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
//