POLG_KUNJM
ID POLG_KUNJM Reviewed; 3433 AA.
AC P14335; Q7T4P4; Q7T4P5; Q82983;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Peptide 2k;
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/Helicase NS3;
DE EC=3.4.21.91;
DE EC=3.6.1.15;
DE EC=3.6.4.13 {ECO:0000269|PubMed:17658551};
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=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=NS5;
OS Kunjin virus (strain MRM61C).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11078;
OH NCBI_TaxID=8920; Ciconiiformes (storks and others).
OH NCBI_TaxID=162997; Culex annulirostris (Common banded mosquito).
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2826659; DOI=10.1099/0022-1317-69-1-1;
RA Coia G., Parker M.D., Speight G., Byrne M.E., Westaway E.G.;
RT "Nucleotide and complete amino acid sequences of Kunjin virus: definitive
RT gene order and characteristics of the virus-specified proteins.";
RL J. Gen. Virol. 69:1-21(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Infectious clone FLSDX, and Infectious clone pAKUN;
RX PubMed=12829820; DOI=10.1128/jvi.77.14.7804-7813.2003;
RA Liu W.J., Chen H.B., Khromykh A.A.;
RT "Molecular and functional analyses of Kunjin virus infectious cDNA clones
RT demonstrate the essential role for NS2A in virus assembly and for a
RT nonconservative residue in NS3 in RNA replication.";
RL J. Virol. 77:7804-7813(2003).
RN [3]
RP SUBCELLULAR LOCATION (NON-STRUCTURAL PROTEIN 2A), AND SUBCELLULAR LOCATION
RP (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=9636360; DOI=10.1006/viro.1998.9156;
RA Mackenzie J.M., Khromykh A.A., Jones M.K., Westaway E.G.;
RT "Subcellular localization and some biochemical properties of the flavivirus
RT Kunjin nonstructural proteins NS2A and NS4A.";
RL Virology 245:203-215(1998).
RN [4]
RP FUNCTION (NON-STRUCTURAL PROTEIN 2A), AND MUTAGENESIS OF ALA-1173; ASN-1244
RP AND PRO-2798.
RX PubMed=15507609; DOI=10.1128/jvi.78.22.12225-12235.2004;
RA Liu W.J., Chen H.B., Wang X.J., Huang H., Khromykh A.A.;
RT "Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a
RT novel role for the flavivirus nonstructural protein NS2A in inhibition of
RT beta interferon promoter-driven transcription.";
RL J. Virol. 78:12225-12235(2004).
RN [5]
RP FUNCTION (NON-STRUCTURAL PROTEIN 2A), FUNCTION (NON-STRUCTURAL PROTEIN 2B),
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), FUNCTION (NON-STRUCTURAL PROTEIN 4A),
RP AND FUNCTION (NON-STRUCTURAL PROTEIN 4B).
RX PubMed=15650219; DOI=10.1128/jvi.79.3.1934-1942.2005;
RA Liu W.J., Wang X.J., Mokhonov V.V., Shi P.Y., Randall R., Khromykh A.A.;
RT "Inhibition of interferon signaling by the New York 99 strain and Kunjin
RT subtype of West Nile virus involves blockage of STAT1 and STAT2 activation
RT by nonstructural proteins.";
RL J. Virol. 79:1934-1942(2005).
RN [6]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5).
RX PubMed=15650160; DOI=10.1128/jvi.79.3.1343-1350.2005;
RA Guo J.T., Hayashi J., Seeger C.;
RT "West Nile virus inhibits the signal transduction pathway of alpha
RT interferon.";
RL J. Virol. 79:1343-1350(2005).
RN [7]
RP MUTAGENESIS OF ALA-1173.
RX PubMed=16474146; DOI=10.1128/jvi.80.5.2396-2404.2006;
RA Liu W.J., Wang X.J., Clark D.C., Lobigs M., Hall R.A., Khromykh A.A.;
RT "A single amino acid substitution in the West Nile virus nonstructural
RT protein NS2A disables its ability to inhibit alpha/beta interferon
RT induction and attenuates virus virulence in mice.";
RL J. Virol. 80:2396-2404(2006).
RN [8]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A).
RX PubMed=16611922; DOI=10.1128/jvi.80.9.4623-4632.2006;
RA Roosendaal J., Westaway E.G., Khromykh A., Mackenzie J.M.;
RT "Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a
RT major role in rearranging cytoplasmic membranes and Golgi trafficking of
RT the NS4A protein.";
RL J. Virol. 80:4623-4632(2006).
RN [9]
RP FUNCTION (NON-STRUCTURAL PROTEIN 2A), MUTAGENESIS OF THR-1292, AND
RP CHARACTERIZATION OF VARIANT ASN-1202.
RX PubMed=18337583; DOI=10.1128/jvi.00002-08;
RA Leung J.Y., Pijlman G.P., Kondratieva N., Hyde J., Mackenzie J.M.,
RA Khromykh A.A.;
RT "Role of nonstructural protein NS2A in flavivirus assembly.";
RL J. Virol. 82:4731-4741(2008).
RN [10]
RP FUNCTION (RNA-DIRECTED RNA POLYMERASE NS5), AND MUTAGENESIS OF SER-3181.
RX PubMed=20106931; DOI=10.1128/jvi.01161-09;
RA Laurent-Rolle M., Boer E.F., Lubick K.J., Wolfinbarger J.B., Carmody A.B.,
RA Rockx B., Liu W., Ashour J., Shupert W.L., Holbrook M.R., Barrett A.D.,
RA Mason P.W., Bloom M.E., Garcia-Sastre A., Khromykh A.A., Best S.M.;
RT "The NS5 protein of the virulent West Nile virus NY99 strain is a potent
RT antagonist of type I interferon-mediated JAK-STAT signaling.";
RL J. Virol. 84:3503-3515(2010).
RN [11]
RP MUTAGENESIS OF PRO-2244; GLU-2245; PRO-2246 AND GLU-2247.
RX PubMed=21880777; DOI=10.1128/jvi.05864-11;
RA Ambrose R.L., Mackenzie J.M.;
RT "A conserved peptide in West Nile virus NS4A protein contributes to
RT proteolytic processing and is essential for replication.";
RL J. Virol. 85:11274-11282(2011).
RN [12]
RP FUNCTION (NON-STRUCTURAL PROTEIN 4A), AND MUTAGENESIS OF PRO-2137;
RP PRO-2172; ASP-2173 AND GLY-2190.
RX PubMed=25771497; DOI=10.1016/j.virol.2015.02.045;
RA Ambrose R.L., Mackenzie J.M.;
RT "Conserved amino acids within the N-terminus of the West Nile virus NS4A
RT protein contribute to virus replication, protein stability and membrane
RT proliferation.";
RL Virology 481:95-106(2015).
RN [13]
RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NS5), MUTAGENESIS OF
RP 2901-LYS-TYR-2902 AND 2917-ARG--LYS-2919, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=29582535; DOI=10.1111/cmi.12848;
RA Lopez-Denman A.J., Russo A., Wagstaff K.M., White P.A., Jans D.A.,
RA Mackenzie J.M.;
RT "Nucleocytoplasmic shuttling of the West Nile virus RNA-dependent RNA
RT polymerase NS5 is critical to infection.";
RL Cell. Microbiol. 20:e12848-e12848(2018).
RN [14]
RP FUNCTION.
RX PubMed=33866234; DOI=10.1016/j.virol.2021.03.018;
RA Lopez-Denman A.J., Tuipulotu D.E., Ross J.B., Trenerry A.M., White P.A.,
RA Mackenzie J.M.;
RT "Nuclear localisation of West Nile virus NS5 protein modulates host gene
RT expression.";
RL Virology 559:131-144(2021).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 23-98 IN COMPLEX WITH CALCIUM,
RP AND SUBUNIT (CAPSID PROTEIN C).
RX PubMed=15242592; DOI=10.1016/j.str.2004.04.024;
RA Dokland T., Walsh M., Mackenzie J.M., Khromykh A.A., Ee K.H., Wang S.;
RT "West Nile virus core protein; tetramer structure and ribbon formation.";
RL Structure 12:1157-1163(2004).
RN [16] {ECO:0007744|PDB:2HCN, ECO:0007744|PDB:2HCS, ECO:0007744|PDB:2HFZ}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 2846-3433 IN COMPLEX WITH ZINC.
RX PubMed=17287213; DOI=10.1074/jbc.m607273200;
RA Malet H., Egloff M.P., Selisko B., Butcher R.E., Wright P.J., Roberts M.,
RA Gruez A., Sulzenbacher G., Vonrhein C., Bricogne G., Mackenzie J.M.,
RA Khromykh A.A., Davidson A.D., Canard B.;
RT "Crystal structure of the RNA polymerase domain of the West Nile virus non-
RT structural protein 5.";
RL J. Biol. Chem. 282:10678-10689(2007).
RN [17] {ECO:0007744|PDB:2QEQ}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1691-2124, AND CATALYTIC ACTIVITY
RP (SERINE PROTEASE/HELICASE NS3).
RX PubMed=17658551; DOI=10.1016/j.jmb.2007.06.055;
RA Mastrangelo E., Milani M., Bollati M., Selisko B., Peyrane F., Pandini V.,
RA Sorrentino G., Canard B., Konarev P.V., Svergun D.I., de Lamballerie X.,
RA Coutard B., Khromykh A.A., Bolognesi M.;
RT "Crystal structure and activity of Kunjin virus NS3 helicase; protease and
RT helicase domain assembly in the full length NS3 protein.";
RL J. Mol. Biol. 372:444-455(2007).
RN [18] {ECO:0007744|PDB:2OF6}
RP STRUCTURE BY ELECTRON MICROSCOPY (24.00 ANGSTROMS) OF 291-690, SUBCELLULAR
RP LOCATION (ENVELOPE PROTEIN E), AND GLYCOSYLATION AT ASN-138.
RX PubMed=17376919; DOI=10.1128/jvi.00037-07;
RA Zhang Y., Kaufmann B., Chipman P.R., Kuhn R.J., Rossmann M.G.;
RT "Structure of immature West Nile virus.";
RL J. Virol. 81:6141-6145(2007).
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 2A]: Component of the viral RNA
CC replication complex that functions in virion assembly and antagonizes
CC the host alpha/beta interferon antiviral response (PubMed:15507609,
CC PubMed:18337583). Inhibits STAT2 translocation in the nucleus after
CC IFN-alpha treatment (PubMed:15650219). {ECO:0000269|PubMed:15507609,
CC ECO:0000269|PubMed:15650219, ECO:0000269|PubMed:18337583}.
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). Inhibits STAT2
CC translocation in the nucleus after IFN-alpha treatment
CC (PubMed:15650219). {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-
CC ProRule:PRU00859, ECO:0000269|PubMed:15650219}.
CC -!- FUNCTION: [Serine protease/Helicase NS3]: Displays three enzymatic
CC activities: serine protease, NTPase and RNA helicase. NS3 serine
CC protease, in association with NS2B, performs its autocleavage and
CC cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-
CC NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds
CC RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). NS3
CC supports the separation of RNA daughter and template strands during
CC viral replication. The helicase part is involved in the inhibition of
CC phosphorylation of host STAT1, and thereby inhibition of host type-I
CC IFN signaling (By similarity). In addition, NS3 assists the initiation
CC of replication by unwinding the RNA secondary structure in the 3' non-
CC translated region (NTR). Inhibits STAT2 translocation in the nucleus
CC after IFN-alpha treatment (PubMed:15650219).
CC {ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000255|PROSITE-ProRule:PRU00860,
CC ECO:0000269|PubMed:15650219}.
CC -!- FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of
CC the NS3 helicase activity (By similarity). NS4A allows NS3 helicase to
CC conserve energy during unwinding (By similarity). Induces host ER
CC membrane rearrangements to provide a compartment where viral
CC replication can take part (PubMed:16611922, PubMed:25771497). Inhibits
CC STAT2 translocation in the nucleus after IFN-alpha treatment
CC (PubMed:15650219). {ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:15650219, ECO:0000269|PubMed:16611922,
CC ECO:0000269|PubMed:25771497}.
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 (By
CC similarity). Inhibits interferon (IFN)-induced host STAT1
CC phosphorylation and nuclear translocation, thereby preventing the
CC establishment of cellular antiviral state by blocking the IFN-
CC alpha/beta pathway (PubMed:15650219). Inhibits STAT2 translocation in
CC the nucleus after IFN-alpha treatment (PubMed:15650219).
CC {ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000269|PubMed:15650219}.
CC -!- FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+)
CC and (-) genome, and performs the capping of genomes in the cytoplasm
CC (By similarity). NS5 methylates viral RNA cap at guanine N-7 and ribose
CC 2'-O positions (By similarity). Besides its role in genome replication,
CC also prevents the establishment of cellular antiviral state by blocking
CC the interferon-alpha/beta (IFN-alpha/beta) signaling pathway
CC (PubMed:20106931, PubMed:15650160). Inhibits host JAK1 and TYK2
CC phosphorylation, thereby preventing activation of JAK-STAT signaling
CC pathway (PubMed:15650160). May transcriptionally regulate host genes
CC involved in antiviral response when localized in the nucleus
CC (PubMed:33866234). {ECO:0000250|UniProtKB:Q9Q6P4,
CC ECO:0000269|PubMed:15650160, ECO:0000269|PubMed:20106931,
CC ECO:0000269|PubMed:33866234}.
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 Evidence={ECO:0000269|PubMed:17658551};
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; further assembles as a
CC homotetramer (PubMed:15242592). Interacts (via N-terminus) with host
CC EXOC1 (via C-terminus); this interaction results in EXOC1 degradation
CC through the proteasome degradation pathway (By similarity).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:15242592}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi. {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 (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted (By similarity). Interacts with envelope protein E (By
CC similarity). NS1 interacts with NS4B (By similarity). Interacts with
CC host complement protein CFH; this interaction leads to the degradation
CC of C3 (By similarity). {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBUNIT: [Non-structural protein 2A]: Interacts (via N-terminus) with
CC serine protease NS3. {ECO:0000250|UniProtKB:P03314}.
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/Helicase NS3]: Forms a heterodimer with NS2B
CC (By similarity). Interacts with non-structural protein 2A (via N-
CC terminus) (By similarity). Interacts with NS4B (By similarity).
CC Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this
CC interaction stimulates RNA-directed RNA polymerase NS5
CC guanylyltransferase activity (By similarity).
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with Serine
CC protease/Helicase NS3 (By similarity). Interacts with NS1 (By
CC similarity). {ECO:0000250|UniProtKB:P17763,
CC ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Homodimer. Interacts with
CC host STAT2; this interaction inhibits the phosphorylation of the
CC latter, and, when all viral proteins are present (polyprotein), targets
CC STAT2 for degradation. Interacts with serine protease NS3.
CC {ECO:0000250|UniProtKB:P17763}.
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:P06935}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:P06935}.
CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000269|PubMed:17376919}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P03314}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P03314}; Multi-pass membrane protein
CC {ECO:0000255}. Note=ER membrane retention is mediated by the
CC transmembrane domains. {ECO:0000250|UniProtKB:P03314}.
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:9636360}; 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/Helicase NS3]: Host endoplasmic
CC reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral
CC membrane protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic
CC side {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-
CC covalently associated to serine protease subunit NS2B.
CC {ECO:0000255|PROSITE-ProRule:PRU00860}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:9636360}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated
CC vesicles hosting the replication complex.
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; Peripheral membrane protein;
CC Cytoplasmic side. Host nucleus {ECO:0000269|PubMed:29582535}. Host
CC cytoplasm {ECO:0000269|PubMed:29582535}. Note=Located in RE-associated
CC vesicles hosting the replication complex. NS5 protein is mainly
CC localized in the nucleus rather than in ER vesicles (By similarity).
CC Shuttles between the cytoplasm and nucleus (PubMed:29582535).
CC {ECO:0000250|UniProtKB:P17763, ECO:0000269|PubMed:29582535}.
CC -!- DOMAIN: [Small envelope protein M]: The transmembrane domains contain
CC an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [Envelope protein E]: The transmembrane domains contain an
CC endoplasmic reticulum retention signal. {ECO:0000250|UniProtKB:P17763}.
CC -!- DOMAIN: [RNA-directed RNA polymerase NS5]: Contains a PDZ-binding motif
CC that binds to several PDZ-containing cellular proteins. These
CC interactions seem necessary for an optimal viral replication.
CC {ECO:0000250|UniProtKB:P06935}.
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 -!- 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:0000269|PubMed:17376919}.
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]: 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}.
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DR EMBL; D00246; BAA00176.1; -; Genomic_RNA.
DR EMBL; AY274504; AAP78941.1; -; Genomic_RNA.
DR EMBL; AY274505; AAP78942.1; -; Genomic_RNA.
DR PIR; A28697; GNWVKV.
DR PDB; 1SFK; X-ray; 3.20 A; A/B/C/D/E/F/G/H=23-98.
DR PDB; 2HCN; X-ray; 2.35 A; A=2846-3433.
DR PDB; 2HCS; X-ray; 2.50 A; A=2846-3433.
DR PDB; 2HFZ; X-ray; 3.00 A; A=2802-3433.
DR PDB; 2OF6; EM; 24.00 A; A/B/C=291-690.
DR PDB; 2QEQ; X-ray; 3.10 A; A/B=1691-2124.
DR PDBsum; 1SFK; -.
DR PDBsum; 2HCN; -.
DR PDBsum; 2HCS; -.
DR PDBsum; 2HFZ; -.
DR PDBsum; 2OF6; -.
DR PDBsum; 2QEQ; -.
DR SMR; P14335; -.
DR IntAct; P14335; 37.
DR MEROPS; S07.003; -.
DR TCDB; 1.G.3.1.7; the viral pore-forming membrane fusion protein-3 (vmfp3) family.
DR iPTMnet; P14335; -.
DR PeptideAtlas; P14335; -.
DR PRIDE; P14335; -.
DR BRENDA; 3.4.21.91; 2834.
DR BRENDA; 3.6.4.13; 2834.
DR EvolutionaryTrace; P14335; -.
DR Proteomes; UP000008379; Genome.
DR Proteomes; UP000099558; Genome.
DR Proteomes; UP000138183; 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: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: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004483; F:mRNA (nucleoside-2'-O-)-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039520; P:induction by virus of host autophagy; IEA:UniProtKB-KW.
DR GO; GO: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:0039576; P:suppression by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IDA:UniProtKB.
DR GO; GO:0039564; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity; IDA:UniProtKB.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IDA:UniProtKB.
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; 2.60.260.50; -; 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; 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; Host nucleus;
KW 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 JAK1 by virus; Inhibition of host STAT1 by virus;
KW Inhibition of host STAT2 by virus; Inhibition of host TYK2 by virus;
KW Membrane; Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW Phosphoprotein; Protease; RNA-binding; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Secreted; Serine protease;
KW Suppressor of RNA silencing; Transcription; Transcription regulation;
KW Transferase; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral envelope protein; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Viral RNA replication; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT CHAIN 1..3433
FT /note="Genome polyprotein"
FT /id="PRO_0000405136"
FT CHAIN 1..105
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037703"
FT PROPEP 106..123
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000405137"
FT CHAIN 124..290
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000405138"
FT CHAIN 124..215
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037704"
FT CHAIN 216..290
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037705"
FT CHAIN 291..791
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037706"
FT CHAIN 792..1143
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037707"
FT CHAIN 1144..1374
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037708"
FT CHAIN 1375..1505
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037709"
FT CHAIN 1506..2124
FT /note="Serine protease/Helicase NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037710"
FT CHAIN 2125..2250
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037711"
FT PEPTIDE 2251..2273
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000405139"
FT CHAIN 2274..2528
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037712"
FT CHAIN 2529..3433
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037713"
FT TOPO_DOM 2..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..273
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..290
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 291..743
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 744..764
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 765..770
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 771..791
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 792..1216
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1217..1237
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1238..1247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1248..1268
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1269..1288
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1289..1309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1310..1316
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1317..1335
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1336..1345
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1346..1366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1367..1375
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1376..1396
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1397..1399
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1400..1420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1421..1477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1478..1498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1499..2174
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2175..2195
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2196..2200
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2201..2221
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2222
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2223..2243
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2244..2258
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2259..2273
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000305"
FT TOPO_DOM 2274..2312
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2313..2333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2334..2380
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2381..2401
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2402..2444
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2445..2465
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2466..2470
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2471..2491
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2492..3433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1506..1683
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1686..1842
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1853..2018
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2529..2794
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3058..3210
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 2..15
FT /note="Interaction with host EXOC1"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT REGION 37..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 388..401
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1428..1467
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1690..1693
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT REGION 2169..2173
FT /note="Regulates the ATPase activity of NS3 helicase"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT MOTIF 1790..1793
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOTIF 2917..2919
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:29582535"
FT MOTIF 3431..3433
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT ACT_SITE 1556
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1580
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1640
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2589
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2674
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2710
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2746
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1699..1706
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2584
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2614
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2615
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2632
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2633
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2659
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2660
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2675
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2748
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2968
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 2972
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 2977
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 2980
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 3245
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 3261
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17287213"
FT BINDING 3380
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17287213"
FT SITE 105..106
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 123..124
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 215..216
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 290..291
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 791..792
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1143..1144
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1374..1375
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935, ECO:0000255"
FT SITE 1505..1506
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1963
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000269|PubMed:17658551"
FT SITE 1966
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000269|PubMed:17658551"
FT SITE 2124..2125
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2250..2251
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2273..2274
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2528..2529
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000255"
FT SITE 2541
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2544
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2545
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2547
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2552
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2556
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2589
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2674
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2678
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2710
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2741
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2743
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2746
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2584
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000269|PubMed:17376919"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 921
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 966
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 998
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 293..320
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 350..411
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 350..406
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 364..395
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 382..411
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 382..406
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 480..578
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 595..626
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 795..806
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 846..934
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 970..1014
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1071..1120
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1082..1103
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1104..1107
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT VARIANT 150
FT /note="P -> T (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT VARIANT 820
FT /note="I -> M (in strain: Infectious clone pAKUNa and
FT Infectious clone FLSDX)"
FT VARIANT 943
FT /note="N -> S (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT VARIANT 1041
FT /note="P -> L (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT VARIANT 1202
FT /note="I -> N (in strain: Infectious clone pAKUN; blocks
FT induction of virus-specific membrane structures)"
FT /evidence="ECO:0000269|PubMed:18337583"
FT VARIANT 1318
FT /note="R -> K (in strain: Infectious clone pAKUN)"
FT VARIANT 1967
FT /note="T -> I (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT VARIANT 1974
FT /note="A -> V (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT VARIANT 2023
FT /note="Y -> H (in strain: Infectious clone pAKUN)"
FT VARIANT 2062
FT /note="S -> P (in strain: Infectious clone pAKUN)"
FT VARIANT 2339
FT /note="T -> N (in strain: Infectious clone pAKUN and
FT Infectious clone FLSDX)"
FT MUTAGEN 1173
FT /note="A->P: No effect on viral RNA replication and
FT packaging; drastic increase in IFN-alpha and IFN-beta host
FT cell response."
FT /evidence="ECO:0000269|PubMed:15507609,
FT ECO:0000269|PubMed:16474146"
FT MUTAGEN 1244
FT /note="N->D: 28% decrease in viral RNA replication;
FT decreased packaging efficiency."
FT /evidence="ECO:0000269|PubMed:15507609"
FT MUTAGEN 1292
FT /note="T->P: Restores induction of virus-specific membrane
FT structures; when associated with N-1202."
FT /evidence="ECO:0000269|PubMed:18337583"
FT MUTAGEN 2137
FT /note="P->A: Complete loss of viral replication."
FT /evidence="ECO:0000269|PubMed:25771497"
FT MUTAGEN 2172
FT /note="P->A: Reduced membrane proliferation and efficiency
FT of replication; no effect on replication complex
FT formation."
FT /evidence="ECO:0000269|PubMed:25771497"
FT MUTAGEN 2173
FT /note="D->A: Slightly reduced membrane proliferation and
FT efficiency of replication at early time of infection; no
FT effect on replication complex formation."
FT /evidence="ECO:0000269|PubMed:25771497"
FT MUTAGEN 2190
FT /note="G->A: Reduced membrane proliferation and efficiency
FT of replication; no effect on replication complex
FT formation."
FT /evidence="ECO:0000269|PubMed:25771497"
FT MUTAGEN 2244
FT /note="P->A: Complete loss of viral replication."
FT /evidence="ECO:0000269|PubMed:21880777"
FT MUTAGEN 2245
FT /note="E->A: Complete loss of viral replication."
FT /evidence="ECO:0000269|PubMed:21880777"
FT MUTAGEN 2246
FT /note="P->A: 20% decrease in viral replication."
FT /evidence="ECO:0000269|PubMed:21880777"
FT MUTAGEN 2247
FT /note="E->A: Complete loss of viral replication."
FT /evidence="ECO:0000269|PubMed:21880777"
FT MUTAGEN 2798
FT /note="P->S: 88% decrease in viral RNA replication;
FT decreased packaging efficiency."
FT /evidence="ECO:0000269|PubMed:15507609"
FT MUTAGEN 2901..2902
FT /note="KY->AA: No effect on the subcellular localization of
FT RNA-directed RNA polymerase NS5."
FT /evidence="ECO:0000269|PubMed:29582535"
FT MUTAGEN 2917..2919
FT /note="REK->AAA: Complete loss of nuclear localization of
FT RNA-directed RNA polymerase NS5."
FT /evidence="ECO:0000269|PubMed:29582535"
FT MUTAGEN 3181
FT /note="S->F: Increases STAT1 inhibitory function of NS5."
FT /evidence="ECO:0000269|PubMed:20106931"
FT HELIX 26..38
FT /evidence="ECO:0007829|PDB:1SFK"
FT HELIX 44..56
FT /evidence="ECO:0007829|PDB:1SFK"
FT HELIX 63..69
FT /evidence="ECO:0007829|PDB:1SFK"
FT HELIX 74..95
FT /evidence="ECO:0007829|PDB:1SFK"
FT STRAND 1694..1697
FT /evidence="ECO:0007829|PDB:2QEQ"
FT TURN 1703..1708
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1709..1719
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1724..1730
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1731..1740
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1763..1767
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1768..1776
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1777..1779
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1785..1791
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1797..1811
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1816..1820
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1839..1842
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1851..1853
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1855..1859
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1864..1867
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1871..1883
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1888..1891
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1909..1914
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1926..1930
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1937..1944
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1946..1949
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1957..1964
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 1977..1980
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 1992..2002
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2007..2009
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2016..2021
FT /evidence="ECO:0007829|PDB:2QEQ"
FT TURN 2026..2029
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2034..2044
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2050..2058
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2066..2069
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2074..2076
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 2079..2084
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 2086..2088
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 2094..2096
FT /evidence="ECO:0007829|PDB:2QEQ"
FT STRAND 2100..2103
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2104..2106
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2110..2121
FT /evidence="ECO:0007829|PDB:2QEQ"
FT HELIX 2808..2815
FT /evidence="ECO:0007829|PDB:2HFZ"
FT TURN 2819..2821
FT /evidence="ECO:0007829|PDB:2HFZ"
FT STRAND 2831..2840
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 2853..2857
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 2860..2862
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 2870..2872
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 2878..2885
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 2898..2915
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 2916..2918
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 2926..2934
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 2951..2957
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 2959..2974
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3004..3019
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3021..3024
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 3025..3028
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3030..3033
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3034..3036
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3042..3052
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3055..3058
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3065..3067
FT /evidence="ECO:0007829|PDB:2HCS"
FT HELIX 3068..3070
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3074..3080
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3081..3086
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3089..3099
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 3100..3103
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3104..3113
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 3115..3117
FT /evidence="ECO:0007829|PDB:2HFZ"
FT STRAND 3119..3128
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 3134..3156
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3164..3167
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3172..3188
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3191..3194
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3197..3200
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3205..3209
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3212..3216
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 3236..3238
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3244..3250
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3256..3261
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3264..3271
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3275..3278
FT /evidence="ECO:0007829|PDB:2HFZ"
FT HELIX 3282..3298
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3303..3315
FT /evidence="ECO:0007829|PDB:2HCN"
FT STRAND 3338..3340
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3342..3350
FT /evidence="ECO:0007829|PDB:2HCN"
FT TURN 3351..3353
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3366..3368
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3374..3379
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3387..3394
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3396..3407
FT /evidence="ECO:0007829|PDB:2HCN"
FT HELIX 3416..3418
FT /evidence="ECO:0007829|PDB:2HCN"
SQ SEQUENCE 3433 AA; 381369 MW; EE4B888A7D040B99 CRC64;
MSKKPGGPGK SRAVNMLKRG MPRVLSLTGL KRAMLSLIDG RGPTRFVLAL LAFFRFTAIA
PTRAVLDRWR SVNKQTAMKH LLSFKKELGT LTSAINRRSS KQKKRGGKTG IAFMIGLIAG
VGAVTLSNFQ GKVMMTVNAT DVTDIITIPP AAGKNLCIVR AMDVGHMCDD TITYECPVLS
AGNDPEDIDC WCTKLAVYVR YGRCTKTRHS RRSRRSLTVQ THGESTLSNK KGAWMDSTKA
TRYLVKTESW ILRNPGYALV AAVIGWMLGS NTMQRVVFAV LLLLVAPAYS FNCLGMSNRD
FLEGVSGATW VDLVLEGDSC VTIMSKDKPT IDVKMMNMEA ANLAEVRSYC YLATVSELST
KAACPTMGEA HNDKRADPSF VCKQGVVDRG WGNGCGLFGK GSIDTCAKFA CSTKATGRTI
LKENIKYEVA IFVHGPTTVE SHGNYFTQTG AAQAGRFSIT PAAPSYTLKL GEYGEVTVDC
EPRSGIDTSA YYVMTVGTKT FLVHREWFMD LNLPWSSAES NVWRNRETLM EFEEPHATKQ
SVIALGSQEG ALHQALAGAI PVEFSSNTVK LTSGHLKCRV KMEKLQLKGT TYGVCSKAFR
FLGTPADTGH GTVVLELQYT GTDGPCKIPI SSVASLNDLT PVGRLVTVNP FVSVSTANAK
VLIELEPPFG DSYIVVGRGE QQINHHWHKS GSSIGKAFTA TLKGAQRLAA LGDTAWDFGS
VGGVFTSVGK AVHQVFGGAF RSLFGGMSWI TQGLLGALLL WMGINARDRS IALTFLAVGG
VLLFLSVNVH ADTGCAIDIS RQELRCGSGV FIHNDVEAWI DRYKYYPETP QGLAKIIQKA
HKEGVCGLRS VSRLEHQMWE AVKDELNTLL KENGVDLSIV VEKQEGMYKS APRRLTATTE
KLEIGWKAWG KSILFAPELA NNTFVIDGPE TKECPTQNRA WNNLEVEDFG FGLTSTRMFL
RVRESNTTEC DSKIIGTAVK NNLAIHSDLS YWIESRFNDT WKLERAVLGE VKSCTWPETH
TLWGDGVLES DLIIPITLAG PRSNHNRRPG YKTQSQGPWD EGRVEIDFDY CPGTTVTLSE
SCGHRGPATR TTTESGKLIT DWCCRSCTLP PLRYQTDNGC WYGMEIRPQR HDEKTLVQSQ
VNAYNADMID PFQLGLLVVF LATQEVLRKR WTAKISMPAI LIALLVLVFG GITYTDVLRY
VILVGAAFAE SNSGGDVVHL ALMATFKIQP VFMVASFLKA RWTNQENILL MLAAAFFQMA
YYDARQILLW EMPDVLNSLA VAWMILRAIT FTTTSNVVVP LLALLTPGLR CLNLDVYRIL
LLMVGIGSLI REKRSAAAKK KGASLLCLAL ASTGFFNPMI LAAGLVACDP NRKRGWPATE
VMTAVGLMFA IVGGLAELDI DSMAIPMTIA GLMFAAFVIS GKSTDMWIER TADISWEGDA
EITGSSERVD VRLDDDGNFQ LMNDPGAPWK IWMLRMACLA ISAYTPWAIL PSVVGFWITL
QYTKRGGVLW DTPSPKEYKR GDTTTGVYRI MTRGLLGSYQ AGAGVMVEGV FHTLWHTTKG
AALMSGEGRL DPYWGSVKED RLCYGGPWKL QHKWNGQDEV QMIVVEPGKN VKNVQTKPGV
FKTPEGEIGA VTLDFPTGTS GSPIVDKNGD VIGLYGNGVI MPNGSYISAI VQGERMDEPV
PAGFEPEMLR KKQITVLDLH PGAGKTRRIL PQIIKEAINR RLRTAVLAPT RVVAAEMAEA
LRGLPIRYQT SAVAREHNGN EIVDVMCHAT LTHRLMSPHR VPNYNLFVMD EAHFTDPASI
AARGYISTRV ELGEAAAIFM TATPPGTSDP FPESNAPISD LQTEIPDRAW NSGYEWITEY
IGKTVWFVPS VKMGNEIALC LQRAGKKVIQ LNRKSYETEY PKCKNDDWDF VVTTDISEMG
ANFKASRVID SRKSVKPTII TEGEGRVILG EPSAVTAASA AQRRGRTGRN PSQAGDEYCY
GGHTNEDDSN CAHWTEARIM LDNINMPNGL IAQFYQPERE KVYTMDGEYR LRGEERKNFL
ELLRTADLPV WLAYKVAAAG VSYHDRRWCF DGPRTNTILE DNNEVEVITK LGERKILRPR
WIDARVYSDH QALKSFKDFA SGKRSQIGFI EVLGKMPEHF MGKTWEALDT MYVVATAEKG
GRAHRMALEE LPDALQTIAL IALLSVMTMG VFFLLMQRKG IGKIGLGGVV LGAATFFCWM
AEVPGTKIAG MLLLSLLLMI VLIPEPEKQR SQTDNQLAVF LICVLTLVGA VAANEMGWLD
KTKSDISGLF GQRIETKENF SIGEFLLDLR PATAWSLYAV TTAVLTPLLK HLITSDYITT
SLTSINVQAS ALFTLARGFP FVDVGVSALL LAAGCWGQVT LTVTVTSATL LFCHYAYMVP
GWQAEAMRSA QRRTAAGIMK NAVVDGIVAT DVPELERTTP IMQKKVGQVM LILVSLAALV
VNPSVKTVRE AGILITAAAV TLWENGASSV WNATTAIGLC HIMRGGWLSC LSITWTLVKN
MEKPGLKRGG AKGRTLGEVW KERLNQMTKE EFIRYRKEAI TEVDRSAAKH ARKERNITGG
HPVSRGTAKL RWLVERRFLE PVGKVIDLGC GRGGWCYYMA TQKRVQEVRG YTKGGPGHEE
PQLVQSYGWN IVTMKSGVDV FYRPSECCDT LLCDIGESSS SAEVEEHRTL RVLEMVEDWL
HRGPKEFCVK VLCPYMPKVI EKMELLQRRY GGGLVRNPLS RNSTHEMYWV SRASGNVVHS
VNMTSQVLLG RMEKKTWKGP QYEEDVNLGS GTRAVGKPLL NSDTSKIKNR IERLRREYSS
TWHHDENHPY RTWNYHGSYE VKPTGSASSL VNGVVRLLSK PWDTITNVTT MAMTDTTPFG
QQRVFKEKVD TKAPEPPEGV KYVLNETTNW LWAFLAREKR PRMCSREEFI RKVNSNAALG
AMFEEQNQWR SAREAVEDPK FWEMVDEERE AHLRGECHTC IYNMMGKREK KPGEFGKAKG
SRAIWFMWLG ARFLEFEALG FLNEDHWLGR KNSGGGVEGL GLQKLGYILR EVGTRPGGRI
YADDTAGWDT RITRADLENE AKVLELLDGE HRRLARAIIE LTYRHKVVKV MRPAADGRTV
MDVISREDQR GSGQVVTYAL NTFTNLAVQL VRMMEGEGVI GPDDVEKLTK GKGPKVRTWL
SENGEERLSR MAVSGDDCVV KPLDDRFATS LHFLNAMSKV RKDIQEWKPS TGWYDWQQVP
FCSNHFTELI MKDGRTLVTP CRGQDELVGR ARISPGAGWN VRDTACLAKS YAQMWLLLYF
HRRDLRLMAN AICSAVPVNW VPTGRTTWSI HAGGEWMTTE DMLEVWNRVW IEENEWMEDK
TPVEKWSDVP YSGKREDIWC GSLIGTRARA TWAENIQVAI NQVRSIIGDE KYVDYMSSLK
RYEDTTLVED TVL
