VP35_EBOZ5
ID VP35_EBOZ5 Reviewed; 340 AA.
AC Q6V1Q9;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Polymerase cofactor VP35;
DE AltName: Full=Ebola VP35;
DE Short=eVP35;
GN Name=VP35;
OS Zaire ebolavirus (strain Kikwit-95) (ZEBOV) (Zaire Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128951;
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].
RA Chain P.S.G., Ichou M.A., Malfatti S.A., Hajjaj A., Vergez L.M.,
RA Paragas J., Do L.H., Jahrling P.B., Smith K.L., McCready P.M.,
RA Ibrahim M.S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, INTERACTION WITH HOST DICER1, INTERACTION WITH HOST TARBP2/TRBP,
RP AND INTERACTION WITH HOST PRKRA/PACT.
RX PubMed=21228243; DOI=10.1128/jvi.01160-10;
RA Fabozzi G., Nabel C.S., Dolan M.A., Sullivan N.J.;
RT "Ebolavirus proteins suppress the effects of small interfering RNA by
RT direct interaction with the mammalian RNA interference pathway.";
RL J. Virol. 85:2512-2523(2011).
RN [3] {ECO:0007744|PDB:5BPV}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 217-340.
RA Fadda V., Cannas V., Zinzula L., Distinto S., Daino G.L., Bianco G.,
RA Corona A., Esposito F., Alcaro S., Maccioni E., Tramontano E., Taylor G.L.;
RT "Crystal Structure of Zaire ebolavirus VP35 RNA binding domain mutant
RT I278A.";
RL Submitted (MAY-2015) to the PDB data bank.
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 DDX58/RIG-I activation both by
CC shielding dsRNA from detection and by preventing PRKRA binding to
CC DDX58. Blocks virus-induced phosphorylation and activation of
CC interferon regulatory factor 3/IRF3, a transcription factor critical
CC for the induction of interferons alpha and beta. This blockage is
CC produced through the interaction with and inhibition of host IKBKE and
CC TBK1, producing a strong inhibition of the phosphorylation and
CC activation of IRF3. Also inhibits the antiviral effect mediated by the
CC host interferon-induced, double-stranded RNA-activated protein kinase
CC EIF2AK2/PKR. Increases PIAS1-mediated SUMOylation of IRF7, thereby
CC repressing interferon transcription (By similarity). Also acts as a
CC suppressor of RNA silencing by interacting with host DICER1,
CC TARBP2/TRBP and PRKRA/PACT (PubMed:21228243). As a dimer, binds and
CC sequesters dsRNA contributing to the inhibition of interferon
CC production (By similarity). {ECO:0000250|UniProtKB:Q05127,
CC ECO:0000250|UniProtKB:Q5XX07, ECO:0000250|UniProtKB:Q8JPY0,
CC ECO:0000269|PubMed:21228243}.
CC -!- SUBUNIT: Homodimer (By similarity). Homooligomer; via the coiled coil
CC domain. Interacts with nucleoprotein NP and polymerase L; VP35 bridges
CC L and NP and allows the formation of the polymerase complex. Also
CC interacts with VP30; this interaction is regulated by VP30
CC phosphorylation. Interacts with host IKBKE and TBK1; the interactions
CC lead to inhibition of cellular antiviral response by blocking necessary
CC interactions of IKBKE and TBK1 with their substrate IRF3. Interacts
CC with host DYNLL1; this interaction stabilizes VP35 N-terminal
CC oligomerization domain, enhances viral RNA synthesis but does not
CC participate in suppressing the host innate immune response. Interacts
CC with host PRKRA; this interaction inhibits the interaction between
CC DDX58 and PRKRA. Interacts with dsRNA. Interacts with host TRIM6; this
CC interaction plays an important role in promoting efficient viral
CC replication. Interacts with host STAU1. Interacts with host IRF7, PIAS1
CC and UBE2I/UBC9; these interactions mediate the sumoylation of IRF7 and
CC contribute to the inhibition of IFN-type I production (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 (PubMed:21228243). Interacts with host TARBP2/TRBP and
CC PRKRA/PACT; these interactions prevent TARBP2 and PRKRA binding to
CC DICER1 and thus allows the virus to counteract host RNA silencing
CC (PubMed:21228243). {ECO:0000250|UniProtKB:Q05127,
CC ECO:0000250|UniProtKB:Q8JPY0, ECO:0000269|PubMed:21228243}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:Q05127}. Host
CC cytoplasm {ECO:0000250|UniProtKB:Q05127}.
CC -!- PTM: Phosphorylated by host IKBKE. Phosphorylation contributes to
CC efficient viral replication and transcription.
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; AY354458; AAQ55046.1; -; Genomic_RNA.
DR PDB; 5BPV; X-ray; 1.95 A; A/B=217-340.
DR PDB; 7D35; X-ray; 2.40 A; B=67-76.
DR PDBsum; 5BPV; -.
DR PDBsum; 7D35; -.
DR SMR; Q6V1Q9; -.
DR Proteomes; UP000007208; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
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 Gene3D; 1.10.8.950; -; 1.
DR Gene3D; 2.10.10.70; -; 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; Phosphoprotein; Reference proteome;
KW RNA-binding; Suppressor of RNA silencing; Transcription;
KW Viral immunoevasion; Viral RNA replication; Virion.
FT CHAIN 1..340
FT /note="Polymerase cofactor VP35"
FT /id="PRO_0000245078"
FT DOMAIN 215..340
FT /note="VP35 IID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01071"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 96..116
FT /evidence="ECO:0000255"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 206
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 210
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT HELIX 221..231
FT /evidence="ECO:0007829|PDB:5BPV"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 238..252
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 256..268
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 273..283
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:5BPV"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 305..310
FT /evidence="ECO:0007829|PDB:5BPV"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:5BPV"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:5BPV"
FT STRAND 335..339
FT /evidence="ECO:0007829|PDB:5BPV"
SQ SEQUENCE 340 AA; 37363 MW; B4BEAF5FBB5B171F CRC64;
MTTRTKGRGH TAATTQNDRM PGPELSGWIS EQLMTGRIPV SDIFCDIENN PGLCYASQMQ
QTKPNPKTRN SQTQTDPICN HSFEEVVQTL ASLATVVQQQ TIASESLEQR ITSLENGLKP
VYDMAKTISS LNRVCAEMVA KYDLLVMTTG RATATAAATE AYWAEHGQPP PGPSLYEESA
IRGKIESRDE TVPQSVREAF NNLDSTTSLT EENFGKPDIS AKDLRNIMYD HLPGFGTAFH
QLVQVICKLG KDSNSLDIIH AEFQASLAEG DSPQCALIQI TKRVPIFQDA APPVIHIRSR
GDIPRACQKS LRPVPPSPKI DRGWVCVFQL QDGKTLGLKI
