POLG_DEN2N
ID POLG_DEN2N Reviewed; 3391 AA.
AC P14340; Q66347; Q66348; Q66349; Q66350; Q66351; Q66352; Q66353; Q66354;
AC Q66355; Q66356; Q89579;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 196.
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; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; 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., 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., Wright P.J.;
RT "Characterization of protease cleavage sites involved in the formation of
RT the envelope glycoprotein and three non-structural proteins of dengue virus
RT 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 the
RT putative RNA replicase is linked to differential phosphorylation of NS5.";
RL J. Biol. Chem. 270:19100-19106(1995).
RN [5]
RP INTERACTION WITH SERINE PROTEASE NS3 (RNA-DIRECTED RNA POLYMERASE NS5),
RP INTERACTION WITH RNA-DIRECTED RNA POLYMERASE NS5 (SERINE PROTEASE NS3),
RP BIOPHYSICOCHEMICAL PROPERTIES (SERINE PROTEASE NS3), CATALYTIC ACTIVITY
RP (SERINE PROTEASE NS3), AND MUTAGENESIS OF 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 3
RT (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 TOPOLOGY
RP (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 type 2
RT Non-structural protein 4B.";
RL J. Biol. Chem. 281:8854-8863(2006).
RN [7]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A), SUBCELLULAR LOCATION (NON-STRUCTURAL
RP PROTEIN 4A), AND MEMBRANE TOPOLOGY (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=17276984; DOI=10.1074/jbc.m609919200;
RA Miller S., Kastner S., Krijnse-Locker J., Buhler S., 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 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. {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 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. Envelope protein
CC is synthesized in the endoplasmic reticulum in the form of heterodimer
CC with protein prM. They play a role in virion budding in the ER, and the
CC newly formed immature particle is covered with 60 spikes composed of
CC heterodimer between precursor prM and envelope protein E. The virion is
CC transported to the Golgi apparatus where the low pH causes dissociation
CC of PrM-E 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 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.
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 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:0000269|PubMed:17276984}.
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: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 cellular
CC 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 2'-O
CC positions. Besides its role in RNA genome replication, also prevents
CC the establishment of cellular antiviral state by blocking the
CC interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host
CC TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-
CC STAT signaling pathway (By similarity). May reduce immune responses by
CC preventing the recruitment of the host PAF1 complex to interferon-
CC responsive genes (By similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29990}.
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 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)-(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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29.3 uM for triphosphorylated RNA {ECO:0000269|PubMed:15917225};
CC Note=Vmax with 0.65 nmol/s/ug enzyme for RTPase activity with
CC triphosphorylated RNA as substrate. {ECO:0000269|PubMed:15917225};
CC -!- SUBUNIT: [Capsid protein C]: Homodimer (By similarity). Interacts (via
CC N-terminus) with host EXOC1 (via C-terminus); this interaction results
CC in EXOC1 degradation through the proteasome degradation pathway (By
CC similarity). {ECO:0000250|UniProtKB:P17763}.
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 (By similarity). Interacts with protein prM (By similarity).
CC Interacts with non-structural protein 1.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (By similarity). Interacts with envelope protein E.
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 (By similarity). May form homooligomers (By
CC similarity). {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:15917225). Interacts with host SHFL (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:15917225}.
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 MAVS; this interaction inhibits the synthesis of
CC IFN-beta. Interacts with host SHFL (By similarity). Interacts with host
CC AUP1; the interaction occurs in the presence of Dengue virus NS4B and
CC induces lipophagy which facilitates production of virus progeny
CC particles (By similarity). May interact with host SRPRA and SEC61G (By
CC similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:P29990, ECO:0000250|UniProtKB:P29991}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease NS
CC (By similarity). {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 (By similarity). Interacts
CC with serine protease NS3 (PubMed:15917225). Interacts with host PAF1
CC complex; the interaction may prevent the recruitment of the PAF1
CC complex to interferon-responsive genes, and thus reduces the immune
CC response (By similarity). {ECO:0000250|UniProtKB:P29990,
CC ECO:0000269|PubMed:15917225}.
CC -!- INTERACTION:
CC P14340; P25963: NFKBIA; Xeno; NbExp=2; IntAct=EBI-465733, EBI-307386;
CC P14340; Q15653: NFKBIB; Xeno; NbExp=2; IntAct=EBI-465733, EBI-352889;
CC P14340; Q9UHY1: NRBP1; Xeno; NbExp=4; IntAct=EBI-465733, EBI-749731;
CC PRO_0000037965; P55265: ADAR; Xeno; NbExp=2; IntAct=EBI-9825968, EBI-2462104;
CC PRO_0000037965; P25963: NFKBIA; Xeno; NbExp=2; IntAct=EBI-9825968, EBI-307386;
CC PRO_0000037965; Q15653: NFKBIB; Xeno; NbExp=2; IntAct=EBI-9825968, EBI-352889;
CC PRO_0000037966; 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 region
CC {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 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:0000269|PubMed:23408612}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:23408612}.
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}. Note=Remains non-covalently
CC associated 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:17276984}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:17276984}. 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:0000269|PubMed:16436383}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:16436383}. 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; Peripheral membrane protein;
CC Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}.
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: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. This
CC cleavage is incomplete as up to 30% of viral particles still carry
CC 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 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:0000250|UniProtKB:P29990}.
CC -!- PTM: [RNA-directed RNA polymerase NS5]: Phosphorylated on serines
CC residues (PubMed:7642575). This phosphorylation may trigger NS5 nuclear
CC localization. {ECO:0000250|UniProtKB:P17763,
CC ECO:0000269|PubMed:7642575}.
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; 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 PDB; 6IZX; X-ray; 2.43 A; A=2735-3387.
DR PDB; 6IZY; X-ray; 2.11 A; A=2735-3387.
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 PDBsum; 6IZX; -.
DR PDBsum; 6IZY; -.
DR BMRB; P14340; -.
DR SASBDB; P14340; -.
DR SMR; P14340; -.
DR IntAct; P14340; 13.
DR BindingDB; P14340; -.
DR MEROPS; S07.001; -.
DR TCDB; 1.G.3.1.2; the viral pore-forming membrane fusion protein-3 (vmfp3) family.
DR iPTMnet; P14340; -.
DR ABCD; P14340; 9 sequenced antibodies.
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:0016887; F:ATP hydrolysis activity; IEA:RHEA.
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; 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: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_0000405216"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037958"
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:0000250|UniProtKB:P29990"
FT /id="PRO_0000261388"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000261389"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037959"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037960"
FT CHAIN 281..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000269|PubMed:2952760"
FT /id="PRO_0000037961"
FT CHAIN 776..1127
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037962"
FT CHAIN 1128..1345
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037963"
FT CHAIN 1346..1475
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037964"
FT CHAIN 1476..2093
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037965"
FT CHAIN 2094..2220
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037966"
FT PEPTIDE 2221..2243
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000261391"
FT CHAIN 2244..2491
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037967"
FT CHAIN 2492..3391
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037968"
FT TOPO_DOM 1..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..238
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 260..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 266..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:0000303|PubMed:23408612"
FT TOPO_DOM 1221..1226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000303|PubMed:23408612"
FT TRANSMEM 1227..1245
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1246..1269
FT /note="Lumenal"
FT /evidence="ECO:0000303|PubMed:23408612"
FT TRANSMEM 1270..1290
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1291
FT /note="Cytoplasmic"
FT /evidence="ECO:0000303|PubMed:23408612"
FT TRANSMEM 1292..1310
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
FT TOPO_DOM 1311..1317
FT /note="Lumenal"
FT /evidence="ECO:0000303|PubMed:23408612"
FT TRANSMEM 1318..1338
FT /note="Helical"
FT /evidence="ECO:0000255, ECO:0000303|PubMed:23408612"
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:0000305|PubMed:16436383"
FT TOPO_DOM 2169..2170
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16436383"
FT INTRAMEM 2171..2191
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:16436383"
FT TOPO_DOM 2192
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:16436383"
FT TRANSMEM 2193..2213
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:16436383"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2493..2755
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3019..3168
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:0000250|UniProtKB:P29990"
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:0000269|PubMed:15917225"
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:0000250|UniProtKB:P29990"
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:0000250|UniProtKB:P29990"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 205..206
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT SITE 280..281
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:2952760"
FT SITE 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000269|PubMed:2952760"
FT SITE 1127..1128
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1345..1346
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 1475..1476
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:2952760"
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:0000250|UniProtKB:P29990"
FT SITE 2220..2221
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2243..2244
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 2491..2492
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000269|PubMed:2952760"
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 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:0000250|UniProtKB:P17763"
FT DISULFID 340..401
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 354..385
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 372..396
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 465..565
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 582..613
FT /evidence="ECO:0000250|UniProtKB:P17763"
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 1659..1662
FT /note="RKRK->QNGN: Complete loss of RNA-stimulated NTPase
FT activity."
FT /evidence="ECO:0000269|PubMed:15917225"
FT HELIX 2765..2778
FT /evidence="ECO:0007829|PDB:6IZY"
FT TURN 2779..2782
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 2792..2801
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2814..2819
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2821..2825
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2827..2831
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2839..2848
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2859..2876
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2887..2894
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 2895..2897
FT /evidence="ECO:0007829|PDB:6IZX"
FT HELIX 2913..2918
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2920..2934
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 2943..2945
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 2966..2968
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2970..2980
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2982..2985
FT /evidence="ECO:0007829|PDB:6IZY"
FT TURN 2986..2989
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 2991..2994
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 2995..2997
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3003..3014
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3016..3019
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3029..3032
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3035..3042
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3043..3047
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3050..3062
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3065..3075
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3078..3088
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3097..3116
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3128..3146
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3149..3152
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3155..3158
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3163..3167
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3170..3174
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3191..3193
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3194..3196
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3202..3208
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3214..3219
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3222..3229
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3233..3236
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3239..3256
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3261..3273
FT /evidence="ECO:0007829|PDB:6IZY"
FT STRAND 3295..3298
FT /evidence="ECO:0007829|PDB:6IZX"
FT HELIX 3300..3308
FT /evidence="ECO:0007829|PDB:6IZY"
FT TURN 3309..3311
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3324..3326
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3332..3335
FT /evidence="ECO:0007829|PDB:6IZY"
FT TURN 3336..3339
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3345..3352
FT /evidence="ECO:0007829|PDB:6IZY"
FT HELIX 3354..3365
FT /evidence="ECO:0007829|PDB:6IZY"
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
