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 24-JAN-2024, entry version 100. 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; 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]. 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 CC host STAT1 (PubMed:22383882). Interacts with host KEAP1; this CC interaction activates host transcription factor NRF2 by blocking its CC interaction 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}. 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; 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 EMDB; EMD-3871; -. DR EMDB; EMD-3872; -. DR EMDB; EMD-3873; -. 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:0039563; P:disruption by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW. DR GO; GO:0046774; P:suppression by virus of host intracellular interferon activity; IDA:CACAO. 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 //