ID   VSGP_EBOZM              Reviewed;         364 AA.
AC   P60170; O12421; O12717; Q66801; Q66819; Q77LU4; Q8JS61; Q9YMG3;
DT   15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   24-JAN-2024, entry version 85.
DE   RecName: Full=Pre-small/secreted glycoprotein;
DE            Short=pre-sGP;
DE   Contains:
DE     RecName: Full=Small/secreted glycoprotein;
DE              Short=sGP;
DE   Contains:
DE     RecName: Full=Delta-peptide;
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 / 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   [2]
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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Volchkov V.E.;
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [5]
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   [6]
RP   SUBUNIT (SMALL/SECRETED GLYCOPROTEIN), AND DISULFIDE BOND.
RX   PubMed=9792851; DOI=10.1006/viro.1998.9389;
RA   Volchkova V.A., Feldmann H., Klenk H.D., Volchkov V.E.;
RT   "The nonstructural small glycoprotein sGP of Ebola virus is secreted as an
RT   antiparallel-orientated homodimer.";
RL   Virology 250:408-414(1998).
RN   [7]
RP   PROTEOLYTIC PROCESSING (PRE-SMALL/SECRETED GLYCOPROTEIN), MUTAGENESIS OF
RP   ARG-324, SUBCELLULAR LOCATION (DELTA-PEPTIDE), GLYCOSYLATION
RP   (DELTA-PEPTIDE), SUBCELLULAR LOCATION (SMALL/SECRETED GLYCOPROTEIN), AND
RP   GLYCOSYLATION (SMALL/SECRETED GLYCOPROTEIN).
RX   PubMed=10603327; DOI=10.1006/viro.1999.0034;
RA   Volchkova V.A., Klenk H.-D., Volchkov V.E.;
RT   "Delta-peptide is the carboxy-terminal cleavage fragment of the
RT   nonstructural small glycoprotein sGP of Ebola virus.";
RL   Virology 265:164-171(1999).
RN   [8]
RP   DISULFIDE BONDS.
RX   PubMed=15369806; DOI=10.1016/j.bbrc.2004.08.148;
RA   Barrientos L.G., Martin A.M., Rollin P.E., Sanchez A.;
RT   "Disulfide bond assignment of the Ebola virus secreted glycoprotein SGP.";
RL   Biochem. Biophys. Res. Commun. 323:696-702(2004).
RN   [9]
RP   FUNCTION (SMALL/SECRETED GLYCOPROTEIN).
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   [10]
RP   FUNCTION (SMALL/SECRETED GLYCOPROTEIN).
RX   PubMed=12482654; DOI=10.1006/viro.2002.1715;
RA   Sui J., Marasco W.A.;
RT   "Evidence against Ebola virus sGP binding to human neutrophils by a
RT   specific receptor.";
RL   Virology 303:9-14(2002).
RN   [11]
RP   FUNCTION (SMALL/SECRETED GLYCOPROTEIN).
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   [12]
RP   FUNCTION.
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   [13]
RP   FUNCTION (DELTA-PEPTIDE).
RX   PubMed=25609303; DOI=10.3390/v7010285;
RA   Gallaher W.R., Garry R.F.;
RT   "Modeling of the Ebola virus delta peptide reveals a potential lytic
RT   sequence motif.";
RL   Viruses 7:285-305(2015).
RN   [14]
RP   FUNCTION (DELTA-PEPTIDE).
RC   STRAIN=Zaire ebolavirus Makona;
RX   PubMed=28539454; DOI=10.1128/jvi.00438-17;
RA   He J., Melnik L.I., Komin A., Wiedman G., Fuselier T., Morris C.F.,
RA   Starr C.G., Searson P.C., Gallaher W.R., Hristova K., Garry R.F.,
RA   Wimley W.C.;
RT   "Ebola virus delta peptide is a viroporin.";
RL   J. Virol. 0:0-0(2017).
CC   -!- FUNCTION: [Small/secreted glycoprotein]: Seems to possess an anti-
CC       inflammatory activity as it can reverse the barrier-decreasing effects
CC       of TNF alpha. Might therefore contribute to the lack of inflammatory
CC       reaction seen during infection in spite the of extensive necrosis and
CC       massive virus production. Does not seem to be involved in activation of
CC       primary macrophages. Does not seem to interact specifically with
CC       neutrophils. {ECO:0000269|PubMed:11152533, ECO:0000269|PubMed:12482654,
CC       ECO:0000269|PubMed:16051836}.
CC   -!- FUNCTION: [Delta-peptide]: Viroporin that permeabilizes mammalian cell
CC       plasma membranes. It acts by altering permeation of ionic compounds and
CC       small molecules. This activity may lead to viral enterotoxic activity.
CC       {ECO:0000269|PubMed:28539454, ECO:0000305|PubMed:25609303}.
CC   -!- SUBUNIT: [Small/secreted glycoprotein]: Homodimer; disulfide-linked
CC       (PubMed:9792851). The homodimers are linked by two disulfide bonds in a
CC       parallel orientation (PubMed:9792851). {ECO:0000269|PubMed:9792851}.
CC   -!- SUBUNIT: [Delta-peptide]: Monomer.
CC   -!- SUBCELLULAR LOCATION: [Small/secreted glycoprotein]: Secreted
CC       {ECO:0000269|PubMed:10603327}.
CC   -!- SUBCELLULAR LOCATION: [Delta-peptide]: Secreted
CC       {ECO:0000269|PubMed:10603327}.
CC   -!- PTM: [Pre-small/secreted glycoprotein]: This precursor is processed
CC       into mature sGP and delta-peptide by host furin or furin-like
CC       proteases. The cleavage site corresponds to the furin optimal cleavage
CC       sequence [KR]-X-[KR]-R. {ECO:0000269|PubMed:10603327}.
CC   -!- PTM: [Small/secreted glycoprotein]: N-glycosylated.
CC       {ECO:0000269|PubMed:10603327}.
CC   -!- PTM: [Delta-peptide]: O-glycosylated. {ECO:0000269|PubMed:10603327}.
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 small secreted glycoprotein, derived
CC       from the unedited RNA. The sequence derived from the +1A edited gives
CC       rise to the full-length transmembrane glycoprotein GP (AC Q05320), the
CC       +2A edited RNA gives rise to the super small secreted glycoprotein ssGP
CC       (AC Q9YMG2).;
CC   -!- SIMILARITY: Belongs to the filoviruses glycoprotein family.
CC       {ECO:0000305}.
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DR   EMBL; U31033; AAA96745.1; -; Genomic_RNA.
DR   EMBL; U23187; AAC54886.1; -; Genomic_RNA.
DR   EMBL; AF272001; AAG40167.1; -; Genomic_RNA.
DR   EMBL; AY142960; AAN37508.1; -; Genomic_RNA.
DR   EMBL; AF086833; AAD14584.1; -; Genomic_RNA.
DR   EMBL; AF499101; AAM76035.1; -; Genomic_RNA.
DR   RefSeq; NP_066247.1; NC_002549.1.
DR   SMR; P60170; -.
DR   ELM; P60170; -.
DR   GlyCosmos; P60170; 6 sites, No reported glycans.
DR   DNASU; 911829; -.
DR   GeneID; 911829; -.
DR   Proteomes; UP000007209; Genome.
DR   Proteomes; UP000149419; Genome.
DR   Proteomes; UP000150973; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005216; F:monoatomic ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0039707; P:virus-mediated pore formation in host cell membrane; IEA:UniProtKB-KW.
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.
PE   1: Evidence at protein level;
KW   Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW   Ion channel; Ion transport; Reference proteome; RNA editing; Secreted;
KW   Signal; Transport; Viral ion channel.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..364
FT                   /note="Pre-small/secreted glycoprotein"
FT                   /id="PRO_0000037512"
FT   CHAIN           33..324
FT                   /note="Small/secreted glycoprotein"
FT                   /id="PRO_0000037513"
FT   CHAIN           325..364
FT                   /note="Delta-peptide"
FT                   /id="PRO_0000037514"
FT   SITE            324..325
FT                   /note="Cleavage; by host furin"
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   DISULFID        53
FT                   /note="Interchain"
FT                   /evidence="ECO:0000269|PubMed:15369806,
FT                   ECO:0000269|PubMed:9792851"
FT   DISULFID        108..135
FT                   /evidence="ECO:0000269|PubMed:15369806"
FT   DISULFID        121..147
FT                   /evidence="ECO:0000269|PubMed:15369806"
FT   DISULFID        306
FT                   /note="Interchain"
FT                   /evidence="ECO:0000269|PubMed:15369806,
FT                   ECO:0000269|PubMed:9792851"
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   MUTAGEN         324
FT                   /note="R->S: Loss of cleavage."
FT                   /evidence="ECO:0000269|PubMed:10603327"
SQ   SEQUENCE   364 AA;  41175 MW;  67376A454CE5F362 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 WETKKTSLEK
     FAVKSCLSQL YQTEPKTSVV RVRRELLPTQ GPTQQLKTTK SWLQKIPLQW FKCTVKEGKL
     QCRI
//