ID   R1AB_SARS2              Reviewed;        7096 AA.
AC   P0DTD1;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   22-APR-2020, sequence version 1.
DT   17-JUN-2020, entry version 2.
DE   RecName: Full=Replicase polyprotein 1ab;
DE            Short=pp1ab;
DE   AltName: Full=ORF1ab polyprotein;
DE   Contains:
DE     RecName: Full=Host translation inhibitor nsp1;
DE              Short=nsp1;
DE     AltName: Full=Leader protein;
DE   Contains:
DE     RecName: Full=Non-structural protein 2;
DE              Short=nsp2;
DE     AltName: Full=p65 homolog;
DE   Contains:
DE     RecName: Full=Non-structural protein 3;
DE              Short=nsp3;
DE              EC=3.4.19.12;
DE              EC=3.4.22.-;
DE     AltName: Full=PL2-PRO;
DE     AltName: Full=Papain-like proteinase;
DE              Short=PL-PRO;
DE   Contains:
DE     RecName: Full=Non-structural protein 4;
DE              Short=nsp4;
DE   Contains:
DE     RecName: Full=3C-like proteinase;
DE              Short=3CL-PRO;
DE              Short=3CLp;
DE              EC=3.4.22.69 {ECO:0000269|PubMed:32198291};
DE     AltName: Full=SARS coronavirus main proteinase;
DE     AltName: Full=nsp5;
DE   Contains:
DE     RecName: Full=Non-structural protein 6;
DE              Short=nsp6;
DE   Contains:
DE     RecName: Full=Non-structural protein 7;
DE              Short=nsp7;
DE   Contains:
DE     RecName: Full=Non-structural protein 8;
DE              Short=nsp8;
DE   Contains:
DE     RecName: Full=Non-structural protein 9;
DE              Short=nsp9;
DE   Contains:
DE     RecName: Full=Non-structural protein 10;
DE              Short=nsp10;
DE     AltName: Full=Growth factor-like peptide;
DE              Short=GFL;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              Short=Pol;
DE              Short=RdRp;
DE              EC=2.7.7.48;
DE     AltName: Full=nsp12;
DE   Contains:
DE     RecName: Full=Helicase;
DE              Short=Hel;
DE              EC=3.6.4.12;
DE              EC=3.6.4.13;
DE     AltName: Full=nsp13;
DE   Contains:
DE     RecName: Full=Proofreading exoribonuclease;
DE              Short=ExoN;
DE              EC=3.1.13.-;
DE     AltName: Full=Guanine-N7 methyltransferase;
DE     AltName: Full=Non-structural protein 14;
DE              Short=nsp14;
DE   Contains:
DE     RecName: Full=Uridylate-specific endoribonuclease;
DE              EC=3.1.-.-;
DE     AltName: Full=NendoU;
DE     AltName: Full=nsp15;
DE   Contains:
DE     RecName: Full=2'-O-methyltransferase;
DE              EC=2.1.1.-;
DE     AltName: Full=nsp16;
GN   Name=rep; ORFNames=1a-1b;
OS   Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC   Viruses; Riboviria; Nidovirales; Cornidovirineae; Coronaviridae;
OC   Orthocoronavirinae; Betacoronavirus; Sarbecovirus.
OX   NCBI_TaxID=2697049;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA   Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA   Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA   Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT   "A new coronavirus associated with human respiratory disease in China.";
RL   Nature 579:265-269(2020).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.16 ANGSTROMS) OF 3C-LIKE PROTEINASE.
RA   Liu X., Zhang B., Jin Z., Yang H., Rao Z.;
RT   "The crystal structure of 2019-nCoV main protease in complex with an
RT   inhibitor N3.";
RL   Submitted (FEB-2020) to the PDB data bank.
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 3C-LIKE PROTEINASE APOENZYME AND
RP   IN COMPLEX WITH ALPHA-KETOAMIDE 13B INHIBITOR, SUBUNIT (3C-LIKE
RP   PROTEINASE), FUNCTION (3C-LIKE PROTEINASE), CATALYTIC ACTIVITY (3C-LIKE
RP   PROTEINASE), ACTIVE SITE, AND ACTIVITY REGULATION.
RX   PubMed=32198291; DOI=10.1126/science.abb3405;
RA   Zhang L., Lin D., Sun X., Curth U., Drosten C., Sauerhering L., Becker S.,
RA   Rox K., Hilgenfeld R.;
RT   "Crystal structure of SARS-CoV-2 main protease provides a basis for design
RT   of improved alpha-ketoamide inhibitors.";
RL   Science 0:0-0(2020).
CC   -!- FUNCTION: [Replicase polyprotein 1ab]: Multifunctional protein involved
CC       in the transcription and replication of viral RNAs. Contains the
CC       proteinases responsible for the cleavages of the polyprotein.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Host translation inhibitor nsp1]: Inhibits host translation
CC       by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome
CC       complex further induces an endonucleolytic cleavage near the 5'UTR of
CC       host mRNAs, targeting them for degradation. Viral mRNAs are not
CC       susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the
CC       presence of a 5'-end leader sequence and are therefore protected from
CC       degradation. By suppressing host gene expression, nsp1 facilitates
CC       efficient viral gene expression in infected cells and evasion from host
CC       immune response. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 2]: May play a role in the modulation
CC       of host cell survival signaling pathway by interacting with host PHB
CC       and PHB2. Indeed, these two proteins play a role in maintaining the
CC       functional integrity of the mitochondria and protecting cells from
CC       various stresses. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 3]: Responsible for the cleavages
CC       located at the N-terminus of the replicase polyprotein. In addition,
CC       PL-PRO possesses a deubiquitinating/deISGylating activity and processes
CC       both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular
CC       substrates. Participates together with nsp4 in the assembly of virally-
CC       induced cytoplasmic double-membrane vesicles necessary for viral
CC       replication. Antagonizes innate immune induction of type I interferon
CC       by blocking the phosphorylation, dimerization and subsequent nuclear
CC       translocation of host IRF3. Prevents also host NF-kappa-B signaling.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 4]: Participates in the assembly of
CC       virally-induced cytoplasmic double-membrane vesicles necessary for
CC       viral replication. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [3C-like proteinase]: Cleaves the C-terminus of replicase
CC       polyprotein at 11 sites. Recognizes substrates containing the core
CC       sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291). Also able to bind an
CC       ADP-ribose-1''-phosphate (ADRP). {ECO:0000250|UniProtKB:P0C6X7,
CC       ECO:0000269|PubMed:32198291}.
CC   -!- FUNCTION: [Non-structural protein 6]: Plays a role in the initial
CC       induction of autophagosomes from host reticulum endoplasmic. Later,
CC       limits the expansion of these phagosomes that are no longer able to
CC       deliver viral components to lysosomes. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8
CC       subunits of each) that may participate in viral replication by acting
CC       as a primase. Alternatively, may synthesize substantially longer
CC       products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8
CC       subunits of each) that may participate in viral replication by acting
CC       as a primase. Alternatively, may synthesize substantially longer
CC       products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 9]: May participate in viral
CC       replication by acting as a ssRNA-binding protein.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral
CC       transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16
CC       2'-O-methyltransferase activities. Therefore plays an essential role in
CC       viral mRNAs cap methylation. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication
CC       and transcription of the viral RNA genome.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Helicase]: Multi-functional protein with a zinc-binding
CC       domain in N-terminus displaying RNA and DNA duplex-unwinding activities
CC       with 5' to 3' polarity. Activity of helicase is dependent on magnesium.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Proofreading exoribonuclease]: Enzyme possessing two
CC       different activities: an exoribonuclease activity acting on both ssRNA
CC       and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase
CC       activity. Acts as a proofreading exoribonuclease for RNA replication,
CC       thereby lowering The sensitivity of the virus to RNA mutagens.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [Uridylate-specific endoribonuclease]: Mn(2+)-dependent,
CC       uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to
CC       the cleaved bond. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- FUNCTION: [2'-O-methyltransferase]: Methyltransferase that mediates
CC       mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral
CC       mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16.
CC       Therefore plays an essential role in viral mRNAs cap methylation which
CC       is essential to evade immune system. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]:
CC       Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC         RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:11128, Rhea:RHEA-
CC         COMP:11129, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:83400;
CC         EC=2.7.7.48; Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC   -!- CATALYTIC ACTIVITY: [Helicase]:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC         Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC   -!- CATALYTIC ACTIVITY: [Helicase]:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC         Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC   -!- CATALYTIC ACTIVITY: [3C-like proteinase]:
CC       Reaction=TSAVLQ-|-SGFRK-NH(2) and SGVTFQ-|-GKFKK the two peptides
CC         corresponding to the two self-cleavage sites of the SARS 3C-like
CC         proteinase are the two most reactive peptide substrates. The enzyme
CC         exhibits a strong preference for substrates containing Gln at P1
CC         position and Leu at P2 position.; EC=3.4.22.69;
CC         Evidence={ECO:0000269|PubMed:32198291};
CC   -!- CATALYTIC ACTIVITY: [Non-structural protein 3]:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:P0C6X7};
CC   -!- ACTIVITY REGULATION: [Proofreading exoribonuclease]: Inhibited by
CC       Remdesivir (GS-5734). {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- ACTIVITY REGULATION: [3C-like proteinase]: Inhibited by pyridone-
CC       containing alpha-ketoamides compounds 13a and 13b. In turn, alpha-
CC       ketoamide 13b (tert-butyl (1-((S)-1-(((S)-4-(benzylamino)-3,4-dioxo-1-
CC       ((S)-2-oxopyrrolidin-3-yl)butan-2-yl)amino)-3-cyclopropyl-1-oxopropan-
CC       2-yl)-2-oxo-1,2-dihydropyridin-3-yl)carbamate) inhibits SARS-CoV-2
CC       replication in human lung cells. {ECO:0000269|PubMed:32198291}.
CC   -!- SUBUNIT: [Non-structural protein 2]: Interacts with host PHB and PHB2.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [3C-like proteinase]: 3CL-PRO exists as monomer and homodimer.
CC       Only the homodimer shows catalytic activity.
CC       {ECO:0000269|PubMed:32198291}.
CC   -!- SUBUNIT: [Non-structural protein 4]: Interacts with PL-PRO and nsp6.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Non-structural protein 7]: Eight copies of nsp7 and eight
CC       copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC       ring structure. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Non-structural protein 8]: Eight copies of nsp7 and eight
CC       copies of nsp8 assemble to form a heterohexadecamer dsRNA-encircling
CC       ring structure. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Non-structural protein 9]: Is a dimer.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Non-structural protein 10]: Forms a dodecamer and interacts
CC       with nsp14 and nsp16; these interactions enhance nsp14 and nsp16
CC       enzymatic activities. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [Proofreading exoribonuclease]: Interacts (via N-terminus)
CC       with DDX1. Interacts with nsp10. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBUNIT: [2'-O-methyltransferase]: Interacts with nsp10.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane
CC       {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane
CC       {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P0C6X7}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P0C6X7}. Note=Localizes in virally-induced
CC       cytoplasmic double-membrane vesicles. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane
CC       {ECO:0000250|UniProtKB:P0C6X7}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Note=nsp7, nsp8,
CC       nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear.
CC       Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Note=nsp7, nsp8,
CC       nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear.
CC       Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Note=nsp7, nsp8,
CC       nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear.
CC       Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host
CC       perinuclear region {ECO:0000250|UniProtKB:P0C6X9}. Note=nsp7, nsp8,
CC       nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear.
CC       Late in infection, they merge into confluent complexes.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Helicase]: Host endoplasmic reticulum-Golgi
CC       intermediate compartment {ECO:0000250|UniProtKB:P0C6X7}. Note=The
CC       helicase interacts with the N protein in membranous complexes and
CC       colocalizes with sites of synthesis of new viral RNA.
CC       {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease]: Host
CC       cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6X9}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Ribosomal frameshifting; Named isoforms=2;
CC         Comment=Normal translation results in Replicase polyprotein 1a.
CC         Ribosomal frameshifting at the end of this protein occurs at low
CC         frequency and produces Replicase polyprotein 1ab.;
CC       Name=Replicase polyprotein 1ab;
CC         IsoId=P0DTD1-1; Sequence=Displayed;
CC       Name=Replicase polyprotein 1a;
CC         IsoId=P0DTC1-1; Sequence=External;
CC   -!- DOMAIN: The hydrophobic domains (HD) could mediate the membrane
CC       association of the replication complex and thereby alter the
CC       architecture of the host cell membrane. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- PTM: Specific enzymatic cleavages in vivo by its own proteases yield
CC       mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically
CC       processed. {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- MISCELLANEOUS: [Replicase polyprotein 1ab]: Produced by -1 ribosomal
CC       frameshifting at the 1a-1b genes boundary.
CC       {ECO:0000250|UniProtKB:P0C6X7}.
CC   -!- SIMILARITY: Belongs to the coronaviruses polyprotein 1ab family.
CC       {ECO:0000305}.
DR   EMBL; MN908947; QHD43415.1; -; Genomic_RNA.
DR   PDB; 5R7Y; X-ray; 1.65 A; A=3264-3569.
DR   PDB; 5R7Z; X-ray; 1.59 A; A=3264-3569.
DR   PDB; 5R80; X-ray; 1.93 A; A=3264-3569.
DR   PDB; 5R81; X-ray; 1.95 A; A=3264-3569.
DR   PDB; 5R82; X-ray; 1.31 A; A=3264-3569.
DR   PDB; 5R83; X-ray; 1.58 A; A=3264-3569.
DR   PDB; 5R84; X-ray; 1.83 A; A=3264-3569.
DR   PDB; 5RE4; X-ray; 1.88 A; A=3264-3569.
DR   PDB; 5RE5; X-ray; 2.07 A; A=3264-3569.
DR   PDB; 5RE6; X-ray; 1.87 A; A=3264-3569.
DR   PDB; 5RE7; X-ray; 1.79 A; A=3264-3569.
DR   PDB; 5RE8; X-ray; 1.81 A; A=3264-3569.
DR   PDB; 5RE9; X-ray; 1.72 A; A=3264-3569.
DR   PDB; 5REA; X-ray; 1.63 A; A=3264-3569.
DR   PDB; 5REB; X-ray; 1.68 A; A=3264-3569.
DR   PDB; 5REC; X-ray; 1.73 A; A=3264-3569.
DR   PDB; 5RED; X-ray; 1.47 A; A=3264-3569.
DR   PDB; 5REE; X-ray; 1.77 A; A=3264-3569.
DR   PDB; 5REF; X-ray; 1.61 A; A=3264-3569.
DR   PDB; 5REG; X-ray; 1.67 A; A=3264-3569.
DR   PDB; 5REH; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 5REI; X-ray; 1.82 A; A=3264-3569.
DR   PDB; 5REJ; X-ray; 1.72 A; A=3264-3569.
DR   PDB; 5REK; X-ray; 1.74 A; A=3264-3569.
DR   PDB; 5REL; X-ray; 1.62 A; A=3264-3569.
DR   PDB; 5REM; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 5REN; X-ray; 2.15 A; A=3264-3569.
DR   PDB; 5REO; X-ray; 1.88 A; A=3264-3569.
DR   PDB; 5REP; X-ray; 1.81 A; A=3264-3569.
DR   PDB; 5RER; X-ray; 1.88 A; A=3264-3569.
DR   PDB; 5RES; X-ray; 1.65 A; A=3264-3569.
DR   PDB; 5RET; X-ray; 1.68 A; A=3264-3569.
DR   PDB; 5REU; X-ray; 1.69 A; A=3264-3569.
DR   PDB; 5REV; X-ray; 1.60 A; A=3264-3569.
DR   PDB; 5REW; X-ray; 1.55 A; A=3264-3569.
DR   PDB; 5REX; X-ray; 2.07 A; A=3264-3569.
DR   PDB; 5REY; X-ray; 1.96 A; A=3264-3569.
DR   PDB; 5REZ; X-ray; 1.79 A; A=3264-3569.
DR   PDB; 5RF0; X-ray; 1.65 A; A=3264-3569.
DR   PDB; 5RF1; X-ray; 1.73 A; A=3264-3569.
DR   PDB; 5RF2; X-ray; 1.53 A; A=3264-3569.
DR   PDB; 5RF3; X-ray; 1.50 A; A=3264-3569.
DR   PDB; 5RF4; X-ray; 1.61 A; A=3264-3569.
DR   PDB; 5RF5; X-ray; 1.74 A; A=3264-3569.
DR   PDB; 5RF6; X-ray; 1.45 A; A=3264-3569.
DR   PDB; 5RF7; X-ray; 1.54 A; A=3264-3569.
DR   PDB; 5RF8; X-ray; 1.44 A; A=3264-3569.
DR   PDB; 5RF9; X-ray; 1.43 A; A=3264-3569.
DR   PDB; 5RFA; X-ray; 1.52 A; A=3264-3569.
DR   PDB; 5RFB; X-ray; 1.48 A; A=3264-3569.
DR   PDB; 5RFC; X-ray; 1.40 A; A=3264-3569.
DR   PDB; 5RFD; X-ray; 1.41 A; A=3264-3569.
DR   PDB; 5RFE; X-ray; 1.46 A; A=3264-3569.
DR   PDB; 5RFF; X-ray; 1.78 A; A=3264-3569.
DR   PDB; 5RFG; X-ray; 2.32 A; A=3264-3569.
DR   PDB; 5RFH; X-ray; 1.58 A; A=3264-3569.
DR   PDB; 5RFI; X-ray; 1.69 A; A=3264-3569.
DR   PDB; 5RFJ; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 5RFK; X-ray; 1.75 A; A=3264-3569.
DR   PDB; 5RFL; X-ray; 1.64 A; A=3264-3569.
DR   PDB; 5RFM; X-ray; 2.06 A; A=3264-3569.
DR   PDB; 5RFN; X-ray; 1.80 A; A=3264-3569.
DR   PDB; 5RFO; X-ray; 1.83 A; A=3264-3569.
DR   PDB; 5RFP; X-ray; 2.03 A; A=3264-3569.
DR   PDB; 5RFQ; X-ray; 1.76 A; A=3264-3569.
DR   PDB; 5RFR; X-ray; 1.71 A; A=3264-3569.
DR   PDB; 5RFS; X-ray; 1.70 A; A=3264-3569.
DR   PDB; 5RFT; X-ray; 1.58 A; A=3264-3569.
DR   PDB; 5RFU; X-ray; 1.53 A; A=3264-3569.
DR   PDB; 5RFV; X-ray; 1.48 A; A=3264-3569.
DR   PDB; 5RFW; X-ray; 1.43 A; A=3264-3569.
DR   PDB; 5RFX; X-ray; 1.55 A; A=3264-3569.
DR   PDB; 5RFY; X-ray; 1.90 A; A=3264-3569.
DR   PDB; 5RFZ; X-ray; 1.68 A; A=3264-3569.
DR   PDB; 5RG0; X-ray; 1.72 A; A=3264-3569.
DR   PDB; 6LU7; X-ray; 2.16 A; A=3264-3569.
DR   PDB; 6M03; X-ray; 2.00 A; A=3264-3569.
DR   PDB; 6VWW; X-ray; 2.20 A; A/B=6453-6798.
DR   PDB; 6W01; X-ray; 1.90 A; A/B=6453-6798.
DR   PDB; 6W02; X-ray; 1.50 A; A/B=1024-1192.
DR   PDB; 6W61; X-ray; 2.00 A; B=4254-4392, A=6799-7096.
DR   PDB; 6W63; X-ray; 2.10 A; A=3264-3569.
DR   PDB; 6W6Y; X-ray; 1.45 A; A/B=1024-1192.
DR   PDB; 6W75; X-ray; 1.95 A; B/D=4254-4392, A/C=6799-7096.
DR   PDB; 6Y2E; X-ray; 1.75 A; A=3264-3569.
DR   PDB; 6Y2F; X-ray; 2.16 A; A=3264-3569.
DR   PDB; 6Y2G; X-ray; 2.16 A; A=3264-3569.
DR   PDB; 6Y84; X-ray; 1.39 A; A=3264-3569.
DR   PDB; 6YB7; X-ray; 1.25 A; A=3264-3569.
DR   PDBsum; 5R7Y; -.
DR   PDBsum; 5R7Z; -.
DR   PDBsum; 5R80; -.
DR   PDBsum; 5R81; -.
DR   PDBsum; 5R82; -.
DR   PDBsum; 5R83; -.
DR   PDBsum; 5R84; -.
DR   PDBsum; 5RE4; -.
DR   PDBsum; 5RE5; -.
DR   PDBsum; 5RE6; -.
DR   PDBsum; 5RE7; -.
DR   PDBsum; 5RE8; -.
DR   PDBsum; 5RE9; -.
DR   PDBsum; 5REA; -.
DR   PDBsum; 5REB; -.
DR   PDBsum; 5REC; -.
DR   PDBsum; 5RED; -.
DR   PDBsum; 5REE; -.
DR   PDBsum; 5REF; -.
DR   PDBsum; 5REG; -.
DR   PDBsum; 5REH; -.
DR   PDBsum; 5REI; -.
DR   PDBsum; 5REJ; -.
DR   PDBsum; 5REK; -.
DR   PDBsum; 5REL; -.
DR   PDBsum; 5REM; -.
DR   PDBsum; 5REN; -.
DR   PDBsum; 5REO; -.
DR   PDBsum; 5REP; -.
DR   PDBsum; 5RER; -.
DR   PDBsum; 5RES; -.
DR   PDBsum; 5RET; -.
DR   PDBsum; 5REU; -.
DR   PDBsum; 5REV; -.
DR   PDBsum; 5REW; -.
DR   PDBsum; 5REX; -.
DR   PDBsum; 5REY; -.
DR   PDBsum; 5REZ; -.
DR   PDBsum; 5RF0; -.
DR   PDBsum; 5RF1; -.
DR   PDBsum; 5RF2; -.
DR   PDBsum; 5RF3; -.
DR   PDBsum; 5RF4; -.
DR   PDBsum; 5RF5; -.
DR   PDBsum; 5RF6; -.
DR   PDBsum; 5RF7; -.
DR   PDBsum; 5RF8; -.
DR   PDBsum; 5RF9; -.
DR   PDBsum; 5RFA; -.
DR   PDBsum; 5RFB; -.
DR   PDBsum; 5RFC; -.
DR   PDBsum; 5RFD; -.
DR   PDBsum; 5RFE; -.
DR   PDBsum; 5RFF; -.
DR   PDBsum; 5RFG; -.
DR   PDBsum; 5RFH; -.
DR   PDBsum; 5RFI; -.
DR   PDBsum; 5RFJ; -.
DR   PDBsum; 5RFK; -.
DR   PDBsum; 5RFL; -.
DR   PDBsum; 5RFM; -.
DR   PDBsum; 5RFN; -.
DR   PDBsum; 5RFO; -.
DR   PDBsum; 5RFP; -.
DR   PDBsum; 5RFQ; -.
DR   PDBsum; 5RFR; -.
DR   PDBsum; 5RFS; -.
DR   PDBsum; 5RFT; -.
DR   PDBsum; 5RFU; -.
DR   PDBsum; 5RFV; -.
DR   PDBsum; 5RFW; -.
DR   PDBsum; 5RFX; -.
DR   PDBsum; 5RFY; -.
DR   PDBsum; 5RFZ; -.
DR   PDBsum; 5RG0; -.
DR   PDBsum; 6LU7; -.
DR   PDBsum; 6M03; -.
DR   PDBsum; 6VWW; -.
DR   PDBsum; 6W01; -.
DR   PDBsum; 6W02; -.
DR   PDBsum; 6W61; -.
DR   PDBsum; 6W63; -.
DR   PDBsum; 6W6Y; -.
DR   PDBsum; 6W75; -.
DR   PDBsum; 6Y2E; -.
DR   PDBsum; 6Y2F; -.
DR   PDBsum; 6Y2G; -.
DR   PDBsum; 6Y84; -.
DR   PDBsum; 6YB7; -.
DR   ComplexPortal; CPX-5685; SARS-CoV-2 main protease complex.
DR   ComplexPortal; CPX-5687; SARS-CoV-2 NSP9 complex.
DR   ComplexPortal; CPX-5688; SARS-CoV-2 NSP10-NSP16 complex.
DR   ComplexPortal; CPX-5689; SARS-CoV-2 NSP15 complex.
DR   ComplexPortal; CPX-5690; SARS-CoV-2 primase complex.
DR   ComplexPortal; CPX-5691; SARS-CoV-2 NSP3-NSP4-NSP6 complex.
DR   ComplexPortal; CPX-5692; SARS-CoV-2 Guanine-N7 methyltransferase complex.
DR   IntAct; P0DTD1; 171.
DR   Proteomes; UP000464024; Genome.
DR   GO; GO:0044172; C:host cell endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR   GO; GO:0033644; C:host cell membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003678; F:DNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0036459; F:thiol-dependent ubiquitinyl hydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0039595; P:induction by virus of catabolism of host mRNA; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0039648; P:modulation by virus of host protein ubiquitination; IEA:UniProtKB-KW.
DR   GO; GO:0039579; P:suppression by virus of host ISG15 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB transcription factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.150.420; -; 1.
DR   Gene3D; 1.10.8.1190; -; 1.
DR   Gene3D; 1.10.8.370; -; 1.
DR   Gene3D; 2.20.25.360; -; 1.
DR   Gene3D; 2.30.30.590; -; 1.
DR   Gene3D; 2.40.10.250; -; 1.
DR   Gene3D; 2.40.10.290; -; 1.
DR   Gene3D; 3.10.20.350; -; 1.
DR   Gene3D; 3.10.20.540; -; 1.
DR   Gene3D; 3.40.220.20; -; 1.
DR   Gene3D; 3.40.50.11020; -; 1.
DR   Gene3D; 3.40.50.11580; -; 1.
DR   InterPro; IPR032505; Corona_NSP4_C.
DR   InterPro; IPR009461; Coronavirus_NSP16.
DR   InterPro; IPR037227; EndoU-like.
DR   InterPro; IPR002589; Macro_dom.
DR   InterPro; IPR032592; NAR_dom.
DR   InterPro; IPR042570; NAR_sf.
DR   InterPro; IPR021590; NSP1.
DR   InterPro; IPR036333; NSP10_sf.
DR   InterPro; IPR009466; NSP11.
DR   InterPro; IPR043174; Nsp15_middle.
DR   InterPro; IPR042515; Nsp15_N.
DR   InterPro; IPR038030; NSP1_sf.
DR   InterPro; IPR024375; Nsp3_coronavir.
DR   InterPro; IPR038400; Nsp3_coronavir_sf.
DR   InterPro; IPR022733; Nsp3_PL2pro.
DR   InterPro; IPR038166; Nsp3_PL2pro_sf.
DR   InterPro; IPR038123; NSP4_C_sf.
DR   InterPro; IPR014828; NSP7.
DR   InterPro; IPR037204; NSP7_sf.
DR   InterPro; IPR014829; NSP8.
DR   InterPro; IPR037230; NSP8_sf.
DR   InterPro; IPR014822; NSP9.
DR   InterPro; IPR036499; NSP9_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR008740; Peptidase_C30.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR038083; R1a/1ab.
DR   InterPro; IPR043177; R1a/1ab_N.
DR   InterPro; IPR043178; R1a/1ab_thumb.
DR   InterPro; IPR009469; RNA_pol_N_coronovir.
DR   InterPro; IPR018995; RNA_synth_NSP10_coronavirus.
DR   InterPro; IPR029063; SAM-dependent_MTases.
DR   InterPro; IPR024358; SARS-CoV_Nsp3_N.
DR   InterPro; IPR014827; Viral_protease.
DR   Pfam; PF16251; bCoV_NAR; 1.
DR   Pfam; PF11501; bCoV_NSP1; 1.
DR   Pfam; PF12379; bCoV_NSP3_N; 1.
DR   Pfam; PF12124; bCoV_PL2pro; 1.
DR   Pfam; PF11633; bCoV_SUD-M; 1.
DR   Pfam; PF06471; CoV_Methyltr_1; 1.
DR   Pfam; PF06460; CoV_Methyltr_2; 1.
DR   Pfam; PF09401; CoV_NSP10; 1.
DR   Pfam; PF19215; CoV_NSP15_C; 1.
DR   Pfam; PF19216; CoV_NSP15_M; 1.
DR   Pfam; PF19219; CoV_NSP15_N; 1.
DR   Pfam; PF19212; CoV_NSP2_C; 1.
DR   Pfam; PF19211; CoV_NSP2_N; 1.
DR   Pfam; PF19218; CoV_NSP3_C; 1.
DR   Pfam; PF16348; CoV_NSP4_C; 1.
DR   Pfam; PF19217; CoV_NSP4_N; 1.
DR   Pfam; PF19213; CoV_NSP6; 1.
DR   Pfam; PF08716; CoV_NSP7; 1.
DR   Pfam; PF08717; CoV_NSP8; 1.
DR   Pfam; PF08710; CoV_NSP9; 1.
DR   Pfam; PF08715; CoV_peptidase; 1.
DR   Pfam; PF06478; CoV_RPol_N; 1.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF05409; Peptidase_C30; 1.
DR   Pfam; PF00680; RdRP_1; 1.
DR   Pfam; PF01443; Viral_helicase1; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF101816; SSF101816; 1.
DR   SUPFAM; SSF140367; SSF140367; 1.
DR   SUPFAM; SSF142877; SSF142877; 1.
DR   SUPFAM; SSF143076; SSF143076; 1.
DR   SUPFAM; SSF144246; SSF144246; 1.
DR   SUPFAM; SSF159936; SSF159936; 1.
DR   SUPFAM; SSF160099; SSF160099; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS00867; CPSASE_2; 1.
DR   PROSITE; PS51653; CV_ZBD; 1.
DR   PROSITE; PS00213; LIPOCALIN; 1.
DR   PROSITE; PS51442; M_PRO; 1.
DR   PROSITE; PS51154; MACRO; 1.
DR   PROSITE; PS51124; PEPTIDASE_C16; 1.
DR   PROSITE; PS51657; PSRV_HELICASE; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus; ATP-binding;
KW   Decay of host mRNAs by virus; Endonuclease;
KW   Eukaryotic host gene expression shutoff by virus;
KW   Eukaryotic host translation shutoff by virus; Exonuclease; Helicase;
KW   Host cytoplasm; Host gene expression shutoff by virus; Host membrane;
KW   Host mRNA suppression by virus; Host-virus interaction; Hydrolase;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host ISG15 by virus; Inhibition of host NF-kappa-B by virus;
KW   Leucine-rich repeat; Membrane; Metal-binding; Methyltransferase;
KW   Modulation of host ubiquitin pathway by viral deubiquitinase;
KW   Modulation of host ubiquitin pathway by virus; Nuclease;
KW   Nucleotide-binding; Nucleotidyltransferase; Protease; Reference proteome;
KW   Repeat; Ribosomal frameshifting; RNA-binding; RNA-directed RNA polymerase;
KW   Thiol protease; Transferase; Transmembrane; Transmembrane helix;
KW   Ubl conjugation pathway; Viral immunoevasion; Viral RNA replication; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..7096
FT                   /note="Replicase polyprotein 1ab"
FT                   /id="PRO_0000449618"
FT   CHAIN           1..180
FT                   /note="Host translation inhibitor nsp1"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449619"
FT   CHAIN           181..818
FT                   /note="Non-structural protein 2"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449620"
FT   CHAIN           819..2763
FT                   /note="Non-structural protein 3"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449621"
FT   CHAIN           2764..3263
FT                   /note="Non-structural protein 4"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449622"
FT   CHAIN           3264..3569
FT                   /note="3C-like proteinase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449623"
FT   CHAIN           3570..3859
FT                   /note="Non-structural protein 6"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449624"
FT   CHAIN           3860..3942
FT                   /note="Non-structural protein 7"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449625"
FT   CHAIN           3943..4140
FT                   /note="Non-structural protein 8"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449626"
FT   CHAIN           4141..4253
FT                   /note="Non-structural protein 9"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449627"
FT   CHAIN           4254..4392
FT                   /note="Non-structural protein 10"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449628"
FT   CHAIN           4393..5324
FT                   /note="RNA-directed RNA polymerase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449629"
FT   CHAIN           5325..5925
FT                   /note="Helicase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449630"
FT   CHAIN           5926..6452
FT                   /note="Proofreading exoribonuclease"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449631"
FT   CHAIN           6453..6798
FT                   /note="Uridylate-specific endoribonuclease"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449632"
FT   CHAIN           6799..7096
FT                   /note="2'-O-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT                   /id="PRO_0000449633"
FT   TOPO_DOM        1..2225
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2226..2246
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2247..2317
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2318..2338
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2339..2775
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        2776..2796
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        2797..3044
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3045..3065
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3066..3099
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3100..3120
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3121..3127
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3128..3148
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3149..3586
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3587..3607
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3608
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3609..3629
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3630..3634
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3635..3655
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3656..3673
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3674..3694
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3695..3729
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3730..3750
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3751..3778
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        3779..3799
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        3800..7096
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REPEAT          545..569
FT                   /note="LRR 1"
FT                   /evidence="ECO:0000255"
FT   REPEAT          697..719
FT                   /note="LRR 2"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          1025..1194
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          1634..1898
FT                   /note="Peptidase C16"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   REPEAT          1680..1702
FT                   /note="LRR 3"
FT                   /evidence="ECO:0000255"
FT   REPEAT          3185..3206
FT                   /note="LRR 4"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          3264..3569
FT                   /note="Peptidase C30"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772"
FT   REPEAT          3935..3959
FT                   /note="LRR 5"
FT                   /evidence="ECO:0000255"
FT   REPEAT          3977..4004
FT                   /note="LRR 6"
FT                   /evidence="ECO:0000255"
FT   REPEAT          4591..4616
FT                   /note="LRR 7"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          5004..5166
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          5325..5408
FT                   /note="CV ZBD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   REPEAT          5552..5572
FT                   /note="LRR 8"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          5581..5762
FT                   /note="(+)RNA virus helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          5763..5932
FT                   /note="(+)RNA virus helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   REPEAT          6817..6841
FT                   /note="LRR 9"
FT                   /evidence="ECO:0000255"
FT   ZN_FING         1752..1789
FT                   /note="C4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   NP_BIND         5606..5613
FT                   /note="NTP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   ACT_SITE        1674
FT                   /note="For PL1-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        1835
FT                   /note="For PL2-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00444"
FT   ACT_SITE        3304
FT                   /note="For 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772,
FT                   ECO:0000305|PubMed:32198291"
FT   ACT_SITE        3408
FT                   /note="Nucleophile; for 3CL-PRO activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00772,
FT                   ECO:0000269|PubMed:32198291"
FT   METAL           5329
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5332
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5340
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5343
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5350
FT                   /note="Zinc 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5353
FT                   /note="Zinc 2; via tele nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5357
FT                   /note="Zinc 2; via pros nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5363
FT                   /note="Zinc 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5374
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5379
FT                   /note="Zinc 3; via pros nitrogen"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5396
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   METAL           5399
FT                   /note="Zinc 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00986"
FT   SITE            180..181
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            818..819
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            2763..2764
FT                   /note="Cleavage; by PL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3263..3264
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3569..3570
FT                   /note="Cleavage; aby 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3859..3860
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            3942..3943
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4140..4141
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4253..4254
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            4392..4393
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            5324..5325
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            5925..5926
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            6452..6453
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
FT   SITE            6798..6799
FT                   /note="Cleavage; by 3CL-PRO"
FT                   /evidence="ECO:0000250|UniProtKB:P0C6V3"
SQ   SEQUENCE   7096 AA;  794058 MW;  A4E62D97150BB8CC CRC64;
     MESLVPGFNE KTHVQLSLPV LQVRDVLVRG FGDSVEEVLS EARQHLKDGT CGLVEVEKGV
     LPQLEQPYVF IKRSDARTAP HGHVMVELVA ELEGIQYGRS GETLGVLVPH VGEIPVAYRK
     VLLRKNGNKG AGGHSYGADL KSFDLGDELG TDPYEDFQEN WNTKHSSGVT RELMRELNGG
     AYTRYVDNNF CGPDGYPLEC IKDLLARAGK ASCTLSEQLD FIDTKRGVYC CREHEHEIAW
     YTERSEKSYE LQTPFEIKLA KKFDTFNGEC PNFVFPLNSI IKTIQPRVEK KKLDGFMGRI
     RSVYPVASPN ECNQMCLSTL MKCDHCGETS WQTGDFVKAT CEFCGTENLT KEGATTCGYL
     PQNAVVKIYC PACHNSEVGP EHSLAEYHNE SGLKTILRKG GRTIAFGGCV FSYVGCHNKC
     AYWVPRASAN IGCNHTGVVG EGSEGLNDNL LEILQKEKVN INIVGDFKLN EEIAIILASF
     SASTSAFVET VKGLDYKAFK QIVESCGNFK VTKGKAKKGA WNIGEQKSIL SPLYAFASEA
     ARVVRSIFSR TLETAQNSVR VLQKAAITIL DGISQYSLRL IDAMMFTSDL ATNNLVVMAY
     ITGGVVQLTS QWLTNIFGTV YEKLKPVLDW LEEKFKEGVE FLRDGWEIVK FISTCACEIV
     GGQIVTCAKE IKESVQTFFK LVNKFLALCA DSIIIGGAKL KALNLGETFV THSKGLYRKC
     VKSREETGLL MPLKAPKEII FLEGETLPTE VLTEEVVLKT GDLQPLEQPT SEAVEAPLVG
     TPVCINGLML LEIKDTEKYC ALAPNMMVTN NTFTLKGGAP TKVTFGDDTV IEVQGYKSVN
     ITFELDERID KVLNEKCSAY TVELGTEVNE FACVVADAVI KTLQPVSELL TPLGIDLDEW
     SMATYYLFDE SGEFKLASHM YCSFYPPDED EEEGDCEEEE FEPSTQYEYG TEDDYQGKPL
     EFGATSAALQ PEEEQEEDWL DDDSQQTVGQ QDGSEDNQTT TIQTIVEVQP QLEMELTPVV
     QTIEVNSFSG YLKLTDNVYI KNADIVEEAK KVKPTVVVNA ANVYLKHGGG VAGALNKATN
     NAMQVESDDY IATNGPLKVG GSCVLSGHNL AKHCLHVVGP NVNKGEDIQL LKSAYENFNQ
     HEVLLAPLLS AGIFGADPIH SLRVCVDTVR TNVYLAVFDK NLYDKLVSSF LEMKSEKQVE
     QKIAEIPKEE VKPFITESKP SVEQRKQDDK KIKACVEEVT TTLEETKFLT ENLLLYIDIN
     GNLHPDSATL VSDIDITFLK KDAPYIVGDV VQEGVLTAVV IPTKKAGGTT EMLAKALRKV
     PTDNYITTYP GQGLNGYTVE EAKTVLKKCK SAFYILPSII SNEKQEILGT VSWNLREMLA
     HAEETRKLMP VCVETKAIVS TIQRKYKGIK IQEGVVDYGA RFYFYTSKTT VASLINTLND
     LNETLVTMPL GYVTHGLNLE EAARYMRSLK VPATVSVSSP DAVTAYNGYL TSSSKTPEEH
     FIETISLAGS YKDWSYSGQS TQLGIEFLKR GDKSVYYTSN PTTFHLDGEV ITFDNLKTLL
     SLREVRTIKV FTTVDNINLH TQVVDMSMTY GQQFGPTYLD GADVTKIKPH NSHEGKTFYV
     LPNDDTLRVE AFEYYHTTDP SFLGRYMSAL NHTKKWKYPQ VNGLTSIKWA DNNCYLATAL
     LTLQQIELKF NPPALQDAYY RARAGEAANF CALILAYCNK TVGELGDVRE TMSYLFQHAN
     LDSCKRVLNV VCKTCGQQQT TLKGVEAVMY MGTLSYEQFK KGVQIPCTCG KQATKYLVQQ
     ESPFVMMSAP PAQYELKHGT FTCASEYTGN YQCGHYKHIT SKETLYCIDG ALLTKSSEYK
     GPITDVFYKE NSYTTTIKPV TYKLDGVVCT EIDPKLDNYY KKDNSYFTEQ PIDLVPNQPY
     PNASFDNFKF VCDNIKFADD LNQLTGYKKP ASRELKVTFF PDLNGDVVAI DYKHYTPSFK
     KGAKLLHKPI VWHVNNATNK ATYKPNTWCI RCLWSTKPVE TSNSFDVLKS EDAQGMDNLA
     CEDLKPVSEE VVENPTIQKD VLECNVKTTE VVGDIILKPA NNSLKITEEV GHTDLMAAYV
     DNSSLTIKKP NELSRVLGLK TLATHGLAAV NSVPWDTIAN YAKPFLNKVV STTTNIVTRC
     LNRVCTNYMP YFFTLLLQLC TFTRSTNSRI KASMPTTIAK NTVKSVGKFC LEASFNYLKS
     PNFSKLINII IWFLLLSVCL GSLIYSTAAL GVLMSNLGMP SYCTGYREGY LNSTNVTIAT
     YCTGSIPCSV CLSGLDSLDT YPSLETIQIT ISSFKWDLTA FGLVAEWFLA YILFTRFFYV
     LGLAAIMQLF FSYFAVHFIS NSWLMWLIIN LVQMAPISAM VRMYIFFASF YYVWKSYVHV
     VDGCNSSTCM MCYKRNRATR VECTTIVNGV RRSFYVYANG GKGFCKLHNW NCVNCDTFCA
     GSTFISDEVA RDLSLQFKRP INPTDQSSYI VDSVTVKNGS IHLYFDKAGQ KTYERHSLSH
     FVNLDNLRAN NTKGSLPINV IVFDGKSKCE ESSAKSASVY YSQLMCQPIL LLDQALVSDV
     GDSAEVAVKM FDAYVNTFSS TFNVPMEKLK TLVATAEAEL AKNVSLDNVL STFISAARQG
     FVDSDVETKD VVECLKLSHQ SDIEVTGDSC NNYMLTYNKV ENMTPRDLGA CIDCSARHIN
     AQVAKSHNIA LIWNVKDFMS LSEQLRKQIR SAAKKNNLPF KLTCATTRQV VNVVTTKIAL
     KGGKIVNNWL KQLIKVTLVF LFVAAIFYLI TPVHVMSKHT DFSSEIIGYK AIDGGVTRDI
     ASTDTCFANK HADFDTWFSQ RGGSYTNDKA CPLIAAVITR EVGFVVPGLP GTILRTTNGD
     FLHFLPRVFS AVGNICYTPS KLIEYTDFAT SACVLAAECT IFKDASGKPV PYCYDTNVLE
     GSVAYESLRP DTRYVLMDGS IIQFPNTYLE GSVRVVTTFD SEYCRHGTCE RSEAGVCVST
     SGRWVLNNDY YRSLPGVFCG VDAVNLLTNM FTPLIQPIGA LDISASIVAG GIVAIVVTCL
     AYYFMRFRRA FGEYSHVVAF NTLLFLMSFT VLCLTPVYSF LPGVYSVIYL YLTFYLTNDV
     SFLAHIQWMV MFTPLVPFWI TIAYIICIST KHFYWFFSNY LKRRVVFNGV SFSTFEEAAL
     CTFLLNKEMY LKLRSDVLLP LTQYNRYLAL YNKYKYFSGA MDTTSYREAA CCHLAKALND
     FSNSGSDVLY QPPQTSITSA VLQSGFRKMA FPSGKVEGCM VQVTCGTTTL NGLWLDDVVY
     CPRHVICTSE DMLNPNYEDL LIRKSNHNFL VQAGNVQLRV IGHSMQNCVL KLKVDTANPK
     TPKYKFVRIQ PGQTFSVLAC YNGSPSGVYQ CAMRPNFTIK GSFLNGSCGS VGFNIDYDCV
     SFCYMHHMEL PTGVHAGTDL EGNFYGPFVD RQTAQAAGTD TTITVNVLAW LYAAVINGDR
     WFLNRFTTTL NDFNLVAMKY NYEPLTQDHV DILGPLSAQT GIAVLDMCAS LKELLQNGMN
     GRTILGSALL EDEFTPFDVV RQCSGVTFQS AVKRTIKGTH HWLLLTILTS LLVLVQSTQW
     SLFFFLYENA FLPFAMGIIA MSAFAMMFVK HKHAFLCLFL LPSLATVAYF NMVYMPASWV
     MRIMTWLDMV DTSLSGFKLK DCVMYASAVV LLILMTARTV YDDGARRVWT LMNVLTLVYK
     VYYGNALDQA ISMWALIISV TSNYSGVVTT VMFLARGIVF MCVEYCPIFF ITGNTLQCIM
     LVYCFLGYFC TCYFGLFCLL NRYFRLTLGV YDYLVSTQEF RYMNSQGLLP PKNSIDAFKL
     NIKLLGVGGK PCIKVATVQS KMSDVKCTSV VLLSVLQQLR VESSSKLWAQ CVQLHNDILL
     AKDTTEAFEK MVSLLSVLLS MQGAVDINKL CEEMLDNRAT LQAIASEFSS LPSYAAFATA
     QEAYEQAVAN GDSEVVLKKL KKSLNVAKSE FDRDAAMQRK LEKMADQAMT QMYKQARSED
     KRAKVTSAMQ TMLFTMLRKL DNDALNNIIN NARDGCVPLN IIPLTTAAKL MVVIPDYNTY
     KNTCDGTTFT YASALWEIQQ VVDADSKIVQ LSEISMDNSP NLAWPLIVTA LRANSAVKLQ
     NNELSPVALR QMSCAAGTTQ TACTDDNALA YYNTTKGGRF VLALLSDLQD LKWARFPKSD
     GTGTIYTELE PPCRFVTDTP KGPKVKYLYF IKGLNNLNRG MVLGSLAATV RLQAGNATEV
     PANSTVLSFC AFAVDAAKAY KDYLASGGQP ITNCVKMLCT HTGTGQAITV TPEANMDQES
     FGGASCCLYC RCHIDHPNPK GFCDLKGKYV QIPTTCANDP VGFTLKNTVC TVCGMWKGYG
     CSCDQLREPM LQSADAQSFL NRVCGVSAAR LTPCGTGTST DVVYRAFDIY NDKVAGFAKF
     LKTNCCRFQE KDEDDNLIDS YFVVKRHTFS NYQHEETIYN LLKDCPAVAK HDFFKFRIDG
     DMVPHISRQR LTKYTMADLV YALRHFDEGN CDTLKEILVT YNCCDDDYFN KKDWYDFVEN
     PDILRVYANL GERVRQALLK TVQFCDAMRN AGIVGVLTLD NQDLNGNWYD FGDFIQTTPG
     SGVPVVDSYY SLLMPILTLT RALTAESHVD TDLTKPYIKW DLLKYDFTEE RLKLFDRYFK
     YWDQTYHPNC VNCLDDRCIL HCANFNVLFS TVFPPTSFGP LVRKIFVDGV PFVVSTGYHF
     RELGVVHNQD VNLHSSRLSF KELLVYAADP AMHAASGNLL LDKRTTCFSV AALTNNVAFQ
     TVKPGNFNKD FYDFAVSKGF FKEGSSVELK HFFFAQDGNA AISDYDYYRY NLPTMCDIRQ
     LLFVVEVVDK YFDCYDGGCI NANQVIVNNL DKSAGFPFNK WGKARLYYDS MSYEDQDALF
     AYTKRNVIPT ITQMNLKYAI SAKNRARTVA GVSICSTMTN RQFHQKLLKS IAATRGATVV
     IGTSKFYGGW HNMLKTVYSD VENPHLMGWD YPKCDRAMPN MLRIMASLVL ARKHTTCCSL
     SHRFYRLANE CAQVLSEMVM CGGSLYVKPG GTSSGDATTA YANSVFNICQ AVTANVNALL
     STDGNKIADK YVRNLQHRLY ECLYRNRDVD TDFVNEFYAY LRKHFSMMIL SDDAVVCFNS
     TYASQGLVAS IKNFKSVLYY QNNVFMSEAK CWTETDLTKG PHEFCSQHTM LVKQGDDYVY
     LPYPDPSRIL GAGCFVDDIV KTDGTLMIER FVSLAIDAYP LTKHPNQEYA DVFHLYLQYI
     RKLHDELTGH MLDMYSVMLT NDNTSRYWEP EFYEAMYTPH TVLQAVGACV LCNSQTSLRC
     GACIRRPFLC CKCCYDHVIS TSHKLVLSVN PYVCNAPGCD VTDVTQLYLG GMSYYCKSHK
     PPISFPLCAN GQVFGLYKNT CVGSDNVTDF NAIATCDWTN AGDYILANTC TERLKLFAAE
     TLKATEETFK LSYGIATVRE VLSDRELHLS WEVGKPRPPL NRNYVFTGYR VTKNSKVQIG
     EYTFEKGDYG DAVVYRGTTT YKLNVGDYFV LTSHTVMPLS APTLVPQEHY VRITGLYPTL
     NISDEFSSNV ANYQKVGMQK YSTLQGPPGT GKSHFAIGLA LYYPSARIVY TACSHAAVDA
     LCEKALKYLP IDKCSRIIPA RARVECFDKF KVNSTLEQYV FCTVNALPET TADIVVFDEI
     SMATNYDLSV VNARLRAKHY VYIGDPAQLP APRTLLTKGT LEPEYFNSVC RLMKTIGPDM
     FLGTCRRCPA EIVDTVSALV YDNKLKAHKD KSAQCFKMFY KGVITHDVSS AINRPQIGVV
     REFLTRNPAW RKAVFISPYN SQNAVASKIL GLPTQTVDSS QGSEYDYVIF TQTTETAHSC
     NVNRFNVAIT RAKVGILCIM SDRDLYDKLQ FTSLEIPRRN VATLQAENVT GLFKDCSKVI
     TGLHPTQAPT HLSVDTKFKT EGLCVDIPGI PKDMTYRRLI SMMGFKMNYQ VNGYPNMFIT
     REEAIRHVRA WIGFDVEGCH ATREAVGTNL PLQLGFSTGV NLVAVPTGYV DTPNNTDFSR
     VSAKPPPGDQ FKHLIPLMYK GLPWNVVRIK IVQMLSDTLK NLSDRVVFVL WAHGFELTSM
     KYFVKIGPER TCCLCDRRAT CFSTASDTYA CWHHSIGFDY VYNPFMIDVQ QWGFTGNLQS
     NHDLYCQVHG NAHVASCDAI MTRCLAVHEC FVKRVDWTIE YPIIGDELKI NAACRKVQHM
     VVKAALLADK FPVLHDIGNP KAIKCVPQAD VEWKFYDAQP CSDKAYKIEE LFYSYATHSD
     KFTDGVCLFW NCNVDRYPAN SIVCRFDTRV LSNLNLPGCD GGSLYVNKHA FHTPAFDKSA
     FVNLKQLPFF YYSDSPCESH GKQVVSDIDY VPLKSATCIT RCNLGGAVCR HHANEYRLYL
     DAYNMMISAG FSLWVYKQFD TYNLWNTFTR LQSLENVAFN VVNKGHFDGQ QGEVPVSIIN
     NTVYTKVDGV DVELFENKTT LPVNVAFELW AKRNIKPVPE VKILNNLGVD IAANTVIWDY
     KRDAPAHIST IGVCSMTDIA KKPTETICAP LTVFFDGRVD GQVDLFRNAR NGVLITEGSV
     KGLQPSVGPK QASLNGVTLI GEAVKTQFNY YKKVDGVVQQ LPETYFTQSR NLQEFKPRSQ
     MEIDFLELAM DEFIERYKLE GYAFEHIVYG DFSHSQLGGL HLLIGLAKRF KESPFELEDF
     IPMDSTVKNY FITDAQTGSS KCVCSVIDLL LDDFVEIIKS QDLSVVSKVV KVTIDYTEIS
     FMLWCKDGHV ETFYPKLQSS QAWQPGVAMP NLYKMQRMLL EKCDLQNYGD SATLPKGIMM
     NVAKYTQLCQ YLNTLTLAVP YNMRVIHFGA GSDKGVAPGT AVLRQWLPTG TLLVDSDLND
     FVSDADSTLI GDCATVHTAN KWDLIISDMY DPKTKNVTKE NDSKEGFFTY ICGFIQQKLA
     LGGSVAIKIT EHSWNADLYK LMGHFAWWTA FVTNVNASSS EAFLIGCNYL GKPREQIDGY
     VMHANYIFWR NTNPIQLSSY SLFDMSKFPL KLRGTAVMSL KEGQINDMIL SLLSKGRLII
     RENNRVVISS DVLVNN
//