VP35_EBOSU
ID VP35_EBOSU Reviewed; 329 AA.
AC Q5XX07;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 63.
DE RecName: Full=Polymerase cofactor VP35;
GN Name=VP35;
OS Sudan ebolavirus (strain Human/Uganda/Gulu/2000) (SEBOV) (Sudan Ebola
OS virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=386033;
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=16139097; DOI=10.1016/j.virusres.2005.03.028;
RA Sanchez A., Rollin P.E.;
RT "Complete genome sequence of an Ebola virus (Sudan species) responsible for
RT a 2000 outbreak of human disease in Uganda.";
RL Virus Res. 113:16-25(2005).
RN [2] {ECO:0007744|PDB:6OAF}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-49, FUNCTION, AND INTERACTION
RP WITH THE NUCLEOPROTEIN.
RX PubMed=31337716; DOI=10.1128/mbio.00734-19;
RA Landeras-Bueno S., Oda S.I., Norris M.J., Li Salie Z., Guenaga J.,
RA Wyatt R.T., Saphire E.O.;
RT "Sudan Ebolavirus VP35-NP Crystal Structure Reveals a Potential Target for
RT Pan-Filovirus Treatment.";
RL MBio 10:0-0(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
CC (PubMed:31337716). Regulates RNA synthesis by modulating NP-RNA
CC interactions and interacting with DYNLL1. VP35-NP interaction controls
CC the switch between RNA-bound NP and free NP and thus the switch between
CC genome 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 (By similarity). 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:Q6V1Q9, ECO:0000250|UniProtKB:Q8JPY0,
CC ECO:0000269|PubMed:31337716}.
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 (Probable).
CC Also 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. Interacts with host TARBP2/TRBP and PRKRA/PACT; these
CC interactions prevent TARBP2 and PRKRA binding to DICER1 and thus allows
CC the virus to counteract host RNA silencing (By similarity).
CC {ECO:0000250|UniProtKB:Q05127, ECO:0000250|UniProtKB:Q6V1Q9,
CC ECO:0000250|UniProtKB:Q8JPY0, ECO:0000305|PubMed:31337716}.
CC -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm {ECO:0000250}.
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}.
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DR EMBL; AY729654; AAU43884.1; -; Genomic_RNA.
DR RefSeq; YP_138521.1; NC_006432.1.
DR PDB; 6OAF; X-ray; 2.20 A; A=1-49.
DR PDBsum; 6OAF; -.
DR SMR; Q5XX07; -.
DR GeneID; 3160776; -.
DR KEGG; vg:3160776; -.
DR Proteomes; UP000000277; 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; RNA-binding;
KW Suppressor of RNA silencing; Transcription; Viral immunoevasion;
KW Viral RNA replication; Virion.
FT CHAIN 1..329
FT /note="Polymerase cofactor VP35"
FT /id="PRO_0000245077"
FT DOMAIN 204..329
FT /note="VP35 IID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01071"
FT REGION 1..49
FT /note="Chaperones the nucleoprotein"
FT /evidence="ECO:0000269|PubMed:31337716"
FT COILED 84..108
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 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05127"
FT STRAND 9..12
FT /evidence="ECO:0007829|PDB:6OAF"
FT HELIX 17..23
FT /evidence="ECO:0007829|PDB:6OAF"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:6OAF"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:6OAF"
SQ SEQUENCE 329 AA; 36116 MW; 1B85B4EDF83FB011 CRC64;
MQQDRTYRHH GPEVSGWFSE QLMTGKIPLT EVFVDVENKP SPAPITIISK NPKTTRKSDK
QVQTDDASSL LTEEVKAAIN SVISAVRRQT NAIESLEGRV TTLEASLKPV QDMAKTISSL
NRSCAEMVAK YDLLVMTTGR ATATAAATEA YWNEHGQAPP GPSLYEDDAI KAKLKDPNGK
VPESVKQAYI NLDSTSALNE ENFGRPYISA KDLKEIIYDH LPGFGTAFHQ LVQVICKIGK
DNNILDIIHA EFQASLAEGD SPQCALIQIT KRIPAFQDAS PPIVHIKSRG DIPKACQKSL
RPVPPSPKID RGWVCIFQFQ DGKALGLKI
