POLG_POWVL
ID POLG_POWVL Reviewed; 3415 AA.
AC Q04538;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 166.
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 NS3;
DE EC=3.4.21.91;
DE EC=3.6.1.15;
DE EC=3.6.4.13;
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 Tick-borne powassan virus (strain LB) (POWV) (Powassan virus).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=39008;
OH NCBI_TaxID=34620; Dermacentor andersoni (Rocky mountain wood tick).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=35565; Ixodes cookei.
OH NCBI_TaxID=6945; Ixodes scapularis (Black-legged tick) (Deer tick).
OH NCBI_TaxID=34614; Ixodes spinipalpis.
OH NCBI_TaxID=48086; Lepus americanus (Snowshoe hare).
OH NCBI_TaxID=9995; Marmota monax (Woodchuck).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=8097605; DOI=10.1006/viro.1993.1247;
RA Mandl C.W., Holzmann H., Kunz C., Heinz F.X.;
RT "Complete genomic sequence of Powassan virus: evaluation of genetic
RT elements in tick-borne versus mosquito-borne flaviviruses.";
RL Virology 194:173-184(1993).
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. {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 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. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is
CC required for the interferon antagonism activity of the latter.
CC {ECO: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. Inhibits STAT2
CC translocation in the nucleus after IFN-alpha treatment.
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. {ECO:0000250|UniProtKB:P17763}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of
CC the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.;
CC EC=3.4.21.91;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA +
CC S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-
CC COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461,
CC ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00924};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside
CC in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167,
CC Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609;
CC EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924};
CC -!- SUBUNIT: [Capsid protein C]: Homodimer (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. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 1]: Forms homodimers as well as
CC homohexamers. NS1 may interact with NS4A.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease subunit NS2B]: Forms a heterodimer with
CC serine protease NS3. May form homooligomers.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Serine protease NS3]: Forms a heterodimer with NS2B.
CC Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA
CC polymerase NS5; this interaction stimulates RNA-directed RNA polymerase
CC NS5 guanylyltransferase activity. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase NS5]: Interacts with host STAT2;
CC this interaction inhibits the phosphorylation of the latter, and, when
CC all viral proteins are present (polyprotein), targets STAT2 for
CC degradation. {ECO:0000250|UniProtKB:Q01299}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
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: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:0000305}; 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:0000250|UniProtKB:P14335}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic
CC reticulum membrane; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum
CC membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane
CC protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side
CC {ECO:0000255|PROSITE-ProRule:PRU00860}. 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:0000250|UniProtKB:P14335}; 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:0000250|UniProtKB:P06935}.
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. {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 -!- 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]: Phosphorylated on serines
CC residues. This phosphorylation may trigger NS5 nuclear localization.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. mRNA cap 0-1 NS5-type
CC methyltransferase family. {ECO:0000255|PROSITE-ProRule:PRU00924}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L06436; AAA02739.1; -; Genomic_RNA.
DR PIR; A46105; A46105.
DR RefSeq; NP_620099.1; NC_003687.1.
DR SMR; Q04538; -.
DR PRIDE; Q04538; -.
DR GeneID; 940442; -.
DR KEGG; vg:940442; -.
DR Proteomes; UP000006848; 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:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 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: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; 1.10.8.970; -; 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; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR001122; Flavi_capsidC.
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; PF00948; Flavi_NS1; 1.
DR Pfam; PF01005; Flavi_NS2A; 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; 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 3: Inferred from homology;
KW Activation of host autophagy by virus; ATP-binding; Capsid protein;
KW 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 STAT1 by virus; Inhibition of host STAT2 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..3415
FT /note="Genome polyprotein"
FT /id="PRO_0000037724"
FT CHAIN 1..94
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000405239"
FT PROPEP 95..115
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000405140"
FT CHAIN 116..278
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000405141"
FT CHAIN 116..203
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037725"
FT CHAIN 204..278
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037726"
FT CHAIN 279..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037727"
FT CHAIN 776..1128
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037728"
FT CHAIN 1129..1358
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000037729"
FT CHAIN 1359..1489
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037730"
FT CHAIN 1490..2111
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037731"
FT CHAIN 2112..2237
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037732"
FT PEPTIDE 2238..2260
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000405142"
FT CHAIN 2261..2512
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037733"
FT CHAIN 2513..3415
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT /id="PRO_0000037734"
FT TOPO_DOM 1..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 118..243
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..278
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 279..726
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 727..747
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 748..754
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 755..775
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 776..1187
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1188..1208
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TOPO_DOM 1209..1233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TRANSMEM 1234..1253
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TOPO_DOM 1254
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TRANSMEM 1255..1275
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TOPO_DOM 1276..1292
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TRANSMEM 1293..1313
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TOPO_DOM 1314..1327
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TRANSMEM 1328..1348
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TOPO_DOM 1349..1359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P17763, ECO:0000255"
FT TRANSMEM 1360..1378
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1379..1382
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1383..1403
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1404..1452
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1453..1473
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1474..2163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2164..2184
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2185..2190
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2191..2210
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2211
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2212..2232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2233..2243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2244..2264
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2265..2300
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2301..2321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2322..2344
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2345..2365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2366..2369
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2370..2390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2391..2433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2434..2454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2455..2479
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2480..2500
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2501..3415
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1490..1669
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1675..1832
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1842..2001
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2513..2777
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3041..3190
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..389
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1410..1449
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 2731..2735
FT /note="Interaction with host SCRIB"
FT /evidence="ECO:0000250|UniProtKB:Q01299"
FT MOTIF 1780..1783
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT ACT_SITE 1543
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1567
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1627
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2573
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2658
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2695
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2731
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1688..1695
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2568
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2598
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2599
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2616
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2617
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2643
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2644
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 2733
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2951
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2955
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2960
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2963
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 94..95
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 115..116
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 203..204
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 278..279
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 1128..1129
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1358..1359
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1489..1490
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 1950
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1953
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2111..2112
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2237..2238
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2260..2261
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2512..2513
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT SITE 2525
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2528
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2529
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2531
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2536
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2540
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2573
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2658
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2662
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2695
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2726
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2728
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2731
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2568
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P14336,
FT ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 860
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 983
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 999
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 281..308
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 338..399
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 338..394
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 352..383
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 370..399
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 370..394
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 464..568
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 585..617
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT DISULFID 779..790
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 830..920
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 955..1000
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1057..1106
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1068..1090
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1089..1093
FT /evidence="ECO:0000250|UniProtKB:P17763"
SQ SEQUENCE 3415 AA; 378570 MW; E71092FE64049F46 CRC64;
MMTTSKGKGG GPPRRKLKVT ANKSRPATSP MPKGFVLSRM LGILWHAVTG TARPPVLKMF
WKTVPLRQAE AVLKKIKRVI GNLMQSLHMR GRRRSGVDWT WIFLTMALMT MAMATTIHRD
REGYMVMRAS GRDAASQVRV QNGTCVILAT DMGEWCEDSI TYSCVTIDQE EEPVDVDCFC
RGVDRVKLEY GRCGRQAGSR GKRSVVIPTH AQKDMVGRGH AWLKGDNIRD HVTRVEGWMW
KNKLLTAAIV ALAWLMVDSW MARVTVILLA LSLGPVYATR CTHLENRDFV TGTQGTTRVS
LVLELGGCVT ITAEGKPSID VWLEDIFQES PAETREYCLH AKLTNTKVEA RCPTTGPATL
PEEHQANMVC KRDQSDRGWG NHCGFFGKGS IVACAKFECE EAKKAVGHVY DSTKITYVVK
VEPHTGDYLA ANETNSNRKS AQFTVASEKV ILRLGDYGDV SLTCKVASGI DVAQTVVMSL
DSSKDHLPSA WQVHRDWFED LALPWKHKDN QDWNSVEKLV EFGPPHAVKM DVFNLGDQTA
VLLKSLAGVP LASVEGQKYH LKSGHVTCDV GLEKLKLKGT TYSMCDKAKF KWKRVPVDSG
HDTVVMEVSY TGSDKPCRIP VRAVAHGVPA VNVAMLITPN PTIETNGGGF IEMQLPPGDN
IIYVGDLSQQ WFQKGSTIGR MFEKTRRGLE RLSVVGEHAW DFGSVGGVLS SVGKAIHTVL
GGAFNTLFGG VGFIPKMLLG VALVWLGLNA RNPTMSMTFL AVGALTLMMT MGVGADYGCA
IDPERMEIRC GEGLVVWKEV SEWYDGYAYH PESPDTLAQA LREAFERGVC GVVPQNRLEM
AMWRSTAPEL NLVLSEGEAN LTIVVDKTDP ADYRGGTPMV LKKTGKESKV SWKSWGKSIL
WSVPDSPRRM MMGVDGVGEC PLYRRATGVF TVAEFGVGLR TKVFLDLRGE ASKECDTGVM
GAAVKNGKAI HTDQSMWMSS FRNDTGTYIH ELILTDLRNC TWPASHTIDN DGVLDSHLFL
PVTLAGPRSK YNRIPGYSEQ VRGPWDQTPL RVVRDHCPGT SVRIDSHCDK RGASVRSTTE
SGKIIPEWCC RACELPPVTF RSGTDCWYAM EIRPVHSQGG LVRSMVVADN GALLSEGGVP
GLVAVFVLME FLLRRRPGSV TSILWGGILM LGLLVTGLVR VEEIVRYVIA VGVTFHLELG
PETMVLVMLQ AVFNMRTCYL MGFLVKRVIT TREVVTVYFL LLVLEMGIPE MNFGHLWEWA
DALAMGLLII KASAMEDRRG LGFLLAGLMT QRHLVAVHHG LMVFLTVALA VVGRNIYNGQ
KERKGLCFTV PLASLLGGSG SGLRMLALWE CLGGRGRRSL SEPLTVVGVM LAMASGLLRH
SSQEALLALS AGSFLILMLI LGTRRLQLTA EWAGVVEWNP ELVNEGGEVS LKVRQDAMGN
LHLTEVEREE RRLALWLVFG LLASAYHWSG ILVTMGAWTV YELFSSTRRT DLVFSGQLPD
QGEKRSFDIK EGVYRIYAPG LFWGYRQIGV GYGTKGVLHT MWHVTRGAAL SVEGATSGPY
WADVREDVVC YGGAWGLDKK WGGEVVQVHA FPPDSGHKIH QCQPGKLNLE GGRVLGAIPI
DLPRGTSGSP IINAQGDVLG LYGNGLKSND VYISSIAQGN VEKSRPEMPL AVQGGKWTSK
GSITVLDMHP GSGKTHRVLP ELIRECIDKR LRTVVLAPTR VVLKEMERAL QGKRVKFHSA
AVDNASSSSG AIVDVMCHAT YVNRRLLPQG RQNWEVAIMD EAHWTDPHSI AARGHLYSLA
KENRCALVLM TATPPGKSEA FPESKGAIVS EEKPIPEGEW RDGFDWITEF EGRTAWFVPS
IAKGGAIART LRQKGKSVIC LNSKTFDKDY GRVHEEKPDF VVTTDISEMG ANLDVNRVID
GRTNIKPEEI DGKVELIGTR RVTTASAAQR RGRVGRHEGR TDLYVYSGQC DDDDSSLVQW
KEAQILLDNI TTVRGPVATF YGPEQGKMLE VAGHFRLTEE KRKHFRHLLT NCDFTPWLAW
HVAANTACVT DRKWTWEGPD ENAIDGPGGE LVTFRSPNGA ERKLKPIWKD SRMFREGRDV
ADFIQYASGR RSAVDILTGL GGVPDLLRLR CTAAWDVVYT LLNETPGSRA MKMAERDAPE
AMLTLLEVAV LGIATLGVVW CFIVRTSVSR MVLGTLVLAV ALILLWLGGM DYGTMAGVAL
IFYLLLTVLQ PEPGKQRSGE DNRLAFLLIG LGSVVGLVAA NELGYLEQTK TDISGLFRRE
DQGGMVWDAW TNIDIQPARS WGTYVLIVSL FTPYMLHQLQ TKIQRLVNSS VAAGTQAMRD
LGGGTPFFGV AGHVVALGVT SLVGATPTSL ALGVALAALH LAVVTSGLEA ELTQRAHRAF
FSAMVKNPMV DGEIINPIPD GDPKPALYER KMSLFLAIGL CIAAVALNRT AAAMTEAGAV
AVAALGQLLR PEEESWWTMP MACGMAGLVR GSLWGLLPVL HRIWLRTQGA RRGGAEGSTL
GDIWKQRLNS CTKEEFFAYR RTGVMETNRD QARELLRRGE TNMGLAVSRG CAKLAWLEER
GYATLKGEVV DLGCGRGGWS YYAASRPSVM AVRAYTIGGK GHEAPRLVTS LGWNLIKFRS
GMDVFSMATT RADTILCDIG ESSPDPEKEG ARSRRVILLM EQWKARNPDA AAVFKVLAPY
RPEVLEALHR FQLQWGGGLV RVPFSRNSTH EMYYSTAVTG NLVNSVNVLS RKLLARFGET
RGPIQVPEID LGTGTRCVTL AEDKVKPRDV AERIGALREQ YSESWHEDKE HPYRTWQYWG
SYRTPATGSA ASLINGVVKL LSWPWNARED VTRMAMTDTT AFGQQRVFKE KVDTKAQEPQ
PGTRVIMRAV SDWLLEHLSR RAKVRMCTKD EFIAKVRSNA ALGAWSDEQN KWSSAKEAVE
DPEFWKLVDE ERSRHLKGQC RHCVYNMMGK REKKLGEFGV AKGSRAIWYM WLGSRFLEFE
VLGFLNEEHW ASREVSGAGV EGTSLNYLGW LLRELGMKDG GKLYADDTAG WDTRITNADL
EDEEQILRYM EGEHHVLAKT ILEKAYHAKV VKVARPSPQG GCVMDVITRR DQRGSGQVVT
YALNTITNMK VQLIRMMEGE GVIGPADSQD PRLKRVETWL KEHGVERLGR MLVSGDDCVV
KPIDDRFGKA LYFLNDMAKV RKDVGEWEPS MGFTEWEEVP FCSHHFHELV MKDGRSLIVP
CRDQDELVGR ARVSPGCGWS VRETACLSKA YGQMWLLNYF HRRDLRTLGF AICSAVPVSW
VPMGRTTWSI HASGEWMTTE DMLRIWNKVW ILDNPHMEDK QTVDEWRDIP YLPKTQDLVC
SSLVGRKERA EWAKNIWGSV EKVRKLIGPE DYRDYLSSMD RHDLHWELKL ESSII
