ID VGP_MABVM Reviewed; 681 AA. AC P35253; Q38L42; Q6T6U0; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 27-MAR-2024, entry version 114. DE RecName: Full=Envelope glycoprotein; DE AltName: Full=GP1,2; DE Short=GP; DE AltName: Full=Virion spike glycoprotein; DE Contains: DE RecName: Full=GP1; DE Contains: DE RecName: Full=GP2; DE Flags: Precursor; GN Name=GP; OS Lake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strain OS Kenya/Musoke/1980)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Filoviridae; Orthomarburgvirus; OC Orthomarburgvirus marburgense. OX NCBI_TaxID=33727; OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9407; Rousettus aegyptiacus (Egyptian fruit bat) (Pteropus aegyptiacus). RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 19-37. RX PubMed=8437211; DOI=10.1128/jvi.67.3.1203-1210.1993; RA Will C., Muehlberger E., Linder D., Slenczka W., Klenk H.-D., Feldmann H.; RT "Marburg virus gene 4 encodes the virion membrane protein, a type I RT transmembrane glycoprotein."; RL J. Virol. 67:1203-1210(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal; RA Chain P.S.G., Malfatti S.A., Hajjaj A., Vergez L.M., Do L.H., Smith K.L., RA McCready P.M.; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal; RA Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M., RA Schmaljohn A.; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=16379005; DOI=10.1128/jvi.80.2.1038-1043.2006; RA Enterlein S., Volchkov V., Weik M., Kolesnikova L., Volchkova V., RA Klenk H.-D., Muehlberger E.; RT "Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid RT protein VP30."; RL J. Virol. 80:1038-1043(2006). RN [5] RP SUBUNIT, AND GLYCOSYLATION. RX PubMed=2024471; DOI=10.1016/0042-6822(91)90680-a; RA Feldmann H., Will C., Schikore M., Slenczka W., Klenk H.-D.; RT "Glycosylation and oligomerization of the spike protein of Marburg virus."; RL Virology 182:353-356(1991). RN [6] RP PALMITOYLATION AT CYS-671 AND CYS-673. RX PubMed=11831710; DOI=10.1006/viro.1995.1151; RA Funke C., Becker S., Dartsch H., Klenk H.-D., Muehlberger E.; RT "Acylation of the Marburg virus glycoprotein."; RL Virology 208:289-297(1995). RN [7] RP GLYCOSYLATION. RX PubMed=1421752; DOI=10.1093/glycob/2.4.299; RA Geyer H., Will C., Feldmann H., Klenk H.-D., Geyer R.; RT "Carbohydrate structure of Marburg virus glycoprotein."; RL Glycobiology 2:299-312(1992). RN [8] RP INTERACTION WITH HUMAN ASIALOGLYCOPROTEIN RECEPTOR. RX PubMed=7844558; DOI=10.1099/0022-1317-76-2-393; RA Becker S., Spiess M., Klenk H.-D.; RT "The asialoglycoprotein receptor is a potential liver-specific receptor for RT Marburg virus."; RL J. Gen. Virol. 76:393-399(1995). RN [9] RP PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN, AND MUTAGENESIS OF LYS-434 RP AND ARG-435. RX PubMed=10683320; DOI=10.1006/viro.1999.0110; RA Volchkov V.E., Volchkova V.A., Stroeher U., Becker S., Dolnik O., RA Cieplik M., Garten W., Klenk H.-D., Feldmann H.; RT "Proteolytic processing of Marburg virus glycoprotein."; RL Virology 268:1-6(2000). RN [10] RP PHOSPHORYLATION. RX PubMed=12033762; DOI=10.1006/viro.2002.1374; RA Saenger C., Muehlberger E., Loetfering B., Klenk H.-D., Becker S.; RT "The Marburg virus surface protein GP is phosphorylated at its RT ectodomain."; RL Virology 295:20-29(2002). RN [11] RP INTERACTION WITH HUMAN CD209 AND CLEC4M. RX PubMed=15479853; DOI=10.1128/jvi.78.21.12090-12095.2004; RA Marzi A., Gramberg T., Simmons G., Moeller P., Rennekamp A.J., RA Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B., RA Steinkasserer A., Becker S., Bates P., Hofmann H., Poehlmann S.; RT "DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and RT the S protein of severe acute respiratory syndrome coronavirus."; RL J. Virol. 78:12090-12095(2004). RN [12] RP FUNCTION. RX PubMed=17005688; DOI=10.1128/jvi.01157-06; RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T., RA Jones S., Feldmann H., Kawaoka Y.; RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses."; RL J. Virol. 80:10109-10116(2006). RN [13] 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 [14] RP TRANSMEMBRANE DOMAIN. RX PubMed=17267489; DOI=10.1128/jvi.02263-06; RA Mittler E., Kolesnikova L., Strecker T., Garten W., Becker S.; RT "Role of the transmembrane domain of marburg virus surface protein GP in RT assembly of the viral envelope."; RL J. Virol. 81:3942-3948(2007). CC -!- FUNCTION: GP1 is 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 the host cell. Binding to CD209 and CC CLEC4M, which are respectively found on dendritic cells (DCs), and on CC endothelial cells of liver sinusoids and lymph node sinuses, facilitate CC infection of macrophages and endothelial cells. These interactions not CC only facilitate virus cell entry, but also allow capture of viral CC particles by DCs and subsequent transmission to susceptible cells CC without DCs infection (trans infection) (By similarity). {ECO:0000250}. CC -!- FUNCTION: GP2 acts as a class I viral fusion protein. Under the current CC model, the protein has at least 3 conformational states: pre-fusion CC native state, pre-hairpin intermediate state, and post-fusion hairpin CC state. During viral and target cell membrane fusion, the coiled coil CC 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 (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Homotrimer; each monomer consists of a GP1 and a GP2 subunit CC linked by disulfide bonds. The resulting peplomers (GP1,2) protrude CC from the virus surface as spikes. GP1,2 interacts with human CD209 and CC CLEC4M (collectively referred to as DC-SIGN(R)). Asialoglycoprotein CC receptor (ASGP-R) may be a liver-specific receptor for GP1,2. Members CC of the Tyro3 receptor tyrosine kinase family may be cell entry factors CC interacting with GP1,2. {ECO:0000269|PubMed:15479853, CC ECO:0000269|PubMed:2024471, ECO:0000269|PubMed:7844558}. CC -!- SUBCELLULAR LOCATION: [GP2]: Virion membrane CC {ECO:0000250|UniProtKB:Q05320}; Single-pass type I membrane protein CC {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:Q05320}; 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:0000250|UniProtKB:Q05320}. CC -!- SUBCELLULAR LOCATION: [GP1]: Virion membrane CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q05320}. Host cell membrane CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q05320}. Note=GP1 is not anchored to the viral CC envelope, but forms a disulfid-linked complex with the extravirion CC surface GP2. In the cell, both GP1 and GP2 localize to the plasma CC membrane lipid rafts, which probably represent the assembly and budding CC site. GP1 can also be shed after proteolytic processing. CC {ECO:0000250|UniProtKB:Q05320}. CC -!- DOMAIN: The coiled coil regions play a role in oligomerization and CC fusion activity. {ECO:0000250}. CC -!- DOMAIN: The transmembrane domain is essential and sufficient for CC recruitment envelope glycoproteins into VP40-enriched multivesicular CC bodies. CC -!- PTM: N-glycosylated. CC -!- PTM: O-glycosylated in the mucin-like region. {ECO:0000305}. 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. The cleavage site corresponds to the furin optimal CC cleavage sequence [KR]-X-[KR]-R. {ECO:0000269|PubMed:10683320}. CC -!- PTM: GP1 is phosphorylated on serine residues between residues 260 and CC 273. {ECO:0000269|PubMed:12033762}. CC -!- MISCELLANEOUS: Filoviruses entry requires functional lipid rafts at the CC host cell surface. {ECO:0000250}. CC -!- MISCELLANEOUS: Essential for infectivity, as it is the sole viral CC protein expressed at the virion surface. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the filoviruses glycoprotein family. CC {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; Z12132; CAA78117.1; -; mRNA. DR EMBL; AY430365; AAR85463.1; -; Genomic_RNA. DR EMBL; AY430366; AAR85456.1; -; Genomic_RNA. DR EMBL; DQ217792; ABA87127.1; -; Genomic_RNA. DR PIR; A45705; A45705. DR RefSeq; YP_001531156.1; NC_001608.3. DR SMR; P35253; -. DR GlyConnect; 579; 7 N-Linked glycans, 5 O-Linked glycans. DR GlyCosmos; P35253; 21 sites, 23 glycans. DR GeneID; 920945; -. DR KEGG; vg:920945; -. DR Proteomes; UP000007771; Genome. DR Proteomes; UP000137266; Genome. DR Proteomes; UP000160614; Genome. DR Proteomes; UP000180448; Genome. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW. DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW. DR GO; GO:0046718; P:viral entry into host cell; IEA:UniProtKB-KW. DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW. 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 InterPro; IPR018154; TLV/ENV_coat_polyprotein. DR PANTHER; PTHR10424:SF74; ENDOGENOUS RETROVIRUS GROUP V MEMBER 1 ENV POLYPROTEIN-RELATED; 1. DR PANTHER; PTHR10424; VIRAL ENVELOPE PROTEIN; 1. 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 Cleavage on pair of basic residues; Direct protein sequencing; KW Disulfide bond; 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; Lipoprotein; KW Membrane; Palmitate; Reference proteome; Signal; Transmembrane; KW Transmembrane helix; Viral attachment to host cell; Viral envelope protein; KW Viral penetration into host cytoplasm; Virion; Virus entry into host cell. FT SIGNAL 1..18 FT /evidence="ECO:0000269|PubMed:8437211" FT CHAIN 19..681 FT /note="Envelope glycoprotein" FT /id="PRO_0000037515" FT CHAIN 33..435 FT /note="GP1" FT /evidence="ECO:0000250" FT /id="PRO_0000314979" FT CHAIN 436..681 FT /note="GP2" FT /evidence="ECO:0000250" FT /id="PRO_0000314980" FT TOPO_DOM 19..648 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 649..669 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 670..681 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 38..188 FT /note="Receptor-binding" FT REGION 223..427 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 277..455 FT /note="Mucin-like region" FT /evidence="ECO:0000250" FT REGION 529..549 FT /note="Fusion peptide" FT /evidence="ECO:0000250" FT COMPBIAS 242..294 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 304..427 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 435..436 FT /note="Cleavage; by host furin" FT /evidence="ECO:0000250" FT LIPID 671 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000305|PubMed:11831710" FT LIPID 673 FT /note="S-palmitoyl cysteine; by host" FT /evidence="ECO:0000305|PubMed:11831710" FT CARBOHYD 94 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 171 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 190 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 202 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 207 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 219 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 223 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 255 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 310 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 313 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 325 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 326 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 337 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 344 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 345 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 350 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 360 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 408 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 487 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 564 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT CARBOHYD 619 FT /note="N-linked (GlcNAc...) asparagine; by host" FT /evidence="ECO:0000255" FT DISULFID 37..610 FT /note="Interchain (between GP1 and GP2 chains)" FT /evidence="ECO:0000250" FT DISULFID 92..119 FT /evidence="ECO:0000255" FT DISULFID 211..226 FT /evidence="ECO:0000255" FT DISULFID 512..557 FT /evidence="ECO:0000255" FT DISULFID 602..609 FT /evidence="ECO:0000250" FT VARIANT 547 FT /note="V -> G (in strain: pp3/guinea pig lethal and FT pp4/guinea pig nonlethal)" FT MUTAGEN 434 FT /note="K->M: Partial loss of cleavage between GP1 and GP2." FT /evidence="ECO:0000269|PubMed:10683320" FT MUTAGEN 435 FT /note="R->L: Complete loss of cleavage between GP1 and FT GP2." FT /evidence="ECO:0000269|PubMed:10683320" SQ SEQUENCE 681 AA; 74376 MW; CC89305C64D34B0B CRC64; MKTTCFLISL ILIQGTKNLP ILEIASNNQP QNVDSVCSGT LQKTEDVHLM GFTLSGQKVA DSPLEASKRW AFRTGVPPKN VEYTEGEEAK TCYNISVTDP SGKSLLLDPP TNIRDYPKCK TIHHIQGQNP HAQGIALHLW GAFFLYDRIA STTMYRGKVF TEGNIAAMIV NKTVHKMIFS RQGQGYRHMN LTSTNKYWTS SNGTQTNDTG CFGALQEYNS TKNQTCAPSK IPPPLPTARP EIKLTSTPTD ATKLNTTDPS SDDEDLATSG SGSGEREPHT TSDAVTKQGL SSTMPPTPSP QPSTPQQGGN NTNHSQDAVT ELDKNNTTAQ PSMPPHNTTT ISTNNTSKHN FSTLSAPLQN TTNDNTQSTI TENEQTSAPS ITTLPPTGNP TTAKSTSSKK GPATTAPNTT NEHFTSPPPT PSSTAQHLVY FRRKRSILWR EGDMFPFLDG LINAPIDFDP VPNTKTIFDE SSSSGASAEE DQHASPNISL TLSYFPNINE NTAYSGENEN DCDAELRIWS VQEDDLAAGL SWIPFFGPGI EGLYTAVLIK NQNNLVCRLR RLANQTAKSL ELLLRVTTEE RTFSLINRHA IDFLLTRWGG TCKVLGPDCC IGIEDLSKNI SEQIDQIKKD EQKEGTGWGL GGKWWTSDWG VLTNLGILLL LSIAVLIALS CICRIFTKYI G //