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P35253 (VGP_MABVM) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 78. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Envelope glycoprotein
Alternative name(s):
GP1,2
Short name=GP
Virion spike glycoprotein

Cleaved into the following 2 chains:

  1. GP1
  2. GP2
Gene names
Name:GP
OrganismLake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strain Kenya/Musoke/1980)) [Reference proteome]
Taxonomic identifier33727 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesMononegaviralesFiloviridaeMarburgvirus
Virus hostChlorocebus aethiops (Green monkey) (Cercopithecus aethiops) [TaxID: 9534]
Homo sapiens (Human) [TaxID: 9606]
Rousettus aegyptiacus (Egyptian rousette) (Egyptian fruit bat) [TaxID: 9407]

Protein attributes

Sequence length681 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

GP1 is responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into the host cell. Binding to CD209 and CLEC4M, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses, facilitate infection of macrophages and endothelial cells. These interactions not only facilitate virus cell entry, but also allow capture of viral particles by DCs and subsequent transmission to susceptible cells without DCs infection (trans infection) By similarity. Ref.12

GP2 acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide By similarity. Ref.12

Subunit structure

Homotrimer; each monomer consists of a GP1 and a GP2 subunit linked by disulfide bonds. The resulting peplomers (GP1,2) protrude from the virus surface as spikes. GP1,2 interacts with human CD209 and CLEC4M (collectively referred to as DC-SIGN(R)). Asialoglycoprotein receptor (ASGP-R) may be a liver-specific receptor for GP1,2. Members of the Tyro3 receptor tyrosine kinase family may be cell entry factors interacting with GP1,2. Ref.5 Ref.8 Ref.11

Subcellular location

GP2: Virion membrane; Single-pass type I membrane protein By similarity. Virion membrane; Lipid-anchor By similarity. Host cell membrane; Single-pass type I membrane protein By similarity. Host cell membrane; Lipid-anchor By similarity. Note: In the cell, localizes to the plasma membrane lipid rafts, which probably represent the assembly and budding site By similarity.

GP1: Virion membrane; Peripheral membrane protein By similarity. Host cell membrane; Peripheral membrane protein By similarity. Note: GP1 is not anchored to the viral envelope, but associates with the extravirion surface through its binding to GP2. In the cell, both GP1 and GP2 localize to the plasma membrane lipid rafts, which probably represent the assembly and budding site By similarity.

Domain

The coiled coil regions play a role in oligomerization and fusion activity By similarity. Ref.14

The transmembrane domain is essential and sufficient for recruitment envelope glycoproteins into VP40-enriched multivesicular bodies. Ref.14

Post-translational modification

N-glycosylated. Ref.5 Ref.7

O-glycosylated in the mucin-like region Probable. Ref.5 Ref.7

Specific enzymatic cleavages in vivo yield mature proteins. The precursor is processed into GP1 and GP2 by host cell furin in the trans Golgi, and maybe by other host proteases, to yield the mature GP1 and GP2 proteins. The cleavage site corresponds to the furin optimal cleavage sequence [KR]-X-[KR]-R.

GP1 is phosphorylated on serine residues between residues 260 and 273. Ref.10

Miscellaneous

Filoviruses entry requires functional lipid rafts at the host cell surface By similarity.

Essential for infectivity, as it is the sole viral protein expressed at the virion surface By similarity.

Sequence similarities

Belongs to the filoviruses glycoprotein family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.1
Chain19 – 681663Envelope glycoprotein
PRO_0000037515
Chain33 – 435403GP1 By similarity
PRO_0000314979
Chain436 – 681246GP2 By similarity
PRO_0000314980

Regions

Topological domain19 – 648630Extracellular Potential
Transmembrane649 – 66921Helical; Potential
Topological domain670 – 68112Cytoplasmic Potential
Region38 – 188151Receptor-binding
Region277 – 455179Mucin-like region By similarity
Region529 – 54921Fusion peptide By similarity
Compositional bias192 – 424233Thr-rich
Compositional bias471 – 4744Poly-Ser

Sites

Site435 – 4362Cleavage; by host furin By similarity

Amino acid modifications

Lipidation6711S-palmitoyl cysteine; by host Ref.6
Lipidation6731S-palmitoyl cysteine; by host Ref.6
Glycosylation941N-linked (GlcNAc...); by host Potential
Glycosylation1711N-linked (GlcNAc...); by host Potential
Glycosylation1901N-linked (GlcNAc...); by host Potential
Glycosylation2021N-linked (GlcNAc...); by host Potential
Glycosylation2071N-linked (GlcNAc...); by host Potential
Glycosylation2191N-linked (GlcNAc...); by host Potential
Glycosylation2231N-linked (GlcNAc...); by host Potential
Glycosylation2551N-linked (GlcNAc...); by host Potential
Glycosylation3101N-linked (GlcNAc...); by host Potential
Glycosylation3131N-linked (GlcNAc...); by host Potential
Glycosylation3251N-linked (GlcNAc...); by host Potential
Glycosylation3261N-linked (GlcNAc...); by host Potential
Glycosylation3371N-linked (GlcNAc...); by host Potential
Glycosylation3441N-linked (GlcNAc...); by host Potential
Glycosylation3451N-linked (GlcNAc...); by host Potential
Glycosylation3501N-linked (GlcNAc...); by host Potential
Glycosylation3601N-linked (GlcNAc...); by host Potential
Glycosylation4081N-linked (GlcNAc...); by host Potential
Glycosylation4871N-linked (GlcNAc...); by host Potential
Glycosylation5641N-linked (GlcNAc...); by host Potential
Glycosylation6191N-linked (GlcNAc...); by host Potential
Disulfide bond37 ↔ 610Interchain (between GP1 and GP2 chains) By similarity
Disulfide bond92 ↔ 119 Potential
Disulfide bond211 ↔ 226 Potential
Disulfide bond512 ↔ 557 Potential
Disulfide bond602 ↔ 609 By similarity

Natural variations

Natural variant5471V → G in strain: pp3/guinea pig lethal and pp4/guinea pig nonlethal.

Experimental info

Mutagenesis4341K → M: Partial loss of cleavage between GP1 and GP2. Ref.9
Mutagenesis4351R → L: Complete loss of cleavage between GP1 and GP2. Ref.9

Sequences

Sequence LengthMass (Da)Tools
P35253 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: CC89305C64D34B0B

FASTA68174,376
        10         20         30         40         50         60 
MKTTCFLISL ILIQGTKNLP ILEIASNNQP QNVDSVCSGT LQKTEDVHLM GFTLSGQKVA 

        70         80         90        100        110        120 
DSPLEASKRW AFRTGVPPKN VEYTEGEEAK TCYNISVTDP SGKSLLLDPP TNIRDYPKCK 

       130        140        150        160        170        180 
TIHHIQGQNP HAQGIALHLW GAFFLYDRIA STTMYRGKVF TEGNIAAMIV NKTVHKMIFS 

       190        200        210        220        230        240 
RQGQGYRHMN LTSTNKYWTS SNGTQTNDTG CFGALQEYNS TKNQTCAPSK IPPPLPTARP 

       250        260        270        280        290        300 
EIKLTSTPTD ATKLNTTDPS SDDEDLATSG SGSGEREPHT TSDAVTKQGL SSTMPPTPSP 

       310        320        330        340        350        360 
QPSTPQQGGN NTNHSQDAVT ELDKNNTTAQ PSMPPHNTTT ISTNNTSKHN FSTLSAPLQN 

       370        380        390        400        410        420 
TTNDNTQSTI TENEQTSAPS ITTLPPTGNP TTAKSTSSKK GPATTAPNTT NEHFTSPPPT 

       430        440        450        460        470        480 
PSSTAQHLVY FRRKRSILWR EGDMFPFLDG LINAPIDFDP VPNTKTIFDE SSSSGASAEE 

       490        500        510        520        530        540 
DQHASPNISL TLSYFPNINE NTAYSGENEN DCDAELRIWS VQEDDLAAGL SWIPFFGPGI 

       550        560        570        580        590        600 
EGLYTAVLIK NQNNLVCRLR RLANQTAKSL ELLLRVTTEE RTFSLINRHA IDFLLTRWGG 

       610        620        630        640        650        660 
TCKVLGPDCC IGIEDLSKNI SEQIDQIKKD EQKEGTGWGL GGKWWTSDWG VLTNLGILLL 

       670        680 
LSIAVLIALS CICRIFTKYI G 

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References

[1]"Marburg virus gene 4 encodes the virion membrane protein, a type I transmembrane glycoprotein."
Will C., Muehlberger E., Linder D., Slenczka W., Klenk H.-D., Feldmann H.
J. Virol. 67:1203-1210(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 19-37.
[2]Chain P.S.G., Malfatti S.A., Hajjaj A., Vergez L.M., Do L.H., Smith K.L., McCready P.M.
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: pp3/guinea pig lethal and pp4/guinea pig nonlethal.
[3]Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M., Schmaljohn A.
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: pp3/guinea pig lethal and pp4/guinea pig nonlethal.
[4]"Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid protein VP30."
Enterlein S., Volchkov V., Weik M., Kolesnikova L., Volchkova V., Klenk H.-D., Muehlberger E.
J. Virol. 80:1038-1043(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[5]"Glycosylation and oligomerization of the spike protein of Marburg virus."
Feldmann H., Will C., Schikore M., Slenczka W., Klenk H.-D.
Virology 182:353-356(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, GLYCOSYLATION.
[6]"Acylation of the Marburg virus glycoprotein."
Funke C., Becker S., Dartsch H., Klenk H.-D., Muehlberger E.
Virology 208:289-297(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION.
[7]"Carbohydrate structure of Marburg virus glycoprotein."
Geyer H., Will C., Feldmann H., Klenk H.-D., Geyer R.
Glycobiology 2:299-312(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION.
[8]"The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus."
Becker S., Spiess M., Klenk H.-D.
J. Gen. Virol. 76:393-399(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN ASIALOGLYCOPROTEIN RECEPTOR.
[9]"Proteolytic processing of Marburg virus glycoprotein."
Volchkov V.E., Volchkova V.A., Stroeher U., Becker S., Dolnik O., Cieplik M., Garten W., Klenk H.-D., Feldmann H.
Virology 268:1-6(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN, MUTAGENESIS OF LYS-434 AND ARG-435.
[10]"The Marburg virus surface protein GP is phosphorylated at its ectodomain."
Saenger C., Muehlberger E., Loetfering B., Klenk H.-D., Becker S.
Virology 295:20-29(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[11]"DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus."
Marzi A., Gramberg T., Simmons G., Moeller P., Rennekamp A.J., Krumbiegel M., Geier M., Eisemann J., Turza N., Saunier B., Steinkasserer A., Becker S., Bates P., Hofmann H., Poehlmann S.
J. Virol. 78:12090-12095(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN CD209 AND CLEC4M.
[12]"Tyro3 family-mediated cell entry of Ebola and Marburg viruses."
Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T., Jones S., Feldmann H., Kawaoka Y.
J. Virol. 80:10109-10116(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor."
Kuhn J.H., Radoshitzky S.R., Guth A.C., Warfield K.L., Li W., Vincent M.J., Towner J.S., Nichol S.T., Bavari S., Choe H., Aman M.J., Farzan M.
J. Biol. Chem. 281:15951-15958(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: RECEPTOR-BINDING REGION.
[14]"Role of the transmembrane domain of marburg virus surface protein GP in assembly of the viral envelope."
Mittler E., Kolesnikova L., Strecker T., Garten W., Becker S.
J. Virol. 81:3942-3948(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSMEMBRANE DOMAIN.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z12132 mRNA. Translation: CAA78117.1.
AY430365 Genomic RNA. Translation: AAR85463.1.
AY430366 Genomic RNA. Translation: AAR85456.1.
DQ217792 Genomic RNA. Translation: ABA87127.1.
PIRA45705.
RefSeqYP_001531156.1. NC_001608.3.

3D structure databases

ProteinModelPortalP35253.
SMRP35253. Positions 559-630.
ModBaseSearch...
MobiDBSearch...

PTM databases

UniCarbKBP35253.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID920945.

Family and domain databases

InterProIPR014625. GPC_FiloV.
IPR002561. GPC_filovir-type_extra_dom.
[Graphical view]
PfamPF01611. Filo_glycop. 1 hit.
[Graphical view]
PIRSFPIRSF036874. GPC_FiloV. 1 hit.
ProtoNetSearch...

Entry information

Entry nameVGP_MABVM
AccessionPrimary (citable) accession number: P35253
Secondary accession number(s): Q38L42, Q6T6U0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: February 19, 2014
This is version 78 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families