ID   VP35_EBORR              Reviewed;         329 AA.
AC   Q8JPY0;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 89.
DE   RecName: Full=Polymerase cofactor VP35;
GN   Name=VP35; ORFNames=REBOVgp2;
OS   Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus;
OC   Orthoebolavirus restonense; Reston ebolavirus.
OX   NCBI_TaxID=386032;
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).
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=12191779; DOI=10.1016/s0168-1702(02)00087-4;
RA   Groseth A., Stroeher U., Theriault S., Feldmann H.;
RT   "Molecular characterization of an isolate from the 1989/90 epizootic of
RT   Ebola virus Reston among macaques imported into the United States.";
RL   Virus Res. 87:155-163(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Pennsylvania-89;
RX   PubMed=15661171; DOI=10.1016/j.virol.2004.11.018;
RA   Boehmann Y., Enterlein S., Randolf A., Muehlberger E.I.;
RT   "A reconstituted replication and transcription system for Ebola virus
RT   Reston and comparison with Ebola virus Zaire.";
RL   Virology 332:406-417(2005).
RN   [3] {ECO:0007744|PDB:3L2A}
RP   X-RAY CRYSTALLOGRAPHY (1.71 ANGSTROMS) OF 204-329, AND DOMAIN.
RX   PubMed=20399790; DOI=10.1016/j.jmb.2010.04.022;
RA   Leung D.W., Shabman R.S., Farahbakhsh M., Prins K.C., Borek D.M., Wang T.,
RA   Muhlberger E., Basler C.F., Amarasinghe G.K.;
RT   "Structural and functional characterization of Reston Ebola virus VP35
RT   interferon inhibitory domain.";
RL   J. Mol. Biol. 399:347-357(2010).
RN   [4] {ECO:0007744|PDB:3KS4, ECO:0007744|PDB:3KS8}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 160-329, SUBUNIT, FUNCTION,
RP   RNA-BINDING, AND DOMAIN.
RX   PubMed=20018665; DOI=10.1073/pnas.0910547107;
RA   Kimberlin C.R., Bornholdt Z.A., Li S., Woods V.L. Jr., MacRae I.J.,
RA   Saphire E.O.;
RT   "Ebolavirus VP35 uses a bimodal strategy to bind dsRNA for innate immune
RT   suppression.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:314-319(2010).
RN   [5] {ECO:0007744|PDB:4LG2}
RP   X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 205-329, RNA-BINDING, AND DOMAIN.
RX   PubMed=23824825; DOI=10.1128/jvi.01452-13;
RA   Bale S., Julien J.P., Bornholdt Z.A., Krois A.S., Wilson I.A.,
RA   Saphire E.O.;
RT   "Ebolavirus VP35 coats the backbone of double-stranded RNA for interferon
RT   antagonism.";
RL   J. Virol. 87:10385-10388(2013).
RN   [6] {ECO:0007744|PDB:6GBQ, ECO:0007744|PDB:6GBR}
RP   X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) OF 71-134, AND SUBUNIT.
RX   PubMed=30482729; DOI=10.1016/j.str.2018.09.009;
RA   Zinzula L., Nagy I., Orsini M., Weyher-Stingl E., Bracher A.,
RA   Baumeister W.;
RT   "Structures of Ebola and Reston Virus VP35 Oligomerization Domains and
RT   Comparative Biophysical Characterization in All Ebolavirus Species.";
RL   Structure 27:39-54.e6(2019).
CC   -!- FUNCTION: Plays an essential role in viral RNA synthesis and also a
CC       role in suppressing innate immune signaling. Acts as a polymerase
CC       cofactor in the RNA polymerase transcription and replication complexes
CC       (By similarity). Serves as nucleoprotein/NP monomer chaperone prior to
CC       the formation of the large oligomeric RNA-bound complexes (By
CC       similarity). Regulates RNA synthesis by modulating NP-RNA interactions
CC       and interacting with DYNLL1. VP35-NP interaction controls the switch
CC       between RNA-bound NP and free NP and thus the switch between genome
CC       replication and genome packaging into the nucleocapsid. Prevents
CC       establishment of cellular antiviral state, thereby suppressing host DC
CC       maturation. Acts by inhibiting host RIGI activation both by shielding
CC       dsRNA from detection and by preventing PRKRA binding to RIGI. Blocks
CC       virus-induced phosphorylation and activation of interferon regulatory
CC       factor 3/IRF3, a transcription factor critical for the induction of
CC       interferons alpha and beta. This blockage is produced through the
CC       interaction with and inhibition of host IKBKE and TBK1, producing a
CC       strong inhibition of the phosphorylation and activation of IRF3. Also
CC       inhibits the antiviral effect mediated by the host interferon-induced,
CC       double-stranded RNA-activated protein kinase EIF2AK2/PKR. Increases
CC       PIAS1-mediated SUMOylation of IRF7, thereby repressing interferon
CC       transcription (By similarity). Also acts as a suppressor of RNA
CC       silencing by interacting with host DICER1, TARBP2/TRBP and PRKRA/PACT
CC       (By similarity). As a dimer, binds and sequesters dsRNA contributing to
CC       the inhibition of interferon production (PubMed:20018665).
CC       {ECO:0000250|UniProtKB:Q05127, ECO:0000250|UniProtKB:Q5XX07,
CC       ECO:0000250|UniProtKB:Q6V1Q9, ECO:0000269|PubMed:20018665}.
CC   -!- SUBUNIT: Homodimer (PubMed:20018665). Homooligomer; via the coiled coil
CC       domain (PubMed:30482729). Interacts with nucleoprotein NP and
CC       polymerase L; VP35 bridges L and NP and allows the formation of the
CC       polymerase complex. Also interacts with VP30; this interaction is
CC       regulated by VP30 phosphorylation. Interacts with host IKBKE and TBK1;
CC       the interactions lead to inhibition of cellular antiviral response by
CC       blocking necessary interactions of IKBKE and TBK1 with their substrate
CC       IRF3. Interacts with host DYNLL1; this interaction stabilizes VP35 N-
CC       terminal oligomerization domain, enhances viral RNA synthesis but does
CC       not participate in suppressing the host innate immune response.
CC       Interacts with host PRKRA; this interaction inhibits the interaction
CC       between RIGI and PRKRA. Interacts with dsRNA. Interacts with host
CC       TRIM6; this interaction plays an important role in promoting efficient
CC       viral replication. Interacts with host STAU1. Interacts with host IRF7,
CC       PIAS1 and UBE2I/UBC9; these interactions mediate the sumoylation of
CC       IRF7 and contribute to the inhibition of IFN-type I production (By
CC       similarity). Interacts with host DICER1; this interaction prevents
CC       TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract
CC       host RNA silencing. Interacts with host TARBP2/TRBP and PRKRA/PACT;
CC       these interactions prevent TARBP2 and PRKRA binding to DICER1 and thus
CC       allows the virus to counteract host RNA silencing (By similarity).
CC       {ECO:0000250|UniProtKB:Q05127, ECO:0000250|UniProtKB:Q6V1Q9,
CC       ECO:0000269|PubMed:20018665, ECO:0000269|PubMed:30482729}.
CC   -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm {ECO:0000250}.
CC   -!- DOMAIN: The interferon inhibitory domain (IID) binds dsRNA.
CC       {ECO:0000269|PubMed:20018665, ECO:0000269|PubMed:20399790,
CC       ECO:0000269|PubMed:23824825}.
CC   -!- PTM: Phosphorylated by host IKBKE. Phosphorylation contributes to
CC       efficient viral replication and transcription.
CC       {ECO:0000250|UniProtKB:Q05127}.
CC   -!- PTM: Ubiquitinated by host TRIM6 to facilitate virus replication.
CC       {ECO:0000250|UniProtKB:Q05127}.
CC   -!- SIMILARITY: Belongs to the filoviridae polymerase cofactor VP35 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01071}.
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; AF522874; AAN04449.1; -; Genomic_RNA.
DR   EMBL; AY769362; AAV48575.1; -; Genomic_RNA.
DR   RefSeq; NP_690581.1; NC_004161.1.
DR   PDB; 3KS4; X-ray; 2.40 A; A/B=160-329.
DR   PDB; 3KS8; X-ray; 2.40 A; A/B/C/D=160-329.
DR   PDB; 3L2A; X-ray; 1.71 A; A=204-329.
DR   PDB; 4LG2; X-ray; 2.70 A; A/B/C/D=205-329.
DR   PDB; 6GBQ; X-ray; 2.43 A; A/B/C/D/E/F/G/H=71-134.
DR   PDB; 6GBR; X-ray; 3.15 A; A/B/C/D=71-134.
DR   PDBsum; 3KS4; -.
DR   PDBsum; 3KS8; -.
DR   PDBsum; 3L2A; -.
DR   PDBsum; 4LG2; -.
DR   PDBsum; 6GBQ; -.
DR   PDBsum; 6GBR; -.
DR   SMR; Q8JPY0; -.
DR   GeneID; 955189; -.
DR   KEGG; vg:955189; -.
DR   EvolutionaryTrace; Q8JPY0; -.
DR   Proteomes; UP000007207; Segment.
DR   Proteomes; UP000138664; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0044423; C:virion component; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039724; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IKBKE activity; IEA:UniProtKB-KW.
DR   GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039723; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity; IEA:UniProtKB-KW.
DR   CDD; cd21030; V35-RBD_P-protein-C_like; 1.
DR   Gene3D; 2.10.10.70; Filoviridae VP35, C-terminal inhibitory domain, beta-sheet subdomain; 1.
DR   Gene3D; 1.10.8.950; Filoviridae VP35, C-terminal inhibitory domain, helical subdomain; 1.
DR   InterPro; IPR002953; Filo_VP35.
DR   InterPro; IPR031163; VP35_IID.
DR   InterPro; IPR043061; VP35_IID_b-sht.
DR   InterPro; IPR043060; VP35_IID_hlx.
DR   Pfam; PF02097; Filo_VP35; 1.
DR   PIRSF; PIRSF018326; VP35_FiloV; 1.
DR   PRINTS; PR01240; FILOVP35.
DR   PROSITE; PS51735; VP35_IID; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Coiled coil; Host cytoplasm; Host-virus interaction;
KW   Inhibition of host IKBKE by virus;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host IRF7 by virus; Inhibition of host RLR pathway by virus;
KW   Inhibition of host TBK1 by virus; Inhibition of host TLR pathway by virus;
KW   Interferon antiviral system evasion; Isopeptide bond; Phosphoprotein;
KW   RNA-binding; Suppressor of RNA silencing; Transcription; Ubl conjugation;
KW   Viral immunoevasion; Viral RNA replication; Virion.
FT   CHAIN           1..329
FT                   /note="Polymerase cofactor VP35"
FT                   /id="PRO_0000245076"
FT   DOMAIN          204..329
FT                   /note="VP35 IID"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01071,
FT                   ECO:0000269|PubMed:23824825"
FT   REGION          83..145
FT                   /note="Homooligomerization"
FT                   /evidence="ECO:0000269|PubMed:30482729"
FT   COILED          84..112
FT                   /evidence="ECO:0000255"
FT   MOD_RES         194
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05127"
FT   MOD_RES         195
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05127"
FT   MOD_RES         199
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05127"
FT   MOD_RES         306
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05127"
FT   CROSSLNK        298
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:Q05127"
FT   HELIX           73..134
FT                   /evidence="ECO:0007829|PDB:6GBQ"
FT   HELIX           210..219
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           227..241
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           245..257
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           262..272
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           275..278
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   STRAND          283..285
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           289..291
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           294..296
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   STRAND          299..302
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   HELIX           309..311
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   STRAND          313..318
FT                   /evidence="ECO:0007829|PDB:3L2A"
FT   STRAND          324..328
FT                   /evidence="ECO:0007829|PDB:3L2A"
SQ   SEQUENCE   329 AA;  36410 MW;  398BA99B4603C5CC CRC64;
     MYNNKLKVCS GPETTGWISE QLMTGKIPVT DIFIDIDNKP DQMEVRLKPS SRSSTRTCTS
     SSQTEVNYVP LLKKVEDTLT MLVNATSRQN AAIEALENRL STLESSLKPI QDMGKVISSL
     NRSCAEMVAK YDLLVMTTGR ATSTAAAVDA YWKEHKQPPP GPALYEENAL KGKIDDPNSY
     VPDAVQEAYK NLDSTSTLTE ENFGKPYISA KDLKEIMYDH LPGFGTAFHQ LVQVICKIGK
     DNNLLDTIHA EFQASLADGD SPQCALIQIT KRVPIFQDVP PPIIHIRSRG DIPRACQKSL
     RPAPPSPKID RGWVCLFKMQ DGKTLGLKI
//