POLG_DEN26
ID POLG_DEN26 Reviewed; 3391 AA.
AC P29990;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 186.
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/16681/1984) (DENV-2).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=31634;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=299627; Aedes furcifer (Mosquito).
OH NCBI_TaxID=299628; Aedes taylori (Mosquito).
OH NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1312269; DOI=10.1016/0042-6822(92)90460-7;
RA Blok J., McWilliam S.M., Butler H.C., Gibbs A.J., Weiller G., Herring B.L.,
RA Hemsley A.C., Aaskov J.G., Yoksan S., Bhamarapravati N.;
RT "Comparison of a dengue-2 virus and its candidate vaccine derivative:
RT sequence relationships with the flaviviruses and other viruses.";
RL Virology 187:573-590(1992).
RN [2]
RP SUBUNIT (CAPSID PROTEIN C).
RX PubMed=12768036; DOI=10.1128/jvi.77.12.7143-7149.2003;
RA Jones C.T., Ma L., Burgner J.W., Groesch T.D., Post C.B., Kuhn R.J.;
RT "Flavivirus capsid is a dimeric alpha-helical protein.";
RL J. Virol. 77:7143-7149(2003).
RN [3]
RP PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX PubMed=14963133; DOI=10.1128/jvi.78.5.2367-2381.2004;
RA Keelapang P., Sriburi R., Supasa S., Panyadee N., Songjaeng A.,
RA Jairungsri A., Puttikhunt C., Kasinrerk W., Malasit P., Sittisombut N.;
RT "Alterations of pr-M cleavage and virus export in pr-M junction chimeric
RT dengue viruses.";
RL J. Virol. 78:2367-2381(2004).
RN [4]
RP SUBUNIT (CAPSID PROTEIN C), AND REGION OF HOMODIMERIZATION (CAPSID PROTEIN
RP C).
RX PubMed=15269372; DOI=10.1099/vir.0.80067-0;
RA Wang S.H., Syu W.J., Hu S.T.;
RT "Identification of the homotypic interaction domain of the core protein of
RT dengue virus type 2.";
RL J. Gen. Virol. 85:2307-2314(2004).
RN [5]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4B), AND FUNCTION (PEPTIDE 2K).
RX PubMed=15956546; DOI=10.1128/jvi.79.13.8004-8013.2005;
RA Munoz-Jordan J.L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L.,
RA Ashok M., Lipkin W.I., Garcia-Sastre A.;
RT "Inhibition of alpha/beta interferon signaling by the NS4B protein of
RT flaviviruses.";
RL J. Virol. 79:8004-8013(2005).
RN [6]
RP FUNCTION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=16544248; DOI=10.1086/500949;
RA Avirutnan P., Punyadee N., Noisakran S., Komoltri C., Thiemmeca S.,
RA Auethavornanan K., Jairungsri A., Kanlaya R., Tangthawornchaikul N.,
RA Puttikhunt C., Pattanakitsakul S.N., Yenchitsomanus P.T., Mongkolsapaya J.,
RA Kasinrerk W., Sittisombut N., Husmann M., Blettner M., Vasanawathana S.,
RA Bhakdi S., Malasit P.;
RT "Vascular leakage in severe dengue virus infections: a potential role for
RT the nonstructural viral protein NS1 and complement.";
RL J. Infect. Dis. 193:1078-1088(2006).
RN [7]
RP SUBCELLULAR LOCATION (SERINE PROTEASE NS3), AND SUBCELLULAR LOCATION
RP (RNA-DIRECTED RNA POLYMERASE NS5).
RC STRAIN=TR 1751;
RX PubMed=16699025; DOI=10.1128/jvi.01982-05;
RA Uchil P.D., Kumar A.V., Satchidanandam V.;
RT "Nuclear localization of flavivirus RNA synthesis in infected cells.";
RL J. Virol. 80:5451-5464(2006).
RN [8]
RP PROTEOLYTIC PROCESSING (GENOME POLYPROTEIN).
RX PubMed=17067286; DOI=10.1042/bj20061136;
RA Shiryaev S.A., Kozlov I.A., Ratnikov B.I., Smith J.W., Lebl M.,
RA Strongin A.Y.;
RT "Cleavage preference distinguishes the two-component NS2B-NS3 serine
RT proteinases of Dengue and West Nile viruses.";
RL Biochem. J. 401:743-752(2007).
RN [9]
RP DISULFIDE BOND (ENVELOPE PROTEIN E).
RX PubMed=14963174; DOI=10.1128/jvi.78.5.2648-2652.2004;
RA Roehrig J.T., Volpe K.E., Squires J., Hunt A.R., Davis B.S., Chang G.J.;
RT "Contribution of disulfide bridging to epitope expression of the dengue
RT type 2 virus envelope glycoprotein.";
RL J. Virol. 78:2648-2652(2004).
RN [10]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=15944325; DOI=10.4049/jimmunol.174.12.8163;
RA Ho L.J., Hung L.F., Weng C.Y., Wu W.L., Chou P., Lin Y.L., Chang D.M.,
RA Tai T.Y., Lai J.H.;
RT "Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral
RT effect via down-regulating Tyk2-STAT signaling in the human dendritic
RT cell.";
RL J. Immunol. 174:8163-8172(2005).
RN [11]
RP CHARACTERIZATION (NON-STRUCTURAL PROTEIN 1).
RX PubMed=17331594; DOI=10.1016/j.jviromet.2007.01.008;
RA Noisakran S., Dechtawewat T., Rinkaewkan P., Puttikhunt C.,
RA Kanjanahaluethai A., Kasinrerk W., Sittisombut N., Malasit P.;
RT "Characterization of dengue virus NS1 stably expressed in 293T cell
RT lines.";
RL J. Virol. Methods 142:67-80(2007).
RN [12]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), INTERACTION WITH RNA-DIRECTED
RP RNA POLYMERASE NS5 (SERINE PROTEASE NS3), AND INTERACTION WITH SERINE
RP PROTEASE NS3 (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=19850911; DOI=10.1261/rna.1609709;
RA Issur M., Geiss B.J., Bougie I., Picard-Jean F., Despins S., Mayette J.,
RA Hobdey S.E., Bisaillon M.;
RT "The flavivirus NS5 protein is a true RNA guanylyltransferase that
RT catalyzes a two-step reaction to form the RNA cap structure.";
RL RNA 15:2340-2350(2009).
RN [13]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND INTERACTION WITH HUMAN
RP STAT2 (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=19754307; DOI=10.1086/605847;
RA Mazzon M., Jones M., Davidson A., Chain B., Jacobs M.;
RT "Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal
RT transducer and activator of transcription 2 phosphorylation.";
RL J. Infect. Dis. 200:1261-1270(2009).
RN [14]
RP FUNCTION (ENVELOPE PROTEIN E).
RX PubMed=19272179; DOI=10.1186/1423-0127-16-17;
RA Suksanpaisan L., Susantad T., Smith D.R.;
RT "Characterization of dengue virus entry into HepG2 cells.";
RL J. Biomed. Sci. 16:17-17(2009).
RN [15]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), AND SUBCELLULAR LOCATION
RP (CAPSID PROTEIN C).
RX PubMed=19889084; DOI=10.1111/j.1462-5822.2009.01407.x;
RA Bhuvanakantham R., Li J., Tan T.T., Ng M.L.;
RT "Human Sec3 protein is a novel transcriptional and translational repressor
RT of flavivirus.";
RL Cell. Microbiol. 12:453-472(2010).
RN [16]
RP INTERACTION WITH HUMAN EXOC1 (CAPSID PROTEIN C), FUNCTION (CAPSID PROTEIN
RP C), AND MUTAGENESIS OF PHE-13.
RX PubMed=23522008; DOI=10.1111/cmi.12143;
RA Bhuvanakantham R., Ng M.L.;
RT "West Nile virus and dengue virus capsid protein negates the antiviral
RT activity of human Sec3 protein through the proteasome pathway.";
RL Cell. Microbiol. 15:1688-1706(2013).
RN [17]
RP SUMOYLATION (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF
RP 2568-VAL--LEU-2571.
RX PubMed=26889037; DOI=10.1128/jvi.00223-16;
RA Su C.I., Tseng C.H., Yu C.Y., Lai M.M.;
RT "SUMO modification stabilizes dengue virus nonstructural protein 5 to
RT support virus replication.";
RL J. Virol. 90:4308-4319(2016).
RN [18]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), INTERACTION WITH HUMAN STAT2
RP (RNA-DIRECTED RNA POLYMERASE NS5), INTERACTION WITH HUMAN PAF1 COMPLEX
RP (RNA-DIRECTED RNA POLYMERASE NS5), INTERACTION WITH HUMAN SRPRA
RP (NON-STRUCTURAL PROTEIN 4A), INTERACTION WITH HUMAN SEC61G (NON-STRUCTURAL
RP PROTEIN 4A), SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 4A), AND
RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=30550790; DOI=10.1016/j.cell.2018.11.028;
RA Shah P.S., Link N., Jang G.M., Sharp P.P., Zhu T., Swaney D.L.,
RA Johnson J.R., Von Dollen J., Ramage H.R., Satkamp L., Newton B.,
RA Huettenhain R., Petit M.J., Baum T., Everitt A., Laufman O., Tassetto M.,
RA Shales M., Stevenson E., Iglesias G.N., Shokat L., Tripathi S.,
RA Balasubramaniam V., Webb L.G., Aguirre S., Willsey A.J., Garcia-Sastre A.,
RA Pollard K.S., Cherry S., Gamarnik A.V., Marazzi I., Taunton J.,
RA Fernandez-Sesma A., Bellen H.J., Andino R., Krogan N.J.;
RT "Comparative Flavivirus-Host Protein Interaction Mapping Reveals Mechanisms
RT of Dengue and Zika Virus Pathogenesis.";
RL Cell 175:1931-1945(2018).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 578-674.
RX PubMed=18264114; DOI=10.1038/nsmb.1382;
RA Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., Battisti A.J.,
RA Sukupolvi-Petty S., Sedlak D., Fremont D.H., Chipman P.R., Roehrig J.T.,
RA Diamond M.S., Kuhn R.J., Rossmann M.G.;
RT "Binding of a neutralizing antibody to dengue virus alters the arrangement
RT of surface glycoproteins.";
RL Nat. Struct. Mol. Biol. 15:312-317(2008).
CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding
CC to the cell membrane and gathering the viral RNA into a nucleocapsid
CC that forms the core of a mature virus particle. During virus entry, may
CC induce genome penetration into the host cytoplasm after hemifusion
CC induced by the surface proteins. Can migrate to the cell nucleus where
CC it modulates host functions. Overcomes the anti-viral effects of host
CC EXOC1 by sequestering and degrading the latter through the proteasome
CC degradation pathway (PubMed:23522008). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:23522008}.
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 envelope
CC proteins in trans-Golgi by binding to envelope protein E at pH6.0.
CC After virion release in extracellular space, gets dissociated from E
CC 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 Golgi
CC compartment prior to virion release. prM-E cleavage is inefficient, and
CC many virions are only partially matured. These uncleaved prM would play
CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding.
CC Exerts cytotoxic effects by activating a mitochondrial apoptotic
CC pathway through M ectodomain. May display a viroporin activity.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and
CC mediates fusion between viral and cellular membranes (PubMed:19272179).
CC Envelope protein is synthesized in the endoplasmic reticulum in the
CC form of heterodimer with protein prM (By similarity). They play a role
CC in virion budding in the ER, and the newly formed immature particle is
CC covered with 60 spikes composed of heterodimer between precursor prM
CC and envelope protein E (By similarity). The virion is transported to
CC the Golgi apparatus where the low pH causes dissociation of PrM-E
CC heterodimers and formation of E homodimers (By similarity). prM-E
CC cleavage is inefficient, and many virions are only partially matured.
CC These uncleaved prM would play a role in immune evasion (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds 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 cells,
CC inducing degradation of sialic acid and shedding of heparan sulfate
CC proteoglycans. NS1 induces expression of sialidases, heparanase, and
CC activates cathepsin L, which activates heparanase via enzymatic
CC cleavage. These effects are probably linked to the endothelial
CC hyperpermeability observed in severe dengue disease (By similarity).
CC Mediates complement activation, which may contribute to the
CC pathogenesis of the vascular leakage that occurs in severe dengue
CC disease (PubMed:16544248). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:16544248}.
CC -!- FUNCTION: [Non-structural protein 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host immune response. {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-ProRule:PRU00859}.
CC -!- FUNCTION: [Serine protease NS3]: Displays three enzymatic activities:
CC serine protease, NTPase and RNA helicase. NS3 serine protease, in
CC association with NS2B, performs its autocleavage and cleaves the
CC polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-
CC NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and
CC unwinds dsRNA in the 3' to 5' direction. {ECO:0000255|PROSITE-
CC ProRule:PRU00860}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy
CC during unwinding. Plays a role in the inhibition of the host innate
CC immune response. Interacts with host MAVS and thereby prevents the
CC interaction between DDX58 and MAVS. In turn, IFN-beta production is
CC impaired. Interacts with host AUP1 which mediates induction of
CC lipophagy in host cells and facilitates production of virus progeny
CC particles (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29991, ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC required for the interferon antagonism activity of the latter.
CC {ECO:0000269|PubMed:15956546}.
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 cellular
CC antiviral state by blocking the IFN-alpha/beta pathway
CC (PubMed:15956546). {ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:15956546}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) RNA genome, and performs the capping of genomes in the
CC cytoplasm (By similarity). NS5 methylates viral RNA cap at guanine N-7
CC and ribose 2'-O positions (PubMed:19850911). Besides its role in RNA
CC genome replication, also prevents the establishment of cellular
CC antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta)
CC signaling pathway (PubMed:15944325). Inhibits host TYK2 and STAT2
CC phosphorylation, thereby preventing activation of JAK-STAT signaling
CC pathway (PubMed:19754307). May reduce immune responses by preventing
CC the recruitment of the host PAF1 complex to interferon-responsive genes
CC (PubMed:30550790). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:15944325, ECO:0000269|PubMed:19754307,
CC ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:30550790}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of
CC the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.;
CC 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:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC 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 -!- 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 -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924};
CC -!- SUBUNIT: [Capsid protein C]: Homodimer (PubMed:12768036,
CC PubMed:15269372). Interacts (via N-terminus) with host EXOC1 (via C-
CC terminus); this interaction results in EXOC1 degradation through the
CC proteasome degradation pathway (PubMed:19889084, PubMed:23522008).
CC {ECO:0000269|PubMed:12768036, ECO:0000269|PubMed:15269372,
CC ECO:0000269|PubMed:19889084, ECO:0000269|PubMed:23522008}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi. Interacts with protein prM. Interacts with non-structural
CC protein 1 (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3 (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3. May form homooligomers (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B (By
CC similarity). Interacts with NS4B (By similarity). Interacts with
CC unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC (PubMed:19850911). Interacts with host SHFL (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:19850911}.
CC -!- SUBUNIT: [Non-structural protein 4A]: Interacts with host MAVS; this
CC interaction inhibits the synthesis of IFN-beta (By similarity).
CC Interacts with host SHFL (By similarity). Interacts with host AUP1; the
CC interaction occurs in the presence of Dengue virus NS4B and induces
CC lipophagy which facilitates production of virus progeny particles (By
CC similarity). May interact with host SRPRA and SEC61G (PubMed:30550790).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000250|UniProtKB:P29991,
CC ECO:0000269|PubMed:30550790}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer (By similarity).
CC Interacts with host STAT2; this interaction inhibits the
CC phosphorylation of the latter, and, when all viral proteins are present
CC (polyprotein), targets STAT2 for degradation (PubMed:19754307,
CC PubMed:30550790). Interacts with serine protease NS3 (PubMed:19850911).
CC Interacts with host PAF1 complex; the interaction may prevent the
CC recruitment of the PAF1 complex to interferon-responsive genes, and
CC thus reduces the immune response (PubMed:30550790).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:19754307,
CC ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:30550790}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC {ECO:0000269|PubMed:19889084}. Host cytoplasm, host perinuclear region
CC {ECO:0000269|PubMed:19889084}.
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 membrane;
CC Peripheral membrane protein; Lumenal side
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC reticulum membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane
CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side
CC {ECO:0000255|PROSITE-ProRule:PRU00860}. Host nucleus
CC {ECO:0000269|PubMed:16699025}. Note=Remains non-covalently associated
CC to 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:30550790}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Host mitochondrion
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles
CC hosting the replication complex. Interacts with host MAVS in the
CC mitochondrion-associated endoplasmic reticulum membranes.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived
CC vesicles hosting the replication complex.
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase NS5]: Host
CC endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P17763}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000269|PubMed:16699025, ECO:0000269|PubMed:30550790}.
CC Note=Located in RE-associated vesicles hosting the replication complex.
CC NS5 protein is mainly localized in the nucleus rather than in ER
CC 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 and
CC envelope protein E contain an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC mature proteins. Cleavages in the lumen of endoplasmic reticulum are
CC performed by host signal peptidase, whereas cleavages in the
CC cytoplasmic side are performed by serine protease NS3. Signal cleavage
CC at the 2K-4B site requires a prior NS3 protease-mediated cleavage at
CC the 4A-2K site. {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:17067286}.
CC -!- PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin,
CC releasing the mature small envelope protein M, and peptide pr. This
CC cleavage is incomplete as up to 30% of viral particles still carry
CC uncleaved prM. {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:14963133}.
CC -!- PTM: [Envelope protein E]: N-glycosylated.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is
CC glycosylated and this is required for efficient secretion of the
CC protein from infected cells. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Sumoylation of RNA-directed RNA
CC polymerase NS5 increases NS5 protein stability allowing proper viral
CC RNA replication. {ECO:0000269|PubMed:26889037}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Phosphorylated on serines
CC residues. This phosphorylation may trigger NS5 nuclear localization.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC 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="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue";
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DR EMBL; M84727; AAA73185.1; -; Genomic_RNA.
DR PIR; A42451; GNWV16.
DR PDB; 2R69; X-ray; 3.80 A; A=578-674.
DR PDB; 4O6B; X-ray; 3.00 A; A/B=775-1127.
DR PDB; 6WER; X-ray; 3.96 A; A/B=775-1127.
DR PDB; 6ZQU; EM; 3.10 A; A/C/E=281-775.
DR PDB; 7K93; X-ray; 2.89 A; A/B/C/D=775-1127.
DR PDBsum; 2R69; -.
DR PDBsum; 4O6B; -.
DR PDBsum; 6WER; -.
DR PDBsum; 6ZQU; -.
DR PDBsum; 7K93; -.
DR BMRB; P29990; -.
DR SMR; P29990; -.
DR IntAct; P29990; 4.
DR MINT; P29990; -.
DR BindingDB; P29990; -.
DR ChEMBL; CHEMBL5980; -.
DR MEROPS; S07.001; -.
DR iPTMnet; P29990; -.
DR PRIDE; P29990; -.
DR ABCD; P29990; 2 sequenced antibodies.
DR BRENDA; 2.7.7.50; 1867.
DR BRENDA; 3.4.21.91; 8413.
DR EvolutionaryTrace; P29990; -.
DR PRO; PR:P29990; -.
DR Proteomes; UP000002324; 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:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
DR GO; GO:0140272; F:exogenous protein binding; IDA:UniProtKB.
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; ISS:UniProtKB.
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:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039574; P:suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IEA:UniProtKB-KW.
DR GO; GO:0039653; P:suppression by virus of host transcription; IDA:UniProtKB.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; 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; cd20761; capping_2-OMTase_Flaviviridae; 1.
DR CDD; cd12149; Flavi_E_C; 1.
DR Gene3D; 1.10.10.930; -; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.40.10.10; -; 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 Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR011492; DEAD_Flavivir.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
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; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR000208; RNA-dir_pol_flavivirus.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
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; SSF56672; SSF56672; 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; 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; 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; Methyltransferase;
KW mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; Phosphoprotein; Protease; RNA-binding;
KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Secreted;
KW Serine protease; Suppressor of RNA silencing; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Transport; 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
FT /note="Genome polyprotein"
FT /id="PRO_0000405213"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037925"
FT PROPEP 101..114
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037926"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000264673"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000269|PubMed:14963133"
FT /id="PRO_0000264674"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037927"
FT CHAIN 281..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037928"
FT CHAIN 776..1127
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037929"
FT CHAIN 1128..1345
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037930"
FT CHAIN 1346..1475
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037931"
FT CHAIN 1476..2093
FT /note="Serine protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037932"
FT CHAIN 2094..2220
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037933"
FT PEPTIDE 2221..2243
FT /note="Peptide 2k"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000264676"
FT CHAIN 2244..2491
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037934"
FT CHAIN 2492..3391
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000269|PubMed:17067286"
FT /id="PRO_0000037935"
FT TOPO_DOM 1..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..242
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..725
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 747..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 753..773
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 774..1195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1196..1220
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1221..1226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1227..1245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1246..1269
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1270..1290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1291
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1292..1310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1311..1317
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1318..1338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1339..1346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1347..1367
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1368..1370
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1371..1391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1392..1447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1448..1468
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1469..2147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2148..2168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2169..2170
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2171..2191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2192
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2193..2213
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2214..2228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2229..2249
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2250..2274
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2275..2295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2296..2316
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2317..2337
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2338..2347
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2348..2368
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2369..2413
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2414..2434
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2435..2459
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2460..2480
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2481..3391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1476..1653
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1655..1811
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1821..1988
FT /note="Helicase C-terminal"
FT DOMAIN 2493..2755
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3020..3169
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1..15
FT /note="Interaction with host EXOC1"
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT REGION 37..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000269|PubMed:15269372"
FT REGION 378..391
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1398..1437
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1659..1662
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT MOTIF 1759..1762
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2568..2571
FT /note="SUMO-interacting motif"
FT /evidence="ECO:0000269|PubMed:26889037"
FT ACT_SITE 1526
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1550
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1610
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2552
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2637
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2672
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2708
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1668..1675
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2547
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2577
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2578
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2595
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2596
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2622
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2623
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2638
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2710
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2929
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2933
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2938
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 2941
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3203
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3219
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 3338
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT SITE 100..101
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 205..206
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:14963133"
FT SITE 280..281
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1127..1128
FT /note="Cleavage; by host"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1345..1346
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1475..1476
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 1932
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1935
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2093..2094
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 2220..2221
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 2243..2244
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 2491..2492
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:17067286"
FT SITE 2505
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2508
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2509
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2511
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2516
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2520
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2552
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2637
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2641
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2672
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2703
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2705
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2708
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2547
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 905
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 982
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1134
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1174
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2301
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2305
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 2457
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 283..310
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 340..401
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 354..385
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 372..396
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 465..565
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 582..613
FT /evidence="ECO:0000269|PubMed:14963174"
FT DISULFID 779..790
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 830..918
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 954..998
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1055..1104
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1066..1088
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1087..1091
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT MUTAGEN 13
FT /note="F->A: Loss of degradation of hSec3p."
FT /evidence="ECO:0000269|PubMed:23522008"
FT MUTAGEN 2568..2571
FT /note="VVDL->AAAA: Complete loss of NS5 sumoylation and
FT decreased viral replication."
FT /evidence="ECO:0000269|PubMed:26889037"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 287..292
FT /evidence="ECO:0007829|PDB:6ZQU"
FT TURN 297..299
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 300..308
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 321..330
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 334..352
FT /evidence="ECO:0007829|PDB:6ZQU"
FT TURN 363..366
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 370..380
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 389..409
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 415..423
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 437..445
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 456..466
FT /evidence="ECO:0007829|PDB:6ZQU"
FT TURN 467..471
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 473..475
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 490..494
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 500..502
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 517..521
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 523..525
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 529..532
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 537..543
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 545..558
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 561..568
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 570..572
FT /evidence="ECO:0007829|PDB:6ZQU"
FT TURN 575..578
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 586..594
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 600..606
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 612..614
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 618..620
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 629..635
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 645..650
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 653..659
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 663..665
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 668..673
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 677..695
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 696..701
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 708..727
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 728..730
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 733..749
FT /evidence="ECO:0007829|PDB:6ZQU"
FT TURN 753..755
FT /evidence="ECO:0007829|PDB:6ZQU"
FT HELIX 756..771
FT /evidence="ECO:0007829|PDB:6ZQU"
FT STRAND 775..782
FT /evidence="ECO:0007829|PDB:7K93"
FT TURN 783..786
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 787..797
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 799..801
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 808..812
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 814..826
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 837..856
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 863..865
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 870..872
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 908..913
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 916..918
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 920..922
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 928..932
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 941..946
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 956..958
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 960..964
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 967..971
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 973..993
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 1002..1004
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 1013..1015
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 1020..1022
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 1043..1045
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1046..1053
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1059..1062
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1073..1076
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1085..1090
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1096..1100
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1103..1106
FT /evidence="ECO:0007829|PDB:7K93"
FT STRAND 1110..1115
FT /evidence="ECO:0007829|PDB:7K93"
FT HELIX 1117..1119
FT /evidence="ECO:0007829|PDB:7K93"
SQ SEQUENCE 3391 AA; 379547 MW; 2E20AD0D6C978ECC CRC64;
MNDQRKKAKN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLYMAL VAFLRFLTIP
PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR SAGMIIMLIP TVMAFHLTTR
NGEPHMIVSR QEKGKSLLFK TEDGVNMCTL MAMDLGELCE DTITYKCPLL RQNEPEDIDC
WCNSTSTWVT YGTCTTMGEH RRQKRSVALV PHVGMGLETR TETWMSSEGA WKHVQRIETW
ILRHPGFTMM AAILAYTIGT THFQRALIFI LLTAVTPSMT MRCIGMSNRD FVEGVSGGSW
VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP
SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFR CKKNMEGKVV QPENLEYTIV
ITPHSGEEHA VGNDTGKHGK EIKITPQSST TEAELTGYGT VTMECSPRTG LDFNEMVLLQ
MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM
HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI
VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE PPFGDSYIII
GVEPGQLKLN WFKKGSSIGQ MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF
GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVTLV LVGIVTLYLG VMVQADSGCV
VSWKNKELKC GSGIFITDNV HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN
LMWKQITPEL NHILSENEVK LTIMTGDIKG IMQAGKRSLR PQPTELKYSW KTWGKAKMLS
TESHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLKEKQ DVFCDSKLMS
AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKNCHW PKSHTLWSNG VLESEMIIPK
NLAGPVSQHN YRPGYHTQIT GPWHLGKLEM DFDFCDGTTV VVTEDCGNRG PSLRTTTASG
KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QVDNFSLGVL
GMALFLEEML RTRVGTKHAI LLVAVSFVTL IIGNMSFRDL GRVMVMVGAT MTDDIGMGVT
YLALLAAFKV RPTFAAGLLL RKLTSKALMM TTIGIVLSSQ STTPETILEL TDALALGMMV
LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKTDWIP
LALTIKGLNP TAIFLTTLSR TSKKRSWPLN EAIMAVGMVS ILASSLLKND IPMTGPLVAG
GPLTVCYVLT GRSADLELER AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL
TILIRTGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPMGK AELEDGAYRI
KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL
EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FKTNAGTIGA VSLDFSPGTS GSPIIDKKGK
VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP
AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF
TMRLLSPVRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF
PQSNAPIIDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KAGNDIAACL SKNGKKVIQL
SRKTFDSEYA KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG
PMPVTHSSAA QRRGRIGRNP KNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII
PSMFEPEREK VDAIDGEYRL RGEARTTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD
GVKNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRKSLTLNLI
TEMGRLPTFM TQKARDALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL LTLLATVTGG
ILLFLMSGRG IGKMTLGMCC IITASILLWY AQIQPHWIAA SIILEFFLIV LLIPEPEKQR
TPQDNQLTYV VIAILTVVAA TMANEMGFLE KTKKDLGLGS IATQQPESNI LDIDLRPASA
WTLYAVATTF VTPMLRHSIE NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG
CYSQVNPTTL TAALFLLVAH YAIIGPALQA KASREAQKRA AAGIMKNPTV DGITVIDLDP
IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEVLTLA TGPISTLWEG NPGRFWNTTI
AVSMANIFRG SYLAGAGLLF SIMKNTTNAR RGTGNIGETL GEKWKSRLNA LGKSEFQIYK
KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS AKLRWFVERN MVTPEGKVVD LGCGRGGWSY
YCGGLKNVRE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFIPPEK CDTLLCDIGE
SSPNPTVEAG RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP
LSRNSTHEMY WVSNASGNIV SSVNMISRML INRFTMRYKK ATYEPDVDLG SGTRNIGIES
EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY ETKQTGSASS MVNGVFRLLT
KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV DTRTQEPKEG TKKLMKITAE WLWKELGKKK
TPRMCTREEF TRKVRSNAAL GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET
CVYNIMGKRE KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG
EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EAMVTNHMEG EHKKLAEAIF
KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL NTFTNMEAQL IRQMEGEGVF
KSIQHLTITE EIAVQNWLAR VGRERLSRMA ISGDDCVVKP LDDRLPSALT ALNDTGKIRK
DIQQWEPSRG WNDWTQVPFC SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR
ETACLGKSYD QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM
LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW AKNIQAAINQ
VRSLIGNEEY TDYMPSMKRF RREEEEAGVL W
