ID POLN_CRPVC Reviewed; 1771 AA.
AC Q9IJX4;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 102.
DE RecName: Full=Replicase polyprotein;
DE Contains:
DE RecName: Full=Protein 1A;
DE AltName: Full=CrPV-1A;
DE Contains:
DE RecName: Full=Protein 2A;
DE Contains:
DE RecName: Full=Protein 2B;
DE Contains:
DE RecName: Full=Protein 2C;
DE Contains:
DE RecName: Full=Protein 3A;
DE Contains:
DE RecName: Full=Protein 3B;
DE Contains:
DE RecName: Full=3C-like protease;
DE EC=3.4.22.-;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase 3D-POL;
DE EC=2.7.7.48;
GN ORFNames=ORF1;
OS Cricket paralysis virus (isolate Teleogryllus
OS commodus/Australia/CrPVVIC/1968) (CrPV).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Picornavirales; Dicistroviridae; Cripavirus; Cripavirus grylli.
OX NCBI_TaxID=928300;
OH NCBI_TaxID=128161; Teleogryllus oceanicus (black field cricket).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=10866656; DOI=10.1128/mcb.20.14.4990-4999.2000;
RA Wilson J.E., Powell M.J., Hoover S.E., Sarnow P.;
RT "Naturally occurring dicistronic cricket paralysis virus RNA is regulated
RT by two internal ribosome entry sites.";
RL Mol. Cell. Biol. 20:4990-4999(2000).
RN [2]
RP PROTEOLYTIC PROCESSING OF POLYPROTEIN.
RX PubMed=18810573; DOI=10.1007/s00705-008-0208-5;
RA Nakashima N., Nakamura Y.;
RT "Cleavage sites of the 'P3 region' in the nonstructural polyprotein
RT precursor of a dicistrovirus.";
RL Arch. Virol. 153:1955-1960(2008).
RN [3]
RP FUNCTION (PROTEIN 1A), AND INTERACTION WITH HOST AGO2 (PROTEIN 1A).
RX PubMed=20400949; DOI=10.1038/nsmb.1810;
RA Nayak A., Berry B., Tassetto M., Kunitomi M., Acevedo A., Deng C.,
RA Krutchinsky A., Gross J., Antoniewski C., Andino R.;
RT "Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral
RT defense in Drosophila.";
RL Nat. Struct. Mol. Biol. 17:547-554(2010).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-146.
RX PubMed=28003491; DOI=10.1128/jvi.01779-16;
RA Khong A., Kerr C.H., Yeung C.H.L., Keatings K., Nayak A., Allan D.W.,
RA Jan E.;
RT "Disruption of Stress Granule Formation by the Multifunctional Cricket
RT Paralysis Virus 1A Protein.";
RL J. Virol. 91:0-0(2017).
RN [5]
RP FUNCTION.
RX PubMed=36455064; DOI=10.1371/journal.ppat.1010598;
RA Sadasivan J., Vlok M., Wang X., Nayak A., Andino R., Jan E.;
RT "Targeting Nup358/RanBP2 by a viral protein disrupts stress granule
RT formation.";
RL PLoS Pathog. 18:e1010598-e1010598(2022).
RN [6] {ECO:0007744|PDB:6C3R}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 14-154, INTERACTION WITH HOST
RP AGO2, MUTAGENESIS OF PRO-106 AND PHE-114, AND DOMAIN.
RX PubMed=30308158; DOI=10.1016/j.chom.2018.09.006;
RA Nayak A., Kim D.Y., Trnka M.J., Kerr C.H., Lidsky P.V., Stanley D.J.,
RA Rivera B.M., Li K.H., Burlingame A.L., Jan E., Frydman J., Gross J.D.,
RA Andino R.;
RT "A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute
RT Activity and Stability.";
RL Cell Host Microbe 24:542-557.e9(2018).
CC -!- FUNCTION: [Protein 1A]: Suppressor of RNA-mediated gene silencing, an
CC antiviral defense mechanism of insect cells (PubMed:20400949). Inhibits
CC siRNA function through the direct enzymatic inactivation of host AGO2,
CC but does not interfere with miRNA pathway (PubMed:20400949).
CC Facilitates viral replication via the recruitment of a cellular
CC ubiquitin ligase complex that promotes host AGO2 degradation
CC (PubMed:30308158). Inhibits the integrated stress response (ISR) in the
CC infected cell possiby by degrading host Nup358 (PubMed:28003491,
CC PubMed:36455064). Stress granule formation is thus inhibited, which
CC allows protein synthesis and viral replication (PubMed:28003491,
CC PubMed:36455064). Does not bind to dsRNA or siRNA (PubMed:20400949).
CC {ECO:0000269|PubMed:20400949, ECO:0000269|PubMed:28003491,
CC ECO:0000269|PubMed:30308158, ECO:0000269|PubMed:36455064}.
CC -!- FUNCTION: [RNA-directed RNA polymerase 3D-POL]: Replicates the genomic
CC and antigenomic RNA. {ECO:0000255|PROSITE-ProRule:PRU00539,
CC ECO:0000269|PubMed:20400949}.
CC -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase 3D-POL]:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- SUBUNIT: [Protein 1A]: Interacts with host AGO2; this interaction leads
CC to AGO2 degradation via an E3 ubiquitin ligase-dependent pathway and
CC may block the RNA-induced silencing complexes (RISC) activity.
CC {ECO:0000269|PubMed:20400949, ECO:0000305|PubMed:30308158}.
CC -!- INTERACTION:
CC Q9IJX4; Q9VUQ5: AGO2; Xeno; NbExp=3; IntAct=EBI-15848754, EBI-442476;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:28003491}.
CC -!- DOMAIN: The BC-box mediates viral E3 ligase assembly in order to
CC degrade host AGO2. {ECO:0000269|PubMed:30308158}.
CC -!- PTM: [Protein 1A]: Might be expressed through a ribosomal skip from one
CC codon to the next without formation of a peptide bond.
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DR EMBL; AF218039; AAF80998.1; -; Genomic_RNA.
DR RefSeq; NP_647481.1; NC_003924.1.
DR PDB; 6C3R; X-ray; 2.60 A; A/B=14-154.
DR PDBsum; 6C3R; -.
DR SMR; Q9IJX4; -.
DR DIP; DIP-59000N; -.
DR IntAct; Q9IJX4; 1.
DR MEROPS; C03.015; -.
DR GeneID; 944541; -.
DR KEGG; vg:944541; -.
DR Proteomes; UP000008590; Segment.
DR GO; GO:0031462; C:Cul2-RING ubiquitin ligase complex; IPI:FlyBase.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0060698; F:endoribonuclease inhibitor activity; IDA:FlyBase.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-dependent RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:FlyBase.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0140533; P:suppression of host RNAi-mediated antiviral immune response; IGI:FlyBase.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd23194; Dicistroviridae_RdRp; 1.
DR Gene3D; 1.20.960.20; -; 1.
DR Gene3D; 3.30.70.270; -; 1.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR004004; Helic/Pol/Pept_Calicivir-typ.
DR InterPro; IPR000605; Helicase_SF3_ssDNA/RNA_vir.
DR InterPro; IPR014759; Helicase_SF3_ssRNA_vir.
DR InterPro; IPR044067; PCV_3C_PRO.
DR InterPro; IPR024387; Pept_C3G_Picornavir.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR InterPro; IPR001205; RNA-dir_pol_C.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR Pfam; PF12381; Peptidase_C3G; 1.
DR Pfam; PF00680; RdRP_1; 1.
DR Pfam; PF00910; RNA_helicase; 1.
DR PRINTS; PR00918; CALICVIRUSNS.
DR SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS51874; PCV_3C_PRO; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR PROSITE; PS51218; SF3_HELICASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Coiled coil; Helicase; Host cytoplasm;
KW Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus; Nucleotide-binding;
KW Nucleotidyltransferase; Protease; Reference proteome; RNA-binding;
KW RNA-directed RNA polymerase; Suppressor of RNA silencing; Thiol protease;
KW Transferase; Viral immunoevasion; Viral RNA replication.
FT CHAIN 1..1771
FT /note="Replicase polyprotein"
FT /id="PRO_0000398372"
FT CHAIN 1..166
FT /note="Protein 1A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398374"
FT CHAIN 167..190
FT /note="Protein 2A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398373"
FT CHAIN 191..328
FT /note="Protein 2B"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398375"
FT CHAIN 329..739
FT /note="Protein 2C"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398376"
FT CHAIN 740..?
FT /note="Protein 3A"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398377"
FT CHAIN ?..908
FT /note="Protein 3B"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398378"
FT CHAIN 909..1220
FT /note="3C-like protease"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398379"
FT CHAIN 1221..1771
FT /note="RNA-directed RNA polymerase 3D-POL"
FT /evidence="ECO:0000255"
FT /id="PRO_0000398380"
FT DOMAIN 482..656
FT /note="SF3 helicase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT DOMAIN 954..1201
FT /note="Peptidase C3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT DOMAIN 1495..1634
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 16..25
FT /note="BC-box"
FT /evidence="ECO:0000269|PubMed:30308158"
FT REGION 106..114
FT /note="Interaction with and inhibition of host AGO2"
FT /evidence="ECO:0000269|PubMed:30308158"
FT REGION 919..942
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1..29
FT /evidence="ECO:0000255"
FT COILED 1385..1413
FT /evidence="ECO:0000255"
FT ACT_SITE 1003
FT /note="For picornain 3C-like protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1063
FT /note="For picornain 3C-like protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT ACT_SITE 1162
FT /note="For picornain 3C-like protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"
FT BINDING 510..517
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00551"
FT SITE 146
FT /note="Involved in the inhibition of host stress granules
FT formation"
FT /evidence="ECO:0000269|PubMed:28003491"
FT SITE 166..167
FT /note="Cleavage; by ribosomal skip"
FT /evidence="ECO:0000255"
FT SITE 190..191
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT SITE 328..329
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT SITE 739..740
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT SITE 884..885
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT SITE 908..909
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT SITE 1220..1221
FT /note="Cleavage; by 3C-like protease"
FT /evidence="ECO:0000255"
FT MUTAGEN 106
FT /note="P->A: Reduced host AGO2 binding, loss of AGO2
FT inhibition and loss of RNA silencing inhibition."
FT /evidence="ECO:0000269|PubMed:30308158"
FT MUTAGEN 114
FT /note="F->A,D,G,N,P,R: Reduced host AGO2 binding, loss of
FT AGO2 inhibition and loss of RNA silencing inhibition. Loss
FT of replication efficiency."
FT /evidence="ECO:0000269|PubMed:30308158"
FT MUTAGEN 146
FT /note="R->A: Attenuated infection. Loss of inhibition of
FT host stress granules formation."
FT /evidence="ECO:0000269|PubMed:28003491"
FT HELIX 15..29
FT /evidence="ECO:0007829|PDB:6C3R"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:6C3R"
FT TURN 49..52
FT /evidence="ECO:0007829|PDB:6C3R"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:6C3R"
FT HELIX 66..83
FT /evidence="ECO:0007829|PDB:6C3R"
FT HELIX 90..103
FT /evidence="ECO:0007829|PDB:6C3R"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:6C3R"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:6C3R"
FT HELIX 123..127
FT /evidence="ECO:0007829|PDB:6C3R"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:6C3R"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:6C3R"
SQ SEQUENCE 1771 AA; 203830 MW; 78C5969469EAA716 CRC64;
MSFQQTNNNA TNNINSLEEL AAQELIAAQF EGNLDGFFCT FYVQSKPQLL DLESECYCMD
DFDCGCDRIK REEELRKLIF LTSDVYGYNF EEWKGLVWKF VQNYCPEHRY GSTFGNGLLI
VSPRFFMDHL DWFQQWKLVS SNDECRAFLR KRTQLLMSGD VESNPGPVQS RPVYACDNDP
RAIRLEKALQ RRDEKISTLI KKLRQEIKNN RIYTQGFFDD LKGAKGEVGQ LNGNLTRICD
FLENSLPTLT AQIQTTVLTT TDKYVNLKED LLKVAILLVL VRLLMVWKKY RAALIVIILF
VMHFYGFDKQ ILDIVLDLKD KILQTTTQAG TETLEEVVYH PWFDTCGKLI FAVLAFFAIK
KIPGKQDWDN YISRLDRIPK AIEGSKKIVD YCSEYFNLSV DEVKKVVLGK ELKGTQGLYD
EIHVWAKEIR HYLDLDERNK ITLDTETAAK VEDLYKRGLK YSEEKIPDRD IARFITTMLF
PAKSLYEQVL LSPVKGGGPK MRPITVWLTG ESGIGKTQMI YPLCIDILRE MGIVKPDAYK
HQAYARQVET EYWDGYNGQK IVIYDDAFQL KDDKTKPNPE IFEVIRTCNT FPQHLHMAAL
QDKNMYSQAE VLLYTTNQFQ VQLESITFPD AFYNRMKTHA YRVQIKQEKS IWVRNARGEE
YNALDVTKLN KDEAIDLSVY EFQKMRFDDE SATKWIDDGE PISYDEFART ICKAWKEEKE
KTFHQLQWLE AYASRTVAQG GSETSEYYDV WDETYFSNLL SQGFMAGKSL IEMEAEFASD
AETFNAYIEY KKNIPKETKW SKWMTILDEQ ISALSTKIRE LKNKAYKFIS EHPYLTALGF
IGVMISAFAM YSFFERTLTD DTITSEVGSS GDNKTQKISK RVVEVGGSGD VKTTKPAKTA
VEVGSSGDSK TMKNKITKVE VGSSGDSKTQ KQRNTKVEVG KELEKEAETQ GCSDPAAHAL
VLDVLQKNTY CLYYERMVKG EMKRYRLATA TFLRGWVCMM PYHFIETLYA RKVAPSTNIY
FSQPNCDDVI VVPVSHFIAP NAERVELTTA CTRIHYKDET PRDCVLVNLH RRMCHPHRDI
LKHFVKKSDQ GNLRGVFQGT LATFHQSANE LCRAYQWLQA IRPLDQEITI YHEDTDMFDY
ESESYTQRDC YEYNAPTQTG NCGSIVGLYN KRMERKLIGM HIPGNVSECH GYACPLTQEA
IMDGLNRLEK LDPVNNITVQ CCFEPPSDIK DTMSGETPEG KFCAIGKSNI KVGQAVKTTL
LKSCIYGMLS KPITKPAHLT RTRLPNGEIV DPLMKGLKKC GVDTAVLDAE IVESAALDVK
QVVLTQYNSM LDVNKYRRFL TYEEATQGTG DDDFMKGIAR QTSPGYRYFQ MPRKLPGKQD
WMGSGEQYDF TSQRAQELRR DVEELIDNCA KGIIKDVVFV DTLKDERRPI EKVDAGKTRV
FSAGPQHFVV AFRKYFLPFA AYLMNNRIDN EIAVGTNVYS TDWERIAKRL KKHGNKVIAG
DFGNFDGSLV AQFFGQSCGK SFYPWFKTFN DVNTEDGKRN LMICIGLWTH IVHSVHSYGD
NVYMWTHSQP SGNPFTVIIN CLYNSMIMRI VWILLARKLA PEMQSMKKFR ENVSMISYGD
DNCLNISDRV VEWFNQITIS EQMKEIKHEY TDEGKTGDMV KFPSLSEIHF LKKRFVFSHQ
LQRTVAPLQK DVIYEMLNWT RNTIDPNEIL MMNINTAFRE IVYHGKSEYQ KLRSGIEDLA
MKGILPQQPQ ILTFKAYLWD ATMLADEVYD F
//
