ID   VP30_EBOZM              Reviewed;         288 AA.
AC   Q05323; Q9YMG1;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   27-MAR-2024, entry version 103.
DE   RecName: Full=Transcriptional activator VP30 {ECO:0000303|PubMed:29290611};
DE   AltName: Full=Ebola VP30 {ECO:0000303|PubMed:28593988};
DE            Short=eVP30 {ECO:0000303|PubMed:28593988};
DE   AltName: Full=Minor nucleoprotein VP30;
GN   Name=VP30;
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].
RA   Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.;
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
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   Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M.,
RA   Schmaljohn A.;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   PHOSPHORYLATION.
RX   PubMed=12052831; DOI=10.1074/jbc.m203775200;
RA   Modrof J., Muhlberger E., Klenk H.D., Becker S.;
RT   "Phosphorylation of VP30 impairs ebola virus transcription.";
RL   J. Biol. Chem. 277:33099-33104(2002).
RN   [6]
RP   FUNCTION.
RX   PubMed=12163572; DOI=10.1128/jvi.76.17.8532-8539.2002;
RA   Weik M., Modrof J., Klenk H.D., Becker S., Muhlberger E.;
RT   "Ebola virus VP30-mediated transcription is regulated by RNA secondary
RT   structure formation.";
RL   J. Virol. 76:8532-8539(2002).
RN   [7]
RP   INTERACTION WITH THE NUCLEOPROTEIN.
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   [8]
RP   ZINC-FINGER.
RX   PubMed=12584359; DOI=10.1128/jvi.77.5.3334-3338.2003;
RA   Modrof J., Becker S., Muhlberger E.;
RT   "Ebola virus transcription activator VP30 is a zinc-binding protein.";
RL   J. Virol. 77:3334-3338(2003).
RN   [9]
RP   MUTAGENESIS OF LEU-100 AND LEU-102.
RX   PubMed=12912982; DOI=10.1074/jbc.m307036200;
RA   Hartlieb B., Modrof J., Muhlberger E., Klenk H.D., Becker S.;
RT   "Oligomerization of Ebola virus VP30 is essential for viral transcription
RT   and can be inhibited by a synthetic peptide.";
RL   J. Biol. Chem. 278:41830-41836(2003).
RN   [10]
RP   RNA-BINDING, AND INTRINSICALLY DISORDERED REGION.
RX   PubMed=17567691; DOI=10.1128/jvi.02523-06;
RA   John S.P., Wang T., Steffen S., Longhi S., Schmaljohn C.S., Jonsson C.B.;
RT   "Ebola virus VP30 is an RNA binding protein.";
RL   J. Virol. 81:8967-8976(2007).
RN   [11]
RP   FUNCTION.
RX   PubMed=18829754; DOI=10.1128/jvi.01395-08;
RA   Martinez M.J., Biedenkopf N., Volchkova V., Hartlieb B., Alazard-Dany N.,
RA   Reynard O., Becker S., Volchkov V.;
RT   "Role of Ebola virus VP30 in transcription reinitiation.";
RL   J. Virol. 82:12569-12573(2008).
RN   [12]
RP   FUNCTION, SUBUNIT, RNA BINDING, AND MUTAGENESIS OF CYS-72.
RX   PubMed=27279615; DOI=10.1128/jvi.00271-16;
RA   Biedenkopf N., Schlereth J., Gruenweller A., Becker S., Hartmann R.K.;
RT   "RNA Binding of Ebola Virus VP30 Is Essential for Activating Viral
RT   Transcription.";
RL   J. Virol. 90:7481-7496(2016).
RN   [13]
RP   FUNCTION, AND RNA-BINDING.
RX   PubMed=27315567; DOI=10.1080/15476286.2016.1194160;
RA   Schlereth J., Gruenweller A., Biedenkopf N., Becker S., Hartmann R.K.;
RT   "RNA binding specificity of Ebola virus transcription factor VP30.";
RL   RNA Biol. 13:783-798(2016).
RN   [14]
RP   PHOSPHORYLATION AT SER-29, AND SUBCELLULAR LOCATION.
RX   PubMed=28915404; DOI=10.1016/j.virol.2017.09.006;
RA   Lier C., Becker S., Biedenkopf N.;
RT   "Dynamic phosphorylation of Ebola virus VP30 in NP-induced inclusion
RT   bodies.";
RL   Virology 512:39-47(2017).
RN   [15]
RP   FUNCTION, INTERACTION WITH NP, AND NOMENCLATURE.
RC   STRAIN=isolate IRF0164;
RX   PubMed=28593988; DOI=10.1038/ncomms15576;
RA   Xu W., Luthra P., Wu C., Batra J., Leung D.W., Basler C.F.,
RA   Amarasinghe G.K.;
RT   "Ebola virus VP30 and nucleoprotein interactions modulate viral RNA
RT   synthesis.";
RL   Nat. Commun. 8:15576-15576(2017).
RN   [16]
RP   DEPHOSPHORYLATION BY HOST PPP2R5C.
RX   PubMed=29290611; DOI=10.1016/j.molcel.2017.11.034;
RA   Kruse T., Biedenkopf N., Hertz E.P.T., Dietzel E., Stalmann G.,
RA   Lopez-Mendez B., Davey N.E., Nilsson J., Becker S.;
RT   "The Ebola virus nucleoprotein recruits the host PP2A-B56 Phosphatase to
RT   activate transcriptional support activity of VP30.";
RL   Mol. Cell 69:136-145(2018).
RN   [17]
RP   INTERACTION WITH HOST STAU1.
RX   PubMed=30301857; DOI=10.1128/mbio.01771-18;
RA   Fang J., Pietzsch C., Ramanathan P., Santos R.I., Ilinykh P.A.,
RA   Garcia-Blanco M.A., Bukreyev A., Bradrick S.S.;
RT   "Staufen1 Interacts with Multiple Components of the Ebola Virus
RT   Ribonucleoprotein and Enhances Viral RNA Synthesis.";
RL   MBio 9:0-0(2018).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 139-288, INTERACTION WITH NP AND
RP   VP35, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-197; ASP-202; GLN-203;
RP   GLN-229; TRP-230 AND SER-234.
RX   PubMed=27755595; DOI=10.1371/journal.ppat.1005937;
RA   Kirchdoerfer R.N., Moyer C.L., Abelson D.M., Saphire E.O.;
RT   "The Ebola virus VP30-NP interaction is a regulator of viral RNA
RT   synthesis.";
RL   PLoS Pathog. 12:E1005937-E1005937(2016).
CC   -!- FUNCTION: Multifunctional protein that acts as a viral transcriptional
CC       activator (PubMed:12163572, PubMed:27279615). Promotes read-through of
CC       an RNA hairpin in the NP open reading frame to enhance viral
CC       transcription (PubMed:12163572). Mechanistically, nonphosphorylated
CC       VP30 hexamers form a ternary complex with the viral leader RNA
CC       (PubMed:27315567). Clamps the RNA template and the complex VP35-
CC       polymerase L together, thereby increasing the polymerase affinity for
CC       the RNA template to increase transcription initiation despite the
CC       presence of RNA secondary structures. Assists also stop-start
CC       transcription at gene junctions to promote transcription of downstream
CC       genes (PubMed:18829754). Interaction with NP plays a critical role in
CC       transcription initiation by recognizing the RNA stem loop
CC       (PubMed:28593988). Interaction with host RBBP6 interferes with NP-VP30
CC       interaction and inhibits viral RNA synthesis. Also acts as a suppressor
CC       of RNA silencing by interacting with host DICER1 and TARBP2/TRBP (By
CC       similarity). {ECO:0000250|UniProtKB:Q77DJ5,
CC       ECO:0000269|PubMed:12163572, ECO:0000269|PubMed:18829754,
CC       ECO:0000269|PubMed:27279615, ECO:0000269|PubMed:27315567,
CC       ECO:0000269|PubMed:28593988}.
CC   -!- SUBUNIT: Homohexamer; hexamerization is essential for RNA binding
CC       (PubMed:27279615). Interacts with the nucleoprotein/NP; this
CC       interaction plays both essential and inhibitory roles in viral RNA
CC       synthesis (PubMed:28593988). Interacts with VP35 (PubMed:12191476,
CC       PubMed:27755595). Interacts with host STAU1 (PubMed:30301857).
CC       Interacts (via C-terminus) with host RBBP6 isoform 1 (By similarity).
CC       Interacts with host DICER1; this interaction prevents TARBP2/TRBP
CC       binding to DICER1 and thus allows the virus to counteract host RNA
CC       silencing (By similarity). Interacts with host TARBP2/TRBP; this
CC       interaction, which occurs only in the presence of siRNA, prevents
CC       TARBP2 binding to DICER1 and thus allows the virus to counteract host
CC       RNA silencing (By similarity). {ECO:0000250|UniProtKB:Q77DJ5,
CC       ECO:0000269|PubMed:12191476, ECO:0000269|PubMed:27279615,
CC       ECO:0000269|PubMed:27755595, ECO:0000269|PubMed:28593988,
CC       ECO:0000269|PubMed:30301857}.
CC   -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm
CC       {ECO:0000269|PubMed:27755595, ECO:0000269|PubMed:28915404}.
CC       Note=Present in viral inclusion bodies due to its interaction with NP.
CC       {ECO:0000269|PubMed:28915404}.
CC   -!- PTM: Phosphorylated by host (PubMed:12052831, PubMed:28915404).
CC       Phosphorylation negatively regulates the transcription activation
CC       (PubMed:12052831). Phosphorylation and dephosphorylation take place in
CC       viral inclusion bodies and are largely influenced by the presence of NP
CC       (PubMed:28915404). Dephosphorylated by host PPP2R5C; this
CC       dephosphorylation enhances viral transcription and is mediated by NP.
CC       {ECO:0000269|PubMed:12052831, ECO:0000269|PubMed:28915404}.
CC   -!- SIMILARITY: Belongs to the filoviridae transcriptional activator VP30
CC       family. {ECO:0000305}.
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DR   EMBL; L11365; AAB81005.1; -; Genomic_RNA.
DR   EMBL; AF086833; AAD14587.1; -; Genomic_RNA.
DR   EMBL; AF499101; AAM76036.1; -; Genomic_RNA.
DR   EMBL; AY142960; AAN37509.1; -; Genomic_RNA.
DR   EMBL; AF272001; AAG40169.1; -; Genomic_RNA.
DR   RefSeq; NP_066249.1; NC_002549.1.
DR   PDB; 5DVW; X-ray; 1.75 A; A/B/C/D=142-272.
DR   PDB; 5T3T; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J=139-288.
DR   PDBsum; 5DVW; -.
DR   PDBsum; 5T3T; -.
DR   SMR; Q05323; -.
DR   iPTMnet; Q05323; -.
DR   DNASU; 911826; -.
DR   GeneID; 911826; -.
DR   KEGG; vg:911826; -.
DR   Proteomes; UP000007209; Genome.
DR   Proteomes; UP000109874; Genome.
DR   Proteomes; UP000149419; Genome.
DR   Proteomes; UP000150973; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:1990904; C:ribonucleoprotein complex; IMP:CAFA.
DR   GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IPI:CAFA.
DR   GO; GO:0003727; F:single-stranded RNA binding; IMP:CAFA.
DR   GO; GO:0008270; F:zinc ion binding; IDA:CAFA.
DR   GO; GO:0050434; P:positive regulation of viral transcription; IDA:CACAO.
DR   GO; GO:0044414; P:suppression of host defenses by symbiont; IMP:CACAO.
DR   GO; GO:0140533; P:suppression of host RNAi-mediated antiviral immune response; IMP:GO_Central.
DR   Gene3D; 1.20.120.1160; -; 1.
DR   InterPro; IPR014459; VP30_FiloV.
DR   Pfam; PF11507; Transcript_VP30; 1.
DR   PIRSF; PIRSF011356; VP30_FiloV; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Host cytoplasm; Host-virus interaction;
KW   Inhibition of host innate immune response by virus; Metal-binding;
KW   Phosphoprotein; Reference proteome; RNA-binding;
KW   Suppressor of RNA silencing; Transcription; Viral immunoevasion;
KW   Viral nucleoprotein; Virion; Zinc; Zinc-finger.
FT   CHAIN           1..288
FT                   /note="Transcriptional activator VP30"
FT                   /id="PRO_0000222158"
FT   ZN_FING         72..90
FT                   /note="C3H1-type; atypical"
FT   REGION          1..44
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:17567691"
FT   REGION          26..40
FT                   /note="RNA-binding"
FT                   /evidence="ECO:0000269|PubMed:27315567"
FT   REGION          100..104
FT                   /note="Oligomerization"
FT                   /evidence="ECO:0000269|PubMed:12912982"
FT   REGION          121..140
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:17567691"
FT   REGION          202..237
FT                   /note="Interaction with the nucleoprotein"
FT                   /evidence="ECO:0000269|PubMed:28593988"
FT   REGION          268..288
FT                   /note="Disordered"
FT                   /evidence="ECO:0000305|PubMed:17567691"
FT   COMPBIAS        1..39
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         29
FT                   /note="Phosphoserine; by host"
FT                   /evidence="ECO:0000269|PubMed:28915404"
FT   MUTAGEN         72
FT                   /note="C->S: More than 70% loss of RNA-binding."
FT                   /evidence="ECO:0000269|PubMed:27279615"
FT   MUTAGEN         100
FT                   /note="L->A: Complete loss of homo-oligomerization."
FT                   /evidence="ECO:0000269|PubMed:12912982"
FT   MUTAGEN         102
FT                   /note="L->A: Complete loss of homooligomerization."
FT                   /evidence="ECO:0000269|PubMed:12912982"
FT   MUTAGEN         197
FT                   /note="E->R: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   MUTAGEN         202
FT                   /note="D->R: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   MUTAGEN         203
FT                   /note="Q->R: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   MUTAGEN         229
FT                   /note="Q->R: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   MUTAGEN         230
FT                   /note="W->F: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   MUTAGEN         234
FT                   /note="S->R: Complete loss of interaction with
FT                   nucleoprotein/NP."
FT                   /evidence="ECO:0000269|PubMed:27755595"
FT   CONFLICT        256..288
FT                   /note="VVVSGLRTLVPQSDNEEASTNPGTCSWSDEGTP -> ALFQG (in Ref.
FT                   1; AAB81005)"
FT                   /evidence="ECO:0000305"
FT   HELIX           144..155
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   STRAND          160..162
FT                   /evidence="ECO:0007829|PDB:5T3T"
FT   HELIX           164..178
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           183..185
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           186..196
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           201..203
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           204..215
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           221..229
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           232..246
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           254..257
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   TURN            258..260
FT                   /evidence="ECO:0007829|PDB:5DVW"
FT   HELIX           261..264
FT                   /evidence="ECO:0007829|PDB:5DVW"
SQ   SEQUENCE   288 AA;  32521 MW;  1FE40E93AB80454B CRC64;
     MEASYERGRP RAARQHSRDG HDHHVRARSS SRENYRGEYR QSRSASQVRV PTVFHKKRVE
     PLTVPPAPKD ICPTLKKGFL CDSSFCKKDH QLESLTDREL LLLIARKTCG SVEQQLNITA
     PKDSRLANPT ADDFQQEEGP KITLLTLIKT AEHWARQDIR TIEDSKLRAL LTLCAVMTRK
     FSKSQLSLLC ETHLRREGLG QDQAEPVLEV YQRLHSDKGG SFEAALWQQW DRQSLIMFIT
     AFLNIALQLP CESSAVVVSG LRTLVPQSDN EEASTNPGTC SWSDEGTP
//