VP24_EBOZM
ID VP24_EBOZM Reviewed; 251 AA.
AC Q05322; Q773N1; Q8JS60; Q9DQD2;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 25-MAY-2022, entry version 96.
DE RecName: Full=Membrane-associated protein VP24;
DE AltName: Full=Ebola VP24 {ECO:0000303|PubMed:27974555};
DE Short=eVP24 {ECO:0000303|PubMed:27974555};
GN Name=VP24;
OS Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128952;
OH NCBI_TaxID=77231; Epomops franqueti (Franquet's epauleted fruit bat).
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].
RX PubMed=10073695; DOI=10.1099/0022-1317-80-2-355;
RA Volchkov V.E., Volchkova V.A., Chepurnov A.A., Blinov V.M., Netesov S.V.,
RA Feldmann H.;
RT "Characterization of the L gene and 5' trailer region of Ebola virus.";
RL J. Gen. Virol. 80:355-362(1999).
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].
RC STRAIN=Isolate mouse-adapted;
RA Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=12191476; DOI=10.1016/s1097-2765(02)00588-9;
RA Huang Y., Xu L., Sun Y., Nabel G.J.;
RT "The assembly of Ebola virus nucleocapsid requires virion-associated
RT proteins 35 and 24 and posttranslational modification of nucleoprotein.";
RL Mol. Cell 10:307-316(2002).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12525613; DOI=10.1128/jvi.77.3.1793-1800.2003;
RA Han Z., Boshra H., Sunyer J.O., Zwiers S.H., Paragas J., Harty R.N.;
RT "Biochemical and functional characterization of the Ebola virus VP24
RT protein: implications for a role in virus assembly and budding.";
RL J. Virol. 77:1793-1800(2003).
RN [7]
RP FUNCTION.
RX PubMed=15220407; DOI=10.1128/jvi.78.14.7344-7351.2004;
RA Licata J.M., Johnson R.F., Han Z., Harty R.N.;
RT "Contribution of ebola virus glycoprotein, nucleoprotein, and VP24 to
RT budding of VP40 virus-like particles.";
RL J. Virol. 78:7344-7351(2004).
RN [8]
RP INTERACTION WITH HOST KPNA1.
RX PubMed=16698996; DOI=10.1128/jvi.02349-05;
RA Reid S.P., Leung L.W., Hartman A.L., Martinez O., Shaw M.L.,
RA Carbonnelle C., Volchkov V.E., Nichol S.T., Basler C.F.;
RT "Ebola virus VP24 binds karyopherin alpha-1 and blocks STAT1 nuclear
RT accumulation.";
RL J. Virol. 80:5156-5167(2006).
RN [9]
RP FUNCTION, AND INTERACTION WITH HOST KPNA1; KPNA5 AND KPNA6.
RX PubMed=17928350; DOI=10.1128/jvi.01097-07;
RA Reid S.P., Valmas C., Martinez O., Sanchez F.M., Basler C.F.;
RT "Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily
RT karyopherin alpha proteins with activated STAT1.";
RL J. Virol. 81:13469-13477(2007).
RN [10]
RP FUNCTION, AND INTERACTION WITH HOST STAT1.
RX PubMed=22383882; DOI=10.1371/journal.ppat.1002550;
RA Zhang A.P., Bornholdt Z.A., Liu T., Abelson D.M., Lee D.E., Li S.,
RA Woods V.L. Jr., Saphire E.O.;
RT "The ebola virus interferon antagonist VP24 directly binds STAT1 and has a
RT novel, pyramidal fold.";
RL PLoS Pathog. 8:E1002550-E1002550(2012).
RN [11]
RP FUNCTION, INTERACTION WITH NUCLEOPROTEIN NP AND VP35, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF VAL-170 AND ASN-171.
RX PubMed=28794491; DOI=10.1038/s41598-017-08167-8;
RA Banadyga L., Hoenen T., Ambroggio X., Dunham E., Groseth A., Ebihara H.;
RT "Ebola virus VP24 interacts with NP to facilitate nucleocapsid assembly and
RT genome packaging.";
RL Sci. Rep. 7:7698-7698(2017).
RN [12]
RP STRUCTURE BY ELECTRON MICROSCOPY (7.30 ANGSTROMS).
RX PubMed=29144446; DOI=10.1038/nature24490;
RA Wan W., Kolesnikova L., Clarke M., Koehler A., Noda T., Becker S.,
RA Briggs J.A.G.;
RT "Structure and assembly of the Ebola virus nucleocapsid.";
RL Nature 551:394-397(2017).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.15 ANGSTROMS) OF 16-231, INTERACTION WITH HOST
RP KPNA5, MUTAGENESIS OF ARG-137, AND FUNCTION.
RX PubMed=25121748; DOI=10.1016/j.chom.2014.07.008;
RA Xu W., Edwards M.R., Borek D.M., Feagins A.R., Mittal A., Alinger J.B.,
RA Berry K.N., Yen B., Hamilton J., Brett T.J., Pappu R.V., Leung D.W.,
RA Basler C.F., Amarasinghe G.K.;
RT "Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5
RT to selectively compete with nuclear import of phosphorylated STAT1.";
RL Cell Host Microbe 16:187-200(2014).
RN [14]
RP INTERACTION WITH HOST KPNA1; KPNA5 AND KPNA6, AND NOMENCLATURE.
RX PubMed=27974555; DOI=10.1128/jvi.01715-16;
RA Schwarz T.M., Edwards M.R., Diederichs A., Alinger J.B., Leung D.W.,
RA Amarasinghe G.K., Basler C.F.;
RT "VP24-Karyopherin Alpha Binding Affinities Differ between Ebolavirus
RT Species, Influencing Interferon Inhibition and VP24 Stability.";
RL J. Virol. 91:0-0(2017).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 11-237, AND INTERACTION WITH HOST
RP KEAP1.
RX PubMed=24630991; DOI=10.1016/j.celrep.2014.01.043;
RA Edwards M.R., Johnson B., Mire C.E., Xu W., Shabman R.S., Speller L.N.,
RA Leung D.W., Geisbert T.W., Amarasinghe G.K., Basler C.F.;
RT "The Marburg virus VP24 protein interacts with Keap1 to activate the
RT cytoprotective antioxidant response pathway.";
RL Cell Rep. 6:1017-1025(2014).
CC -!- FUNCTION: Prevents the establishment of cellular antiviral state by
CC blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma
CC signaling pathways. Blocks the IFN-induced nuclear accumulation of host
CC phosphorylated STAT1 by interacting with the STAT1-binding region of
CC host importins. Alternatively interacts also directly with host STAT1
CC and may additionally inhibit its non-phosphorylated form. Plays a role
CC in assembly of viral nucleocapsid and virion budding. May act as a
CC minor matrix protein that plays a role in assembly of viral
CC nucleocapsid and virion budding. {ECO:0000269|PubMed:12191476,
CC ECO:0000269|PubMed:12525613, ECO:0000269|PubMed:15220407,
CC ECO:0000269|PubMed:17928350, ECO:0000269|PubMed:25121748}.
CC -!- SUBUNIT: Interacts with host importins KPNA1, KPNA5 and KPNA6
CC (PubMed:17928350, PubMed:25121748,PubMed:27974555). Interacts with host
CC STAT1 (PubMed:22383882). Interacts with host KEAP1; this interaction
CC activates host transcription factor NRF2 by blocking its interaction
CC with KEAP1 (PubMed:24630991). {ECO:0000269|PubMed:17928350,
CC ECO:0000269|PubMed:22383882, ECO:0000269|PubMed:24630991,
CC ECO:0000269|PubMed:25121748}.
CC -!- INTERACTION:
CC Q05322; O60684: KPNA6; Xeno; NbExp=7; IntAct=EBI-6153153, EBI-359923;
CC Q05322; P20700: LMNB1; Xeno; NbExp=6; IntAct=EBI-6153153, EBI-968218;
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000269|PubMed:12525613};
CC Peripheral membrane protein {ECO:0000269|PubMed:12525613}. Host cell
CC membrane {ECO:0000269|PubMed:12525613}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12525613}; Cytoplasmic side
CC {ECO:0000269|PubMed:12525613}. Host endomembrane system
CC {ECO:0000269|PubMed:12525613}; Peripheral membrane protein
CC {ECO:0000269|PubMed:12525613}. Note=In virion, localizes on the
CC intravirional side of the membrane. In the host cell, it is found
CC associated with virus-induced membrane proliferation foci and to the
CC plasma membrane where budding takes place (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the filoviridae membrane-associated protein VP24
CC family. {ECO:0000305}.
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DR EMBL; L11365; AAB81006.1; -; Genomic_RNA.
DR EMBL; AF086833; AAD14588.1; -; Genomic_RNA.
DR EMBL; AF272001; AAG40170.1; -; Genomic_RNA.
DR EMBL; AY142960; AAN37510.1; -; Genomic_RNA.
DR EMBL; AF499101; AAM76037.1; -; Genomic_RNA.
DR RefSeq; NP_066250.1; NC_002549.1.
DR PDB; 4M0Q; X-ray; 1.92 A; A/B=11-237.
DR PDB; 4U2X; X-ray; 3.15 A; A/B/C=16-231.
DR PDB; 6EHM; EM; 7.30 A; C/D=1-251.
DR PDBsum; 4M0Q; -.
DR PDBsum; 4U2X; -.
DR PDBsum; 6EHM; -.
DR SMR; Q05322; -.
DR IntAct; Q05322; 91.
DR DNASU; 911828; -.
DR GeneID; 911828; -.
DR KEGG; vg:911828; -.
DR Proteomes; UP000007209; Genome.
DR Proteomes; UP000109874; Genome.
DR Proteomes; UP000149419; Genome.
DR Proteomes; UP000150973; Genome.
DR GO; GO:0033645; C:host cell endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:CACAO.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0046774; P:suppression by virus of host intracellular interferon activity; IDA:CACAO.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 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 InterPro; IPR009433; Filo_VP24.
DR Pfam; PF06389; Filo_VP24; 1.
DR PIRSF; PIRSF011355; VP24; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host STAT1 by virus; Interferon antiviral system evasion;
KW Membrane; Reference proteome; Viral immunoevasion; Virion.
FT CHAIN 1..251
FT /note="Membrane-associated protein VP24"
FT /id="PRO_0000222154"
FT VARIANT 50
FT /note="T -> I (in strain: Isolate mouse-adapted)"
FT VARIANT 71
FT /note="M -> I (in strain: Isolate guinea pig-adapted)"
FT VARIANT 147
FT /note="L -> P (in strain: Isolate guinea pig-adapted)"
FT VARIANT 187
FT /note="T -> I (in strain: Isolate guinea pig-adapted)"
FT MUTAGEN 137
FT /note="R->A: More than 90% loss of interaction with host
FT KPNA5."
FT /evidence="ECO:0000269|PubMed:25121748"
FT MUTAGEN 170
FT /note="V->A: Complete loss of interaction with NP."
FT /evidence="ECO:0000269|PubMed:28794491"
FT MUTAGEN 171
FT /note="N->A: Complete loss of interaction with NP."
FT /evidence="ECO:0000269|PubMed:28794491"
FT HELIX 16..26
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 54..60
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:4M0Q"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 90..105
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:4M0Q"
FT TURN 113..115
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 116..128
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 139..142
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 147..165
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 196..202
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:4M0Q"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:4M0Q"
FT HELIX 224..228
FT /evidence="ECO:0007829|PDB:4M0Q"
SQ SEQUENCE 251 AA; 28219 MW; 5A8F356AF2CC5A5C CRC64;
MAKATGRYNL ISPKKDLEKG VVLSDLCNFL VSQTIQGWKV YWAGIEFDVT HKGMALLHRL
KTNDFAPAWS MTRNLFPHLF QNPNSTIESP LWALRVILAA GIQDQLIDQS LIEPLAGALG
LISDWLLTTN TNHFNMRTQR VKEQLSLKML SLIRSNILKF INKLDALHVV NYNGLLSSIE
IGTQNHTIII TRTNMGFLVE LQEPDKSAMN RMKPGPAKFS LLHESTLKAF TQGSSTRMQS
LILEFNSSLA I
