and GP2. Greatly reduced GP processing and association with FT retrovirus particle. 43% loss of virus capability to enter FT into host cell. Loss of localization to the rafts; when FT associated with A-672." FT /evidence="ECO:0000269|PubMed:11152533, FT ECO:0000269|PubMed:11877482, ECO:0000269|PubMed:12438572" FT MUTAGEN 672 FT /note="C->A: Reduced palmitoylation. No effect on GP FT processing and association with retrovirus particle. No FT loss of virus capability to enter into host cell." FT /evidence="ECO:0000269|PubMed:11152533, FT ECO:0000269|PubMed:12438572" FT MUTAGEN 672 FT /note="C->F: Slightly reduced levels of expression of GP1 FT and GP2. Almost no effect on GP processing and association FT with retrovirus particle. 24% loss of virus capability to FT enter into host cell." FT /evidence="ECO:0000269|PubMed:11152533, FT ECO:0000269|PubMed:12438572" FT STRAND 35..39 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 42..46 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 48..50 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:6QD7" FT HELIX 60..62 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 63..69 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 79..83 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 86..91 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 100..103 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 105..114 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:3CSY" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 135..144 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 149..154 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 163..169 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 176..185 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 188..190 FT /evidence="ECO:0007829|PDB:7JPI" FT TURN 191..194 FT /evidence="ECO:0007829|PDB:7JPI" FT STRAND 216..224 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 231..237 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 240..243 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 250..262 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 273..277 FT /evidence="ECO:0007829|PDB:6HS4" FT TURN 290..292 FT /evidence="ECO:0007829|PDB:6HS4" FT TURN 303..305 FT /evidence="ECO:0007829|PDB:7TN9" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 314..317 FT /evidence="ECO:0007829|PDB:7LYD" FT STRAND 515..520 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 523..525 FT /evidence="ECO:0007829|PDB:8DPM" FT TURN 528..531 FT /evidence="ECO:0007829|PDB:6HS4" FT TURN 533..535 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 539..541 FT /evidence="ECO:0007829|PDB:6HS4" FT STRAND 543..548 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 551..553 FT /evidence="ECO:0007829|PDB:6HS4" FT HELIX 560..594 FT /evidence="ECO:0007829|PDB:2EBO" FT HELIX 595..597 FT /evidence="ECO:0007829|PDB:2EBO" FT HELIX 600..604 FT /evidence="ECO:0007829|PDB:2EBO" FT HELIX 605..609 FT /evidence="ECO:0007829|PDB:2EBO" FT HELIX 616..628 FT /evidence="ECO:0007829|PDB:2EBO" SQ SEQUENCE 676 AA; 74464 MW; BE8AB3B339F63261 CRC64; MGVTGILQLP RDRFKRTSFF LWVIILFQRT FSIPLGVIHN STLQVSDVDK LVCRDKLSST NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE AGEWAENCYN LEIKKPDGSE CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD FAFHKEGAFF LYDRLASTVI YRGTTFAEGV VAFLILPQAK KDFFSSHPLR EPVNATEDPS SGYYSTTIRY QATGFGTNET EYLFEVDNLT YVQLESRFTP QFLLQLNETI YTSGKRSNTT GKLIWKVNPE IDTTIGEWAF WETKKNLTRK IRSEELSFTV VSNGAKNISG QSPARTSSDP GTNTTTEDHK IMASENSSAM VQVHSQGREA AVSHLTTLAT ISTSPQSLTT KPGPDNSTHN TPVYKLDISE ATQVEQHHRR TDNDSTASDT PSATTAAGPP KAENTNTSKS TDFLDPATTT SPQNHSETAG NNNTHHQDTG EESASSGKLG LITNTIAGVA GLITGGRRTR REAIVNAQPK CNPNLHYWTT QDEGAAIGLA WIPYFGPAAE GIYIEGLMHN QDGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT CHILGPDCCI EPHDWTKNIT DKIDQIIHDF VDKTLPDQGD NDNWWTGWRQ WIPAGIGVTG VIIAVIALFC ICKFVF //