POLG_ROCV
ID POLG_ROCV Reviewed; 3425 AA.
AC Q32ZD4;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C;
DE AltName: Full=Core protein;
DE Contains:
DE RecName: Full=Protein prM;
DE Contains:
DE RecName: Full=Peptide pr;
DE Contains:
DE RecName: Full=Small envelope protein M;
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE Contains:
DE RecName: Full=Non-structural protein 2A;
DE Short=NS2A;
DE Contains:
DE RecName: Full=Serine protease subunit NS2B;
DE AltName: Full=Flavivirin protease NS2B regulatory subunit;
DE AltName: Full=Non-structural protein 2B;
DE Contains:
DE RecName: Full=Serine protease NS3;
DE EC=3.4.21.91;
DE EC=3.6.1.15;
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=Peptide 2k;
DE Contains:
DE RecName: Full=Non-structural protein 4B;
DE Short=NS4B;
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase NS5;
DE EC=2.1.1.56 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE EC=2.1.1.57 {ECO:0000255|PROSITE-ProRule:PRU00924};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Non-structural protein 5;
OS Rocio virus (ROCV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=64315;
OH NCBI_TaxID=7174; Culex.
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC RNA].
RC STRAIN=SPH 34675 {ECO:0000312|EMBL:AAV34158.1};
RX PubMed=16223950; DOI=10.1128/cmr.18.4.608-637.2005;
RA Kuno G., Chang G.J.;
RT "Biological transmission of arboviruses: reexamination of and new insights
RT into components, mechanisms, and unique traits as well as their
RT evolutionary trends.";
RL Clin. Microbiol. Rev. 18:608-637(2005).
RN [2]
RP GLYCOSYLATION (ENVELOPE PROTEIN E).
RX PubMed=2441520; DOI=10.1016/0042-6822(87)90460-0;
RA Winkler G., Heinz F.X., Kunz C.;
RT "Studies on the glycosylation of flavivirus E proteins and the role of
RT carbohydrate in antigenic structure.";
RL Virology 159:237-243(1987).
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.
CC {ECO:0000250|UniProtKB:P14335}.
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:Q9Q6P4}.
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:0000250|UniProtKB:Q9Q6P4};
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 (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 NS3]: Forms a heterodimer with NS2B (By
CC similarity). Interacts with non-structural protein 2A (via N-terminus)
CC (By similarity). Interacts with NS4B (By similarity). Interacts with
CC unphosphorylated RNA-directed RNA polymerase NS5; this interaction
CC stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity
CC (By similarity). {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Non-structural protein 4B]: Interacts with serine protease
CC NS3 (By similarity). {ECO:0000250|UniProtKB:P17763}.
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: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:0000269|PubMed:2441520}.
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; AY632542; AAV34158.1; -; Genomic_RNA.
DR SMR; Q32ZD4; -.
DR MEROPS; S07.003; -.
DR Proteomes; UP000133235; 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; 1.10.10.930; -; 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 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 Nucleotide-binding; Nucleotidyltransferase; Phosphoprotein; Protease;
KW RNA-binding; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW Secreted; Serine protease; Suppressor of RNA silencing; Transcription;
KW Transcription regulation; 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..3425
FT /note="Genome polyprotein"
FT /id="PRO_0000441546"
FT CHAIN 1..101
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441547"
FT PROPEP 102..118
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_0000441548"
FT CHAIN 119..285
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441549"
FT CHAIN 119..210
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441550"
FT CHAIN 211..285
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441551"
FT CHAIN 286..786
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441552"
FT CHAIN 787..1139
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441553"
FT CHAIN 1140..1366
FT /note="Non-structural protein 2A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441554"
FT CHAIN 1367..1497
FT /note="Serine protease subunit NS2B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441555"
FT CHAIN 1498..2116
FT /note="Serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441556"
FT CHAIN 2117..2242
FT /note="Non-structural protein 4A"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441557"
FT PEPTIDE 2243..2265
FT /note="Peptide 2k"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441558"
FT CHAIN 2266..2521
FT /note="Non-structural protein 4B"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441559"
FT CHAIN 2522..3425
FT /note="RNA-directed RNA polymerase NS5"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT /id="PRO_0000441560"
FT TOPO_DOM 1..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..244
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 245..265
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 266..270
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..285
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 286..738
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 739..759
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 760..765
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 766..786
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 787..1170
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1171..1191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1192..1213
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1214..1234
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1235..1263
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1264..1284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1285..1301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1302..1322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1323..1333
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1334..1354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1355..1367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1368..1388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1389..1392
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1393..1413
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1414..1469
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 1470..1490
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1491..2166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2167..2187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2188..2192
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2193..2212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2213..2214
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2215..2235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2236..2250
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2251..2265
FT /note="Helical; Note=Signal for NS4B"
FT /evidence="ECO:0000305"
FT TOPO_DOM 2266..2297
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT INTRAMEM 2298..2318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2319..2345
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2346..2366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2367..2373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2374..2394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2395..2441
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 2442..2462
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2463..3425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 1498..1675
FT /note="Peptidase S7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT DOMAIN 1678..1834
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 1845..2010
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT DOMAIN 2522..2786
FT /note="mRNA cap 0-1 NS5-type MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT DOMAIN 3050..3202
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 36..71
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 383..396
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT REGION 1420..1459
FT /note="Interacts with and activates NS3 protease"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00859"
FT REGION 1682..1685
FT /note="Important for RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P14340"
FT REGION 1952..1971
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2161..2165
FT /note="Regulates the ATPase activity of NS3 helicase"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT MOTIF 1782..1785
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT ACT_SITE 1548
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1572
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 1632
FT /note="Charge relay system; for serine protease NS3
FT activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00860"
FT ACT_SITE 2582
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2667
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2702
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT ACT_SITE 2738
FT /note="For 2'-O-MTase activity"
FT /evidence="ECO:0000250|UniProtKB:Q6YMS4"
FT BINDING 1691..1698
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 2577
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2607
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2608
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2625
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2626
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2652
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2653
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2668
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT BINDING 2740
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
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 2964
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2969
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 2972
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3237
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT BINDING 3372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 101..102
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 118..119
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 210..211
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 285..286
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 786..787
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1139..1140
FT /note="Cleavage; by host"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1366..1367
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1497..1498
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 1955
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 1958
FT /note="Involved in NS3 ATPase and RTPase activities"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT SITE 2116..2117
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2242..2243
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2265..2266
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2521..2522
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT SITE 2534
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2537
FT /note="mRNA cap binding; via carbonyl oxygen"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2538
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2540
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 2549
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2582
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2667
FT /note="Essential for 2'-O-methyltransferase and N-7
FT methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2671
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2702
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2733
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2735
FT /note="mRNA cap binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT SITE 2738
FT /note="Essential for 2'-O-methyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00924"
FT MOD_RES 2577
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03314"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:P14335"
FT CARBOHYD 916
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT CARBOHYD 993
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 288..315
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 345..406
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 345..401
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 359..390
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 377..406
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 377..401
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 475..573
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 590..621
FT /evidence="ECO:0000250|UniProtKB:P06935"
FT DISULFID 790..801
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 841..929
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 965..1009
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1067..1116
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1078..1100
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1078..1099
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
FT DISULFID 1099..1103
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 1100..1103
FT /evidence="ECO:0000250|UniProtKB:Q9Q6P4"
SQ SEQUENCE 3425 AA; 380351 MW; BECDB3B4317051FA CRC64;
MSKKPGGPAG RRVVNMLKRP ASVSPIKGIK RLIGNLTDGR GPLRVVLAFI AFFRFAAIMP
TQGLLRRWRV MNKSEALKHL TSFKKEISNM LNIINRRKAK RGNGSVLLWI ALVTGSMALR
LGTYQGKVLM SINKTDVAEI IPIPTTKGDN LCTVRAMDVG YMCQNDITYE CPRLEPGMDP
EDIDCWCDRE AIYVHYGLCT KNHRERRGRR SVNIPSHGES QLENRGTPWL DTAKTTKYLT
KVENWMIRNP GYAIVAVAAA WMLGSNTSQK VIFTIMLLLI APAYSINCLG VTNRDFVEGM
SGGTWVDIVL EGDGCVTIMA KDKPTLDIRL LKMEAKDLAT VRSYCYHATV TSVSSEARCP
TMGEAHNPKA LDSNYLCKST YVDRGWGNGC GLFGKGSLQT CVKFGCTQKA MGMTIQRENL
DYELAIYVHG PTSVAAHGNY TTQLGAKHAA KFSITPSSPS FTANLGEYGE ATVDCEPRAA
LDIDNYYVMS MNNKHWLVNR DWFHDLDLPW TGPATDVWKY RESLVEFEEA HVTRQTVVAL
AAQEGELHIV LAGAIPVTVA GTTLTLTSGH LKCRMKLDKL KIKGSTYLMC KDKFAFAKNP
VDTGHGTIVT EVQYAGSDGP CRIPITMTEN LHDLTPIGRL VTVNPFVPSS ETAQKILIEL
EPPFGTSFIL VGTGPNQVKY QWHKSGSVIG SAFKTTIKGA QRMAVLGETA WDFGSVGGVF
NSIGKGIHGL FGGAFRTLFG GMSWVTQALM GALLLWLGVS SRERTVSITL LATGGILLFL
AMNVHADTGC AIDITRRELK CGSGIFIHND VETWRDNYKY HPSTPKNFAK IIHKAYKEGI
CGVRSASRLE HEMWKHIAPE LNAILEDNEV DLSVVVEEHK GIYKKAPLRL ENTSDEMHFG
WKNWGKSFLF KTQMANSTFV VDGPETKECP TERRAWNSLE IEDFGVGIMS TKVFLKVNGD
KTEVCDSMVM GTAIKGNRAV HSDLGYWIES GKNTSWRLER AVLGEVRSCT WPESHTLWNE
GVEDSDLIIP PTLGGPRTHH NKREGYKTQL KGPWNEEGPI IIEFGECPGT KVTQEESCRN
RAASARTTTA SGKVIRDWCC KNCTMPPLRF TTKNGCWYGM EIRPKHESEE TLIKSKVTAG
TGNDICRFQL GLLMAFVFTQ EVLRKRWTAR LALPTAALLL ACFVLGAFTY SDMIRYFVLV
GCAFAESNSG GDVIHLALIA VFNIQPAALV STFFRNRWTN RENLLLVIAA AMAQMAWSDV
GIEIMPIMNA MALAWMILKA VSIGTVSTIA MPILSGLAPP MEWFGLDVLR CLLLIVGVAA
LIKERKENLA KKKGALLISA GLALTGAFSP LVLQGALMLS ECATKRGWPA SEVLTAIGMT
IALAGSVARL DSGTMAIPLA TTSILFVSYV LSGKSTDMWI ERCADVTWEE EAEITGTSPR
LDVELDDNGD FKMINDPGVP MWMWASRMGL MCMAAYNPVL IPVSVAGYWM TRKIHKRGGV
LWDLPAPKQM GRSDMKPGVY RVMTSGVLGS YQSGVGVMYD GVFHTMWHVT QGAALRNGEG
RLNPTWGSVR DDLITYGGKW KLSATWDGTE EVQLIAAEPG KPVKNFQTRP GVFKTPAGEV
GAITLDFPKG TSGSPIVNKA GAVIGLYGNG LVLSHGAYVS AISQGERQEE EAPEAFTPEM
LRKRQLTILD LHPGAGKTRR VIPQIVREAV KQRLRTVILA PSRVVAAEIA EALRGLPVRF
QTSAVKAEHS GTEIVDVMCH ATLTQRLMTP MRVPNYNVFV MDEAHFTDPA SIAARGYIST
KVESGEAAAI FMTATPPGTI DPFPDSNSPI IDQEAEIPDR AWNSGFEWIT DYTGKTVWFV
PSVRSGNEIA MCLTKAGKKV IQLNRKSYET EYQKCKGNDW DYVVTTDISE MGANFGAHRV
IDSRKCVKPV IINDGEGRVQ LNGPLPITAS SAAQRRGRVG RDPTQSGDEY YYGGPITNDD
TGHAHWIEAK MLLDNIQLQN GLVAQLYKPE RDKVFATDGE YRLRGEQKKH FVELMRTGEL
PVWLSYKVAE AGINYTDRRW CFDGPHNNTI LEDNTEVEIW TRQGERKVLR PRWSDARVYS
DNQALRAFKE FAAGKRSAGS MMDVMARMPD YFWTKTMNAA DNLYVLATTE KGGRAHRAAL
EELPDTLETV LLIAMMSLAS CGMLALMMQR KGIGKTGMGT AVLTAVTILL WMADVPAPKI
AGVLLISFLL MIVLIPEPEK QRSQTDNHLA VFLICALLLV SAVSANEMGW LDTTKRDLGK
LFSGPSAVTT SRWEPLKLAL ALKPATAWAG YAGMTMLLTP LFRHLITTQY ISFSLTAITS
QASALFGLNS GYPFVGVDLS VVFLLVGCYG QYNLPTTMAT IGLLVGHYAF MIPGWQAEAM
RAAQRRTAAG VMKNAVVDGI VATDIPEMDT ATPIVEKKMG QVMLLIISAL AILLNPDTMT
VVEGGVLITA ALATLLEGNA NTVWNSTVAV GVCHLMRGGW AAGPSIGWTI IRNLEAPKVK
RGGIAAPTLG EIWKSRLNQL TREQFMEYRK DGIIEVDRTA ARRARREGNR TGGHPVSRGT
AKLRWLVERG FAKPLGKVVD LGCGRGGWSY YCATLRHVQE VRGYTKGGPG HEEPMLMQSY
GWNIVSMKSG IDVFYRPTEA CDTVLCDIGE SSPSPGVEEA RTLRVLEMIE PWLRTANQYC
VKVLCPYTPK VIERLEKLQR KYGGGLVRVP LSRNSNHEMY WVSEASSNLI NAVNATSQVL
LQRLEKDHRK GPRYEEDVDL GSGTRSVARR SPFMDTRKIH HRIERLKSEF STTWHYDCEH
PYRTWNYHGS YEVKPTGSAS SMVNGVVKLM SKPWDSIQSV LTMAMTDTTP FGQQRVFKEK
VDTKAPEPAP GVKAVLDLTT DWLWAVLCRR KKPRMCTKEE FIAKVNSHAA LGAIFEEQNQ
WASAREAVED PGFWNFVDKE RQAHLEGRCE TCIYNMMGKR EKKLGEFGKA KGSRAIWYMW
LGARFLEFEA LGFLNEDHWM SRENSYGGVE GKGLQKLGYI LQEISRKEGG HMFADDTAGW
DTRVTLTDLE NEAKITRWME PEHRKLAEAM IELTYKNKVV KVTRPGKEGK TVMDIISRND
QRGSGQVVTY ALNTYTNLAV QLIRCMEGEG LLEEEETMRI SDAKRRAVQA WLDTNGTERL
TPMAVSGDDC VVKPIDNRFA TALHFLNGMS KVRKDIQEWK PSTGWTNWQE VPFCSHHFNE
LVMRDGRKIV VPCRAQDELI GRARVSPGSG WSLRETACLG KAYAQMWLLM YFHRRDLRLM
ANAICSAVPI DWVPTGRTTW SIHGKGEWMT TEDMLAVWNR VWIFENEHME DKTPVYSWTD
VPYIGKREDQ WCGSLIGHRS RATWAENIYT PIMQVRNLIG AERYVDYMPA QTRFAHEAEL
QGGVL
