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Database: UniProt
Entry: P14340
LinkDB: P14340
Original site: P14340 
ID   POLG_DEN2N              Reviewed;        3391 AA.
AC   P14340; Q66347; Q66348; Q66349; Q66350; Q66351; Q66352; Q66353;
AC   Q66354; Q66355; Q66356; Q89579;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   18-SEP-2019, entry version 182.
DE   RecName: Full=Genome polyprotein;
DE   Contains:
DE     RecName: Full=Capsid protein C;
DE     AltName: Full=Core protein;
DE   Contains:
DE     RecName: Full=Protein prM;
DE   Contains:
DE     RecName: Full=Peptide pr;
DE   Contains:
DE     RecName: Full=Small envelope protein M;
DE     AltName: Full=Matrix protein;
DE   Contains:
DE     RecName: Full=Envelope protein E;
DE   Contains:
DE     RecName: Full=Non-structural protein 1;
DE              Short=NS1;
DE   Contains:
DE     RecName: Full=Non-structural protein 2A;
DE              Short=NS2A;
DE   Contains:
DE     RecName: Full=Serine protease subunit NS2B;
DE     AltName: Full=Flavivirin protease NS2B regulatory subunit;
DE     AltName: Full=Non-structural protein 2B;
DE   Contains:
DE     RecName: Full=Serine protease NS3;
DE              EC=3.4.21.91;
DE              EC=3.6.1.15 {ECO:0000250|UniProtKB:Q9Q6P4};
DE              EC=3.6.4.13 {ECO:0000250|UniProtKB:Q9Q6P4};
DE     AltName: Full=Flavivirin protease NS3 catalytic subunit;
DE     AltName: Full=Non-structural protein 3;
DE   Contains:
DE     RecName: Full=Non-structural protein 4A;
DE              Short=NS4A;
DE   Contains:
DE     RecName: Full=Peptide 2k;
DE   Contains:
DE     RecName: Full=Non-structural protein 4B;
DE              Short=NS4B;
DE   Contains:
DE     RecName: Full=RNA-directed RNA polymerase NS5;
DE              EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE              EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE              EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE     AltName: Full=Non-structural protein 5;
OS   Dengue virus type 2 (strain Thailand/NGS-C/1944) (DENV-2).
OC   Viruses; Riboviria; Flaviviridae; Flavivirus.
OX   NCBI_TaxID=11065;
OH   NCBI_TaxID=53540; Aedimorphus.
OH   NCBI_TaxID=53539; Diceromyia.
OH   NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=53541; Stegomyia.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2714651; DOI=10.1016/0378-1119(89)90266-7;
RA   Irie K., Mohan P.M., Sasaguri Y., Putnak R., Padmanabhan R.;
RT   "Sequence analysis of cloned dengue virus type 2 genome (New Guinea-C
RT   strain).";
RL   Gene 75:197-211(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 749-1225.
RX   PubMed=2964755; DOI=10.1016/0042-6822(88)90236-x;
RA   Putnak J.R., Charles P.C., Padmanabhan R., Irie K., Hoke C.H.,
RA   Burke D.S.;
RT   "Functional and antigenic domains of the dengue-2 virus nonstructural
RT   glycoprotein NS-1.";
RL   Virology 163:93-103(1988).
RN   [3]
RP   PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX   PubMed=2952760; DOI=10.1099/0022-1317-68-5-1317;
RA   Biedrzycka A., Cauchi M.R., Bartholomeusz A., Gorman J.J.,
RA   Wright P.J.;
RT   "Characterization of protease cleavage sites involved in the formation
RT   of the envelope glycoprotein and three non-structural proteins of
RT   dengue virus type 2, New Guinea C strain.";
RL   J. Gen. Virol. 68:1317-1326(1987).
RN   [4]
RP   PHOSPHORYLATION (RNA-DIRECTED RNA POLYMERASE NS5).
RX   PubMed=7642575; DOI=10.1074/jbc.270.32.19100;
RA   Kapoor M., Zhang L., Ramachandra M., Kusukawa J., Ebner K.E.,
RA   Padmanabhan R.;
RT   "Association between NS3 and NS5 proteins of dengue virus type 2 in
RT   the putative RNA replicase is linked to differential phosphorylation
RT   of NS5.";
RL   J. Biol. Chem. 270:19100-19106(1995).
RN   [5]
RP   INTERACTION WITH SERINE PROTEASE NS3 (RNA-DIRECTED RNA POLYMERASE
RP   NS5), INTERACTION WITH RNA-DIRECTED RNA POLYMERASE NS5 (SERINE
RP   PROTEASE NS3), BIOPHYSICOCHEMICAL PROPERTIES (SERINE PROTEASE NS3),
RP   CATALYTIC ACTIVITY (SERINE PROTEASE NS3), AND MUTAGENESIS OF
RP   1659-ARG--LYS-1662.
RX   PubMed=15917225; DOI=10.1074/jbc.m501393200;
RA   Yon C., Teramoto T., Mueller N., Phelan J., Ganesh V.K., Murthy K.H.,
RA   Padmanabhan R.;
RT   "Modulation of the nucleoside triphosphatase/RNA helicase and 5'-RNA
RT   triphosphatase activities of Dengue virus type 2 nonstructural protein
RT   3 (NS3) by interaction with NS5, the RNA-dependent RNA polymerase.";
RL   J. Biol. Chem. 280:27412-27419(2005).
RN   [6]
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 4B), AND MEMBRANE
RP   TOPOLOGY (NON-STRUCTURAL PROTEIN 4B).
RX   PubMed=16436383; DOI=10.1074/jbc.m512697200;
RA   Miller S., Sparacio S., Bartenschlager R.;
RT   "Subcellular localization and membrane topology of the Dengue virus
RT   type 2 Non-structural protein 4B.";
RL   J. Biol. Chem. 281:8854-8863(2006).
RN   [7]
RP   FUNCTION (NON-STRUCTURAL PROTEIN 4A), SUBCELLULAR LOCATION
RP   (NON-STRUCTURAL PROTEIN 4A), AND MEMBRANE TOPOLOGY (NON-STRUCTURAL
RP   PROTEIN 4A).
RX   PubMed=17276984; DOI=10.1074/jbc.m609919200;
RA   Miller S., Kastner S., Krijnse-Locker J., Buhler S.,
RA   Bartenschlager R.;
RT   "The non-structural protein 4A of dengue virus is an integral membrane
RT   protein inducing membrane alterations in a 2K-regulated manner.";
RL   J. Biol. Chem. 282:8873-8882(2007).
RN   [8]
RP   SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 2A), AND TOPOLOGY
RP   (NON-STRUCTURAL PROTEIN 2A).
RX   PubMed=23408612; DOI=10.1128/jvi.02424-12;
RA   Xie X., Gayen S., Kang C., Yuan Z., Shi P.Y.;
RT   "Membrane topology and function of dengue virus NS2A protein.";
RL   J. Virol. 87:4609-4622(2013).
CC   -!- FUNCTION: Capsid protein C: Plays a role in virus budding by
CC       binding to the cell membrane and gathering the viral RNA into a
CC       nucleocapsid that forms the core of a mature virus particle.
CC       During virus entry, may induce genome penetration into the host
CC       cytoplasm after hemifusion induced by the surface proteins. Can
CC       migrate to the cell nucleus where it modulates host functions.
CC       Overcomes the anti-viral effects of host EXOC1 by sequestering and
CC       degrading the latter through the proteasome degradation pathway.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Capsid protein C: Inhibits RNA silencing by interfering
CC       with host Dicer. {ECO:0000250|UniProtKB:P03314}.
CC   -!- FUNCTION: Peptide pr: Prevents premature fusion activity of
CC       envelope proteins in trans-Golgi by binding to envelope protein E
CC       at pH6.0. After virion release in extracellular space, gets
CC       dissociated from E dimers. {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Protein prM: Acts as a chaperone for envelope protein E
CC       during intracellular virion assembly by masking and inactivating
CC       envelope protein E fusion peptide. prM is the only viral peptide
CC       matured by host furin in the trans-Golgi network probably to avoid
CC       catastrophic activation of the viral fusion activity in acidic
CC       Golgi compartment prior to virion release. prM-E cleavage is
CC       inefficient, and many virions are only partially matured. These
CC       uncleaved prM would play a role in immune evasion.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Small envelope protein M: May play a role in virus
CC       budding. Exerts cytotoxic effects by activating a mitochondrial
CC       apoptotic pathway through M ectodomain. May display a viroporin
CC       activity. {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Envelope protein E: Binds to host cell surface receptor
CC       and mediates fusion between viral and cellular membranes. Envelope
CC       protein is synthesized in the endoplasmic reticulum in the form of
CC       heterodimer with protein prM. They play a role in virion budding
CC       in the ER, and the newly formed immature particle is covered with
CC       60 spikes composed of heterodimer between precursor prM and
CC       envelope protein E. The virion is transported to the Golgi
CC       apparatus where the low pH causes dissociation of PrM-E
CC       heterodimers and formation of E homodimers. prM-E cleavage is
CC       inefficient, and many virions are only partially matured. These
CC       uncleaved prM would play a role in immune evasion.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Non-structural protein 1: Involved in immune evasion,
CC       pathogenesis and viral replication. Once cleaved off the
CC       polyprotein, is targeted to three destinations: the viral
CC       replication cycle, the plasma membrane and the extracellular
CC       compartment. Essential for viral replication. Required for
CC       formation of the replication complex and recruitment of other non-
CC       structural proteins to the ER-derived membrane structures.
CC       Excreted as a hexameric lipoparticle that plays a role against
CC       host immune response. Antagonizing the complement function. Binds
CC       to the host macrophages and dendritic cells. Inhibits signal
CC       transduction originating from Toll-like receptor 3 (TLR3).
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- FUNCTION: Non-structural protein 1: Disrupts the host endothelial
CC       glycocalyx layer of host pulmonary microvascular endothelial
CC       cells, inducing degradation of sialic acid and shedding of heparan
CC       sulfate proteoglycans. NS1 induces expression of sialidases,
CC       heparanase, and activates cathepsin L, which activates heparanase
CC       via enzymatic cleavage. These effects are probably linked to the
CC       endothelial hyperpermeability observed in severe dengue disease.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Non-structural protein 2A: Component of the viral RNA
CC       replication complex that functions in virion assembly and
CC       antagonizes the host immune response.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Serine protease subunit NS2B: Required cofactor for the
CC       serine protease function of NS3. May have membrane-destabilizing
CC       activity and form viroporins (By similarity).
CC       {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-
CC       ProRule:PRU00859}.
CC   -!- FUNCTION: Serine protease NS3: Displays three enzymatic
CC       activities: serine protease, NTPase and RNA helicase. NS3 serine
CC       protease, in association with NS2B, performs its autocleavage and
CC       cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM,
CC       NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA
CC       helicase binds RNA and unwinds dsRNA in the 3' to 5' direction.
CC       {ECO:0000255|PROSITE-ProRule:PRU00860}.
CC   -!- FUNCTION: Non-structural protein 4A: Regulates the ATPase activity
CC       of the NS3 helicase activity. NS4A allows NS3 helicase to conserve
CC       energy during unwinding. Plays a role in the inhibition of the
CC       host innate immune response. Interacts with host MAVS and thereby
CC       prevents the interaction between DDX58 and MAVS. In turn, IFN-beta
CC       production is impaired. {ECO:0000250|UniProtKB:P17763,
CC       ECO:0000269|PubMed:17276984}.
CC   -!- FUNCTION: Peptide 2k: Functions as a signal peptide for NS4B and
CC       is required for the interferon antagonism activity of the latter.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- FUNCTION: Non-structural protein 4B: Induces the formation of ER-
CC       derived membrane vesicles where the viral replication takes place.
CC       Inhibits interferon (IFN)-induced host STAT1 phosphorylation and
CC       nuclear translocation, thereby preventing the establishment of
CC       cellular antiviral state by blocking the IFN-alpha/beta pathway.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- FUNCTION: RNA-directed RNA polymerase NS5: Replicates the viral
CC       (+) and (-) RNA genome, and performs the capping of genomes in the
CC       cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose
CC       2'-O positions. Besides its role in RNA genome replication, also
CC       prevents the establishment of cellular antiviral state by blocking
CC       the interferon-alpha/beta (IFN-alpha/beta) signaling pathway.
CC       Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing
CC       activation of JAK-STAT signaling pathway.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which
CC         each of the Xaa can be either Arg or Lys and Yaa can be either
CC         Ser or Ala.; EC=3.4.21.91;
CC   -!- CATALYTIC ACTIVITY:
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,
CC         ChEBI:CHEBI:83400; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00539};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside
CC         5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC         Evidence={ECO:0000269|PubMed:15917225};
CC   -!- CATALYTIC ACTIVITY:
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:0000269|PubMed:15917225};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-guanosine in mRNA + S-
CC         adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC         triphosphoguanosine)-guanosine in mRNA + S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60856, Rhea:RHEA-COMP:15681,
CC         Rhea:RHEA-COMP:15683, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:143971, ChEBI:CHEBI:143975; EC=2.1.1.56;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00924};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-adenosine in mRNA + S-
CC         adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC         triphosphoguanosine)-adenosine in mRNA + S-adenosyl-L-
CC         homocysteine; Xref=Rhea:RHEA:60852, Rhea:RHEA-COMP:15680,
CC         Rhea:RHEA-COMP:15682, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:143973, ChEBI:CHEBI:143974; EC=2.1.1.56;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00924};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-guanosine
CC         in mRNA + S-adenosyl-L-methionine = a 5'-end (N7-methyl 5'-
CC         triphosphoguanosine)-(2'-O-methyl-guanosine) in mRNA + H(+) + S-
CC         adenosyl-L-homocysteine; Xref=Rhea:RHEA:60864, Rhea:RHEA-
CC         COMP:15683, Rhea:RHEA-COMP:15685, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:143975,
CC         ChEBI:CHEBI:143977; EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00924};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-adenosine
CC         in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC         triphosphoguanosine)-(2'-O-methyl-adenosine) in mRNA + H(+) + S-
CC         adenosyl-L-homocysteine; Xref=Rhea:RHEA:60860, Rhea:RHEA-
CC         COMP:15682, Rhea:RHEA-COMP:15684, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:143974,
CC         ChEBI:CHEBI:143976; EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00924};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=29.3 uM for triphosphorylated RNA
CC         {ECO:0000269|PubMed:15917225};
CC         Note=Vmax with 0.65 nmol/s/ug enzyme for RTPase activity with
CC         triphosphorylated RNA as substrate.
CC         {ECO:0000269|PubMed:15917225};
CC   -!- SUBUNIT: Capsid protein C: Homodimer (By similarity). Interacts
CC       (via N-terminus) with host EXOC1 (via C-terminus); this
CC       interaction results in EXOC1 degradation through the proteasome
CC       degradation pathway (By similarity). Protein prM: Forms
CC       heterodimers with envelope protein E in the endoplasmic reticulum
CC       and Golgi (By similarity). Envelope protein E: Homodimer; in the
CC       endoplasmic reticulum and Golgi (By similarity). Interacts with
CC       protein prM (By similarity). Interacts with non-structural protein
CC       1. Non-structural protein 1: Homodimer; Homohexamer when secreted
CC       (By similarity). Interacts with envelope protein E. Non-structural
CC       protein 2A: Interacts (via N-terminus) with serine protease NS3
CC       (By similarity). Non-structural protein 2B: Forms a heterodimer
CC       with serine protease NS3 (By similarity). May form homooligomers
CC       (By similarity). Serine protease NS3: Forms a heterodimer with
CC       NS2B (By similarity). Interacts with NS4B (By similarity).
CC       Interacts with unphosphorylated RNA-directed RNA polymerase NS5;
CC       this interaction stimulates RNA-directed RNA polymerase NS5
CC       guanylyltransferase activity (PubMed:15917225). Interacts with
CC       host SHFL (By similarity). Non-structural protein 4A: Interacts
CC       with host MAVS; this interaction inhibits the synthesis of IFN-
CC       beta (By similarity). Non-structural protein 4A: Interacts with
CC       host MAVS; this interaction inhibits the synthesis of IFN-beta.
CC       Interacts with host SHFL (By similarity). Non-structural protein
CC       4B: Interacts with serine protease NS (By similarity). RNA-
CC       directed RNA polymerase NS5: Homodimer (By similarity). Interacts
CC       with host STAT2; this interaction inhibits the phosphorylation of
CC       the latter, and, when all viral proteins are present
CC       (polyprotein), targets STAT2 for degradation (By similarity).
CC       Interacts with serine protease NS3 (PubMed:15917225).
CC       {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:15917225}.
CC   -!- INTERACTION:
CC       P55265:ADAR (xeno); NbExp=2; IntAct=EBI-9825968, EBI-2462104;
CC       P25963:NFKBIA (xeno); NbExp=2; IntAct=EBI-465733, EBI-307386;
CC       Q15653:NFKBIB (xeno); NbExp=2; IntAct=EBI-465733, EBI-352889;
CC       Q9UHY1:NRBP1 (xeno); NbExp=4; IntAct=EBI-465733, EBI-749731;
CC       P08670:VIM (xeno); NbExp=10; IntAct=EBI-9844509, EBI-353844;
CC   -!- SUBCELLULAR LOCATION: Capsid protein C: Virion
CC       {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC       {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear
CC       region {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: Peptide pr: Secreted
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane
CC       {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC       {ECO:0000255}. Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: Envelope protein E: Virion membrane
CC       {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC       {ECO:0000255}. Host endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 1: Secreted
CC       {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum
CC       membrane; Peripheral membrane protein; Lumenal side
CC       {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC       vesicles hosting the replication complex.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 2A: Host endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:23408612}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:23408612}.
CC   -!- SUBCELLULAR LOCATION: Serine protease subunit NS2B: Host
CC       endoplasmic reticulum membrane; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: Serine protease NS3: Host endoplasmic
CC       reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860};
CC       Peripheral membrane protein {ECO:0000255|PROSITE-
CC       ProRule:PRU00860}; Cytoplasmic side {ECO:0000255|PROSITE-
CC       ProRule:PRU00860}. Note=Remains non-covalently associated to
CC       serine protease subunit NS2B. {ECO:0000255|PROSITE-
CC       ProRule:PRU00860}.
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 4A: Host endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:17276984}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:17276984}. Host mitochondrion
CC       {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated
CC       vesicles hosting the replication complex. Interacts with host MAVS
CC       in the mitochondrion-associated endoplasmic reticulum membranes.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- SUBCELLULAR LOCATION: Non-structural protein 4B: Host endoplasmic
CC       reticulum membrane {ECO:0000269|PubMed:16436383}; Multi-pass
CC       membrane protein {ECO:0000269|PubMed:16436383}. Note=Located in
CC       RE-derived vesicles hosting the replication complex.
CC       {ECO:0000250|UniProtKB:Q9Q6P4}.
CC   -!- SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Host
CC       endoplasmic reticulum membrane; Peripheral membrane protein;
CC       Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}.
CC       Note=Located in RE-associated vesicles hosting the replication
CC       complex. NS5 protein is mainly localized in the nucleus rather
CC       than in ER vesicles, especially in the DENV 2, 3, 4 serotypes.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- DOMAIN: The transmembrane domains of the small envelope protein M
CC       and envelope protein E contain an endoplasmic reticulum retention
CC       signal. {ECO:0000250|UniProtKB:P17763}.
CC   -!- PTM: Genome polyprotein: Specific enzymatic cleavages in vivo
CC       yield mature proteins. Cleavages in the lumen of endoplasmic
CC       reticulum are performed by host signal peptidase, whereas
CC       cleavages in the cytoplasmic side are performed by serine protease
CC       NS3. Signal cleavage at the 2K-4B site requires a prior NS3
CC       protease-mediated cleavage at the 4A-2K site.
CC       {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:2952760}.
CC   -!- PTM: Protein prM: Cleaved in post-Golgi vesicles by a host furin,
CC       releasing the mature small envelope protein M, and peptide pr.
CC       This cleavage is incomplete as up to 30% of viral particles still
CC       carry uncleaved prM. {ECO:0000250|UniProtKB:P17763}.
CC   -!- PTM: Envelope protein E: N-glycosylated.
CC       {ECO:0000250|UniProtKB:P17763}.
CC   -!- PTM: Non-structural protein 1: N-glycosylated. The excreted form
CC       is glycosylated and this is required for efficient secretion of
CC       the protein from infected cells. {ECO:0000250|UniProtKB:P17763}.
CC   -!- PTM: RNA-directed RNA polymerase NS5: Sumoylation of RNA-directed
CC       RNA polymerase NS5 increases NS5 protein stability allowing proper
CC       viral RNA replication. {ECO:0000250|UniProtKB:P29990}.
CC   -!- PTM: RNA-directed RNA polymerase NS5: Phosphorylated on serines
CC       residues (PubMed:7642575). This phosphorylation may trigger NS5
CC       nuclear localization. {ECO:0000250|UniProtKB:P17763,
CC       ECO:0000269|PubMed:7642575}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the class I-like
CC       SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type
CC       methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}.
CC   -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC       URL="http://www.viprbrc.org/brc/home.do?decorator=flavi_dengue";
DR   EMBL; M29095; AAA42941.1; -; Genomic_RNA.
DR   PDB; 3IYA; EM; 22.00 A; A/B/C=281-675, D/E/F=115-195.
DR   PDB; 3J27; EM; 3.60 A; A/C/E=281-775, B/D/F=206-280.
DR   PDB; 3J2P; EM; 3.60 A; A/C=281-775, B/D=206-280.
DR   PDB; 4CBF; EM; 4.10 A; A/C/E=288-721.
DR   PDB; 4UIH; EM; 20.00 A; A/B/C=281-775.
DR   PDB; 6FLA; X-ray; 2.90 A; G=577-674.
DR   PDB; 6FLB; X-ray; 2.20 A; G=578-677.
DR   PDB; 6FLC; X-ray; 2.00 A; G/I=577-674.
DR   PDBsum; 3IYA; -.
DR   PDBsum; 3J27; -.
DR   PDBsum; 3J2P; -.
DR   PDBsum; 4CBF; -.
DR   PDBsum; 4UIH; -.
DR   PDBsum; 6FLA; -.
DR   PDBsum; 6FLB; -.
DR   PDBsum; 6FLC; -.
DR   SMR; P14340; -.
DR   IntAct; P14340; 13.
DR   BindingDB; P14340; -.
DR   TCDB; 1.G.3.1.2; the viral pore-forming membrane fusion protein-3 (vmfp3) family.
DR   iPTMnet; P14340; -.
DR   PRIDE; P14340; -.
DR   ABCD; P14340; -.
DR   PRO; PR:P14340; -.
DR   Proteomes; UP000007196; Genome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; 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:0044385; C:integral to membrane of host cell; IEA:UniProtKB-KW.
DR   GO; GO:0019028; C:viral capsid; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR   GO; GO:0005216; F:ion channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
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:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0039707; P:pore formation by virus in membrane of host cell; IEA:UniProtKB-KW.
DR   GO; GO:0051259; P:protein complex oligomerization; IEA:UniProtKB-KW.
DR   GO; GO:0039545; P:suppression by virus of host MAVS activity; IEA:UniProtKB-KW.
DR   GO; GO:0039564; P:suppression by virus of host STAT2 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039574; P:suppression by virus of host TYK2 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   CDD; cd12149; Flavi_E_C; 1.
DR   DisProt; DP00876; -.
DR   Gene3D; 1.10.10.930; -; 1.
DR   Gene3D; 1.10.8.970; -; 1.
DR   Gene3D; 1.20.1280.260; -; 1.
DR   Gene3D; 2.60.260.50; -; 1.
DR   Gene3D; 2.60.40.350; -; 1.
DR   Gene3D; 2.60.98.10; -; 1.
DR   Gene3D; 3.30.387.10; -; 1.
DR   Gene3D; 3.30.67.10; -; 1.
DR   InterPro; IPR011492; DEAD_Flavivir.
DR   InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR   InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR   InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR   InterPro; IPR001122; Flavi_capsidC.
DR   InterPro; IPR037172; Flavi_capsidC_sf.
DR   InterPro; IPR027287; Flavi_E_Ig-like.
DR   InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR   InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR   InterPro; IPR001157; Flavi_NS1.
DR   InterPro; IPR000752; Flavi_NS2A.
DR   InterPro; IPR000487; Flavi_NS2B.
DR   InterPro; IPR000404; Flavi_NS4A.
DR   InterPro; IPR001528; Flavi_NS4B.
DR   InterPro; IPR002535; Flavi_propep.
DR   InterPro; IPR038688; Flavi_propep_sf.
DR   InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR   InterPro; IPR001850; Flavivirus_NS3_S7.
DR   InterPro; IPR014412; Gen_Poly_FLV.
DR   InterPro; IPR011998; Glycoprot_cen/dimer.
DR   InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR   InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR   InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR001650; Helicase_C.
DR   InterPro; IPR014756; Ig_E-set.
DR   InterPro; IPR026490; mRNA_cap_0/1_MeTrfase.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR009003; Peptidase_S1_PA.
DR   InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR002877; rRNA_MeTrfase_FtsJ_dom.
DR   InterPro; IPR029063; SAM-dependent_MTases.
DR   Pfam; PF01003; Flavi_capsid; 1.
DR   Pfam; PF07652; Flavi_DEAD; 1.
DR   Pfam; PF02832; Flavi_glycop_C; 1.
DR   Pfam; PF00869; Flavi_glycoprot; 1.
DR   Pfam; PF01004; Flavi_M; 1.
DR   Pfam; PF00948; Flavi_NS1; 1.
DR   Pfam; PF01005; Flavi_NS2A; 1.
DR   Pfam; PF01002; Flavi_NS2B; 1.
DR   Pfam; PF01350; Flavi_NS4A; 1.
DR   Pfam; PF01349; Flavi_NS4B; 1.
DR   Pfam; PF00972; Flavi_NS5; 1.
DR   Pfam; PF01570; Flavi_propep; 1.
DR   Pfam; PF01728; FtsJ; 1.
DR   Pfam; PF00949; Peptidase_S7; 1.
DR   PIRSF; PIRSF003817; Gen_Poly_FLV; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SMART; SM00490; HELICc; 1.
DR   SUPFAM; SSF101257; SSF101257; 1.
DR   SUPFAM; SSF50494; SSF50494; 1.
DR   SUPFAM; SSF52540; SSF52540; 2.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   SUPFAM; SSF56983; SSF56983; 1.
DR   SUPFAM; SSF81296; SSF81296; 1.
DR   TIGRFAMs; TIGR04240; flavi_E_stem; 1.
DR   PROSITE; PS51527; FLAVIVIRUS_NS2B; 1.
DR   PROSITE; PS51528; FLAVIVIRUS_NS3PRO; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
DR   PROSITE; PS50507; RDRP_SSRNA_POS; 1.
DR   PROSITE; PS51591; RNA_CAP01_NS5_MT; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Activation of host autophagy by virus; ATP-binding;
KW   Capsid protein; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein; Helicase;
KW   Host cytoplasm; Host endoplasmic reticulum; Host membrane;
KW   Host mitochondrion; Host nucleus; 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 MAVS by virus;
KW   Inhibition of host RLR pathway by virus;
KW   Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus;
KW   Ion channel; Ion transport; Membrane; Metal-binding;
KW   Methyltransferase; mRNA capping; mRNA processing;
KW   Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW   Phosphoprotein; Protease; RNA-binding; RNA-directed RNA polymerase;
KW   S-adenosyl-L-methionine; Secreted; Serine protease;
KW   Suppressor of RNA silencing; Transcription; Transcription regulation;
KW   Transferase; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion; Viral ion channel;
KW   Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW   Virus endocytosis by host; Virus entry into host cell; Zinc.
FT   CHAIN         1   3391       Genome polyprotein.
FT                                /FTId=PRO_0000405216.
FT   CHAIN         1    100       Capsid protein C.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037958.
FT   PROPEP      101    114       ER anchor for the capsid protein C,
FT                                removed in mature form by serine protease
FT                                NS3. {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000261388.
FT   CHAIN       115    280       Protein prM.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000261389.
FT   CHAIN       115    205       Peptide pr.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037959.
FT   CHAIN       206    280       Small envelope protein M.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037960.
FT   CHAIN       281    775       Envelope protein E.
FT                                {ECO:0000269|PubMed:2952760}.
FT                                /FTId=PRO_0000037961.
FT   CHAIN       776   1127       Non-structural protein 1.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037962.
FT   CHAIN      1128   1345       Non-structural protein 2A.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037963.
FT   CHAIN      1346   1475       Serine protease subunit NS2B.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037964.
FT   CHAIN      1476   2093       Serine protease NS3.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037965.
FT   CHAIN      2094   2220       Non-structural protein 4A.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037966.
FT   PEPTIDE    2221   2243       Peptide 2k.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000261391.
FT   CHAIN      2244   2491       Non-structural protein 4B.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037967.
FT   CHAIN      2492   3391       RNA-directed RNA polymerase NS5.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT                                /FTId=PRO_0000037968.
FT   TOPO_DOM      1    101       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    102    122       Helical. {ECO:0000255}.
FT   TOPO_DOM    123    238       Extracellular. {ECO:0000255}.
FT   TRANSMEM    239    259       Helical. {ECO:0000255}.
FT   TOPO_DOM    260    265       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    266    280       Helical. {ECO:0000255}.
FT   TOPO_DOM    281    725       Extracellular. {ECO:0000255}.
FT   TRANSMEM    726    746       Helical. {ECO:0000255}.
FT   TOPO_DOM    747    752       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM    753    773       Helical. {ECO:0000255}.
FT   TOPO_DOM    774   1195       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1196   1220       Helical. {ECO:0000303|PubMed:23408612}.
FT   TOPO_DOM   1221   1226       Cytoplasmic.
FT                                {ECO:0000303|PubMed:23408612}.
FT   TRANSMEM   1227   1245       Helical. {ECO:0000255,
FT                                ECO:0000303|PubMed:23408612}.
FT   TOPO_DOM   1246   1269       Lumenal. {ECO:0000303|PubMed:23408612}.
FT   TRANSMEM   1270   1290       Helical. {ECO:0000255,
FT                                ECO:0000303|PubMed:23408612}.
FT   TOPO_DOM   1291   1291       Cytoplasmic.
FT                                {ECO:0000303|PubMed:23408612}.
FT   TRANSMEM   1292   1310       Helical. {ECO:0000255,
FT                                ECO:0000303|PubMed:23408612}.
FT   TOPO_DOM   1311   1317       Lumenal. {ECO:0000303|PubMed:23408612}.
FT   TRANSMEM   1318   1338       Helical. {ECO:0000255,
FT                                ECO:0000303|PubMed:23408612}.
FT   TOPO_DOM   1339   1346       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   1347   1367       Helical. {ECO:0000255}.
FT   TOPO_DOM   1368   1370       Lumenal. {ECO:0000255}.
FT   TRANSMEM   1371   1391       Helical. {ECO:0000255}.
FT   TOPO_DOM   1392   1447       Cytoplasmic. {ECO:0000255}.
FT   INTRAMEM   1448   1468       Helical. {ECO:0000255}.
FT   TOPO_DOM   1469   2147       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   2148   2168       Helical. {ECO:0000305|PubMed:16436383}.
FT   TOPO_DOM   2169   2170       Lumenal. {ECO:0000305|PubMed:16436383}.
FT   INTRAMEM   2171   2191       Helical. {ECO:0000305|PubMed:16436383}.
FT   TOPO_DOM   2192   2192       Lumenal. {ECO:0000305|PubMed:16436383}.
FT   TRANSMEM   2193   2213       Helical. {ECO:0000305|PubMed:16436383}.
FT   TOPO_DOM   2214   2228       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   2229   2249       Helical; Note=Signal for NS4B.
FT                                {ECO:0000255}.
FT   TOPO_DOM   2250   2274       Lumenal. {ECO:0000255}.
FT   INTRAMEM   2275   2295       Helical. {ECO:0000255}.
FT   TOPO_DOM   2296   2316       Lumenal. {ECO:0000255}.
FT   INTRAMEM   2317   2337       Helical. {ECO:0000255}.
FT   TOPO_DOM   2338   2347       Lumenal. {ECO:0000255}.
FT   TRANSMEM   2348   2368       Helical. {ECO:0000255}.
FT   TOPO_DOM   2369   2413       Cytoplasmic. {ECO:0000255}.
FT   TRANSMEM   2414   2434       Helical. {ECO:0000255}.
FT   TOPO_DOM   2435   2459       Lumenal. {ECO:0000255}.
FT   TRANSMEM   2460   2480       Helical. {ECO:0000255}.
FT   TOPO_DOM   2481   3391       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN     1476   1653       Peptidase S7. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00860}.
FT   DOMAIN     1655   1811       Helicase ATP-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00541}.
FT   DOMAIN     1821   1988       Helicase C-terminal.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00542}.
FT   DOMAIN     2493   2755       mRNA cap 0-1 NS5-type MT.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   DOMAIN     3019   3168       RdRp catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00539}.
FT   NP_BIND    1668   1675       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00541}.
FT   REGION        1     15       Interaction with host EXOC1.
FT                                {ECO:0000250|UniProtKB:P17763}.
FT   REGION       37     72       Hydrophobic; homodimerization of capsid
FT                                protein C.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   REGION      378    391       Fusion peptide.
FT                                {ECO:0000250|UniProtKB:P14336}.
FT   REGION     1398   1437       Interacts with and activates NS3
FT                                protease. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00859}.
FT   REGION     1659   1662       Important for RNA-binding.
FT                                {ECO:0000269|PubMed:15917225}.
FT   MOTIF      1759   1762       DEAH box. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00541}.
FT   MOTIF      2568   2571       SUMO-interacting motif.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   COMPBIAS     97    100       Poly-Arg.
FT   COMPBIAS   1434   1437       Poly-Glu.
FT   COMPBIAS   2148   2154       Poly-Leu.
FT   COMPBIAS   3383   3386       Poly-Glu.
FT   ACT_SITE   1526   1526       Charge relay system; for serine protease
FT                                NS3 activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00860}.
FT   ACT_SITE   1550   1550       Charge relay system; for serine protease
FT                                NS3 activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00860}.
FT   ACT_SITE   1610   1610       Charge relay system; for serine protease
FT                                NS3 activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00860}.
FT   ACT_SITE   2552   2552       For 2'-O-MTase activity.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   ACT_SITE   2637   2637       For 2'-O-MTase activity.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   ACT_SITE   2672   2672       For 2'-O-MTase activity.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   ACT_SITE   2708   2708       For 2'-O-MTase activity.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      2929   2929       Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      2933   2933       Zinc 1; via tele nitrogen.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      2938   2938       Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      2941   2941       Zinc 1. {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      3203   3203       Zinc 2; via tele nitrogen.
FT                                {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      3219   3219       Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}.
FT   METAL      3338   3338       Zinc 2. {ECO:0000250|UniProtKB:Q6YMS4}.
FT   BINDING    2547   2547       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   BINDING    2577   2577       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   BINDING    2578   2578       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   BINDING    2595   2595       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   BINDING    2596   2596       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   BINDING    2622   2622       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   BINDING    2623   2623       S-adenosyl-L-methionine; via carbonyl
FT                                oxygen. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   BINDING    2638   2638       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   BINDING    2710   2710       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   SITE        100    101       Cleavage; by viral protease NS3.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE        114    115       Cleavage; by host signal peptidase.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE        205    206       Cleavage; by host furin.
FT                                {ECO:0000250|UniProtKB:P29990,
FT                                ECO:0000255}.
FT   SITE        280    281       Cleavage; by host signal peptidase.
FT                                {ECO:0000269|PubMed:2952760}.
FT   SITE        775    776       Cleavage; by host signal peptidase.
FT                                {ECO:0000269|PubMed:2952760}.
FT   SITE       1127   1128       Cleavage; by host.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE       1345   1346       Cleavage; by viral protease NS3.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE       1475   1476       Cleavage; by autolysis.
FT                                {ECO:0000269|PubMed:2952760}.
FT   SITE       1932   1932       Involved in NS3 ATPase and RTPase
FT                                activities.
FT                                {ECO:0000250|UniProtKB:P14335}.
FT   SITE       1935   1935       Involved in NS3 ATPase and RTPase
FT                                activities.
FT                                {ECO:0000250|UniProtKB:P14335}.
FT   SITE       2093   2094       Cleavage; by autolysis.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE       2220   2221       Cleavage; by viral protease NS3.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE       2243   2244       Cleavage; by host signal peptidase.
FT                                {ECO:0000250|UniProtKB:P29990}.
FT   SITE       2491   2492       Cleavage; by viral protease NS3.
FT                                {ECO:0000269|PubMed:2952760}.
FT   SITE       2505   2505       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2508   2508       mRNA cap binding; via carbonyl oxygen.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   SITE       2509   2509       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2511   2511       mRNA cap binding; via carbonyl oxygen.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   SITE       2516   2516       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2520   2520       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2552   2552       Essential for 2'-O-methyltransferase
FT                                activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2637   2637       Essential for 2'-O-methyltransferase and
FT                                N-7 methyltransferase activity.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00924}.
FT   SITE       2641   2641       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2672   2672       Essential for 2'-O-methyltransferase
FT                                activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2703   2703       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2705   2705       mRNA cap binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   SITE       2708   2708       Essential for 2'-O-methyltransferase
FT                                activity. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00924}.
FT   MOD_RES    2547   2547       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P03314}.
FT   CARBOHYD    183    183       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    347    347       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    433    433       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    905    905       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD    982    982       N-linked (GlcNAc...) asparagine; by host.
FT   CARBOHYD   2301   2301       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD   2305   2305       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   CARBOHYD   2457   2457       N-linked (GlcNAc...) asparagine; by host.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00498}.
FT   DISULFID    283    310       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    340    401       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    354    385       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    372    396       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    465    565       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    582    613       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    779    790       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    830    918       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID    954    998       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID   1055   1104       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID   1066   1088       {ECO:0000250|UniProtKB:P17763}.
FT   DISULFID   1087   1091       {ECO:0000250|UniProtKB:P17763}.
FT   MUTAGEN    1659   1662       RKRK->QNGN: Complete loss of RNA-
FT                                stimulated NTPase activity.
FT                                {ECO:0000269|PubMed:15917225}.
FT   STRAND      586    588       {ECO:0000244|PDB:6FLC}.
FT   STRAND      600    606       {ECO:0000244|PDB:6FLC}.
FT   STRAND      611    614       {ECO:0000244|PDB:6FLC}.
FT   STRAND      617    620       {ECO:0000244|PDB:6FLC}.
FT   STRAND      627    631       {ECO:0000244|PDB:6FLB}.
FT   STRAND      633    635       {ECO:0000244|PDB:6FLC}.
FT   STRAND      637    639       {ECO:0000244|PDB:6FLC}.
FT   STRAND      645    650       {ECO:0000244|PDB:6FLC}.
FT   STRAND      653    661       {ECO:0000244|PDB:6FLC}.
FT   STRAND      663    665       {ECO:0000244|PDB:6FLC}.
FT   STRAND      667    673       {ECO:0000244|PDB:6FLC}.
SQ   SEQUENCE   3391 AA;  379501 MW;  FFF98B4FF5B4BC57 CRC64;
     MNNQRKKARN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLFMAL VAFLRFLTIP
     PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR TAGMIIMLIP TVMAFHLTTR
     NGEPHMIVSR QEKGKSLLFK TEDGVNMCTL MAMDLGELCE DTITYKCPFL KQNEPEDIDC
     WCNSTSTWVT YGTCTTTGEH RREKRSVALV PHVGMGLETR TETWMSSEGA WKHAQRIETW
     ILRHPGFTIM AAILAYTIGT THFQRALIFI LLTAVAPSMT MRCIGISNRD FVEGVSGGSW
     VDIVLEHGSC VTTMAKNKPT LDFELIETEA KQPATLRKYC IEAKLTNTTT DSRCPTQGEP
     SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT CKKNMKGKVV QPENLEYTIV
     ITPHSGEEHA VGNDTGKHGK EIKITPQSSI TEAELTGYGT VTMECSPRTG LDFNEMVLLQ
     MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM
     HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI
     VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE PPFGDSYIII
     GVEPGQLKLN WFKKGSSIGQ MIETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF
     GAIYGAAFSG VSWIMKILIG VIITWIGMNS RSTSLSVSLV LVGVVTLYLG VMVQADSGCV
     VSWKNKELKC GSGIFITDNV HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN
     LMWKQITPEL NHILSENEVK LTIMTGDIKG IMQAGKRSLQ PQPTELKYSW KTWGKAKMLS
     TESHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLREKQ DVFCDSKLMS
     AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKSCHW PKSHTLWSNG VLESEMIIPK
     NFAGPVSQHN YRPGYHTQTA GPWHLGKLEM DFDFCEGTTV VVTEDCGNRG PSLRTTTASG
     KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QIDNFSLGVL
     GMALFLEEML RTRVGTKHAI LLVAVSFVTL ITGNMSFRDL GRVMVMVGAT MTDDIGMGVT
     YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLLSQ STIPETILEL TDALALGMMV
     LKMVRKMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKADWIP
     LALTIKGLNP TAIFLTTLSR TNKKRSWPLN EAIMAVGMVS ILASSLLKND IPMTGPLVAG
     GLLTVCYVLT GRSADLELER AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL
     TILIRTGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPVGK AELEDGAYRI
     KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL
     EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FKTNAGTIGA VSLDFSPGTS GSPIIDKKGK
     VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RKLTIMDLHP GAGKTKRYLP
     AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF
     TMRLLSPVRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF
     PQSNAPIMDE EREIPERSWS SGHEWVTDFK GKTVWFVPSI KAGNDIAACL RKNGKKVIQL
     SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG
     PMPVTHSSAA QRRGRIGRNP KNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII
     PSMFEPEREK VDAIDGEYRL RGEARKTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD
     GIKNNQILEE NVEVEIWTKE GERKKLKPRW LDAKIYSDPL ALKEFKEFAA GRKSLTLNLI
     TEMGRLPTFM TQKARDALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL LTLLATVTGG
     IFLFLMSGRG IGKMTLGMCC IITASILLWY AQIQPHWIAA SIILEFFLIV LLIPEPEKQR
     TPQDNQLTYV VIAILTVVAA TMANEMGFLE KTKKDLGLGS ITTQQPESNI LDIDLRPASA
     WTLYAVATTF VTPMLRHSIE NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG
     CYSQVNPITL TAALFLLVAH YAIIGPGLQA KATREAQKRA AAGIMKNPTV DGITVIDLDP
     IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEALTLA TGPISTLWEG NPGRFWNTTI
     AVSMANIFRG SYLAGAGLLF SIMKNTTNTR RGTGNIGETL GEKWKSRLNA LGKSEFQIYK
     KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS AKLRWFVERN MVTPEGKVVD LGCGRGGWSY
     YCGGLKNVRE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFTPPEK CDTLLCDIGE
     SSPNPTVEAG RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP
     LSRNSTHEMY WLSNASGNIV SSVNMISRML INRFTMRHKK ATYEPDVDLG SGTRNIGIES
     EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY ETKQTGSASS MGNGVVRLLT
     KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV DTRTQEPKEG TKKLMKITAE WLWKELGKKK
     TPRMCTREEF TRKVRSNAAL GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET
     CVYNMMGKRE KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG
     EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EEMVTNHMEG EHKKLAEAIF
     KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL NTFTNMEAQL IRQMEGEGVF
     KSIQHLTVTE EIAVQNWLAR VGRERLSRMA ISGDDCVVKP LDDRFASALT ALNDMGKVRK
     DIQQWEPSRG WNDWTQVPFC SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR
     ETACLGKSYA QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM
     LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW AKNIQTAINQ
     VRSLIGNEEY TDYMPSMKRF RKEEEEAGVL W
//
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